Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary care physicians will be providing longitudinal health care for long-term survivors of childhood acute lymphoblastic leukemia (ALL) with increasing frequency. Late effects (sequelae) secondary to treatment with radiation or chemotherapeutic agents are frequent and may be serious. Depending on treatment exposures, this at-risk population may experience life-threatening late effects, such as cirrhosis secondary to hepatitis C or late-onset anthracycline-induced cardiomyopathy, or life-changing late effects, such as cognitive dysfunction. Many survivors of childhood ALL will develop problems such as obesity and osteopenia at a young age, which will significantly affect their risk for serious health outcomes as they grow older. The goal of our review is to assist primary care physicians in providing longitudinal health care for long-term survivors of childhood ALL. We also highlight areas needing further investigation, including the prevalence of different late effects, determination of risk factors associated with a late effect, a better understanding of the potential impact of late effects on the premature development of common adult health problems, and the value and timing of different tests for screening asymptomatic survivors.
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PMID:Providing primary care for long-term survivors of childhood acute lymphoblastic leukemia. 1113 63

The P300 event related potential (P3ERP) latency has recently been advocated for detection of cognitive disturbances in early encephalopathy associated with chronic liver disease. The present study was undertaken to assess the magnitude of cognitive dysfunction, a marker of subclinical hepatic encephalopathy (SHE), in India, using this widely recommended test. One hundred and one patients with cirrhosis of the liver (17 females, 84 males; Age 43.3 +/- 11 years, 33 alcoholic, 49 viral induced, 19 cryptogenic) attending our tertiary care hospital were studied. P300 responses were elicited by the standard 'auditory odd ball paradigm'. A value of mean+2SD of the latency obtained in 40 age matched controls was established as a cut off to define latency prolongation in patients. The mean P3ERP latency of cirrhotics (363.6 +/- 32.1 msec) was significantly longer (p<0.05) than those of controls (347.8 +/- 24.8 msec). No difference was found in the latencies of cirrhotics with or without alcoholic aetiology of liver disease. 21 (20.8%) cirrhotics were found to have SHE i.e. latency prolongation beyond the cutoff value. A higher proportion of patients in advanced stage of liver disease had prolongation in latencies (p<0.02) compared to less severe cases. Till the time a gold standard is derived for detection of SHE, P3ERP latencies seem to be a reasonable method for detection as well as follow up of patients. Since SHE is considered as a preclinical stage of overt encephalopathy, it would be worthwhile screening cirrhotics for cognitive disturbances using P3ERP latencies and administering prompt therapeutic action.
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PMID:Utility of P300 auditory event related potential in detecting cognitive dysfunction in patients with cirrhosis of the liver. 1179 6

Hepatitis C is the most common cause of chronic liver disease in the United States and it significantly reduces quality of life. The role of cognitive deficits contributing to the morbidity of this disease has not been well characterized. The purpose of this study was to examine cognitive functioning in patients with chronic hepatitis C and to investigate relationships among parameters of disease severity and performance on neuropsychological tests. Sixty-six patients with chronic hepatitis C and 14 patients with other chronic liver diseases were administered a brief battery of neuropsychological tests assessing attention, visuoconstructional ability, learning, memory, and psychomotor speed. Cognitive impairment in patients with chronic hepatitis C ranged from 0% on a visuoconstructional task to 82% on a measure of sustained attention and concentration. Test scores of patients with chronic hepatitis C did not differ from those of patients with other chronic liver diseases. Hence, patients with and without chronic hepatitis C experience cognitive deficits, especially in tasks requiring attention and psychomotor speed. In addition, there was a significant relationship between fibrosis stage and test performance, with greater fibrosis associated with poorer performance. However, both patients with and without cirrhosis exhibited cognitive dysfunction. In conclusion, these findings suggest that progressive hepatic injury may result in cognitive problems even before the development of cirrhosis. Future studies need to determine the effect of this decrease in cognitive function on quality of life.
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PMID:Neuropsychological impairment in patients with chronic hepatitis C. 1182 21

There are at least two types of cannabinoid receptors, CB(1) and CB(2), both coupled to G proteins. CB(1) receptors exist primarily on central and peripheral neurons, one of their functions being to modulate neurotransmitter release. CB(2) receptors are present mainly on immune cells. Their roles are proving more difficult to establish but seem to include the modulation of cytokine release. Endogenous agonists for cannabinoid receptors (endocannabinoids) have also been discovered, the most important being arachidonoyl ethanolamide (anandamide), 2-arachidonoyl glycerol and 2-arachidonyl glyceryl ether. Other endocannabinoids and cannabinoid receptor types may also exist. Although anandamide can act through CB(1) and CB(2) receptors, it is also a vanilloid receptor agonist and some of its metabolites may possess yet other important modes of action. The discovery of the system of cannabinoid receptors and endocannabinoids that constitutes the "endocannabinoid system" has prompted the development of CB(1)- and CB(2)-selective agonists and antagonists/inverse agonists. CB(1)/CB(2) agonists are already used clinically, as anti-emetics or to stimulate appetite. Potential therapeutic uses of cannabinoid receptor agonists include the management of multiple sclerosis/spinal cord injury, pain, inflammatory disorders, glaucoma, bronchial asthma, vasodilation that accompanies advanced cirrhosis, and cancer. Following their release onto cannabinoid receptors, endocannabinoids are removed from the extracellular space by membrane transport and then degraded by intracellular enzymic hydrolysis. Inhibitors of both these processes have been developed. Such inhibitors have therapeutic potential as animal data suggest that released endocannabinoids mediate reductions both in inflammatory pain and in the spasticity and tremor of multiple sclerosis. So too have CB(1) receptor antagonists, for example for the suppression of appetite and the management of cognitive dysfunction or schizophrenia.
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PMID:Cannabinoid receptors and their ligands. 1205 30

Psychometric performance has been reported to be related to brain atrophy in cirrhotics, but the relationship between brain atrophy and EEG findings is still unknown. The aim of this study was to ascertain the relationship among brain atrophy, EEG, and cognitive performance in cirrhotics. Sixty-eight cirrhotics (age = 55 +/- 10 years; males-66%) underwent psychometric evaluation (Symbol Digit Test, Trail Making Test-Part A, Scan test), EEG recording and spectral analysis (S-EEG), and brain CT scan. Central brain atrophy was ascertained by the following indexes of brain atrophy: the Evans' index, the bicaudate index, the cella media index, the bifrontal index, and the ventricular index; cortical brain atrophy by the sulci index. The severity of liver failure was assessed by the Child-Pugh score: 18% of patients were Child-Pugh Class A, 50% Class B, and 32% Class C. Central and cortical atrophies were found to be correlated with age, but not with the Child-Pugh score. Psychometric performance and the EEG mean dominant frequency (MDF) were found to be correlated with brain atrophy. Multivariate analysis showed that a poor psychometric performance was independently predicted by EEG slowing (MDF: p < 0.01) and by central brain atrophy (cella media index: p < 0.01). In conclusion, brain atrophy was associated with a poor psychometric performance and EEG alterations in cirrhosis. Both brain atrophy and EEG alterations independently predicted cognitive dysfunction in cirrhotic patients.
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PMID:Neuropsychological-neurophysiological alterations and brain atrophy in cirrhotic patients. 1260 83

Hepatitis C virus (HCV) infection is a major public-health-care problem, with over 170 million infected worldwide. Patients with chronic HCV infection often complain of various cognitive problems as well as symptoms of depression, anxiety, and fatigue. Relatively little is known, however, about the specific cognitive deficits that are common among HCV patients, and the influence of psychiatric symptomatology on cognitive functioning. In the current study of 21 chronically infected HCV patients, we assessed subjective cognitive dysfunction, depression, anxiety, and fatigue and compared these symptom areas to cognitive tests assessing visuoconstruction, learning, memory, visual attention, psychomotor speed, and mental flexibility. Results revealed that cognitive impairment ranged from 9% of patients on a visuoconstruction task to 38% of patients on a measure of complex attention, visual scanning and tracking, and psychomotor speed, and greater HCV disease severity as indicated by liver fibrosis was associated with greater cognitive dysfunction. Objective cognitive impairment was not related to subjective cognitive complaints or psychiatric symptomatology. These findings suggest that a significant portion of patients with chronic HCV experience cognitive difficulties that may interfere with activities of daily living and quality of life. Future research using cognitive measures with HCV-infected patients may assist researchers in identifying if there is a direct effect of HCV infection on the brain and which patients may be more likely to progress to cirrhosis and hepatic encephalopathy.
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PMID:Cognitive functioning and psychiatric symptomatology in patients with chronic hepatitis C. 1463 43

HE is a serious complication of alcoholic liver disease that contributes to cognitive dysfunction in chronic alcoholic patients. In patients with HE, the damaged liver can no longer remove neurotoxic substances such as ammonia and manganese from the blood. As a result, these molecules may enter the brain, where they can exert a variety of harmful effects that interfere with normal neurotransmitter activity, impair motor functions, and cause structural alterations in the astrocytes. To prevent or treat HE in alcoholic patients with cirrhosis, physicians currently rely primarily on strategies to lower blood ammonia concentrations as well as on liver transplantation in patients with end-stage liver disease; new approaches also are also being investigated.
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PMID:Hepatic encephalopathy--a serious complication of alcoholic liver disease. 1530 24

Hyperammonemia is the main responsible for the neurological alterations in hepatic encephalopathy in patients with liver failure. We studied the function of the glutamate-nitric oxide (NO)-cGMP pathway in brain in animal models of hyperammonemia and liver failure and in patients died with liver cirrhosis. Activation of glutamate receptors increases intracellular calcium that binds to calmodulin and activates neuronal nitric oxide synthase, increasing nitric oxide, which activates soluble guanylate cyclase (sGC), increasing cGMP. This glutamate-NO-cGMP pathway modulates cerebral processes such as circadian rhythms, the sleep-waking cycle, and some forms of learning and memory. These processes are impaired in patients with hepatic encephalopathy. Activation of sGC by NO is significantly increased in cerebral cortex and significantly reduced in cerebellum from cirrhotic patients died in hepatic coma. Portacaval anastomosis in rats, an animal model of liver failure, reproduces the effects of liver failure on modulation of sGC by NO both in cerebral cortex and cerebellum. In vivo brain microdialisis studies showed that sGC activation by NO is also reduced in vivo in cerebellum in hyperammonemic rats with or without liver failure. The content of alpha but not beta subunits of sGC are increased both in frontal cortex and cerebellum from patients died due to liver disease and from rats with portacaval anastomosis. We assessed whether determination of activation of sGC by NO-generating agent SNAP in lymphocytes could serve as a peripheral marker for the impairment of sGC activation by NO in brain. Chronic hyperammonemia and liver failure also alter sGC activation by NO in lymphocytes from rats or patients. These findings show that the content and modulation by NO of sGC are strongly altered in brain of patients with liver disease. These alterations could be responsible for some of the neurological alterations in hepatic encephalopathy such as sleep disturbances and cognitive impairment.
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PMID:Alterations in soluble guanylate cyclase content and modulation by nitric oxide in liver disease. 1531 89

Event-related P300 potentials that closely reflect cognitive brain functions show significant age-related latency prolongations. This aging-P300 interaction can best be approximated by third-order polynomial regressions. To delineate the clinical impact this special kind of regression function may have on detecting early cognitive dysfunction, we applied visual P300 potential data of healthy subjects (n = 344; age range, 18-98 years) to nondemented patients with either (i) chronic liver disease (n = 104; age range, 19-74 years) or (ii) cerebral arteriosclerosis (n = 80; age range, 38-80 years). As compared with linear regressions, third-order polynomial regressions for the age-related changes in P300 potential latencies showed a smaller latency increase during middle age, with an accelerating latency prolongation from age 60 onward. In patients with liver cirrhosis, third-order polynomial regressions yielded a rate of abnormal P300 potential latencies exceeding that of linear regressions absolutely by 17-21%, and relatively by 67-71%. Although the rate of P300 abnormalities was much lower in the CAD patients with either regression model, the relative increase in P300 abnormalities due to third-order polynomial regressions was 40-112.5%. In conclusion, normal data for the latencies of P300 potentials based on third-order polynomial regressions result in a higher sensitivity of P300 potentials for detecting early cognitive dysfunction. This gain in diagnostically important information is not offset by a loss in specificity, and may depend on the kind as well as stage of the disease, the age distribution of the patients and the degree of the P300 potential abnormalities.
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PMID:The impact of age-related changes in event-related P300 potentials on detecting early cognitive dysfunction. 1537 98

Hepatic encephalopathy is the most obvious neurological consequence of chronic hepatitis C virus (HCV) infection. There are also case reports of HCV-associated cerebral vasculitis. This review is concerned with the possibility of an effect of HCV on cerebral dysfunction, occurring at an early stage of chronic infection, prior to the development of cirrhosis and unrelated to vasculitis. There is emerging evidence of mild, but significant neurocognitive impairment in HCV infection, which cannot be attributed to substance abuse, coexistent depression, or hepatic encephalopathy. In vivo magnetic resonance spectroscopy and neurophysiological studies have suggested that a biological mechanism may underlie these cognitive findings. The recent detection of HCV genetic sequences in postmortem brain tissue raises the intriguing possibility that HCV infection of the central nervous system may be related to the reported neuropsychological symptoms and cognitive impairment.
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PMID:Central nervous system involvement in hepatitis C virus infection. 1555 29


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