[Common bile duct tumor in a young woman with ulcerative colitis]. / Ductus choledochus-tumor kialakulása fiatal colitis ulcerosás nóbetegben.

Bile duct carcinoma is a rare complication of ulcerative colitis. In most of the cases it tends to occur together with primary sclerosing cholangitis predominantly in older males. The authors report a case of a 25 year old woman presenting with jaundice, 6 years after the diagnosis of colitis was made. The cause of the extreme extra- and intrahepatic bile duct dilation was revealed by endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography showing polypoid tumor in the common bile duct. The histological result taken during the surgical exploration proved the diagnosis of adenocarcinoma. Radical pylorus preserving pancreato-duodenectomy was performed. Subsequently adjuvant chemotherapy was instituted according to the PAV protocol. This rare case proves, that a malignant bile duct tumor may develop in a young patient with ulcerative colitis without the presence of primary sclerosing cholangitis. The authors emphasise the connection between ulcerative colitis and bile duct carcinoma and the importance of the close follow-up of every patient with ulcerative colitis.

Increased efficacy and tolerability with losartan plus hydrochlorothiazide in patients with uncontrolled hypertension and therapy-related symptoms receiving two monotherapies.

The efficacy and tolerability of losartan 100 mg/hydrochlorothiazide (HCTZ) 25 mg and enalapril 10 mg/HCTZ 25 mg were compared in a double-blind, randomized trial in hypertensive patients inadequately controlled and experiencing side effects on prior therapy. Patients with moderate or severe hypertension, currently treated with at least two single-agent drugs (excluding angiotensin-converting enzyme inhibitors), with a sitting diastolic blood pressure (DBP) above 90 mm Hg, and at least one undesirable drug-related symptom were randomized to once-daily treatment with one of the combinations for 12 weeks. Losartan/HCTZ lowered sitting DBP from the prior therapy baseline by 13.7 mm Hg and sitting systolic blood pressure 19.3 mm Hg; similar reductions occurred with enalapril/HCTZ. Trough sitting DBP was reduced to normal levels (< 90 mm Hg) in 63% of patients switched to the losartan combination and in 58% of those treated with the enalapril combination. Each combination was associated with improved tolerability compared with prior therapy, although fewer patients reported each of 24 undesirable symptoms after 12 weeks of losartan/HCTZ. The improvement from prior therapy in the occurrence of cough was significantly greater with losartan/HCTZ (P = .005). Enalapril/HCTZ, but not losartan/HCTZ, increased serum uric acid levels at week 12. In conclusion, the combination of losartan 100 mg/HCTZ 25 mg offers a beneficial therapeutic option for patients with a history of moderate to severe hypertension whose blood pressure is not adequately controlled or who exhibit side effects while on two or more single-agent antihypertensive drugs. In this population, the switch from prior antihypertensive therapies to once daily losartan 100 mg/HCTZ 25 mg improves blood pressure control and reduces side effects.

[Life-threatening gastrointestinal bleeding in Crohn disease]. / Eletveszélyes gastrointestinalis vérzést okozó Crohn-betegség.

Massive gastrointestinal bleeding is a very rare complication in Crohn's disease. Its occurrence has been quoted as 1-2% in the literature. A case of a 16-year old boy is reported here, who had a three-year history of Crohn's disease. After a three-day's therapy of bronchopneumonia a massive rectal bleeding began and an emergency operation had to be made. Site of the bleeding was localised by intraoperative colonoscopy and an ileocolic resection was made. The patient recovered and has done well since. Some characteristics, diagnostic and therapeutic problems of the massive bleeding in Crohn's disease are discussed.

[Combined injection/endoscopic sclerotherapy of upper gastrointestinal peptic ulcer hemorrhage]. / Felsö gastrointestinalis fekélyvérzések kombinált, injekciós endoszkópos sclerotherapiája.

In the last 8 years period 369 patients with acute upper gastrointestinal bleeding were admitted to the Department of Internal Medicine, District Hospital Siófok. All patients were treated by combined injection sclerotherapy during the urgent endoscopy. The sclerotizing solution contained at the first step ethamsylate, calcium gluconate, epinephrin, hypertonic saline solution, and the second step 1% aethoxysklerol. At he time of urgent endoscopy 77% of the patients had acute bleeding (Forrest I.a., I.b.) and 23% of them showed stigmata of fresh bleeding (Forrest II.a., II.b.). Primary endoscopic hemostasis was achieved in all patients. In 7.9% of patients (n = 29) developed recurrent bleeding during the observation period, who were resclerotized. Twenty of them (5.4%) were treated by elective surgery. No hemorrhagic or sclerotizing therapy associated mortality occurred. Five out of 20 operated patients (1.4% of all sclerotized cases) had died due to the serious complications of their chronic liver disease. Patients with succesful initial endoscopic hemostasis were treated conservatively (proton pump inhibitors, H-2 blockers, antacids, sucralfate, lactulose) and underwent control endoscopy after 24 hours. Using this sclerotizing method in the treatment of acute upper gastrointestinal bleedings the number of acute surgery and mortality decreased significantly. It is supposed, that the locally administered ethamsylate, calcium gluconate, epinephrin, hypertonic saline solution and aethoxysklerol containing sklerotizing solution might play a favorable role in the successful control of acute bleeding ulcers.

[Clinical immunological features and interferon therapy in chronic hepatitis C]. / Klinikai immunológiai megfigyelések és interferon terápia krónikus C hepatitisben.

Clinical and immunological findings of 74 patients with chronic hepatitis C have been reported and experiences with interferon-alpha treatment of 31 patients are summarized. In addition, the first results of anti-HCV screening of blood donors are also briefly described. Transfusion in the history was noted in 69% of patients and the time, elapsed from the transfusion to the diagnosis was a mean of 7.15 +/- 8.1 years. Concerning the severity of the liver disease, chronic persistent hepatitis was established in 40%, active hepatitis in 45% and cirrhosis in 15% of the patients, respectively. Cholestasis was recorded in 32% of the cases. A significant elevation of serum immunoglobulin levels was noted in 83%, an antibody to liver specific protein (anti-LSP) has occurred in 80%, cryoglobulinaemia in 44% and circulating immune complexes in 33% of the patients. Natural killer cell activity of peripheral blood mononuclear cells significantly decreased. HLA B8 and DR3 antigens were found with elevated frequency (36.6% and 42.1%). Recombinant interferon-alpha at a weekly dose of 3MU thrice, for six months, has normalized serum alanine aminotransferase in 45% of patients and a sustained remission was found in 26%. The treatment resulted in the clearance of HCV-RNS from the serum in 40% of patients and that well correlated with the complete remission. In the good responders, a decrease in CD4+ cell count and a moderate decrease in CD8+ cell count as well as a transient rise in B cell count were seen during the treatment. Mitogen-induced lymphoproliferative response and natural killer cell activity increased. Predictors of response were as follows: female sex, shorter time elapsed from transfusion, absence of HLA, A1, B8, DR3 and serum anti-HBc negativity. Anti-HCV has been found in 0.33--0.38% of blood donors screened, and it is suggested, that a liver disease accompanied with elevated serum alanine aminotransferase, may be present in about 25-30% of anti-HCV positive symptom-free persons.

[Comparative clinical study of Neopanpur and Creon]. / Neopanpur és Kreon összehasonlító klinikai vizsgálata.

The aim of the study was to compare the clinical efficacy of Neopanpur (EGIS) and Creon (Kalichemie) in patients with chronic pancreatitis. Fifteen patients were examined for 2 x 10 days. A period: Neopanpur 3 x 2, B period: Creon 10,000 3 x 2. The type of the trial was: randomized, open, crossover study. The complaints of the patients (in score), the characters of the stool (daily weight, fat content, foamy, smell), amylum tolerance test (ATT), H2-breath test, lipjodol-test, Lundh-test and Schilling-test were determined before and during the treatment periods. Both enzyme preparations could effectively decrease the anamnestic complaints, the stool frequency and characteristics together with the laboratory results of pancreatic functions. There is no clinically significant difference between the clinical efficacy of Creon and Neopanpur. Both enzyme preparations can be applied in the treatment of maldigestion in patients with chronic pancreatic insufficiency.

[Isoprinosine therapy in chronic hepatitis C (multicenter placebo-controlled double-blind prospective study)]. / Krónikus C hepatitis isoprinosin kezelése (Multicentrikus, prospektív, placebo-kontrollos kettös-vak vizsgálat).

A placebo controlled clinical trial. Thirty two patients with chronic C hepatitis have been enrolled in a double blinded study to assess the therapeutic effect on an orally given antiviral-immunomodulatory drug, Isoprinosine. Seventeen patients were given Isoprinosine (3 g/day) and fifteen were on placebo. The treatment has been lasted for four months, when patients examined monthly. Clinical signs, liver function tests and side effects were evaluated. At the end of the trial, side effects and elevated serum alanine aminotransferase (ALT/GPT) levels occurred with higher frequency in Isoprinosine-treated patients. The results show that this antiviral drug has no beneficial effect in chronic C hepatitis.

[Hepatitis virus (HBV, HCV, HDV) markers in chronic liver diseases. Comparative studies in two East-Central European countries]. / Hepatitis vírus (HBV, HCV, HDV) markerek idült májbetegségekben. Osszehasonlító vizsgálatok két közép-kelet-európai országban.

The prevalence of hepatitis virus markers in patients with chronic liver diseases from two countries has been studied: 68 patients (38 alcoholic hepatitis or cirrhosis, 30 chronic HBsAg-positive hepatitis) from Hungary as well as 109 patients (55 alcoholic liver disease, 45 chronic hepatitis or cryptogenic cirrhosis and 9 hepatoma) from Romania were examined for HBsAg, anti-HBs, anti-HBc, anti-HCV and anti-HDV, using the corresponding Abbott Elisa test systems. In alcoholic liver disease HBsAg occurred in 6/38 patients from Hungary and in 22/55 patients respectively, that is HBV markers occurred with significantly higher frequency in alcoholic patients from Romania (p less than 0.05). In the Hungarian group a total of 36 patients were HBsAg positive and out of them 5 had anti-HDV (13.9%), while out of 21 Romania HBsAg carriers 10 patients had anti-HDV (47.6%). Among 9 hepatoma patients 4 had HBsAg, 6 anti-HBs and 7 anti-HBc and 4 had anti-HCV and 3 had anti-HDV. One patient with hepatoma had both HBsAg and anti-HCV plus anti-HDV as well. Results suggest that the infection with hepatitis viruses in alcoholic liver diseases is more common in Romania than in Hungary, and the prevalence of delta virus infection in HBV carriers is also significantly higher in Romania than in Hungary.

Measurement of non-steroid antiinflammatory drugs induced gastric microbleeding.

The damage of the mucous membranes in the gastrointestinal tract caused by non-steroid antiinflammatory drugs are well known. The gastrointestinal microbleeding was measured by the method of Fischer and Hunt before and after the intake of indomethacin (4 x 25 mg), naproxen-sodium (4 x 275 mg), diclofenac (3 x 50 mg) and azapropazone (2 x 600 mg). In the indomethacin group microbleeding increased from 0.91 +/- 0.12 ml/24 h to 7.30 +/- 1.20 ml/h. In the naproxen-sodium group from 1.22 +/- 0.16 ml/24 h to 3.56 +/- 0.40 ml/24 h, in the diclofenac group from 0.86 +/- 0.14 ml/24 h to 3.18 +/- 0.28 ml/24 h, in azapropazone group from 0.92 +/- 0.18 ml/24 h to 2.50 +/- 0.20 ml/24 h, respectively. All non-steroid antiinflammatory drugs increased the gastric microbleeding, however, there were considerable differences in the degree of enhancement. This can be explained by the different inhibitory activities of the drugs on the cyclooxygenase enzyme activity.

Efficacy testing of beta-galactosidase with H2 breath test in patients with carbohydrate malabsorption.

The clinical efficacy and the potential side-effects of beta-galactosidase were studied in adult lactose intolerance. Various randomized oral tolerance tests were performed using lactose solution (35 g), glucose + galactose solution (17.5 + 17.5 g), native, skimmed milk and milk pretreated with beta-galactosidase. In each case, simultaneous examinations were made of the glucose concentration of capillary blood by an instrument constructed by the authors, of the H2 content of expired air as also of the subjective complaints and of the number of stools and their pH. It was established that pretreatment of milk with beta-galactosidase has a beneficial effect in adult lactose maldigestion, since it stops dyspeptic complaints and diarrhoea due to milk, it reduces the H2 content of expired air increases blood glucose concentration. Measuring the H2 content of the breath by using and instrument constructed by the authors, exact data can be obtained noninvasively, and rapidly on the degree of carbohydrate malabsorption in patients with lactose-intolerance.

Disorders of biotransformation during the progression of alcoholic liver disease.

Biotransformation capacity was investigated in patients with various degrees of alcoholic liver damage. Aim of the investigation was to study the impairment of biotransformating ability during progression of liver damage. Four groups of patients with various liver diseases (alcoholic fatty liver, chronic persistent hepatitis, chronic active hepatitis, alcoholic cirrhosis) and two groups as controls were studied. The investigations were carried out with exogenous test substances (antipyrine, menthol and sulphadimidine) and by determination of D-glucaric acid excretion. It has been concluded that the depression of biotransformating ability in patients with alcoholic liver diseases is progressing during development of diseases. The changes in various metabolic pathways are different, and they seem to be more marked in the first phase of biotransformation than in the second phases.

The effect of cyclophosphamide and vincristine on glucose absorption in rats using in vivo perfusion experiments.

The effect in rats of cyclophosphamide and vincristine on glucose absorption was studied by the in vivo perfusion method. On testing the local effect of cytostatics, the drugs were dissolved in the perfusion solution, cyclophosphamide at a concentration of 10(-4) M and vincristine at 10(-6) M. Glucose absorption was not reduced by cyclophosphamide, while it was significantly reduced by vincristine. On testing the systemic effect of cytostatics, the drugs were administered intraperitoneally 24 hours prior to perfusion, i.e. in doses of 80 mg/kg in the case of cyclophosphamide, and of 0.05 mg/kg of vincristine. In that case, both cytostatics decreased glucose absorption significantly. Based on the results it was found that, being administered locally, cyclophosphamide did not have a damaging effect on the intestinal wall, and did not reduce absorption either. On the contrary, vincristine impaired the mucosa locally, thereby reducing glucose absorption. On systemic administration, both cytostatics decreased absorption from the small intestine.

The effect of cyclophosphamide and vincristine on intestinal protein loss in rats.

24 and 48 hours after a single intraperitoneal dose of 80 mg/kg cyclophosphamide (I. group) and 0.20 mg/kg vincristine (II. group) the intestinal protein loss has been studied using the 51CrCl3 isotope method. 16 animals were used as control (III. group). In case of both cytostatics, the intestinal protein loss was significantly higher. Histologically the small bowel mucosa, on the first day after injection, showed, in the crypts, necrotic cells and mitoses arrested in metaphase. By the second day, after injection, severe villous atrophy and occasional mucosal erosions were seen. The causes of these changes are discussed together with the question of the disrupted barrier function of the small bowel.

Preventive effect of PGI2, 7-oxo-PGI2 and 17-aza-PGF2 alpha derivate on the development of indomethacin-induced intestinal mucosal damage in rats.

Intestinal mucosal damage was produced in rats by the s.c. administration of indomethacin (10 mg/kg). The number and severity of the small intestinal mucosal lesions was recorded. Different doses of prostacyclin (PGI2), 7-oxo-PGI2 and 17-aza-PGF2 alpha (0.25-0.5-1.00 mg/kg) were given i.p. at the time of administration of indomethacin. The effects of these compounds were studied on the number and severity of the small intestinal mucosal lesions. It was shown that (1) all tested compounds inhibited the number and severity of the intestinal mucosal lesions, however, to different extent; (2) the inhibition of the development of small intestinal mucosal damage displayed a dose-response relationship; (3) 17-aza-PGF2 alpha was found to have the most potent effect on the development of the intestinal lesions as well as on the development of gastric mucosal damage produced by ethanol.

The effect of gastric cytoprotective drugs (atropine, cimetidine, vitamin-A) on the indomethacin induced intestinal ulcers in rats.

The effect of various gastric cytoprotective drugs was studied on the development of indomethacin induced intestinal ulcers. CFY strain rats weighing 200-250 g were used. Indomethacin in a single dose of 20 mg/kg was given intragastrically in 1.5 ml. The animals received atropine (0.025-0.2-1.0 mg/kg), cimetidine (2.5-10-50 mg/kg) or vitamin-A(0.1-1.0-10 mg/kg) intraperitoneally in a single dose 15 min before the administration of indomethacin. In another study the animals received the same doses of atropine twice a day for 3 days. The small intestine was examined for lesions consisting of: (a) palpable nodules on the mesenteric attachement: (b) ulcers in the jejunum and ileum: (c) adhesions as a consequence of ulcer perforation. Neither histamin H2 receptor antagonists, anticholinergics, nor vitamin-A affected the number and the severity of the indomethacin induced intestinal ulcers. These results suggest that, whereas atropine, cimetidine and vitamin-A have a cytoprotecting effect in the stomach, it appears that they have no role in intestinal cytoprotection.

Inhibition of hepatic drug metabolism by (+)-cyanidanol-3 (Catergen) in chronic alcoholic liver disease.

There are some controversies regarding the effect of (+)-cyanidanol-3 on hepatic drug metabolism. In the present study the effect of (+)-cyanidanol-3 was investigated on the microsomal and mitochondrial enzyme functions (hydroxylation, glucuronide production, D-glucaric acid excretion and acetylation) in alcoholic liver disease. Eight patients with biopsy-proven chronic alcoholic hepatitis were investigated before and after a 10-day, as well as after a further 30-day, treatment with (+)-cyanidanol-3 (Catergen), 3000 mg/day orally. Besides biochemical liver function tests (serum bilirubin levels, GOT, GGT), antipyrine metabolic clearance rate, mentholglucuronide production, urinary D-glucaric acid excretion and sulphadimidine kinetics were determined. Biochemical liver function tests improved markedly after the first period of treatment, at the same time antipyrine metabolic clearance rate decreased. Menthol-glucuronide production and D-glucaric acid excretion decreased significantly only after the second two course of Catergen administration. Sulphadimidine kinetics was not remarkably changed. Our findings suggest that (+)-cyanidanol-3 inhibits the hepatic microsomal drug metabolizing enzyme function in chronic alcoholic hepatitis.

[The effect of vincristine on the morpho-functional state of the rat small intestine]. / Vliianie vinkristina na morfofunktsional'noe sostoianie tonkoi kishki krys.

The effect of vincristine treatment on the morphofunctional status of the small intestine was studied morphologically in 80 Wistar rats. The drug was found to possess a general toxic effect. Diarrhea was matched by the arrest of crypt cell-proliferation at metaphase, lysis, a decreased disaccharidase activity and increased levels of cytoplasmic alkaline phosphatase and dipeptidyl(amino)peptidase-IV in enterocytes of the villi. Exudation and degenerated cell organellae prevailed in intramural nervous ganglion cells, smooth muscle cells of intestinal tunica muscularis and vessels and in endothelium. The said changes were transitory in epithelium, but never regressed in nervous structures. At later stages (6-12 months after vincristine, but never regressed in endothelium. The later stages (6-12 months after vincristine treatment), secondary dystrophic changes developed in the small intestine wall, being predominantly confined to neuromuscular and vascular elements.