The plasma clearance of an i.v. bolus of chenodeoxycholic acid (10 micrometer per kg) was determined in rabbits with graded degrees of hepatocellular necrosis produced by i.p. injection of carbon tetrachloride. Plasma chenodeoxycholic acid levels were determined by radioimmunoassay, and the volume fraction of necrosis was quantitated by a computerized (Quantimet 720) system. Impaired plasma clearance was observed only when necrosis was extensive, and the volume fraction of necrosis greater than 34%. In contrast, measurement of fasting plasma chenodeoxycholic acid concentration was more sensitive, and elevated levels were associated with a mean volume fraction of necrosis of 12.5%. This study reinforces the conclusion based on clinical studies that measurement of fasting bile acid concentration is a more sensitive discriminant of hepatic dysfunction than is measurement of the plasma clearance of an i.v. bolus of bile acid.

Animals↗

PubMedDate not supplied

Correlation between liver histology and markers of hepatitis B virus replication in infected patients: a study by in situ hybridization.

Liver sections from 18 patients positive for hepatitis B surface antigen (HBsAg), and from 12 negative patients, were examined for the presence of hepatitis B virus (HBV) DNA using an in situ hybridization assay that would identify only those hepatocytes containing more than 10 to 15 HBV genome equivalents per cell. Such cells are likely to be undergoing active viral replication, rather than latent infection. The findings were correlated with results of tissue immunofluorescence for HBV antigens and the presence of serum hepatitis B e antigen (HBeAg), together with histologic assessment of each liver. HBV DNA detected in the above assay was predominantly cytoplasmic; it was associated with the presence of hepatitis B core antigen (HBcAg) in hepatocytes and HBeAg in serum, and to a lesser extent with cirrhosis and immunosuppression, but not with the presence of HBsAg in hepatocytes, nor with histological evidence of disease activity judged by the presence of piece-meal necrosis and lobular and portal tract inflammation. These findings support the view that liver HBcAg and serum HBeAg are markers of virus replication, and demonstrate that active liver disease in HBsAg-positive patients may occur with or without such markers of replication. It is proposed that alternative mechanisms for hepatocyte injury may apply in different chronic HBV patients, one related to virus replication and one dependent on immunological factors.

Adolescent↗

PubMedDate not supplied

Successful thrombolysis of a chronically occluded femoropopliteal synthetic bypass graft via the popliteal approach: case report.

Thrombolysis of an occluded femoropopliteal synthetic bypass graft was performed via the popliteal artery approach for infusion catheter placement and urokinase delivery. Graft thrombolysis was achieved without complication. The proximal graft anastomosis could not be identified and prevented selective antegrade catheter placement and infusion. Because the distal graft anastomosis was visualized, the percutaneous popliteal approach was used. Subsequently, angioplasty was performed of an unmasked stenosis that presumably led to graft closure. We can conclude that selective thrombolysis via catheter placed from popliteal thrombolysis is an effective technique for recanalization of occluded femoropopliteal bypass grafts if the antegrade approach is not feasible.

Aged↗

PubMedDate not supplied

Hepatotoxicity of methotrexate in rheumatic diseases.

Methotrexate-induced hepatotoxicity is well recognised in the treatment of leukaemia, psoriasis and rheumatoid arthritis. The pathological lesions are non-specific, consisting of fatty change, nuclear pleomorphism, hepatocyte necrosis, portal chronic inflammatory infiltrate, fibrosis and cirrhosis. The mechanism of liver injury is poorly understood; intracellular accumulation of methotrexate polyglutamate and consequent folate depletion are suspected to play a role. Early studies in psoriasis clearly established a relationship of the hepatic injury with the frequency of methotrexate administration. With weekly low dose therapy, however, consensus is lacking regarding the incidence of hepatotoxicity because studies have had disparate control groups, used variable dosage regimens and often failed to document pre-existing liver disease or categorised patients at risk, i.e. elderly patients, alcoholics and obese diabetics. Moreover, current methods of assessing the degree of hepatic injury are subjective, relying on interpretation by an experienced histopathologist. Preliminary evidence suggests less frequent and less severe hepatotoxicity occurs in patients with rheumatoid arthritis, probably as a result of lower methotrexate doses and better patient selection. Nevertheless, until the risk of serious liver disease is better defined it is recommended that patients have a pretreatment liver biopsy, a follow-up biopsy after a cumulative dose of 1500 mg, and then biopsies approximately every 2 years in the absence of other evidence of liver disease or risk factors.

Adolescent↗

PubMedDate not supplied

Coronary angioplasty and cancer risk: a population-based cohort study in Sweden.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) has become the reperfusion method of choice in patients with coronary artery disease. This sometimes complicated and lengthy procedure is performed using fluoroscopy and cineradiography or digital imaging, which may result in considerable exposure to ionizing radiation. Possible cancer risks in PTCA patients have been discussed, but never before examined in a population-based setting. OBJECTIVE: To assess the cancer risks following PTCA. METHODS: A cohort study was carried out based on nationwide registration of all coronary angioplasty procedures in Sweden between 1989 and 1998. The study encompassed a total of 23,097 PTCA patients followed up for cancer outcomes in the Swedish Cancer Register until December 31, 2000. The mean and median follow-up times were 4.8 and 4.5 years, respectively. The main outcome measures were standardized incidence ratios of cancer. RESULTS: Except for a transient excess of lung cancers, observed number of cancers in patients who had undergone coronary angioplasty did not differ from those expected in the general population. If anything, the overall cancer risk was lower in the PTCA group (SIR 0.94; 95% CI 0.88-0.99). In particular, no increased risks were detected for leukemias or thyroid cancer. CONCLUSION: There was no indication of increased risks of leukemia or cancers overall in PTCA patients.

Aged↗

PubMedDate not supplied

Premenstrual relapse of puerperal psychosis.

Eight patients suffering from puerperal psychosis rapidly recovered, then relapsed shortly before the onset of their first menstrual period; five of them had repeated premenstrual relapses. This clinical observation supports a hormonal aetiology for post-partum psychosis.

Adult↗