Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between 1972 and 1980 a histological diagnosis of vasculitis was made on 80 patients from a district general hospital. These were divided into a polyarteritis nodosa (PAN) group, a rheumatoid vasculitis (RV) group and a heterogeneous group of other vasculitides. There was considerable overlap between the clinical and laboratory features in the three groups. Non-specific symptoms (fever and myalgia), leucocytosis and eosinophilia were the most useful features for distinguishing PAN from the other two groups. Hepatitis B infection was rare (two patients) and hypocomplementaemia was a feature of RV but not of PAN. The overall mortality was similar in each group. However, in PAN deaths due to vasculitis were more common within six months of diagnosis. Features associated with a poor prognosis were renal impairment, cutaneous and intestinal vasculitis in PAN; and neuropathy, weight loss and histological evidence of vasculitis at rectal biopsy in RV. Cytoxic drugs combined with corticosteroids were associated with an improved prognosis compared with corticosteroids alone in the PAN group. Pulmonary involvement was associated with less severe renal disease but with a six month mortality similar to that in the whole PAN group. Systemic vasculitis is not uncommon in a district general hospital population. The overlapping clinical and laboratory features in different vasculitic diseases stress the problems in classification between PAN and other groups. Patients with systemic disease complicated by necrotizing arteritis have a severe, life threatening disease which may respond to aggressive cytotoxic therapy.
 ...
PMID:Systemic vasculitis in a district general hospital 1972-1980: clinical and laboratory features, classification and prognosis of 80 cases. 612 63

Six patients with hepatitis B virus (HBV) related chronic liver disease were treated with acyclovir, 5-15 mg/kg 8 hourly, given as an iv bolus or iv infusion over 1 h for up to 7 days. Two patients treated with 10 and 15 mg/kg 8 hourly showed a decrease in HBV-DNA polymerase and HBV-DNA when mean trough acyclovir plasma concentrations of 5.0 +/- 0.6 and 13.2 +/- 3.0 microM were attained. Inhibition of viral replication was not seen in patients treated with lower doses. Transient renal impairment was seen in two patients who received high dosage by the iv bolus mode of administration. This complication may be prevented by a high oral fluid intake or iv infusion of the drug over 1 h. Further study with acyclovir 15 mg/kg 8-hourly given as an iv infusion for longer periods is warranted.
 ...
PMID:Acyclovir in hepatitis B antigen-positive chronic liver disease: inhibition of viral replication and transient renal impairment with iv bolus administration. 684 4

Liver transplantation poses enormous and complex medical problems. Of the infective complications, bacterial infections are the commonest overall, but the single commonest is cytomegalovirus and the most deadly are the fungal infections. Therapeutic options and possibilities for prophylaxis are improving. Rejection, both acute and chronic, is the other major cause of mortality, and the balance between immunosuppression and infection is difficult. Cyclosporin treatment contributes to renal impairment, hypertension, and multitudinous potential neurological problems. The risk of long-term neoplasia is unclear. Relatively more minor is the potential for osteoporosis and metabolic complications, such as diabetes and hyperlipidaemia. Hepatitis B disease has a sizable risk of recurrence, but the most recent prophylaxis regimes have improved relapse rates. Having survived the physical problems following transplantation, most of which occur in the first 6 months, there are considerable psychosocial adjustments to be made particularly in the case of children where growth and development may have been delayed. Despite all these difficulties, liver transplantation is an expanding and optimistic area with enormous potential.
 ...
PMID:Medical complications of liver transplantation. 833 63

Clinical data and renal biopsy study of 186 adult patients found to have nephropathy and seen at the Security Forces Hospital, Riyadh, over a 5-year period (1989 to 1994) were reviewed. Primary glomerular disease accounted for more than three fourths of all patients (79%), and the most common histological lesion was focal segmental glomerulosclerosis (40.8%) associated with a high incidence of hypertension (86.7%), nephrotic syndrome (61.7%), hematuria (48.8%), and renal impairment (33.3%). Mesangioproliferative glomerulonephritis was the second most common lesion (21.1%), followed by membreous glomerulonephritis (13.6%), immunoglobulin A nephropathy (IgAN) (13.6%), membranoproliferative glomerulonephritis (9.5%), and minimal change disease (1.4%). Although not as common as in most other developed countries, IgAN is being increasingly recognized in Saudis. Lupus nephritis remained the commonest cause of secondary glomerulonephritis (48.5%), whereas amyloidosis was conspicuously absent. There is no evidence, at least in this series, that chronic infection such as hepatitis B virus infection has a major role in the development of glomerulonephritis.
 ...
PMID:Pattern of glomerular disease in Saudi Arabia. 865 Dec 43

Recently individualized from polyarteritis nodosa (PAN), microscopic polyangiitis (MPA) is defined as a systemic necrotizing vasculitis that clinically and histologically affects small-sized vessels (ie, capillaries, venules or arterioles) without granulomata and is associated with focal segmental necrotizing glomerulonephritis. Males are more frequently affected than females and the average age of onset is about 50 years old. Most patients experience some systemic symptoms before diagnosis of vasculitis. Clinically, renal involvement is the major feature of MPA and is characterized by rapidly progressive glomerulonephritis (RPGN). Most of the patient have renal impairment at admission and renal function deteriorates rapidly without treatment. Lung involvement is also common. Lung hemorrhage is observed in 12 to 29% of the patients with MPA and is an important contributory factor to morbidity and mortality. Some patients with small-vessel lung vasculitis may present clinical, radiologic and functional findings consistent with an interstitial process mimicking idiopathic pulmonary fibrosis. Others clinical features are similar to those observed in PAN. Musculoskeletal involvement (myalgias, arthralgias and arthritis) are present in 65 to 72% of the patients. Cutaneous lesions (purpura, splinter hemorrhages) are found in 44 to 58% of the patients. Gastrointestinal symptoms are characterized by abdominal pain (32 to 58%) and digestive tract bleeding (29%). Peripheral neuropathy is found in only 14 to 36% of the cases, thus occurring less frequently than in PAN. Ocular manifestations and ear, nose and throat lesions are commonly seen, more frequently than in PAN. Non-specific laboratory tests reflect the systemic inflammatory nature. Almost all patients are negative for hepatitis B virus (HBV) surface antigen. Renal insufficiency with creatininemia > 120 microns/l is present in the majority of patients. Antineutrophil cytoplasm antibodies (ANCA) are found in 75% of MPA patients and the majority of these ANCA detected are perinuclear-staining anti-myeloperoxidase ANCA, although anti-proteinase 3 has also be detected. Microaneurysms, commonly present in PAN, are rarely seen on at visceral angiograms. MPA is part of a spectrum of systemic vasculitides. Differentiation between PAN and MPA should be based on clinical manifestations (especially lung and kidney involvement), biologic signs (ANCA, HBV or HCV infection) and angiographic data. The therapeutic strategies for treatment of PAN and MPA do not differ extensively. Prognosis of systemic vasculitides have been transformed by corticosteroids that are the basis of the treatment. Immunosuppressive drugs, especially cyclophosphamide, also contribute to a better prognosis. Considering the high frequency of renal involvement in MPA, most of the patients should considered as having factors or poor prognosis and the high number of relapses that can occur in patients with MPA could justify prolonged steroid administration or immunosuppressive treatment.
 ...
PMID:Microscopic polyangiitis: clinical aspects and treatment. 879 93

Lamivudine (3TC), the negative enantiomer of 2'-deoxy-3'-thiacytidine, is a dideoxynucleoside analogue used in combination with other agents in the treatment of human immunodeficiency virus type 1 (HIV-1) infection and as monotherapy in the treatment of hepatitis B virus (HBV) infection. Lamivudine undergoes anabolic phosphorylation by intracellular kinases to form lamivudine 5'-triphosphate, the active anabolite which prevents HIV-1 and HBV replication by competitively inhibiting viral reverse transcriptase and terminating proviral DNA chain extension. The pharmacokinetics of lamivudine are similar in patients with HIV-1 or HBV infection, and healthy volunteers. The drug is rapidly absorbed after oral administration, with maximum serum concentrations usually attained 0.5 to 1.5 hours after the dose. The absolute bioavailability is approximately 82 and 68% in adults and children, respectively. Lamivudine systemic exposure, as measured by the area under the serum drug concentration-time curve (AUC), is not altered when it is administered with food. Lamivudine is widely distributed into total body fluid, the mean apparent volume of distribution (Vd) being approximately 1.3 L/kg following intravenous administration. In pregnant women, lamivudine concentrations in maternal serum, amniotic fluid, umbilical cord and neonatal serum are comparable, indicating that the drug diffuses freely across the placenta. In postpartum women lamivudine is secreted into breast milk. The concentration of lamivudine in cerebrospinal fluid (CSF) is low to modest, being 4 to 8% of serum concentrations in adults and 9 to 17% of serum concentrations in children measured at 2 to 4 hours after the dose. In patients with normal renal function, about 5% of the parent compound is metabolised to the trans-sulphoxide metabolite, which is pharmacologically inactive. In patients with renal impairment, the amount of trans-sulphoxide metabolite recovered in the urine increases, presumably as a function of the decreased lamivudine elimination. As approximately 70% of an oral dose is eliminated renally as unchanged drug, the dose needs to be reduced in patients with renal insufficiency. Hepatic impairment does not affect the pharmacokinetics of lamivudine. Systemic clearance following single intravenous doses averages 20 to 25 L/h (approximately 0.3 L/h/kg). The dominant elimination half-life of lamivudine is approximately 5 to 7 hours, and the in vitro intracellular half-life of its active 5'-triphosphate anabolite is 10.5 to 15.5 hours and 17 to 19 hours in HIV-1 and HBV cell lines, respectively. Drug interaction studies have shown that trimethoprim increases the AUC and decreases the renal clearance of lamivudine, although lamivudine does not affect the disposition of trimethoprim. Other studies have demonstrated no significant interaction between lamivudine and zidovudine or between lamivudine and interferon-alpha-2b. There is limited potential for drug-drug interactions with compounds that are metabolised and/or highly protein bound.
 ...
PMID:Clinical pharmacokinetics of lamivudine. 998 42

Cidofovir and adefovir are members of a new class of antiviral compounds. They are acyclic phosphonate analogues of deoxynucleoside monophosphates. Both compounds undergo intracellular activation to form diphosphates that are potent inhibitors of viral DNA polymerases. Cidofovir has broad spectrum antiviral activity against herpesviruses, papillomaviruses and poxviruses, whereas adefovir has potent activity against retroviruses and certain DNA viruses, including herpesviruses and hepadnaviruses. Intravenous cidofovir is approved for treatment of cytomegalovirus retinitis in patients with AIDS. Cidofovir and adefovir are dianionic at physiological pH and have low oral bioavailability in animals and humans. After intravenous administration to HIV-infected patients, the pharmacokinetics of both drugs are independent of dose and are consistent with preclinical data. Systemic exposure is proportional to the intravenous dose and both drugs are cleared by the kidney and excreted extensively as unchanged drug in the urine. Intracellular activation of a small fraction (< 10%) of the dose by cellular kinases leads to prolonged antiviral effects that are not easily predicted from conventional pharmacokinetic studies. The observed rate of elimination of cidofovir and adefovir from serum may not reflect the true duration of action of these drugs, since the antiviral effect is dependent on concentrations of the active phosphorylated metabolites that are present within cells. For both drugs, > 90% of an intravenous dose is recovered unchanged in the urine over 24 hours. Metabolism does not contribute significantly to the total clearance of either drug. Concomitant oral probenecid decreases both the renal clearance of cidofovir and the incidence of nephrotoxicity, presumably by blocking its active tubular secretion. This is the basis of the clinical use of concomitant probenecid as a nephroprotectant during cidofovir therapy. Subcutaneous administration produces exposure equivalent to that following intravenous administration. Drug interaction studies with cidofovir are ongoing, but there is no evidence of an interaction between zidovudine and either cidofovir or adefovir. Clearance of cidofovir in patients with renal impairment showed a linear relationship to creatinine clearance. The low oral bioavailability of adefovir has led to the development of an oral prodrug, adefovir dipivoxil, currently in development for the treatment of HIV and hepatitis B infections.
 ...
PMID:Clinical pharmacokinetics of the antiviral nucleotide analogues cidofovir and adefovir. 1009 59

With improvements in surgical techniques and management of postoperative complications, heart transplantation can now be performed with donors and recipients who were previously considered unsuitable. In this study, we report the results of heart transplantation with marginal donors and recipients in our hospital. From June 1993 through June 1998, we performed 79 heart transplantations. Marginal recipients were defined as those with high pulmonary vascular resistance (> 6 Wood units), severe renal impairment (serum creatinine > 2 mg/dL and creatinine clearance < 50 mL/min), or severe hepatic dysfunction (ALT and AST > 100 IU/L or serum bilirubin > 2.5 mg/dL). Marginal donors were those with any of the following conditions: old age (> 40 years), size mismatch (donor/recipient body weight ratio < 0.8), history of chronic alcohol use, previous cardiopulmonary resuscitation and hypotension, hepatitis B or C virus positivity, coronary artery disease, high-dose dopamine (> 10 micrograms.kg-1.min-1), or prolonged allograft ischemic time (> 4 hours). Of the 79 transplantations performed, 45 (58%) involved marginal recipients or donors. The 30-day mortality rate was 5%, and the 1-year and 5-year survival rates were 87% and 83%, respectively. The survival rates did not differ significantly between cases involving marginal donors or recipients and those involving nonmarginal donors and recipients. There were 27 marginal recipients (34%), only one of whom died during surgery. Five of six recipients with severe renal impairment needed short-term hemodialysis after transplantation. Recipients with high pulmonary vascular resistance had a higher incidence of early acute rejection (5/10 vs 22/69). Thirty-three (42%) of the patients received transplants from marginal donors, four of whom died during surgery; two died of acute vascular rejection, one of allograft failure caused by prolonged ischemic time, and one of bleeding secondary to preoperative sepsis and coagulopathy. These results show that heart transplantation may be performed in marginal recipients and donors, with acceptable operative mortality.
 ...
PMID:Heart transplantation with marginal recipients and donors. 1057 34

Fibrosing cholestatic hepatitis is a deleterious manifestation of hepatitis B virus infection in immunocompromised patients. Without treatment, this condition is usually fatal within weeks of onset. Liver retransplantation has not been successfully performed to date, and treatment intervention was generally unsuccessful before the advent of adefovir dipivoxil. However, concerns have been expressed about the use of this agent in patients who are renally compromised. A 40-year-old liver transplant recipient with hepatitis B virus reinfection, resistance to lamivudine, and fibrosing cholestatic hepatitis complicated by terminal renal impairment and spontaneous bacterial peritonitis was treated with adefovir dipivoxil 10 mg after every dialysis. Since initiating treatment with adefovir dipivoxil 10 mg, a dramatic virologic and clinical improvement was observed in this patient. The patient returned to work full-time within 6 months of starting adefovir dipivoxil without the need for liver retransplantation. Serum HBV DNA (Amplicor HBV; Roche Diagnostics, Basle, Switzerland) decreased by 6 log(10) copies/mL and became negative (< 400 copies/mL) within 8 weeks of treatment and remains negative at the last available assessment. The patient continues to require renal dialysis, but is generally well. Creatinine clearance improved from 8 mL/min to 16 mL/min during the course of treatment. No adverse events related to adefovir dipivoxil were observed. Adefovir dipivoxil resulted in significant clinical improvement in this patient with hepatitis B virus-induced fibrosing cholestatic hepatitis, despite the presence of renal impairment and lamivudine resistance.
 ...
PMID:Successful treatment of fibrosing cholestatic hepatitis using adefovir dipivoxil in a patient with cirrhosis and renal insufficiency. 1254 14

Since the approval of sirolimus (SRL) as an immunosuppressive agent in renal transplantation, several liver transplant centres have introduced this agent to the immunosuppression regimen. We present here a retrospective follow-up study of late conversion to sirolimus and mycophenolate mofetil (MMF) as immunosuppressive agents after liver transplantation (LTX). From July 2001 to March 2002, seven liver transplant recipients (three female, 59 (41-66) years old) were enrolled in this study. Indications for liver transplantation were hepatitis B and/or hepatitis C (three), alcohol-induced cirrhosis (three) and Wilson's syndrome (hepatolenticular degeneration) (one). LTX was performed by standard (four) or piggy-back (three) technique. The switch to SRL was performed 62 (37-118) months after LTX; the reasons for the switch from cyclosporine or tacrolimus to SRL were renal (six) or neurological (one) impairment. As immunosuppressive therapy, SRL at trough levels of 4-10 ng/ml and MMF at trough levels of approximately 1 micro g/ml were administered. Mean follow-up time under SRL per patient was 137 (26-258 days). Patient and graft survival was 100% during SRL therapy, and there were neither rejection episodes nor infections. Renal function improved in five of the six patients (83.3%) whom we had switched to SRL due to renal impairment. In the patient whom we switched to SRL due to neurological impairment, the neurological symptoms abated, and renal function improved. Side effects (hypertriglyceridaemia, hypercholesterolaemia, exanthema) became manifest in three patients (42.8%). Cessation of therapy due to side effects was necessary in two patients (exanthema: one, hypertriglyceridaemia: one). One patient refused to continue the therapy with SRL because he wanted tablets, and we only had SRL in fluid form. The data of our study suggest that SRL is a potent immunosuppressive agent of potential benefit in clinical LTX. SRL in combination with MMF provided sufficient immunosuppression of liver allografts in the late course after LTX. Side effects were reversible with dose reduction or cessation of therapy. We can thus conclude that SRL might offer an immunosuppressive therapy for patients with renal or neurological impairment after LTX.
 ...
PMID:Sirolimus and mycophenolate mofetil after liver transplantation. 1268 25


1 2 3 Next >>