Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the discovery of hepatitis C virus (HCV) in 1989, significant advances have been made in our understanding of this important viral pathogen. Children at risk for HCV infection include recipients of potentially contaminated blood products and organ transplants, and infants born to HCV-infected mothers. Chronic HCV infection is usually asymptomatic in children but active hepatitis, cirrhosis and hepatocellular carcinoma can occur. The development of treatment strategies for chronic hepatitis C in children has directly evolved from clinical trials in adults. Sustained virologic response, defined by undetectable HCV RNA in serum 24 wk after completion of treatment, occurs in approximately 36% of children treated with conventional interferon alone and in about 50% of those given conventional interferon in combination with ribavirin. Pegylated interferon-based treatment regimens are better than those based on conventional interferon in adults but little is known about pegylated interferon in children. Factors associated with a favorable response to antiviral therapy in children are similar to those in adults and include infection with HCV genotype 2 or 3 and low pretreatment serum HCV RNA levels. Treatment related adverse events in children include 'flu-like' syndrome, fatigue, anorexia, weight loss, depression, anemia, leukopenia and thrombocytopenia.
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PMID:Treatment of chronic hepatitis C in children. 1559 40

An outbreak of canine parvovirus type 2 infection caused by the Glu-426 mutant in 2 litters of pups is reported. The infected pups (n = 6) were monitored daily for evidence of clinical signs and hematological changes and for the evaluation of viral shedding in the feces. The disease induced by the Glu-426 mutant was mild in all the infected pups. Vomiting and hemorrhagic diarrhea were not observed; however, the pups developed mucoid diarrhea (3.5 median days), depression (1.5 median days), and relative leukopenia and lymphopenia (2.5 median days). Fever and loss of appetite were observed only in 2 pups. Virus was detected in the feces for 4.5, 6.5, and 46 median days by hemagglutination, virus isolation on cell cultures, and real-time polymerase chain reaction (PCR), respectively. By real-time PCR, the highest viral DNA titers were detected in the feces of both litters at day 10, reaching median values of more than 10(10) DNA copies/mg of feces.
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PMID:Clinical and virological findings in pups naturally infected by canine parvovirus type 2 Glu-426 mutant. 1582 93

Hepatitis C virus is the most common chronic blood-borne infection in the United States. The advent of new treatment regimens using pegylated interferons in combination with ribavirin has led to improved sustained viral response rates for some genotypes in large multicenter trials. Advances in the management of side effects and toxicities have expanded the pool of treatable patients. A recent National Institutes of Health consensus conference recommended that all patients who have bridging hepatic fibrosis and moderate inflammation together with detectable viremia should receive treatment with pegylated interferon and ribavirin. Unfortunately, these medications are very expensive and have significant side effects. Hematologic toxicities include anemia and leukopenia. These can be managed with close monitoring, use of growth factors, or dose reductions. Depression also can be caused or exacerbated by these medicines and may require treatment with a selective serotonin reuptake inhibitor, comanagement with psychiatry, or cessation of pegylated interferon and ribavirin treatment. Contraception is imperative because ribavirin is highly teratogenic. Influenza-like symptoms of fatigue, nausea, and mild fevers can be helped by quality patient education and support including frequent office visits. Data from randomized controlled trials demonstrating improvements in long-term survival as a result of treatment are not yet available, but it appears that patients who have no detectable virus six months after treatment have a good chance of remaining virus free for at least five years.
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PMID:Using pegylated interferon and ribavirin to treat patients with chronic hepatitis C. 1612 55

Quality of life studies in chronic hepatitis C using specific questionnaires have been performed in mono-infected patients; however, these studies have just begun in HIV-HCV co-infected patients. The questionnaires used in mono-infected patients are not well adapted for co-infected patients and need to be redesigned. Typically, co-infected patients have multiple symptoms that may be attributable to HIV, to HCV, to a combination of both diseases or even to side effects related to drug therapy. These patients usually need substitutive therapy to manage side effects related to HCV therapy, particularly anaemia, leukopenia and depression. There are no cost-effectiveness studies published on the current HCV standard therapy with pegylated interferon and ribavirin. However, there is some research on the old standard interferon and ribavirin, which shows that HCV therapy is cost-effective. Cost-effectiveness studies in co-infected patients will have to take into account variables that do not affect mono-infected patients, such as the different levels of CD4, the increase in the fibrosis progression rate and the use of other expensive drugs for the management of side effects. Currently, the literature does not provide adequate information on the effect of HCV infection on the quality of life of HIV-HCV co-infected patients or the most cost-effective HCV therapy.
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PMID:Quality of life and cost-effectiveness of anti-HCV therapy in HIV-infected patients. 1636 Feb 35

Circulating homocysteine is a risk factor of cardiovascular and cerebrovascular events. Hyperhomocysteinemia may be an early indicator for vitamin B12 disorders because cobalamin is a cofactor in the remethylation process of homocysteine. Serum holotranscobalamin (holoTC II) becomes decreased before the development of metabolic dysfunction. In this study, we assessed circulating holoTC II to estimate the diagnosis of vitamin B12 deficiency in the first ischemic cerebrovascular attack. We also compared the efficacy of the measurement of plasma holoTC II with the other standard biochemical and hematological markers used to reach the diagnosis of cobalamin deficiency. Forty-five patients (age 71 years (range 35-90), 16 men/29 women) within the first ischemic cerebrovascular event were included in this prospective study. All the enrolled patients have been administered vitamin B12 1 mg intramuscular injection once a day for 10 days. At the baseline and on the tenth day of treatment, plasma levels of holoTC II and the proper biochemical and hematological markers in diagnosing cobalamin deficiency were measured. After admission, anemia and diminished serum vitamin B12 levels were determined to be only 20% (9/45) and 44% (20/45), respectively; 78% (35/45) of the patients had low serum holoTC II (<37 pmol/l). Serum homocysteine was higher in patients (49% of them) who had previously suffered a stroke. Thrombocytopenia, hypersegmentated neutrophils, and indirect hyperbilirubinemia were observed in 20% of the patients. Leukopenia and macrocytosis were not evident in any of them. In 18 of 27 patients (67%) that had low holoTC II levels after joining the study and who remained in the study until the end of cobalamin treatment, serum holoTC II levels returned to normal values. Cobalamin deficiency should be considered in patients with cerebrovascular diseases, even if anemia, elevated mean cell volume, depression of the serum cobalamin, or other classic hematological and/or biochemical abnormalities are lacking. Furthermore, measurement of serum holoTC II looks promising as a first-line of tests for diagnosing early vitamin B12 deficiency.
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PMID:Measuring holotranscobalamin II, an early indicator of negative vitamin B12 balance, by radioimmunoassay in patients with ischemic cerebrovascular disease. 1799 30

The aim of this study was to assess morbidity and the incidence of adverse effects during interferon (IFN)-alpha-2a treatment of patients with chronic hepatitis B. This prospective study included 48 consecutive patients with chronic hepatitis B who underwent IFN-alpha-2a treatment from January 2003 to August 2005. Adverse effects related to IFN treatment were recorded during this period and for 6 mo after treatment. Adverse effects that led to dose reduction or early discontinuation of IFN treatment were examined. Complete response was reported in 25% of patients. At least 1 adverse effect was documented in 88% of patients. Flu-like symptoms were the most frequently observed adverse effects (88%), and thrombocytopenia (63%), leukopenia (54%), and anemia (23%) were also reported. Bleeding occurred in 2 patients. Other adverse effects included neuropsychiatric signs (21%), alopecia (19%), weight loss (17%), thyroid disorders (19%), menstrual cycle irregularities (8%), skin lesions (8%), and dry cough (4%). Adverse effects that led to dose reduction or early discontinuation of IFN treatment occurred in 19% of patients and included impotence, depression, seizure, thyroid disorders, severe thrombocytopenia, and intestinal bleeding. These effects were found to be unrelated to treatment response. No relationship was detected between patient age, duration of treatment, and adverse effects of IFN. Although IFN-alpha-2a treatment induced various adverse effects in patients with chronic hepatitis B, most of these effects were reversible or could be ameliorated. Adverse effects that led to dose reduction or early discontinuation of IFN treatment were found to be unrelated to complete response.
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PMID:Adverse effects of high-dose interferon-alpha-2a treatment for chronic hepatitis B. 1802 21

Very little is known about the role that evolutionary dynamics plays in diseases caused by mammalian DNA viruses. To address this issue in a natural host model, we compared the pathogenesis and genetics of the attenuated fibrotropic and the virulent lymphohematotropic strains of the parvovirus minute virus of mice (MVM), and of two invasive fibrotropic MVM (MVMp) variants carrying the I362S or K368R change in the VP2 major capsid protein, in the infection of severe combined immunodeficient (SCID) mice. By 14 to 18 weeks after oronasal inoculation, the I362S and K368R viruses caused lethal leukopenia characterized by tissue damage and inclusion bodies in hemopoietic organs, a pattern of disease found by 7 weeks postinfection with the lymphohematotropic MVM (MVMi) strain. The MVMp populations emerging in leukopenic mice showed consensus sequence changes in the MVMi genotype at residues G321E and A551V of VP2 in the I362S virus infections or A551V and V575A changes in the K368R virus infections, as well as a high level of genetic heterogeneity within a capsid domain at the twofold depression where these residues lay. Amino acids forming this capsid domain are important MVM tropism determinants, as exemplified by the switch in MVMi host range toward mouse fibroblasts conferred by coordinated changes of some of these residues and by the essential character of glutamate at residue 321 for maintaining MVMi tropism toward primary hemopoietic precursors. The few viruses within the spectrum of mutants from mice that maintained the respective parental 321G and 575V residues were infectious in a plaque assay, whereas the viruses with the main consensus sequences exhibited low levels of fitness in culture. Consistent with this finding, a recombinant MVMp virus carrying the consensus sequence mutations arising in the K368R virus background in mice failed to initiate infection in cell lines of different tissue origins, even though it caused rapid-course lethal leukopenia in SCID mice. The parental consensus genotype prevailed during leukopenia development, but plaque-forming viruses with the reversion of the 575A residue to valine emerged in affected organs. The disease caused by the DNA virus in mice, therefore, involves the generation of heterogeneous viral populations that may cooperatively interact for the hemopoietic syndrome. The evolutionary changes delineate a sector of the surface of the capsid that determines tropism and that surrounds the sialic acid receptor binding domain.
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PMID:Evolution to pathogenicity of the parvovirus minute virus of mice in immunodeficient mice involves genetic heterogeneity at the capsid domain that determines tropism. 1804 43

Clozapine remains one of the most commonly used antipsychotic medications in China. As China has the largest population internationally on clozapine treatment, its experience and research findings are of keen interest to Western psychiatrists. However, most of the related papers have hitherto been published only in Chinese language journals. Here we review mainly Chinese-language publications on the use of clozapine in China. A descriptive study based on literature identified from searches of Medline and the China National Knowledge Infrastructure (CNKI) databases (1979-2007), and other hand-picked references. Unlike the situation in other countries, clozapine is still widely used for a number of psychiatric disorders in China, though the prescription of other second-generation antipsychotics (SGAs) is also increasing. About 25-60% of all treated patients with schizophrenia receive clozapine; and clozapine is preferred by some as a first-line treatment for schizophrenia. Clozapine is also used for other conditions such as mania, treatment-resistant depression and drug abuse. The average daily dose is between 200 and 400 mg. The incidence of leukopenia is 3.92% and agranulocytosis 0.21% in China, with about one third of reported cases of patients with agranulocytosis dying. Weight gain and clozapine-associated diabetes are also commonly reported in the Chinese population. Clozapine is currently the most commonly used treatment for schizophrenia in China. Chinese psychiatrists need to pay more attention to its potential toxic side effects when they make drug choices.
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PMID:Clozapine in China. 1820 45

Thirty patients with various solid tumors were treated with 5-azacytidine. Total doses ranged from 1.0 to 24.0 mg/kg and were given over a minimal period of 8 days. The major toxic effect was hematologic with significant leukopenia and thrombocytopenia usually occurring 20-30 days after the start of therapy, especially at higher dose levels. The marrow depression lasted 1-5 weeks and was fully reversible. Nausea and mild diarrhea were common following injection of the drug. Serum glutamic oxaloacetic transaminase levels rose in several patients. No other evidence of hepatic toxicity was seen. Objective remissions were noted in seven of 11 patients with cancer of the breast, two of five with melanoma, and two of six with cancer of the colon.
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PMID:Phase I study of 5-azacytidine (NSC-102816) . 1905 3

Valganciclovir is an l-valyl ester pro-drug of ganciclovir that was initially used to treat cytomegalovirus (CMV)-associated retinitis in patients with human immunodeficiency virus. Currently, it is also indicated for the prevention of CMV disease in solid-organ transplantation. It is primarily eliminated via the kidneys through glomerular filtration and tubular secretion. Decreased renal function results in decreased drug clearance. Valganciclovir has been reported to cause usually mild to moderate hematologic adverse effects such as leukopenia, neutropenia, anemia, thrombocytopenia, and pancytopenia. Severe and fatal bone marrow depression has been described in 1 adult patient. Herein, we describe the cases of 4 patients with end-stage renal disease who underwent cadaveric renal transplantation and received valganciclovir prophylaxis for CMV at a standard dose of 900 mg/d despite persistant renal failure. This therapy resulted in severe bone marrow failure after 18 to 20 days in all 4 patients, with fatal infections in 2 patients. This report demonstrates the in vivo pharmacodynamics of valganciclovir overdose in terms of hematotoxicity in the setting of renal impairment. Valganciclovir, as its derivative ganciclovir, should be used cautiously in patients with renal impairment.
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PMID:Severe bone marrow failure due to valganciclovir overdose after renal transplantation from cadaveric donors: four consecutive cases. 1954


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