Search PubMedSearch

Biomedical subjects

L Varga

Publications and source records attributed to L Varga.

At least 19 recordsLinked to original sources

[Experience with long term low dose methotrexate treatment in rheumatoid arthritis and arthritic psoriasis].

The clinical efficacy and the side effects of a long term (max. 42 months, min. 5 months) weekly pulse methotrexate treatment (10 mg/week) were investigated in 31 rheumatoid arthritis patients and in 14 with psoriatic arthritis. A reduction in the number of inflamed joints and diminished duration of morning stiffness could be observed together with a decrease of pain and of the erythrocyte sedimentation rate in rheumatoid arthritis. In patients with psoriatic arthritis the intensity of joint pain was not influenced considerable and the decrease of the erythrocyte sedimentation rate was not as great as in rheumatoid arthritis patients. Ineffectivity of the methotrexate treatment occurred in one rheumatoid arthritic patient. The methotrexate treatment could not be carried on in two rheumatoid arthritic patients because of adverse side effects.

Arthritis, Psoriatic

Low activity of the classical complement pathway predicts short survival of patients with chronic lymphocytic leukaemia.

The activities of the classical (CP) and alternative (AP) complement pathways as well as the levels of some complement components and circulating immune complexes were measured in 43 patients with chronic lymphocytic leukaemia (CLL) between 1980 and 1984. Depressed CP activities were frequently found in these patients. Clinical course of the disease in the patients was followed until 1992, and compared with the initial complement values. During the follow-up period 36 patients died, death of 33 patients being related to the underlying disease. A strong positive correlation (P < 0.01) was found between the length of survival of the patients and the initial CP values. Patients were divided into two groups: group A, short-term survivors, i.e patients who died in CLL-related complications within 3 years after the complement measurements; and group B, long-term survivors who died > or = 4 years after the complement measurements due to any cause, or were alive at the end of the follow-up period. Average CP values in Group B were almost twice those in group A (P = 0.002), and a similar but less pronounced difference was found in C3 levels (P = 0.055). These differences were even more marked (P = 0.0006 and P = 0.0015, respectively) when only patients in Rai stage 2 and 3 were considered. Low classical pathway activities predicted short survival time: according to the logrank test, patients in Rai stage 2-3 with low (< mean - 2s.d. of the normal values), and normal CP levels survived for 2.0 +/- 1.1, and 4.6 +/- 3.0 years, respectively. All the nine and 11/13 patients with low CP and C4 levels, respectively, died within 3 years after the complement measurements were made. These findings indicate that complement measurements performed in CLL patients have a clinical value.

Aged

Influence of acid and angiogenesis on kinetics of gastric ulcer healing in rats: interaction with indomethacin.

Indomethacin delays healing of experimental gastric ulcers. We investigated whether inhibition of gastric acid secretion by omeprazole or stimulation of angiogenesis by basic fibroblast growth factor (bFGF) may reverse this delay. Rats with gastric ulcers induced by cryoprobe were treated subcutaneously with either placebo, indomethacin (2 x 0.5 mg/kg), bFGF (2 x 100 micrograms/kg), omeprazole (1 x 40 mumol/kg), indomethacin plus omeprazole, or indomethacin plus bFGF given daily for 8, 10, 15, and 22 days. Ulcer size, epithelial cell proliferation, angiogenesis, and maturation of granulation tissue were sequentially quantified. Omeprazole significantly accelerated ulcer healing in an early phase (days 3-8). In contrast, bFGF accelerated healing in a late phase (days 10-15). Indomethacin significantly delayed ulcer healing in late phase and decreased prostaglandin generation, cell proliferation, angiogenesis, and maturation of granulation tissue. Despite stimulation of angiogenesis, bFGF did not reverse indomethacin-induced delay in ulcer healing. In contrast, omeprazole reversed indomethacin-induced effects on angiogenesis, cell proliferation, maturation of granulation tissue, and ulcer healing rate.

Animals

Clinical significance of longitudinal complement measurements in recipients of bone marrow transplant.

Overall activity of classical complement pathway, C3 and C4 levels, level of circulating immune complexes and concentration of serum immunoglobulins were measured in 38 patients transplanted with HLA-identical bone marrow before and after transplantation for at least 4 years. Changes of complement parameters and their association with acute and chronic GVHD and with infections were analysed. A strong association was found between the development of chronic GVHD and hypercomplementaemia measured in 16 long-term survivors. Low pre-transplantation C4 activity was found to predict the development of severe acute GVHD. These findings indicate that longitudinal complement measurements may have clinical value in BMT patients.

Acute Disease

[Clinical aspects of IgA deficiency].

The authors have carried out a retrospective study of 33 selective IgA-deficient patients. They have found the high frequency of respiratory infections, gastrointestinal (celiac disease, giardiasis), and also autoimmune-, allergic- and malignant diseases. They have called the attention to the variety of the clinical picture, the possible consequences of the haemo- and immunotherapy, as well as to the importance of the early diagnosis and examination of family members.

Autoimmune Diseases

[Clinical significance of the ultrasensitive TSH assay].

The authors attempted to answer the question whether the low thyroid stimulating hormone (TSH) levels measurable by the TSH ultrasensitive DELFIA kit have any clinical significance and whether they are more informative than the results obtained by the supersensitive TSH assay. No measurable TSH was detected in 111 sera among 896 random specimens, by using a supersensitive fluorimetric kit. These 111 sera were further investigated, TSH was measured by an ultrasensitive assay, in addition, the levels of the peripheral hormones (total T4, total T3, T3-uptake, free T4, free T3), were also determined. On basis of the latter, the patients were classified as having subclinical (n = 28) or manifest (n = 80) hyperthyroidism. The TSH levels of the patients affected by manifest hyperthyroidism were found significantly (p < 0.0001) lower than those encountered in subclinical hyperthyroidism. The groups were then further divided to homogeneous clinical subgroups (patients treated with thyrostatic drugs, untreated patients, toxic adenoma, Graves' disease) and the results were analyzed. It can be stated that the ultrasensitive test safely distinguishes manifest and subclinical disease in all subgroups (range of sensitivity: 90.0-94.7%). Specificity for the diagnosis of subclinical hyperthyroidism was 66.7% for the untreated subgroups, irrespective of aetiology, while in treated patients the value of specificity was 10%. In Graves' disease, specificity was 100%, in toxic adenoma 0% (the number of patients, however, was very small in these homogeneous subgroups). These results suggest that although the ultrasensitive method furnishes more information than the supersensitive test, its exclusive application would not be appropriate in characterizing thyroid function because of the broad range of individual scatter.

Diagnosis, Differential

[Effect of lovastatin on serum lipids and lipoproteins. Hungarian multicenter, open-label study].

The authors studied the effects of lovastatin on the parameters of serum and lipoprotein lipids in an open multicenter trial. 160 patients with hypercholesterolemia participated in the study, 151 of whom completed the trial. After a 4 week period of dietary measures, the patients were treated with lovastatin for 12 weeks while combining standard lipid lowering diet. The initial dose of the drug was 20 mg, this was increased until serum cholesterol level decreased under 5.2 mmol/l, or to a maximal daily dose of 80 mg. By the end of the 12th week, serum cholesterol level was reduced by an average of 33% (p < 0.001), LDL-cholesterol by an average of 45% (p < 0.001), serum triglyceride concentration by an average of 22% (p < 0.001) and HDL-cholesterol increased by an average of 13% (p < 0.001). Lovastatin showed a very good safety profile, therapy had to be cancelled due to the occurrence of adverse events only in 4 cases.

Adult

[Hepatitis B and C markers in alcoholic liver diseases].

Hepatitis B and C virus contamination of 240 patients with alcoholic liver disease was studied. Hepatitis B virus core antibodies were present in 58 alcoholic patients (24%) and hepatitis C virus antibodies in 30 alcoholic patients (12.5%). Both antibodies were present in 17 patients (7.1%). The prevalence of antibodies was more frequent in alcoholic female patients than in males. Data concerning the hepatitis B virus contamination in alcoholic liver patients with or without cirrhosis were similar. The frequency of hepatitis C virus antibodies in cirrhotic patients was more than in patients without cirrhosis. Female cirrhotic patients were more frequently C virus antibody positive than males. In female alcoholics the frequency of C virus antibodies was more in patients with cirrhosis than in the patients without cirrhosis. The viral serology and follow up of patients with alcoholic liver disease may be useful in detection of the early stage hepatocellular carcinoma.

Adult

[Comparative evaluation of dipyridamole and dobutamine 2-dimensional echocardiography in ischemic heart disease].

Dipyridamole and dobutamine stress were performed in the same 41 angiographically controlled patients. Both tests were followed by 2 dimensional-echocardiography. The dose of dipyridamole was 0.56 mg/kg/4 min. or 0.84 mg/kg over 10 min., while the dose of dobutamine was 10-20-30-40 and 40 micrograms/kg/min. over 3 min. each step. In addition, to reach the submaximal heart rate 0.25 mg/min Atropine was also injected for 4 minutes in 13 cases. One vessel disease was found in 15 cases, and 2 vessel disease was in 2 cases. The number of coronarography negative cases was 24. The sensitivity, specificity, positive and negative predictive values for both tests were 70%, 91%, 85% and 81%, respectively. False positive results were observed in 2 cases and false negative ones were found in 5 cases, mainly at left anterior descendent stenosis. There was a good agreement between the wall motion abnormality and the anatomic localization of stenoses. Both non-invasive tests are suitable for the diagnosis of ischaemic heart disease.

Adult

An indirect effect of an antibody on complement deposition and lysis of differently sensitized surrounding cells.

Lysis of papain-treated group A and B erythrocytes by human complement was studied by an anti-A (BRIC. 131) and an anti-B (BRIC. 30) IgM monoclonal antibody in 51Cr release assays. The indirect effect of membrane-bound antibody, i.e. its influence on complement binding to sensitized surrounding cells, was examined in a cold target competition test in which sensitized, non-labelled cells are present along with sensitized labelled cells and complement. The mode by which anti-A antibodies indirectly suppressed lysis of sensitized B cells up to 20-fold was studied by following C1q and C3b binding. C1q binding to both types of erythrocytes was not altered in mixed populations of erythrocytes in the presence of both antibodies. Binding of C3b to a mixture of both cell types was, however, suppressed, when both antibodies were present. C3b deposition in mixed cell populations did not reach a significantly higher extent than deposited to one type of erythrocyte alone. This was consistent with the results from competitive lysis and suggests that the anti-A captured most C3b at high anti-A concentrations and deprived the similarly sensitized B erythrocytes of complement. We think that this phenomenon is not due to an uneven removal of complement regulatory proteins from A and B erythrocytes by papain. Instead, the phenomenon might be due to an inherent property of anti-A mAb to better produce nucleation sites for C3 convertases which, upon binding factor B, better compete for the limiting factor D. A mathematical analysis of cold target competition experiment (containing 2430 individual measurements) also shows that the distribution of complement between the competing A and B erythrocyte population is uneven, since it predicts that in any given antibody combination the majority of complement is bound to A erythrocytes. This is consistent with the measured average percentage of lysis.

ABO Blood-Group System

Cholecystokinin type B receptor antagonist PD-136,450 is a partial secretory agonist in the stomach and a full agonist in the pancreas of the rat.

Gastrin (cholecystokinin type B (CCK-B)) receptor antagonists may help to elucidate the physiological role of gastrin, have therapeutic potential as acid antisecretory drugs, and may be of use as adjuvant therapy for gastrin sensitive tumours. In binding studies, the gastrin receptor antagonist PD-136,450 had at least 1000 fold greater affinity for gastrin (CCK-B) than CCK-A receptors. In this study the biological activity of PD-136,450 was evaluated in conscious and anaesthetised rats. PD-136,450 antagonised gastrin stimulated acid secretion after subcutaneous (IC50: 0.28 mumol/kg; conscious rats) and intravenous (IC50: 0.17 mumol/kg; anaesthetised rats) administration. In basal secreting fistula animals, the compound stimulated acid output to 30 (5)% of the maximal response to gastrin. Stimulant activity was not caused by gastrin release. As an agonist PD-136,450 was about 350 times less potent than gastrin-17 on a molar basis. In addition, PD-136,450 was a powerful agonist of pancreatic secretion in anaesthetised rats. The specific gastrin antagonist L-365,260 inhibited the (partial) agonist activity of PD-136,450 in the stomach and the specific CCK-A receptor antagonist L-364,718 inhibited the agonist activity of PD-136,450 in the pancreas. It is concluded that the agonist effect of PD-136,450 is mediated via interaction with the gastrin (CCK-B) receptor in the stomach and the CCK-A receptor in the pancreas.

Animals

Antacid provides better restoration of glandular structures within the gastric ulcer scar than omeprazole.

Mucosa of healed gastric ulcers displays histological abnormalities that are possibly the basis of ulcer recurrence. The influence of antacid and omeprazole treatment was studied on the quality of ulcer healing. Sixty four rats with gastric cryoulcers were treated daily either with placebo, antacid, omeprazole, or antacid plus omeprazole. Ulcer size was measured three times per week with a novel video endoscopic method. Prostaglandin generation (day 6), cell proliferation (day 8 and 15), height and cell composition of ulcer margin (day 8), and mucosal scar (day 15) were quantitatively assessed. Antacid, omeprazole, and antacid plus omeprazole significantly accelerated ulcer healing predominantly during days 3-8. Compared with placebo, the height of ulcer margin and mucosal ulcer scar was significantly increased in antacid (+7 and +9% respectively) and significantly decreased in omeprazole (-33 and -22% respectively) and antacid plus omeprazole (-26 and -18% respectively) treated rats. The number of bromodeoxyuridine labelled cells (+42%, day 8), epithelial cell mass (+42%, day 15), and the ratios of epithelial cells/connective tissue (+73%, day 15) and epithelial cells/gland lumen (+100%, day 15) were significantly increased in antacid treated rats. In conclusion, both antacid and omeprazole accelerate ulcer healing but antacid provides a better quality of healing. This advantage is lost by cotreatment with omeprazole.

Aluminum Hydroxide

[New strategy for thyroid function testing].

The authors used a new protocol, based upon a supersensitive TSH assay, to examine the thyroid status of 1720 patients. Based upon the serum hormone levels, the patients were divided into different clinical groups. The biochemical relationship between the different hormone levels, and the rate of occurrence of various thyroid diseases were studied. 76.1% of the new patients hadn't received any previous treatment. 15.5% of those patients who had received treatment had hyperthyroidism, while 8.4% of those had hypothyroidism. 76% of the new patients, 38.3% of those who had hyperthyroidism, and only 29.7% of those who had hypothyroidism, were euthyroid. Undetectable TSH levels (< 0.03 mU/L) where observed in 51.8% of the new hyperthyroid patients, and in 33.8% of those who had subclinical hyperthyroidism. Similar results were obtained with those who had been previously treated for hyperthyroidism. The new protocol has the following advantages: it's more convenient to the patients, it's quick, it's economical. With this method it is possible to reduce the assays per patient by 31%. The algorithm was supplemented with results of free hormone levels. By doing this the authors were able to measure free-T4 and T3 hormone levels of 150 more patients. According to the authors, the free-T4 test is more informative than the free-T4-index, especially in the border-line cases and in treated hyperthyroidism. Primarily the free-T3 test is most necessary when examining patients treated with methimasol.

Adrenergic beta-Antagonists

Interactions in the complement-mediated lysis of blood group AB erythrocytes sensitized simultaneously with anti-A and anti-B monoclonal antibodies.

The lysis of group AB erythrocytes by human complement was studied by different anti-A and anti-B IgM monoclonal antibodies (mabs) in a 51Cr-release assay. The concentration of membrane-bound immunoglobulin was detected by ELISA, and the amount of C1q and C3 bound to sensitized red cells was measured by using purified, 125I-labelled molecules. We have demonstrated that there is an exponential relationship between the concentration of the sensitizing IgM mabs and C1q binding to the sensitized AB cell. The efficiency of binding was related to the number of antibodies bound; thus, anti-A sensitized cells bound 3-6 times more C1q than anti-B sensitized cells did. AB cells, on the other hand, bound similar amounts of C3 whether anti-A or anti-B was present. The lytic efficiencies of the various IgM mabs during short incubation times were different, suggesting that the complement activation rates vary widely with different antibodies on the AB cell membrane. The binding of C1q to an antibody-sensitized target activates a cascade, whose components may migrate away from the sensitizing antibody; interactions between the activation processes generated by the anti-A and anti-B antibodies may thus occur. Choosing appropriate pairs of anti-A and anti-B mabs for the simultaneous sensitization of AB cells has indeed resulted in stimulation in some and inhibition in other combinations of mabs. It is suggested that stimulation is observed when the activated intermediates are produced in excess, whereas inhibition occurs when a shortage of activated intermediates prevents mutual utilization.

ABO Blood-Group System

Investigation of premalignant lesions of larynx epithelium with histoautoradiography and HPV-assay.

The histological evaluation of precancerous alterations of larynx epithelium is, in transitional cases, very difficult. The differentiation of harmless metaplasia, hyperplasia and keratosis from abnormal proliferation depends on the pathologist's training and experience. Fine diagnostic lines separate the different grades of dysplastic epithelial alterations. The tritiated thymidine, 3H-TdR, labelling and histoautoradiographic procedure of biopsy specimens taken from the larynx provide the possibility to recognise the DNA synthetiser cells. The number, location and distribution of 3H-TdR labelled cells in the epithelial layers help us to distinguish with clarity the growth activity, the degree of dysplasia. After 3 weeks' exposition time of sections prepared by photoemulsion and stained with haematoxilin-eosin, the result can be assessed. In addition to histoautoradiography HPV-assay was applied, as HPV may play a role in the pathogenesis of laryngeal preneoplastic alterations.

Autoradiography

[With primary liver carcinoma-associated cholestasis].

Icterus is among the symptoms which occur late in carcinoma of the liver. Icterus which occurs through the obstruction of the bile-ducts may be an early symptom in favourable cases. On the basis of literature and the analysis of the case material in our clinic the incidence of cholestasis, its clinical picture and treatment in carcinomas of the liver is evaluated. The differential diagnostic importance of enzymes which are typical of cholestasis--alkaline phosphatase and gamma-glutamyl transferase--and their isoenzymes are discussed. The results obtained in our clinic are compared with those in literature.

Aged

[Treatment of carcinoid syndrome with a somatostatin analogue].

Octreotide, a long-acting somatostatin analogue has recently been introduced in the therapy of gastroenteropancreatic endocrine tumors, but home experience has been lacking. With the aim of drawing attention to this therapeutic possibility, a case of malignant carcinoid syndrome treated with octreotide for 18 months is reported. Despite the therapeutic attempts preceding the octreotide administration a gradual progression in clinical symptoms was observed and cardiac failure due to fibrotic and valvular heart disease developed. Cytotoxic chemotherapy, serotonin antagonists or repeated selective embolisation of the hepatic artery only resulted in a short transitional improvement. Octreotide in a dose of 100 micrograms three times daily by subcutaneous injection provided effective and rapid relief from episodic flushing and serious diarrhoea. Plasma level of serotonin and 24-hour urinary excretion of 5-hydroxyindolacetic acid decreased from 6 micrograms/ml to 2 micrograms/ml and from 800 mumol/day to 70 mumol/day, respectively. No changes in the number and extension of liver metastases could be seen after introducing the octreotide treatment. The patient's compensated cardiac status could be preserved and continuous therapy provided an acceptable quality of life.

Humans