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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunopathologic mechanisms leading to liver tissue injury in hepatitis caused by hepatitis A virus (HAV) were studied in an autologous in vitro model. Data show virus-specific killing by liver-infiltrating T lymphocytes in man and support the hypothesis that hepatocellular damage as well as efficient elimination of virus-infected hepatocytes is mediated by HLA-restricted, HAV-specific CD8+ T lymphocytes. Furthermore, experimental results demonstrate that human interferon-gamma produced by HAV-specific T cells may act as a key factor in T-cell-promoted clearance of HAV-infected hepatocytes. Besides the well-known hepatotropism, the myelotropic properties of HAV have some important clinical implications. Perturbations of hematopoietic regulation, ranging from transient granulocytopenia to rare cases of bone marrow failure, are associated with HAV infection. In an attempt to elucidate the pathogenetic mechanisms, we could show a direct suppressive effect of HAV on human bone marrow progenitors and a significant progressive decline in these cells in HAV-infected long-term bone marrow cultures.
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PMID:Hepatitis A: hepatotropism and influence on myelopoiesis. 840 40

Dapsone, a synthetic sulfone with chemical similarities to sulfapyridine, has been used for a number of years to treat leprosy and dermatitis herpetiformis. Recently, a number of prospective, randomized, double-blind trials have shown their success in the management of rheumatoid arthritis, with dapsone being superior to placebo and comparable to chloroquine and hydroxychloroquine. Its mode of anti-inflammatory actions in rheumatoid arthritis is not clearly understood, but modulation of neutrophil activity or inhibition of neutrophil inflammatory product formation or release appear to play a role. The major limiting side effect is hemolytic anemia, which may be mitigated through careful patient selection, conservative drug dosing, close monitoring, and possibly, concurrent administration of antioxidants or cytochrome P450 inhibitors. Methemoglobinemia is another common finding among patients receiving dapsone therapy, but rarely does it result in prominent symptoms other than transient pallor. Less common adverse events to dapsone include the idiosyncratic reactions of leukopenia and agranulocytosis, cutaneous eruptions, peripheral neuropathy, psychosis, toxic hepatitis, cholestatic jaundice, nephrotic syndrome, renal papillary necrosis, severe hypoalbuminemia without proteinuria, an infectious mononucleosis-like syndrome, and minor neurological and gastrointestinal complaints. In this report, two patients with advanced rheumatoid arthritis, who were safely and effectively treated with dapsone after failure with other second-line agents, are described and the literature is reviewed. We suggest that dapsone is an effective second-line agent in the treatment of rheumatoid arthritis.
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PMID:Dapsone in rheumatoid arthritis. 879 11

This article reviews antipsychotic medication side effects, especially those that require the physician to discontinue or the patient to be noncompliant with otherwise useful medication. They include such common problems as extrapyramidal syndromes (dystonia, akathisia, drug-induced Parkinsonism, tardive dyskinesia), sedation, weight gain, and sexual dysfunction, as well as less frequent concerns, such as seizures, neuroleptic malignant syndrome, agranulocytosis, torsade de pointes, hepatitis, and dermatological and ophthalmological syndrome. The adverse events associated with some of the new antipsychotic drugs are included. Available information about individual susceptibility to side effects is addressed by syndrome.
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PMID:Neuroleptic intolerance. 936 96

The antiepileptic drug hypersensitivity syndrome (AHS) is an adverse drug reaction associated with the aromatic antiepileptic drugs (AEDs) phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), and primidone. The syndrome is defined by the triad of fever, skin rash, and internal organ involvement. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, terbinafine, azathioprine, and allopurinol. Diagnosis of AHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic, or collagen vascular disorders. The incidence is approximately 1 in 3,000 exposures. AHS starts with fever, rash, and lymphadenopathy, within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis, and myostitis. AHS is associated with a relative excess of reactive oxidative metabolites of the AED. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Crossreactivity among PHT, CBZ, and PB is as high as 70-80%.
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PMID:Antiepileptic drug hypersensitivity syndrome. 979 55

Nevirapine (NVP) is a nonnucleoside reverse transcriptase inhibitor widely used in combination with other antiretroviral agents for the treatment of human immunodeficiency virus disease. To establish its safety profile, we conducted a review of data from prospective US and international clinical trials involving a total of 906 adult patients and 468 pediatric patients treated with NVP. Drug-related adverse events were similar in adults and children, with rash and nausea most frequently reported in adults and rash and granulocytopenia most frequently reported in children. A separate analysis of rash based on data from adult patients in controlled trials demonstrated a 16% rate of NVP-attributable rash in these patients. Of patients with NVP-associated rash, 65% developed rash within the first 6 weeks of therapy, and it has been shown that a lower lead-in dose (200 mg/d vs the standard 400 mg/d) for the first 2 weeks of NVP treatment reduces the frequency of drug-associated rash. Serious rash (Stevens-Johnson syndrome [SJS] or SJS/toxic epidermal necrolysis transition syndrome) occurred with an incidence of 0.3% and clinical hepatitis with an incidence of 1.0% among NVP-treated patients in clinical trials. Adverse event data from long-term clinical trials demonstrated a lower incidence of NVP-related adverse events than in short-term trials of NVP therapy. An analysis of abnormal laboratory findings using thresholds similar to those found in the prescribing information for other commonly used antiretroviral agents and data from controlled trials in adults showed that the most frequently observed laboratory abnormalities were elevations in liver function test results. Approximately 50,000 patients in the United States had been treated with marketed NVP at the time of writing, and postmarketing surveillance has supported the overall safety profile observed in clinical trials. NVP has been shown to be well tolerated in both adult and pediatric patients.
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PMID:Safety profile of nevirapine, a nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus infection. 991 3

Hepatitis C virus (HCV) infection is often associated with abnormal immunological responses. We describe four patients with vasculitic neurological signs and symptoms following HCV infection. A 56-year-old woman with HCV infection developed peripheral neuropathy characterized by asymmetric distal painful hypesthesia, dysesthesia and moderate motor weakness of the lower limbs. Serological examinations revealed cryoglobulinemia and low levels of complement C4. A biopsy of the sural nerve revealed vasculitic neuropathy. HCV infection associated immunomediated vasculitis was diagnosed. While steroid therapy was ineffective, treatment with interferon-alpha improved the neuropathy considerably without, however, eliminating HCV infection. A 62-year-old man with HCV infection developed peripheral sensory neuropathy. Complement C3 was slightly diminished. Nerve biopsy revealed vasculitic neuropathy. A 71-year-old woman developed chronic symmetric sensomotor polyneuropathy. HCV hepatitis followed blood transfusions. Cryoglobulins tested positive, consistent with type II cryoglobulinemia. Complements C3 and C4 were diminished. Inflammatory infiltrates in the sural nerve biopsy specimen led to the diagnosis of chronic vasculitic disorder. A 55-year-old woman with HCV infection developed vasculitis of the skin, connective tissue, visceral organs, and kidney, leading to hemodialysis. Neurologically she developed severe apathy and drowsiness, myoclonic jerks, exaggerated deep tendon reflexes, and positive pyramidal signs. Magnetic resonance imaging of the brain showed diffuse increased signal abnormalities involving supra- and infratentorial white matter suggesting cerebral vasculitis. Cryoglobulins were positive, complements C3 and C4 slightly diminished (54 mg/dl, 4.3 mg/dl). Supportive therapy resulted in neurological improvement. Treatment with interferon-alpha was discontinued because of agranulocytosis. In patients with peripheral neuropathy or signs of leucencephalopathy, a hepatitis C associated vasculitis should be considered in the differential diagnosis.
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PMID:Neurological manifestations of chronic hepatitis C. 1043 76

A 73-year-old man had fever, lymphadenopathy, granulocytopenia, thrombocytopenia, ascites, pleural effusion, liver injury, and an allergic-like skin rash. Autoantibodies, such as anti-nuclear antibody, were shown, and there were lactate dehydrogenase and alkaline phosphatase anomalies and platelet-associated IgG. His liver injury resembled that in autoimmune hepatitis. He was diagnosed with Epstein-Barr virus (EBV) infection associated with autoimmunization because of his clinical course, fluctuation of anti EBV antibodies and positive EBV genome in circulating lymphocytes and serum. This case suggests a close relationship between EBV infection and autoimmunization or autoimmune-like hepatitis.
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PMID:Epstein-Barr virus infection resembling autoimmune hepatitis with lactate dehydrogenase and alkaline phosphatase anomaly. 1058 89

Potential risk factors for and the preventability of fatal adverse drug events (ADEs) were studied. Case reports of ADEs published in Clin-Alert during 1976-95 were the source of information on fatal ADEs, Patient, drug, and event variables were identified, and the causality, predictability, and preventability of each case were assessed. Data were entered into a relational database for analysis. The data indicated 447 cases involving a fatal ADE. Ten percent of the fatal ADEs were assessed as definite, 46% as probable, and 44% as possible. Fatal-ADE frequency increased with age. Forty-five percent of the patients were 40-69 years of age, and 40% were healthy. Central-nervous-system agents, antineoplastics, antimicrobials, and cardiovascular agents accounted for 69% of the deaths. Only 33% of patients received more than the usual dosage. Many of the suspected drugs could have been monitored with blood level tests but were not, and baseline testing of critical blood count and liver and renal function was often not performed. The most common causes of death were hepatitis, hepatic failure, cardiopulmonary arrest, overdose, and agranulocytosis. ADE types were distributed as adverse drug reactions (58%), allergic reactions (19%), medication errors (17%), and drug interactions (6%). Sixty-eight percent of the fatal ADEs were judged to have been preventable; of these, a pharmacist could have prevented 57%. Litigation was reported for 14% of the fatal-ADE cases; judgments and settlements averaged $1.1 million. A review of published case reports of ADEs for 1976-95 yielded information on possible risk factors for fatal ADEs and on which events may have been preventable.
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PMID:Potential risks and prevention, Part 1: Fatal adverse drug events. 1147 79

Disulone (dapsone + ferrous oxalate) is a sulphone marketed in France since 1958 and authorized in P. Carinii prophylaxis in HIV+ cotrimoxazole intolerant patients, bullous dermatosis, leprosy and polychondritis. Between 1983 and 1998, 249 adverse reactions were reported to French pharmacovigilance centres and Aventis, the manufacturer. Every side-effect was reviewed and the causal relationship was assessed on the basis of the French method for causality assessment. Main side-effects were divided as follows: 117 blood dyscrasias (generally neutropenia and agranulocytosis, rarely methaemoglobinaemia, haemolysis, macrocytosis, anaemia, aplastic anaemia, haemochromatosis and sulphaemoglobinaemia); 29 hypersensitivity syndrome; 39 cutaneous reactions, generally rash; 27 liver injuries (cholestatic, cytolytic and mixed hepatitis); 27 neurological and psychiatric side-effects including 7 axonal neuropathy; 10 gastrointestinal effects, generally nausea and vomiting. Five deaths were reported (4 septicaemia including one case not due to dapsone and 1 digestive bleeding due to underlying disease). In the other cases the outcome was favourable. The results were compared with the published references. It would seem to be important to reinforce information to prescribers about the possible serious adverse reactions with dapsone, particularly hypersensitivity syndrome and agranulocytosis, that can cause death if the drug is not stopped in time.
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PMID:[Adverse effects of Disulone; results of the France pharmacovigilance inquiry. Regional Centers of Pharmacovigilance]. 1147 11

A 29-year-old male patient with acute hepatitis B developed agranulocytosis about 2 months after the clinical onset of the hepatitis. Bone marrow examination showed hypercellularity and maturation arrest of myeloid leukogenesis at the stage of metamyelocyte. Anti-neutrophil antibody was negative. Since the patient did not show spontaneous recovery for 2 months, the patient received granulocyte-colony stimulating factor, but the therapy was a very short course because he had an elevation of temperature and nausea. Sixty-eight days after admission, he was started on lithium carbonate at a dose of 600 mg per day. About 3 weeks later, peripheral granulocyte counts had recovered to normal level.
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PMID:A case of agranulocytosis associated with severe acute hepatitis B. 1155 38


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