Cervical screening in Hungary: why does the "English model" work but the "Hungarian model" does not?

A comparison has been made between the English practice and the "Hungarian model" of cervical screening. In England, until 1986, extensive opportunistic screening was the practice, but--as it had no effect on cervical cancer mortality--afterwards, the screening policy was changed to be strictly in line with international recommendations. On the other hand, in Hungary, the "old practice" has been petrified: gynaecologists are the "gatekeepers", a "gynaecological examination completed with smear-taking for cytology" makes up the screening strategy. Although in the frame of a National Public Health Programme all the prerequisites for nationwide organised screening have been provided, and an up-to-date screening strategy declared, 20-times as many smears are taken and analysed outside as inside the programme, and the efforts have had no impact on cervical cancer mortality. This is because "old habits die hard". There is an urgent need to reconsider the screening strategy, and to reorganise the cervical screening practice in Hungary.

Effect of cyanidanol-3 on lysosomal enzyme activity of serum and granulocytes in chronic liver disease and active hepatitis.

The authors examined the effect in vivo and in vitro of Catergen (cyanidanol-3) on demonstrable lysosomal enzyme activity in the serum and granulocytes in liver diseases. Acid phosphatase, cathepsin-D and beta-glucuronidase were investigated. In the in vitro studies the direct effect of Catergen was observed by enzyme release. In chronic active hepatitis without treatment the lysosomal activity of the serum increases, the lysosomal activity of the granulocytes decreases and in vitro release increases. Under the effects of Catergen treatment the lysosomal activity of the serum decreases in comparison with initial values, approaching the lysosomal enzyme activity observed in healthy persons. Under in vitro conditions, lysosomal enzyme release from the granulocytes decreases in treated individuals and thus a higher lysosomal enzyme activity in the granulocytes is observed. Granulocytes separated from the blood of healthy persons were incubated with Catergen in isotonic and hypotonic media. In an isotonic medium the release did not change significantly. Under the effect of hypotension the release of lysosomal enzyme increased considerably. In vitro incubation with small doses of Catergen significantly inhibited the degree of release. On the basis of these data it may be supposed that Catergen has a stabilizing effect on the lysosomal membrane and is thus beneficial in the treatment of liver injuries (alcoholic, toxic, inflammatory) with lysosomal membrane alterations.

Free radicals in tissue damage in liver diseases and therapeutic approach.

In vitro and in vivo effects of four hepatoprotective agents: silymarin (LegalonR), (+)-cyanidanol-3 (CatergenR), 6,6-methylene-bis(2,2,4-trimethyl-1, 2-dihydroquinoline) (MTDQ), and 4,5-amino-imidazole-carboxamide-phosphate (Aica-P) on the expression and activity of superoxide dismutase enzyme and on certain cellular immune reactions were studied in lymphocytes (and erythrocytes) from cirrhotic patients and from healthy control subjects. In vitro incubation with these drugs inhibited lectin-induced lymphocyte transformation and some of them decreased the antibody-dependent, spontaneous, and lectin-induced lymphocytotoxicity. MTDQ, silymarin and Aica-P enhanced the superoxide dismutase activity of erythrocytes and lymphocytes and the two latter and (+)-cyanidanol-3 increased the superoxide expression of lymphocytes as measured by flow cytofluorometry. In vivo treatment with Aica-P restored the originally low lymphocyte transformation values of patients' lymphocytes. Our results indirectly suggest that both antioxidant and immunomodulatory activities might be important factors in the hepatoprotective action of these drugs.

Effect of (+)-cyanidanol-3 on rat brain lipid peroxidation.

Non-enzymic lipid peroxidation was stimulated in homogenates, plasma membrane fractions and microsomes of rat brain in vitro by incubation with ascorbic acid. Malondialdehyde formation was determined by the thiobarbituric acid test. It has been established that (+)-cyanidanol-3 inhibits the ascorbic acid-stimulated lipid peroxidation in various fractions of rat brain. On the basis of these results it is suggested that (+)-cyanidanol-3 treatment protects brain suspensions against lipid peroxidation by acting as a free radical scavenger in vitro.

The effect of (+) cyanidanol-3 on the Na+-K+-ATP-ase and Mg++-ATP-ase activities of the rat brain in the presence and absence of ascorbic acid.

The authors investigated the effects of (+) cyanidanol-3-(Catergen) in vitro on the activities of rat brain plasma membrane and microsomal Na+-K+-ATP-ase and Mg++-ATP-ase, in the presence and absence of ascorbic acid. Due to lipid peroxidation induced by low concentration of ascorbid acid, activity of both ATP-ase decreased. (+) cyanidanol-3 proved to be an effective antioxidant in this system. It inhibited the decrease of ATP-ase activity which occurred as a result of lipid peroxidation promoted by ascorbic acid.

Determination of the aminoterminal peptide of procollagen type III and laminin P1 in serum of patients with chronic liver disease.

Serum concentration of the aminoterminal peptide of procollagen type III (P III P) and that of the high-molecular-weight glycoprotein laminin P1 (LP1) were determined by a specific radioimmunoassay (RIA) in patients with different chronic liver diseases. Besides the routine laboratory tests, histological verification of the liver samples obtained by needle biopsy and a complex hepatitis B virus marker analysis by RIA (Biomedica-Sorin), or ELISA (Behringwerke, Marburg, FRG) kits were carried out in order to set up the correct clinical diagnosis. In normal controls, the P III P and LP1 concentrations were 7.8 +/- 1.1 ng/ml (n = 10) and 0.08 +/- 0.1 units/ml (n = 7), respectively. Patients with fatty liver (n = 25) showed a significant elevation in P III P concentration (18.6 +/- 2.7 ng/ml). Such an elevation was not unequivocally demonstrated before. In this group of patients LP1 level was also increased (1.4 +/- 0.2 units/ml, n = 10). In liver cirrhosis (n = 51) both P III P and LP1 concentrations were found to be consistently elevated.

A prospective multicenter study of insulin and glucagon infusion therapy in acute alcoholic hepatitis.

A randomized, single-blind controlled multicenter study of insulin and glucagon infusion was carried out in 66 patients with acute alcoholic hepatitis. Thirty-three patients were treated with insulin 10 U and glucagon 1 mg in 500 ml 5% glucose in water via a peripheral vein for 2-6 h three times every day for 3 weeks. Patients in the control group received 5% glucose in an identical fashion. Fourteen control patients and five treated patients died from liver failure during the study (P less than 0.02). Clinical features of liver disease on entry into the study were similar in the two groups, but the total serum bilirubin, aspartate aminotransferase, gamma-glutamyltranspeptidase activities and prothrombin time significantly improved in the treated patients (P less than 0.05). Insulin and glucagon infusion appears to be a promising treatment of acute alcoholic hepatitis.

Liver cell protection in toxic liver lesion.

Most of the hepatoprotective drugs belong to the group of free radical scavangers. The mechanism of their action involves membrane stabilisation, neutralisation of free radicals and immunomodulation. The authors demonstrate the effect of different-drugs used in therapy of liver diseases (silymarin, silibinin, Aica-P) in human clinico-pharmacological study and in animal experiments. A wide number of methods was used. Both the silymarin preparates and the Aica-P corrected the altered immunreaction and the decreased superoxid-dismutase (SOD) activity of erythrocytes and lymphocytes in patients with alcoholic liver cirrhoses. The scavanger effect of these drugs was demonstrated in the subcellular fractions of liver cells in animal experiments. The data support the therapeutic effect of these drugs in liver diseases.

Experimental models for the study of hepatoprotection.

In the therapy of chronic liver diseases several drugs are currently used. This review summarizes the results of the authors in the therapy of chronic liver diseases with cyanidanol-3, as well as the beneficial effects of the new dihydroquinoline-type antioxidants in acute carbon tetrachloride induced and galactosamine induced liver lesions. In addition, the immunostimulant effects of Aicaphosphate is demonstrated in chronic active hepatitis.

Inhibition of doxorubicin-induced liver toxicity by a new dihydroquinoline type antioxidant.

The influence of a new dihydroquinoline type antioxidant on doxorubicin-induced hepatic toxicity was studied in mice (CFLP, LATI). Four groups of mice were studied: control, doxorubicin-treated, 5,6-methylen-bis (2,2,4/-trimethyl-1,2-dihydroquinoline/-disulphate (MDS)-treated, as well as doxorubicin and MDS-treated groups. Doxorubicin (15 mg/kg) was administered intraperitoneally, the MDS solution was given by a gastric tube. Liver function was assessed by the serum glutaminic-oxaloacetic-transaminase (SGOT) reaction. The lipid peroxidation in liver tissue was determined by the rate of malondialdehyd (MDA) production, the permeability of the liver lysosomal membrane was established by measuring beta-glucuronidase activity and its release from the cells. The MDS treatment proved to be effective in significantly reducing SGOT elevation, MDA production and lysosomal membrane damage in hepatic tissue. Clinical trials seem to be justified in using antioxidative substances to control doxorubicin toxicity.