Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the long-term toxicity and activity profile of 2',3'-dideoxyinosine (ddI), a potent inhibitor of human immunodeficiency virus (HIV) replication, in vitro. 58 patients with AIDS or AIDS-related complex were studied with additional reference to the effect of previous treatment with zidovudine, and the effect of ddI on HIV-induced cognitive dysfunction. Doses above 9.6 mg/kg per day of ddI were frequently associated with toxicity (peripheral neuropathy, pancreatitis, or hepatitis). Doses of 9.6 mg/kg per day or below were well tolerated for up to 21 months. A subset of patients receiving 3.2-9.6 mg/kg per day of ddI had long-term immunological improvement and reduction of serum HIV p24 antigen. Immunological changes were especially seen in patients who had little previous zidovudine therapy. 5 patients with HIV-induced cognitive impairment improved with ddI. Thus, ddI may have anti-HIV activity at doses which are tolerated for long-term therapy, although pancreatitis could be a life-threatening complication.
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PMID:Long-term toxicity/activity profile of 2',3'-dideoxyinosine in AIDS or AIDS-related complex. 197 29

We examined the prevalence of HIV, general medical, and psychiatric comorbidities by age based on a recent multisite cohort of HIV infected veterans receiving care: the Veterans with HIV/AIDS 3 Site Study (VACS 3). VACS 3 includes 881 adult patients with HIV infection enrolled between June 1999 and July 2000. Providers reported their patients' CDC-defined HIV comorbidities, general medical comorbidities (based on Duke and Charlson comorbidity scales), and psychiatric comorbidity. Mean age of participants was 49 years and 54% were African-American. The most common HIV comorbidities were oral candidiasis (21%), peripheral neuropathy (16%), and herpes zoster (16%). The most common general medical comorbidities included chemical hepatitis (53%), hypertension (24%), and hyperlipidemia (17%). The mean number of HIV and general medical comorbidities experienced by patients were respectively 1.1 and 1.4 (P < .001). Older (> or = 50 years) HIV-infected patients experienced a greater number of general medical comorbidities than those < 50 years (respectively 1.7 versus 1.2, P < .001). There was no significant difference in mean HIV comorbidity number by age. Based on patient report, 46% had significant depressive symptoms (> or = 10 on 10-item CES-D) and 21% reported at-risk drinking (> or = 8 on AUDIT). Providers reported 32% of patients had anxiety, 4% mania, 4% schizophrenia, and 11% cognitive impairment/dementia. General medical and psychiatric comorbidities constituted a higher disease burden for HIV-infected veterans than HIV comorbidities. Whether these comorbidities are due to antiretroviral drug toxicity or are age or lifestyle-associated conditions, the substantial prevalence of these "non-HIV" comorbidities suggest an important role for general medical and psychiatric management of HIV-infected patients.
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PMID:General medical and psychiatric comorbidity among HIV-infected veterans in the post-HAART era. 1175 Feb 6

Patients with chronic hepatitis C virus (HCV) infection frequently report fatigue, lassitude, depression, and a perceived inability to function effectively. Several studies have shown that patients exhibit low quality-of-life scores that are independent of disease severity. We therefore considered whether HCV infection has a direct effect on the central nervous system, resulting in cognitive and cerebral metabolite abnormalities. Twenty-seven viremic patients with biopsy-proven mild hepatitis due to HCV and 16 patients with cleared HCV were tested with a computer-based cognitive assessment battery and also completed depression, fatigue, and quality-of-life questionnaires. The HCV-infected patients were impaired on more cognitive tasks than the HCV-cleared group (mean [SD]: HCV-infected, 2.15 [1.56]; HCV-cleared, 1.06 [1.24]; P =.02). A factor analysis showed impairments in power of concentration and speed of working memory, independent of a history of intravenous drug usage (IVDU), depression, fatigue, or symptom severity. A subgroup of 17 HCV-infected patients also underwent cerebral proton magnetic resonance spectroscopy (1H MRS). The choline/creatine ratio was elevated in the basal ganglia and white matter in this group. Patients who were impaired on 2 or more tasks in the battery had a higher mean choline/creatine ratio compared with the unimpaired patients. In conclusion, these preliminary results demonstrate cognitive impairment that is unaccounted for by depression, fatigue, or a history of IVDU in patients with histologically mild HCV infection. The findings on MRS suggest that a biological cause underlies this abnormality.
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PMID:Hepatitis C and cognitive impairment in a cohort of patients with mild liver disease. 1182 20

Drug abuse is a major problem worldwide. The incidence of drug-related deaths attributed to opiate abuse is increasing annually. Apart from routine examination, little is known of the neuropathology of drug abuse. We, and others, have shown previously that drug abuse is associated with microglial activation. We hypothesised that neuroinflammation might lead to premature neurodegeneration in drug abusers. We investigated the brains of young opiate abusers (n=34, all<40 years) for the presence of proteins associated with neurodegenerative diseases and compared them with the brains of age-matched, non-drug users (n=16) all of whom died suddenly. Detailed immunohistochemical analysis of the hippocampus, brainstem and basal ganglia for hyperphosphorylated tau, beta-amyloid, beta-amyloid precursor protein (betaAPP) and ubiquitin demonstrated an excess of AT 8-positive neurofibrillary tangles (NFT) in the drug abusers. These were not only more prevalent in the drug abusers than in controls (44%vs. 19%) but also involved more brain areas. In controls NFT were confined to the entorhinal cortex whereas in drug users they were also found in the subiculum, temporal neocortex, nucleus basalis of Meynert and the locus coeruleus. Virtually no amyloid plaques were present but betaAPP positivity was again much more common in drug abusers than controls (73%vs. 20% in the brainstem and 59%vs. 23% in the temporal lobe). There is no suggestion that these drug abusers had displayed major cognitive impairment although detailed neuropsychological assessment is difficult in this subject group. Likely causes of hyperphosphorylated tau deposition in drug abuse include hypoxic-ischaemic injury, microglial-associated cytokine release and possibly drug-associated neurotoxicity or hepatitis. Head injury, which is another major risk factor, does not appear to have contributed to our findings. Genetic factors also merit consideration. It is unclear at present how much of the hyperphosphorylated tau detected in these young drug abusers represents a transitory phenomenon.
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PMID:Hyperphosphorylated tau and amyloid precursor protein deposition is increased in the brains of young drug abusers. 1600 28

3 patients with liver failure developed hepatic encephalopathy. 2 patients, men aged 60 and 72 years, had chronic liver disease and presented with episodes of confusion. They recovered after being treated with lactulose. The third patient, a 37-year-old woman, became comatose shortly after the onset of acute liver failure due to acute autoimmune hepatitis. She died before a suitable donor liver became available. Hepatic encephalopathy is a syndrome of potential reversible neurological symptoms. Especially in the early stages of the condition, hepatic encephalopathy can be difficult to diagnose. Patients may present with mild cognitive impairment or episodes characterized by neurological symptoms. Hepatic encephalopathy is a clinical diagnosis. The pathophysiologic mechanism is only partly understood but toxicity of ammonia on the central nervous system seems to be of major importance. Raised ammonia concentrations or EEG findings consistent with metabolic encephalopathy may support but are not essential to the diagnosis. Episodes of hepatic encephalopathy are often elicited by an underlying disease such as infection or gastro-intestinal bleeding. It is important to recognize hepatic encephalopathy in its early stages because adequate treatment of the condition and any underlying disease reduces morbidity and mortality.
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PMID:[Confusion and abnormal liver enzyme levels: problems with diagnosing hepatic encephalopathy]. 1836 Nov 99

Alzheimer's disease (AD) is the leading cause of dementia. It is characterized by the presence of senile plaques and neurofibrillary tangles in the brain, and impairment of the central cholinergic system, which contribute to memory loss and cognitive dysfunction. Cholinesterase inhibitors prevent the hydrolysis of acetylcholine and are currently approved for the symptomatic treatment of Alzheimer's disease. Donepezil, a piperidine-based, reversible and specific inhibitor of acetylcholinesterase, has been demonstrated to be clinically effective in the treatment of patients with mild to moderate AD. To date, clinical trials have not reported an association between treatment with donepezil and hepatotoxicity. We describe a case of toxic hepatitis, documented by liver biopsy, in a patient treated with donepezil.
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PMID:Donepezil-related toxic hepatitis. 1918 68

Anti-ribosomal phosphoprotein autoantibodies (anti-RP Abs) are highly specific for SLE, especially for neuropsychiatric manifestations including psychosis, mood disorders, anxiety, cognitive dysfunction and delirium. In addition to the neuropsychiatric involvement, anti-RP antibodies are believed to be correlated with nephritis, hepatitis and dermal diseases in SLE. Several studies indicate the association between increased titers of anti-RP Abs in the patient's sera and active SLE disease. The reported prevalence of anti-RP Abs among SLE patients is 10%-40%. Recently, a connection between the presence of anti-RP Abs in the serum and class V lupus nephritis has been demonstrated. Anti-RP Abs binds 3 ribosomal proteins identified as P0, P1 and P2 (38, 19 and 17-kDa, respectively) by recognizing a certain epitope found in those 3 proteins. This specific epitope contains 22 amino acids at the C terminal end (C-22) of the protein. There are studies in the literature relating to the involvement of anti-RP Abs in the pathogenesis of organ damage. The main pathways described are cross-reaction with anti-dsDNA antibodies, a cytotoxic effect on mesangium cell proliferation, invasion into living cells and onset of apoptosis, a defect in the synthesis of apolipoprotein B resulting in accumulation of lipids inside the cell, and downregulation of the total protein synthesis. The authors provide an updated review concerning the multisystem involvement of anti-RP Abs in SLE, particularly in the brain, kidney and liver. Moreover, this article includes a summary of the most relevant studies regarding the cellular involvement of anti-RP Abs.
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PMID:[The clinical importance of anti-ribosomal-P antibodies]. 2191 4

Hepatic encephalopathy (HE) is a syndrome observed in patients with liver dysfunction such as hepatitis and cirrhosis, and is characterized by cognitive impairment, personality changes, and a depressed level of consciousness. The detailed mechanism underlying the pathogenesis of HE remains unclear. In the present study, our aim was to establish an animal model for HE with cirrhosis. Therefore, we carried out behavioral and biochemical analysis of cirrhotic rats after treatment with thioacetamide (TAA) for 20 weeks. The rats subjected to chronic TAA treatment (TAA rats) showed reduction of cognitive scores in the novel object recognition test (NOR), and a decrease in immobility and an increase in swimming in the forced swim test (FST). In biochemical analyses, the TAA rats exhibited elevated blood levels of ammonia, and increased metabolic activities of serotonergic and noradrenergic neurons in the brain, while the levels of Glu and GABA were not affected. Post-oral treatment of lactulose, a clinically utilized drug for HE, effectively reduced the elevated blood ammonia levels, and restored the reduced cognitive scores and the decreased immobility, without any effects on neurotransmitter contents in the brain, compared with the control. These results indicated lactulose-restorable memory disturbance and irritated mood in the TAA rats. In other words, rats treated chronically with TAA are a potential model for cirrhosis-HE, and the combination of NOR and FST in TAA rats may be useful as a simple assay system for the screening and development of anti-HE agents.
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PMID:Behavioral and biochemical characterization of rats treated chronically with thioacetamide: proposal of an animal model for hepatic encephalopathy associated with cirrhosis. 2320 32

Primary biliary cirrhosis (PBC) is an autoimmune cholestatic liver disease characterised by a breakdown of immune tolerance to mitochondrial and nuclear antigens, causing injury to the biliary epithelial cells (BEC) lining the small intrahepatic bile ducts. This leads to bile duct injury and the retention of hydrophobic bile acids which cause further BEC injury leading to a self-sustaining cycle of bile duct injury. Initially the BEC respond to injury via a homeostatic response including through proliferation. Ultimately they become senescent; an active process with accompanying release of inflammatory cytokines ('the senescent secretome') which contributes to the process of interface hepatitis which is a feature of high-risk and treatment-unresponsive disease. This model for pathogenesis of PBC has implications for potential therapy approaches in targeting both the 'upstream' immune injury and 'downstream' BEC response to the immune injury. Fatigue is the commonest reported symptom in PBC and has a negative impact on patients' perceived quality of life, often through social isolation. It is unrelated to the severity of liver disease and appears unresponsive to current therapies, including ursodeoxycholic acid and transplantation. Fatigue in PBC is complex, with numerous associated peripheral and CNS features. Initially, cholestasis causes degenerative CNS change affecting areas of the brain regulating autonomic dysfunction and sleep, and these changes lead directly to some manifestations of fatigue and the associated cognitive impairment. In addition to this, the anti-mitochondrial antibody has direct muscle level metabolic effects leading to over-utilisation of anaerobic metabolism. Autonomic dysfunction contributes to the impact of this metabolic change by limiting the capacity of the muscle to respond through increased proton/lactate efflux from cells and outflow from tissues. The model has a number of implications for potential therapy approaches.
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PMID:Pathogenesis of primary biliary cirrhosis and its fatigue. 2503 96

Smith-Magenis syndrome (SMS) is a sporadic congenital disorder involving multiple organ systems caused by chromosome 17p11.2 deletions. Smith-Magenis syndrome features craniofacial and skeletal anomalies, cognitive impairment, and neurobehavioral abnormalities. In addition, some SMS patients may exhibit hypogammaglobulinemia. We report the first case of SMS-associated autoimmunity in a woman who presented with adult onset of multiple autoimmune disorders, including systemic lupus erythematosus, antiphospholipid antibody syndrome, and autoimmune hepatitis. Molecular analysis using single-nucleotide polymorphism array confirmed a de novo 3.8-Mb deletion (breakpoints, chr17: 16,660,721-20,417,975), resulting in haploinsufficiency for TACI (transmembrane activator and CAML interactor). Our data are consistent with potential loss of function for the BAFF (B cell-activating factor) receptor TACI as a contributing factor to human autoimmune phenomena.
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PMID:Immune complex-mediated autoimmunity in a patient With Smith-Magenis syndrome (del 17p11.2). 2503 69


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