Clinical trial: a multicentre, randomized, double-blind, placebo-controlled, dose-finding, phase II study of subcutaneous interferon-beta-la in moderately active ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) pathophysiology is characterized by an imbalance between pro- and anti-inflammatory cytokines. Interferon (IFN)-beta-1a has potent immunoregulatory properties, including stimulation of host defence mechanisms and thus represents a potential treatment. AIM: To extend pilot data and identify a suitable dose of IFN-beta-1a to achieve endoscopically confirmed remission (ECR) in patients with moderately active UC and to evaluate safety. METHODS: In this multicentre, double-blind, placebo-controlled trial, adults with moderately active UC were randomized to IFN-beta-1a 44 or 66 microg, or placebo, subcutaneously three times weekly for 8 weeks, with a 4-week follow-up. RESULTS: Endoscopically-confirmed remission was observed in 23.4% [95% confidence interval (CI): 13.8-35.7] of placebo patients, 29.2% (95% CI: 18.6-41.8) of the IFN-beta-la 44 microg group and 20.0% (950% CI: 11.1-31.8) of the 66 microg group (P = 0.45). Improvements with IFN-beta-1a 44 microg were greater than with placebo for most secondary efficacy outcomes, although significance was not achieved. Placebo response rates were higher than expected from previous trials. Adverse events were similar to the known safety profile of IFN treatment. CONCLUSIONS: Interferon-beta-1a was generally well tolerated at the doses tested, but a significant therapeutic benefit in patients with UC was not observed.

Evaluation of derived Coulter red blood cell parameters for the assessment of iron deficiency in adults with congenital heart disease.

INTRODUCTION: The aim of our study was to evaluate derived red blood cell parameters in determining the presence of iron depletion and iron-deficient erythropoiesis, as states that precede iron deficiency anemia, in adults with congenital heart disease. METHODS: Eighty-eight adults who were diagnosed with congenital heart disease were divided into two groups (cyanotic and acyanotic). In both groups, congenital heart disease patients were then divided into three subgroups: with iron depletion, with iron-deficient erythropoiesis, and a control group. The following parameters were measured: complete blood count, reticulocytes, ferritin, soluble transferrin receptor, haptoglobin, lactate dehydrogenase, and calculated parameters: low hemoglobin density (LHD), red cell size factor (RSF), and microcytic anemia factor (MAF). RESULTS: Discriminant analysis indicated statistically significant differences in the first discriminant function: Function 1 - body iron, LHD, MAF, sTfR, and RSF (P < 0.001) in patients with acyanotic congenital heart disease and significant differences in both discriminant functions in patients with cyanotic congenital heart disease: Function 1 - body iron, soluble transferrin receptor, LHD, RSF, MAF, lactate dehydrogenase, and haptoglobin (P = 0.008) and Function 2 - reticulocytes (#), immature reticulocyte fraction and reticulocytes (%) (P = 0.049). CONCLUSIONS: Beside parameters that describe iron metabolism dynamics (body iron and soluble transferrin receptor), LHD, indicator of hypochromia, have the highest potential to differentiate and classify iron deficiency in patients with congenital heart disease.

[Risk factors in chronic ischemic pancolitis].

Ischaemia of the colon wall leads to lesions that are gathered under entity of ischaemic colitis. Acute or chronic tissue hypoxia is caused by various vascular disorders which could be divided into two large groups: occlusive or non-occlusive. Chronic ischaemic colitis is manifested with necrosis of colon wall, with consequent stenosis of the affected area. Clinically, it is manifested with increased number of bloody stools and abdominal pain. Treatment of choice is surgery, and resection of the affected segment is often life saving. We present a case of a patient with chronic ischaemic pancolitis, due to atheromathosis of upper and lower mesenterial arthery branches, corelated with age, cardiovascular diseases, chronic opstipation and drug-intake.

[Alcohol and the liver. Present knowledge of pathogenic mechanisms]. / Alkohol i jetra. Savremena shvatanja o patogenetskom mehanizmu.

Intensive longtime experimental and clinically-experimental investigations have not yet succeeded unriddling the intimate mechanism of liver alcoholic damage. Earlier knowledge on accumulation of fats in liver under the influence of alcohol (ethanol) is still actual, but it probably represents only epiphenomenon and does not explain the intimate mechanism of events. It still can be stated that, although the aim has not been achieved, gradually, as a consequence of very studious investigations we have signification information which bring more light in regard to identify the mechanism of this frequent disease of modern mankind. We have tried to summarize the latest knowledge on alcoholic liver damages. However, some of the most simple questions still do not have an answer: why do, for example, some longtime alcoholics, whose everyday intake of alcohol is big, develop liver cirrhosis at the end of their lives, while the others, under the same circumstances, develop it very early?

[Malignant tumors in patients in our hospital 1985-1989]. / Maligni tumori digestivnog trakta u nasih stacioniranih bolesnika u periodu 1985-1989. godine.

An analysis was conducted concerning the data on malignant digestive-tract tumors which were treated in the period from 1985 to 1989 at the Department for Gastroenterology of the Clinical-Hospital Center in Zemun. The research results showed that malignant digestive-tract tumors are not in an increase, they are rare in persons which are younger than 40 years of age (10%) and are two times more frequent in males. The share of malignant tumors of the large intestine in overall morbidity is somewhat more frequent, they occur two times more in males and with 10.6% in persons younger than 40 years. The malignant tumors of the stomach are the only ones which are in a decrease, they are considerably less frequent in younger persons (3.7%), but are also two times more frequent in males. Malignant tumors of the pancreas are somewhat more represented in overall morbidity, they are very rare in young persons (3.7%) and are more frequent in males. The data on malignant tumors of the liver show that in the last few years they are somewhat more represented in overall morbidity, they are rare in persons younger than 40, and are more frequent in males.

[Whipple's disease. Case report]. / Morbus Whipple. Povodom jednog slucaja.

This is a case report on a 42 years old patient suffering from Whipple's disease. The patient had characteristic symptoms: high temperature, frequent bowel movement, melanoderma, arthralgia and enlarged lymph nodes. After detailed clinical researches, x-ray and endoscopic examination, bacteriology examination of faeces, absorptional tests, the diagnosis was made thanks to pathohistologic analysis of biopsy samples of the small intestine by light and electron microscopy. The differential diagnostic similarity with AIDS, especially at the early phase of the illness, required excluding HTLV III. We examined the aetiophathogenesis of the illness and discussed the clinical and laboratory presentation of the patient considering contemporary ideas regarding this disease.

Histocompatibility antigens in patients with hepatocellular carcinoma.

The distribution of class I (A, B, C) and class II (DR antigens) histocompatibility antigens (HLA) was examined in 82 patients with hepatocellular carcinoma (HCC) and in 147 patients with chronic liver disease as controls. The diagnosis of HCC was confirmed by histological examination of liver tissue. HLA-B15 antigen was found more frequently in the subgroup of HCC patients who were positive for HBsAG (13/36, 36.1%) compared to the control group (8/147; 5.4%) [p < 0.001, Pc < 0.05, RR = 9.8] and a HBsAg positive control subgroup (1/25, 4%) [p < 0.001, Pc < 0.05, RR = 13.6]. No other statistically significant difference was found for any of the HLA antigens examined either in HCC patients as a whole group or in the subgroups according to sex, course of illness, AFP status, alcohol consumption, liver cirrhosis or blood groups. These data are further evidence that there may be a link between hepatitis B viral (HBV) infection and HLA antigens. The association of HLA-B15 antigen and HbsAg supports the idea of some genetic control of HBV infection in the patients with HCC.

Serum alpha-fetoprotein levels and microheterogeneity in patients with different liver diseases.

Serum alpha-fetoprotein levels were determined in patients (268) with liver disease. Markedly elevated concentrations (greater than 100 micrograms/l) were found in twelve patients with malignant tumours and two with cirrhosis. Molecular variants of alpha-fetoprotein were distinguished by lectin affinity chromatography of these sera. Reversible binding to concanavalin A (86 +/- 5%) and to lentil agglutinin (61 +/- 19%) conformed to expected values for primary hepatocellular carcinoma except in one patient with a metastatic carcinoma whose alpha-fetoprotein binding to concanavalin A was similar to non-liver alpha-fetoprotein (44 +/- 13%), and the two patients with cirrhosis in whom binding to lentil agglutinin was typical for benign liver disorders (less than 20%). Since low levels of serum alpha-fetoprotein and non-characteristic alpha-fetoprotein binding patterns assisted in the regrouping of eleven out of 24 patients initially thought to have primary hepatocellular carcinoma, it was concluded that alpha-fetoprotein determination and lectin affinity chromatography are helpful in distinguishing primary hepatocellular carcinoma from metastatic and benign liver diseases. Slight increases in the alpha-fetoprotein level in the presence of serum hepatitis B surface antigen indicated seven patients at risk for primary hepatocellular carcinoma who should be monitored frequently.

The value of ultrasound in staging the severity of acute pancreatitis.

The authors asses the accuracy and role of early ultrasound examination in staging the severity of acute pancreatitis. A total of 110 consecutive patients with acute pancreatitis were included into the study. The ultrasound findings were categorized into six categories and compared with a modification of multiple prognostic criteria, computerized tomography, operative findings (when available) and clinical outcome. The probability of a positive ultrasound finding in a patient with clinically severe acute pancreatitis was 89.6% (sensitivity). In comparison to computerized tomography the sensitivity of ultrasound in discovering CT diagnosed moderate and severe forms of acute pancreatitis was 86.6%. The sensitivity of ultrasound in discovering moderate and severe forms of acute pancreatitis as defined at laparotomy was 77.8%. The specificity of ultrasound was low (44.0%) in comparison with modified prognostic criteria, but high in comparison with computerized tomography (87.5%) and staging at laparotomy (85.7%). There was a good correlation between US defined moderate and severe forms of acute pancreatitis and clinical outcome (average number of hospital days and case fatality). The authors conclude that early ultrasound examination in acute pancreatitis is indicated and can help stage the severity of the disease and affect decision making.

[Hepatitis C virus infection in patients on chronic hemodialysis]. / Infekcija virusom hepatitisa C kod bolesnika na hronicnoj hemodijalizi.

Frequency of HCV infection was examined in patients on chronical program of hemodialysis considering the high risk to which they had been exposed because of frequent blood transfusion. We determined anti-HCV antibodies in 57 patients (29 male and 28 female) average age 52.6 years with terminal chronic renal failure. Frequency of anti-HCV antibodies (determined by ELISA Ortho test of first generation) was in correlation with the number of received transfusions and with duration of dialysis treatment and it was compared with anti-HCV antibody findings in hemodialysis staff (the control group of healthy persons). Results of the examination showed that anti HCV antibodies were positive in 38.95% examined patients (n = 57), and it showed that the patients on hemodialysis were a critical group for HCV infection. There was no correlation with the blood groups. Level of transaminases, HBsAg and immunity test in anti-HCV positive patients were in the physiological range. In order to prevent HCV infection in the dialysis centres, it is necessary to conduct routine test in patients and staff, and undertake all measures of protection.