Capsules (8 x 30 mm) of technetium-99m pertechnetate were designed for measurement of portal blood flow. Most of the radionuclide entered the superior mesenteric vein. The capsule was taken orally and monitored with a collimator for scintigraphy until it reached the small intestine, when a magnetic field completed an electrical circuit in a sensor, burning a thread, releasing a spring, and discharging the preparation. A study in crab-eating monkeys (Macaca fascicularis) showed that the radionuclide in the small intestine circulated through the superior mesenteric vein to the portal vein and liver. Portal scintigraphy through the small intestine could be analysed in the same way as per-rectal portal scintigraphy, in which blood flow mostly from the inferior mesenteric vein is evaluated. A study of four volunteers showed that, after the radionuclide was released, it circulated through the superior mesenteric vein to the portal vein and liver. Use of a capsule enclosing a radioisotope was possible, and the procedure seemed to be safe. The use of the per-small intestine method plus the per-rectal method should give more accurate results than either method used alone, because the haemodynamics of both the superior and inferior mesenteric vein would be reflected.

Administration, Oral↗

PubMedDate not supplied

Proliferation and cytotoxicity of lectin-induced lymphokine-activated killer (LILAK) cells.

More than 10(11) killer cells are needed for adoptive immunotherapy, but it is difficult to obtain so many from patients. Peripheral blood lymphocytes (PBL) treated with lectin and then with recombinant interleukin-2 (rIL-2) give many lectin-induced lymphokine-activated killer (LILAK) cells, studied here for proliferation, cytotoxicity, IL-2 receptors (IL-2R) and subsets. PBL obtained from hepatoma patients or healthy adults were incubated with phytohaemagglutinin (PHA) or concanavalin A (ConA) for 3 days and with rIL-2 for 4 days. Then the medium was replaced with fresh medium containing rIL-2 every 3 or 4 days, with the volume increased as cells proliferated. Cytotoxicity was expressed as the percentage lysis of target cells by 4 h 51Cr release. LILAK cells from healthy adults increased 120-fold in 2 weeks when incubated with ConA; the lymphokine-activated killer (LAK) cells increased 7-fold. The percentage of IL-2R+ cells increased more with ConA than with rIL-2 alone. ConA induced more suppressor T cells than PHA. LILAK cells obtained from patients by PHA treatment increased 180-fold in 2 weeks. Their cytotoxicity to Daudi cells was 1% before culture and 91% in 2 weeks; that of LAK cells was 60%. LILAK cells were cytotoxic to the tumour target cells, but not to allogeneic PBL. Adoptive immunotherapy may become more practical if many LILAK cells can be obtained at once by large-scale culture, such as by a hollow-fibre system.

Carcinoma, Hepatocellular↗

PubMedDate not supplied

Significance of blood flow in the inferior and superior mesenteric veins for the formation of oesophageal varices.

The degree of involvement of blood flow in the superior mesenteric vein and inferior mesenteric vein in the formation of oesophageal varices is not known. We have developed a method by which the contributions of these veins to portal blood flow can be evaluated simultaneously in a relatively non-invasive way. An enteric-coated capsule containing [123I]iodoamphetamine (IMP) is given by mouth and 3 h later [123I]IMP is instilled into the rectum. The data obtained are treated by computer to calculate the portal shunt index via the inferior and superior mesenteric veins. In chronic hepatitis and cirrhosis, when varices were absent, the difference in these indices was not significant. In the presence of varices, the portal shunt index via the inferior mesenteric vein was significantly higher than that via the superior mesenteric vein. It was suggested that the contribution of blood flow in the inferior mesenteric vein the portal/splenic axis is important in the formation of varices.

Amphetamines↗

PubMedDate not supplied

Detection of the preneoplastic lesions of small hepatocellular carcinoma in cirrhotic livers.

To identify the preneoplastic lesions of hepatocellular carcinoma and the fine structure of preneoplastic hepatocytes, we studied proliferative conditions in cirrhosis of the liver. In all, 46 foci of cellular alteration (FCA), three regions of adenomatous hyperplasia (ADH), and 21 small hepatocellular carcinomas (sHCC) were studied by published criteria for sHCC and by the proliferative activity of the lesions as examined with monoclonal antibodies against DNA polymerase alpha and proliferating cell nuclear antigen. The four patients with FCA composed of basophilic hepatocytes were classified by the criteria as having sHCC; cells had features similar to those of sHCC. Two of these four patients with FCA were found to have HCC several years later. The number of hepatocytes stained for proliferating cell nuclear antigen was 72 and 81 per 1000 hepatocyte nuclei in the two patients who developed HCC. In one of the three patients with ADH, a sHCC was found 1 year later, and dysplastic hepatocytes from the region of ADH in this patient had features similar to those of HCC cells by light and electron microscopy. In this patient, the number of hepatocytes stained for DNA polymerase alpha was 452 per 1000 nuclei. Therefore, FCA and ADH might be preneoplastic lesions of sHCC in cirrhosis of the liver. Preneoplastic hepatocytes seem to be small cells with basophilic cytoplasm, with a large nucleus to cytoplasm ratio, finely indented nuclei with a smaller amount of condensed chromatin than normal, and poorly to moderately developed organelles.

Aged↗

PubMedDate not supplied

Homeless patients with hepatocellular carcinoma in Osaka City, Japan.

BACKGROUND/AIMS: Although the number of homeless persons is increasing worldwide, studies delineating the health status of these persons according to various medical perspectives, including hepatology, are limited. However, such studies are important for understanding the pathogenesis of diseases and their prevention. METHODOLOGY: Thirty homeless patients with hepatocellular carcinoma (HCC) and 15 with liver cirrhosis (LC) who were admitted to the Osaka Socio Medical center Hospital during the past 6 years were analyzed clinicopathologically. All were from the Airin district of Osaka City. RESULTS: The patients with HCC had a history of long stay (mean: 25 years) in the district and many infectious opportunities and most of them were malnourished. The main causes of liver disease in the patients with HCC were hepatitis C virus (HCV) (77%), alcohol abuse (73%), and the combination of HCV and alcohol abuse (50%). Serum HCV RNA concentration was 10(5.8 +/- 0.9) copies/50 microliters in the 21 HCC patients and 10(6.5 +/- 0.7) copies/50 microliters in the 14 LC patients (p < 0.02). Six HCC patients (20%) were positive for the GB virus C/Hepatitis G virus (GBV-C/HGV) RNA in association with HCV or hepatitis B virus (HBV). Only 2 patients with HCC underwent the curative operations and most of the HCC cases were in progressed stages. CONCLUSIONS: A long stay in a hygiene-poor environment increases the opportunity for infection in homeless people. The causative agents in the HCC and LC patients were mostly HCV, alcohol abuse, and a combination of the two. Since the quantification of HCV-RNA in the HCC patients was lower, the high level of HCV-RNA may not be a risk factor for the development of HCC. GBV-C/HGV may not also. The reversion to former healthy living conditions and reduction in alcohol consumption as soon as possible may contribute to low incidence of HCC and save the tax dollar expenditures among homeless people.

Biopsy, Needle↗

PubMedDate not supplied

Two-dimensional analysis of production of IL-6 and TNF-alpha can predict the efficacy of IFN-alpha therapy.

BACKGROUND/AIMS: Many patients with chronic hepatitis C are now treated with interferon-alpha (IFN-alpha). The increase in the number of patients treated with IFN-alpha, however, has resulted in increased reports of adverse drug reactions (ADR). This prompted us to investigate for a useful parameter for predicting the effects of IFN-alpha treatment before initiating the therapy for the benefit of patients. METHODOLOGY: Peripheral blood mononuclear cells (PBMCs) obtained from patients with chronic hepatitis C and healthy volunteers were incubated at 37 degrees C for 24 hours at various concentrations of IFN-alpha (1, 10(2), and 10(4) IU/ml). The tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) formed in the culture medium were determined. Also, the binding of 125I-labeled IFN-alpha to PBMCs and 2', 5'-oligoadenylate synthetase (2-5AS) activities were measured. RESULTS: The addition of IFN-alpha to PBMCs at concentrations of 1-10(4) IU/ml showed dose-dependent changes in the binding of 125I-labeled IFN-alpha to PBMCs and 2-5AS activities. There was a strong correlation between the production of IL-6 and that of TNF-alpha (r>0.9). The production of IL-6 by the PBMCs of the high responders is significantly higher than that of the low-responders at the same value of TNF-alpha. A statistically significant difference was demonstrated by analysis of covariance. CONCLUSIONS: The findings of this study suggest that two-dimensional analysis of the in vitro production of TNF-alpha and IL-6 by PBMCs induced by IFN-alpha is useful for predicting the outcome of the IFN-alpha treatment in patients.

Adult↗