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Biomedical subjects

L Varga

Publications and source records attributed to L Varga.

At least 55 records · Page 3Linked to original sources

Ragweed allergy: correlation between skin reactivity and in vitro complement activation.

Recently we have reported on several observations which indicate that allergen-induced complement activation contributes to the development of the symptoms of ragweed allergy. In the present paper a new finding that supports this assumption is summarized. In 48 ragweed-allergic patients individual skin reactivity to ragweed allergen extract (RWA) was assessed using dilution skin prick testing. Sera of these patients were incubated with 20, 100, and 400 U/ml RWA and generation of two complement activation products, alternative pathway C3-convertase (C3bBbP) and terminal pathway activation complex (C5b-9) was measured by ELISA methods. A strong positive correlation (Spearman correlation coefficient r = 0.495, P = 0.0004, and r = 0.454, P = 0.0012, respectively) was found between individual skin reactivity to RWA and C3bBbP generation induced by 20 and 100 A allergological units/ml (U/ml) RWA. This finding further supports the role of complement activation products in the aggravation of the basic IgE-mediated immunopathology of ragweed allergy.

Complement Activation↗

Effects of Helicobacter pylori on gastritis, pentagastrin-stimulated gastric acid secretion, and meal-stimulated plasma gastrin release in the absence of peptic ulcer disease.

OBJECTIVE: There is strong evidence accumulating that chronic infection with Helicobacter pylori (H. pylori) interferes with inhibitory pathways of the regulation of acid secretion. The increase in maximum acid output (MAO), and the increase in the sensitivity of the parietal cell to gastrin commonly observed in patients suffering from duodenal ulcer disease (DU), however, remains largely unexplained. Insufficient evidence is available concerning how these parameters are influenced by H. pylori infection in patients not suffering from peptic ulcer disease (PUD) and how they are related to H. pylori-induced gastritis. The aim of this study was to compare basal gastric acid secretion (BAO), MAO, and the sensitivity of the parietal cell to gastrin in H. pylori-positive and H. pylori-negative patients not suffering from PUD, and to study the relationship with their individual postprandial gastrin release and the degree of gastric antral and corpus gastritis. METHODS: H. pylori status was assessed by CLO test and histology (two biopsies each from the antrum and the corpus) in 14 H. pylori-positive and 16 H. pylori-negative nonulcer patients of comparable age, weight and gender. Gastritis score was assessed by a pathologist, who was unaware of the acid secretory data. Following determination of BAO, the relation of pentagastrin and gastric acid secretion was established with a cumulative pentagastrin dose response curve for the dose range 0.03-6.0 microg/kg(-1) h(-1) and MAO (Vmax) and pentagastrin sensitivity (ED50) were determined. Basal and postprandial gastrin release was measured by radioimmunoassay. RESULTS: There was a significant higher gastritis score in the H. pylori-positive compared with the H. pylori-negative subjects. The dose response curves of the pentagastrin stimulated gastric acid secretion were not different between H. pylori-positive and H. pylori-negative groups. No correlation was seen between the gastritis score, basal acid output (BAO) peak acid output (PAO), maximum acid output (MAO), ED50 values and the plasma gastrin values. There was, however, a considerable larger variation of the PAO and MAO data of the H. pylori-infected subjects and >50% of the respective data was above or below the relatively low range of the respective values of the noninfected subjects. CONCLUSIONS: H. pylori-induced gastritis does not regularly enhance maximum acid output in nonulcer patients, nor does it modify the sensitivity of the parietal cell to gastrin. H. pylori infection is thus unlikely to be directly responsible for an increase of these parameters in DU disease. Our data support, however, the concept that chronic H. pylori infection can either enhance or attenuate maximum acid secretory capacity in certain subgroups of patients.

Adult↗

[Efficacy of short-term danazol treatment in hereditary angioneurotic edema patients undergoing maxillofacial and dental surgical procedures].

The authors evaluated the efficacy of short-term danazol prophylaxis in 12 hereditary angioedema patients undergoing maxillofacial or dental procedures. Hereditary angioedema is an autosomal dominant disorder resulting from the deficiency of the C1 esterase inhibitor. Characteristic clinical manifestations include the formation of subcutaneous and submucosal edema. The latter can lead to fatal upper airway obstruction. Edematous attacks can be precipitated by tissue injury from operative procedures, dental surgery in particular. In patients undergoing surgical and diagnostic procedures performed in the cephalic and cervical regions, such attacks can be prevented by appropriate drug therapy. Short-term danazol prophylaxis was effective in all 12 patients with a history of edematous complications that had occurred after dental procedures; none of them developed postoperative edema. The serum levels of complement components determined pre- and postoperatively as well as at 6- and 12-hour intervals also demonstrated the efficacy of prophylactic therapy.

Adult↗

Changes in left ventricular mass during treatment with minoxidil and cilazapril in hypertensive patients with left ventricular hypertrophy.

Attainment of the regression of hypertension-associated left ventricular hypertrophy (LVH) seems to be a desirable goal of blood pressure (BP)-reducing therapy. Since antihypertensive drugs of differing types may exhibit markedly different abilities to modulate LVH, we examined the effects of the angiotensin-converting enzyme inhibitor cilazapril, and the potassium channel activator minoxidil, alone or in combination with each other, on the left ventricular mass (LVM) in patients with severe essential hypertension who had LVH detected by echocardiography. All patients received the same base therapy of bopindolol and guanfacine. After a run-in period, they were treated with: (1) cilazapril (n = 10); (2) minoxidil, combined with a diuretic (n = 10); or (3) both cilazapril and monoxidil (n = 6) for 12 months. The LVM index (LVMI; LVM per body surface area) was estimated every 3 months by means of echocardiography. Each kind of therapy decreased the arterial pressures to a similar degree. The 1-year treatment with the cilazapril-based regimen resulted in a significantly diminished LVMI (from a mean +/- s.d. of 173 +/- 38 to 152 +/- 22 g/m2; P < 0.05). On the other hand, the minoxidil-based therapy led to a significant increase in LVMI (from 148 +/- 19 to 170 +/- 35 g/m2; P < 0.05). There were no significant LVMI changes in patients receiving the combined, cilazapril + minoxidil-based treatment (172 +/- 34 vs the pretreatment 183 +/- 54 g/m2). The results confirm that long-term treatment with cilazapril is effective both in reducing BP and in reducing LVM. In spite of yielding a satisfactory reduction of BP, minoxidil therapy, even in combination with a diuretic and a beta-blocker, may lead to an aggravation of pre-existing LVH; this effect of minoxidil could be prevented by the simultaneous administration of cilazapril.

Adult↗

Comparative study of the complement-activating and specific IgE-binding properties of ragweed pollen allergen.

Previous reports have defined the capacity of ragweed pollen extract (RWA) to activate human complement (C) in fluid phase through the classical pathway and have ascertained a strong correlation between the extent of complement activation and the severity of symptoms of allergic rhinoconjunctivitis during the ragweed blooming season. In the present study the complement-activating and specific IgE-binding capacities of various ragweed allergen preparations were compared. Elimination of physically adsorbed (flavonoid) pigments from the allergenic proteins had no significant effect on their complement-consuming capacity, although the process strongly diminished specific IgE binding. Removal of an IgE-binding trypsin inhibitor from RWA significantly enhanced RWA-induced complement activation, whereas it did not change IgE binding. These findings indicate that neither the physically adsorbed pigments nor the trypsin inhibitor are involved in complement activation by ragweed pollen allergens, and suggest that complement activation and specific IgE binding are distinct molecular properties of ragweed pollen allergen.

Allergens↗

Inheritance and mapping of Compact (Cmpt), a new mutation causing hypermuscularity in mice.

During selection for protein content in mice at the Technical University of Berlin, individuals showing high protein content and a compact exterior were noted. Animals showing this "Compact" phenotype were separated to form a new line. The present investigations were carried out on a Hungarian subpopulation of this line, selected for maximum expression of the Compact phenotype, and apparently at fixation for the relevant genes. Fertility and viability of the Compact subpopulation was normal. As compared to normal mice, carcass percentage values for male and female Compact mice were 9.4 and 6.8% greater, respectively; and the muscle:bone weight ratio in males was 1.61-fold greater. The Compact phenotype showed variable expressivity and was of intermediate dominance in males, but almost fully recessive in females. The hypothesis that a single gene is solely responsible for the Compact phenotype was rejected by maximum likelihood analysis. Linkage mapping using selective DNA pooling located a single locus (denoted Cmpt) strongly associated with the Compact phenotype on mouse chromosome 1. Fine mapping, using individual selective genotyping and haplotype analysis, located Cmpt to the region between D1Mit375 and D1Mit21, approximately one third of the way to D1Mit21.

Animals↗

The severity of clinical symptoms in ragweed-allergic patients is related to the extent of ragweed-induced complement activation in their sera.

We have previously reported a correlation between the extent of ragweed allergen (RWA)-induced in vitro serum complement activation and the symptom scores registered daily during the ragweed (RW)-blooming season in RW-allergic patients. The present study was performed in 22 15-17-year-old RW-allergic adolescents. Serum samples were incubated with 100 micrograms/ml RWA, and the generation of different complement activation products was measured by ELISA or RIA. Symptom scores were registered for 4 weeks during the RW-blooming season. The patients were divided according to the extent (low or high) of the generation of complement activation products, and symptom scores registered in the two groups were compared by two-way ANOVA. Significantly higher symptom scores were obtained in the high than in the low complement activation group (P values: 0.049 for C1rC1sC1inh, 0.022 for C3bBbP, 0.015 for C5b-9, 0.0001 for C3a, and 0.0008 for C5a). Similar results were obtained at the measurement performed in the sera obtained from the same patients half a year before the season (P values: 0.022 for C3bBbP, and 0.005 for C5b-9). These findings indicate that complement activation induced by the allergen may enhance the clinical symptoms of RW allergy.

Adolescent↗

Difficulties in early diagnosis and treatment of uncommon breast tumours.

The aim of the current study was to analyse the uncommon histological type tumours, occurred in our department in the last 10 years. In the study period 921 patients were treated for breast malignoma, 47.4% of them in early cancer stage. In the latter group 3 cases were observed with rare histological tumour type: secretory juvenile breast cancer T1N0M0, GI /case I/; primary angiosarcoma T1N0M0, GI /caseII/; planocellular breast cancer T2N0M0, GII /caseIII/. In the case of rare histological type tumours: (1) triplet diagnostic procedures are usually able to result in correct preoperative diagnosis; (2) the adequate treatment has to be determined individually; (3) continuous, long term follow-up is necessary; (4) MRI is an appropriate technique in the detection of recurrences.

Biopsy, Needle↗

[Diagnostic value of thyroid antibodies].

Thyroid antibodies against thyroglobulin, the microsomal fraction and TSH receptor have been investigated in 150 patients (41 of them with Graves'disease, 24 of them with Hashimoto thyroiditis, 21 of them with subacute thyroiditis and 34 cases with treated hypothyroidism). 30 patients having thyroid disease without immune etiology served as a control group. As compared with the control group, significant differences were detected in the titers of microsomal and TSH-receptor antibodies in Graves' disease, microsomal and thyroglobulin antibodies in Hashimoto thyroiditis, while significantly higher antibody titers were measured against the microsomal fraction antibodies in hypothyroidism. In subacute thyroiditis, no significant elevation of any of the three antibodies was demonstrated. The diagnostic values of antibodies were investigated; in Graves disease, the antibody against TSH receptor is the most sensitivity method (70%), while in Hashimoto thyroiditis the highest sensitivity (87,5%) is exhibited by the determination antibody against the microsomal fraction. The relationship between the thyroid hormone values and the antibody titer was investigated too. In Hashimoto thyroiditis with hypothyroid state significantly elevated microsomal antibodies were found, as compared with the euthyroid state. It may be concluded that in cases suspect of Graves disease, determination of antibody against of TSH receptor is recommended. In case of normal value, finding the antibody against microsomal fraction can confirm the diagnosis. In further conclusion, antibody measurements are rarely informative in subacute thyroiditis. In cases suspect of other thyroid diseases of immune origin, measurement of the antibodies against the microsomal fraction may be helpful, while the discriminative value of the thyroglobulin antibody is more limited.

Adult↗

[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↗

In vitro complement activation by ragweed allergen extract in the sera of ragweed allergic and non-allergic persons.

Ragweed allergen (RWA)-induced complement activation in sera of 40 RW allergic patients and of 40 non-allergic controls was investigated. After treatment of the sera with RWA, levels of C3a, C5a, C3bBbP, C1rC1sClinh, SC5b-9 and granulocyte-aggregating activity were determined. Concentration of RW-specific IgG was also measured. After RWA treatment dose-dependent complement activation was detected in sera of RW allergic and non-allergic persons. C3a generation was observed mostly in the sera of RW allergic individuals, while levels of C3bBbP and of RW-specific IgG were significantly higher in sera of allergics, and a strong correlation was found between these two parameters. In a prospective clinical study, a significant positive correlation was observed between the extent of RWA-induced alternative pathway (AP) activation and the severity of symptoms of allergic rhinoconjunctivitis that were developed in a 4-week period subsequent to blood sampling. These observations suggest that complement activation has a role in the development of the symptoms of RW allergy.

Complement Activation↗

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↗