Duplications and losses of genes encoding known elements of the stress defence system of the Aspergilli contribute to the evolution of these filamentous fungi but do not directly influence their environmental stress tolerance.

The contribution of stress protein duplication and deletion events to the evolution of the Aspergilli was studied. We performed a large-scale homology analysis of stress proteins and generated and analysed three stress defence system models based on Saccharomyces cerevisiae, Schizosaccharomyces pombe and Aspergillus nidulans. Although both yeast-based and A. nidulans-based models were suitable to trace evolutionary changes, the A. nidulans-based model performed better in mapping stress protein radiations. The strong Mantel correlation found between the positions of species in the phylogenetic tree on the one hand and either in the A. nidulans-based or S. cerevisiae-based models on the other hand demonstrated that stress protein expansions and reductions contributed significantly to the evolution of the Aspergilli. Interestingly, stress tolerance attributes correlated well with the number of orthologs only for a few stress proteins. Notable examples are Ftr1 iron permease and Fet3 ferro-O2-oxidoreductase, elements of the reductive iron assimilation pathway, in the S. cerevisiae-based model, as well as MpkC, a HogA-like mitogen activated protein kinase in the A. nidulans-based model. In the case of the iron assimilation proteins, the number of orthologs showed a positive correlation with H2O2-induced stress tolerance while the number of MpkC orthologs correlated positively with Congo Red induced cell wall stress, sorbitol induced osmotic stress and H2O2 induced oxidative stress tolerances. For most stress proteins, changes in the number of orthologs did not correlate well with any stress tolerance attributes. As a consequence, stress tolerance patterns of the studied Aspergilli did not correlate with either the sets of stress response proteins in general or with the phylogeny of the species studied. These observations suggest that stress protein duplication and deletion events significantly contributed to the evolution of stress tolerance attributes of Aspergilli. In contrast, there are other processes, which may counterbalance the effects of stress gene duplications or deletions including (i) alterations in the structures of stress proteins leading to changes in their biological activities, (ii) varying biosynthesis of stress proteins, (iii) rewiring stress response regulatory networks or even (iv) acquiring new stress response genes by horizontal gene transfer. All these multilevel changes are indispensable for the successful adaptation of filamentous fungi to altering environmental conditions, especially when these organisms are entering new ecological niches.

Adipokines as atherothrombotic risk factors in obese subjects: Associations with haemostatic markers and common carotid wall thickness.

BACKGROUND AND AIMS: Some crucial associations between obesity-related altered adipokine levels and the main factors of atherosclerotic, atherothrombotic processes are not fully known. We analysed the relationships of classic adipokines, namely leptin, resistin, adiponectin, tumour necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) with the markers of platelet activation, including mean platelet volume (MPV), platelet surface/soluble P-selectin, platelet-derived microparticles (PMPs), the parameters of coagulation abnormalities and common carotid intima-media thickness (IMT) in obese patients with or without atherosclerotic comorbidities in comparison to age- and sex-matched controls. METHODS AND RESULTS: We enrolled 154 obese individuals, including 98 suffering from atherosclerotic concomitant conditions, 56 free of atherosclerotic comorbidities and 62 healthy controls. Plasma levels of leptin, resistin, adiponectin, TNF-α, IL-6, soluble P-selectin, and plasminogen activator inhibitor-1 antigen (PAI-1 ag) were analysed by ELISA. Platelet surface P-selectin and PMPs were measured by flow cytometry. IMT was detected by ultrasonography. Adipokines were closely associated with markers of platelet hyperactivity, hypercoagulability, hypofibrinolysis and IMT. Significant independent associations were found between leptin and platelet count (p < 0.0001), MPV (p = 0.019), PMPs (p < 0.0001), fibrinogen (p = 0.001), factor VIII (FVIII) activity (p = 0.035); adiponectin and PAI-1 ag (p = 0.035); resistin and soluble P-selectin (p = 0.002); TNF-α and PAI-1 ag (p < 0.0001); and IL-6 and fibrinogen (p = 0.011). Finally, leptin (p = 0.0005), adiponectin (p = 0.019), IL-6 (p = 0.001), MPV (p = 0.0003), PMP (p = 0.008), and FVIII activity (p = 0.043) were independent predictors of IMT. CONCLUSION: Overall, we suggest that in obese subjects altered adipokine levels play a key role in common carotid atherosclerosis both directly and through haemostatic parameters.

Relationship of serum resistin level to traits of metabolic syndrome and serum paraoxonase 1 activity in a population with a broad range of body mass index.

UNLABELLED: The relationship between resistin, one of the adipokines, and metabolic syndrome is not fully elucidated. Altered activity of the HDL-associated antioxidant enzyme paraoxonase 1 (PON1) that participates in the antioxidant defense mechanisms of HDL may have an important role in the obesity-related accelerated atherosclerosis. Inverse associations of PON1 with obesity and serum levels of leptin have been demonstrated. Our aim was to investigate the association of serum levels of resistin with (i) PON1 activity, and (ii) parameters of metabolic syndrome, including some that are additional for research. A total of 74 Caucasian subjects were recruited into the study and divided into 3 age and sex-matched groups. Group 1, 25 non-diabetic overweight/obese subjects with BMI of 28-39.9 kg/m (2); group 2, 25 non-diabetic obese patients with BMI >or=40 kg/m (2); and the control group 3, 24 healthy, normal-weight control subjects. Serum levels of resistin were correlated negatively with BMI (r=-0.27, P<0.05), waist circumference (r=-0.28, P<0.05), serum levels of leptin (r=-0.28, P<0.05), non-esterified fatty acids (NEFA) (r=-0.23, P<0.05), and HbA (1C) (r=-0.26, P<0.05), systolic BP (r=-0.28, P<0.05), and lipid peroxidation (measured by TBARS) (r=-0.40, P<0.01), and correlated positively with PON1 (r=0.24, P<0.05). No association was detected between the serum concentrations of resistin and the following investigated parameters: diastolic BP, levels of uric acid, glucose, insulin, or insulin resistance (measured by homeostasis model assessment, HOMA-IR), triglyceride, total cholesterol, LDL-C, and HDL-C. During multiple regression analyses BMI and TBARS were independent predictors of PON1, while age, gender, blood pressure, HOMA-IR, LDL-C, HDL-C, and resistin were not. CONCLUSIONS: Among the study subjects, serum levels of resistin showed a positive, although not independent correlation with serum PON1, and a negative correlation with numerous parameters of the metabolic syndrome (i.e. adiposity, blood pressure, levels of leptin, free fatty acid, glycosylated hemoglobin, and lipid peroxidation). BMI and TBARS are independent predictors of PON1 activity.

Prevalence of iodine deficiency and goitre during pregnancy in east Hungary.

OBJECTIVE: To assess the iodine nutritional status and the prevalence of goitre during pregnancy in a region of Hungary that appeared to be iodine sufficient in previous studies. DESIGN: A cross-sectional voluntary screening study was organized in which 313 pregnant women participated. METHODS: Urine iodine concentration and the volume of the thyroid gland were measured in every woman. In the presence of low urinary iodine concentrations, goitre, or both, thyroid function tests were performed. RESULTS: Iodine deficiency was found in 57.1% of the pregnant women, and was severe in 15.6%. The volume of the thyroid gland was enlarged in 19.2% of individuals. Nodular goitre was found in 17 women (5.4%). The frequency of goitre and the mean thyroid volume were increased in the group of iodine-deficient women. In the 89 cases of iodine deficiency or goitre, thyrotrophin concentrations were in the normal range; however, the free triiodothyronine:free throxine ratio was increased in 97% of them, indicating that the thyroid gland was in a stimulated state in these individuals. CONCLUSIONS: Iodine deficiency with high prevalence of goitre was recognized among pregnant women in an area that previously appeared to be iodine sufficient. An unexpected mild iodine deficiency was also noted in the non-pregnant control group. Reassessment and continuous monitoring of iodine nutritional status is warranted even in populations that are apparently considered to be 'at no risk' of iodine deficiency, especially in pregnant women. Regular administration of iodine, starting at preconception or in early pregnancy and continuing during the period of nursing, is recommended in these regions.

Prevalence of cardiovascular risk factors of the smokers and non-smokers in the city of Debrecen, Hungary.

The aim of our study was to compare the major cardiovascular disease (CVD) risk factors of smokers and non-smokers. Risk screening of CVD was estimated by a questionnaire, via interview. Random samples of 20 000 inhabitants of Debrecen, Hungary, aged 30-65 y, took part in the study. 19 922 questionnaires were considered appropriate for further evaluation. 32.2% of the participants (n=6410) were smokers, whose data were compared to those of the 68.8% of non-smokers (n=13 512). There were more male smokers than female (39.3% vs 27.7%), (P<0.001). 36.5% of males and 58.9% of females had not previously smoked regularly (P<0.001). 24.2% of males and only 13.3% of females were able to stop smoking (P<0.001). 8.7% of the participants smoked more than 20 cigarettes per day (14.8% of males, 5.0% of females), (P<0.001). Smokers were younger, with a mean age of 43.4 y vs 47.1 y for non-smokers (P<0.01). The ex-smokers and non-smokers had a higher body mass index than light, moderate and heavy smokers (26. 75+/-4.1 kg/m2 and 26.09+/-4.3 kg/m2 vs 24.87+/-3.9 kg/m2 and 24. 89+/-4.2 kg/m2 and 25.32+/-4.3 kg/m2, respectively), (P<0.001). The results of the last measured blood pressures did not differ between the two groups. 94.8% of smokers and 93.6% of non-smokers did not perform any regular leisure time exercises (P<0.01). 39.8% of smokers regularly ate fatty food, in comparison to 28.0% of non-smokers (P<0.001). 30.6% of smokers vs 28.6% of non-smokers were factory workers while 69.4% of smokers vs 71.4% of non-smokers did sedentary jobs (P<0.001). 2.3% of smokers vs 0.9% of non-smokers admitted regular consumption of alcohol (P<0.001). Amongst the parents and brothers/sisters of smokers the prevalence of heart attack was higher 19.7% vs 18.7%, than for those of non-smokers (P<0. 05). We observed an accumulation of cardiovascular risk factors in the case of smokers, which indicates the higher susceptibility of smokers to CVD.

Graves' ophthalmopathy: eye muscle involvement in patients with diplopia.

BACKGROUND: Diplopia identifies patients with eye muscle involvement in Graves' ophthalmopathy (GO). OBJECTIVE: To identify clinical parameters that could eliminate the need for magnetic resonance imaging (MRI) to assess the activity of inflammation in the eye muscles of GO patients with diplopia. METHODS: In 43 patients with GO with recently developed diplopia, orbital ultrasound and MRI were performed. Muscle diameters and MRI T2 relaxation times were measured, and the amount of orbital connective tissue was calculated from MRI scans and compared with ultrasound readings, diplopia grades, degree of protrusion, ocular pressure, tear production, antibody levels and hormonal parameters of thyroid function. RESULTS: No correlation was found between diameters of 233 extraocular muscles measured by MRI and by ultrasound. For each of the four muscles, there was a diameter above which ultrasound was always unreliable. MRI data were used in further analysis. Of the muscles examined, the inferior rectuses were the most frequently enlarged - at least one, in 93% of cases. Medial, lateral and superior rectuses were enlarged in 59%, 37% and 34% of the orbits respectively. The pattern of muscle involvement of the two orbits tended to be symmetric (r=0.49, P=0.003), particularly for the medial rectuses (r=0.90, P=0.000). Proptosis correlated with the sum of the muscle diameters for a given eye (right eye: r=0.54, P=0.003; left eye: r=0.57, P=0.001), but it failed to correlate with the amount of orbital connective tissue. In 53% of the patients, normal T2 relaxation times were found in all eight muscles. There was only a weak correlation between muscle thickness and T2 relaxation time (r=0.49, P=0.003), indicating that muscle enlargement alone is not a sign of disease activity. The severity of diplopia was independent of T2 relaxation time. The amount of orbital connective tissue showed a negative correlation with the greatest T2 relaxation time for a given eye (r= -0.52, P=0.004); this suggests that disease types exist that have predominant muscle involvement and predominant connective tissue expansion. No correlation between connective tissue expansion and proptosis, diplopia grade, muscle thickness or disease duration was found - that is, connective tissue expansion is not a major factor in diplopia. Both muscle and connective tissue findings were independent of thyroid function. CONCLUSION: Ultrasound and MRI eye muscle diameter readings do not correlate, because of the inherent inaccuracy of orbital ultrasound. Muscle enlargement alone does not mean oedematous swelling and active disease. Neither ultrasound, nor any combination of 11 clinical and laboratory parameters provided the degree of information on muscles and connective tissue that was obtainable by MRI. In unclear cases of recently developed diplopia, before orbital decompression surgery, in the case of treatment failure or if, for any other reason, imaging is needed in GO, MRI is the method of choice.

QT dispersion in patients with end-stage renal failure and during hemodialysis.

Interlead variability of the QT interval in surface electrocardiogram (ECG), i.e., QT dispersion, reflects regional differences in ventricular recovery time, and it has been linked to the occurrence of malignant arrhythmias in different cardiac diseases. The purpose of the study was to assess the effect of hemodialysis on QT and corrected QT (QTc) interval and dispersion in chronic hemodialyzed patients. Data of 34 nondiabetic patients (male/female = 21/13; mean age, 54 +/- 15 yr) on chronic hemodialysis were studied. Polysulfone capillaries and bicarbonate dialysate containing (in mEq/L) 135 Na+, 2.0 K+, 1.5 Ca2+, and 1.0 Mg2+ were used. Simultaneous 12-lead ECG were recorded before and after hemodialysis in a standard setting. The QT intervals for each lead were measured manually on enlarged (x3) ECG by one observer using calipers. Each QT interval was corrected for patient heart rate: QTc = QT/square root of RR (in milliseconds [ms]). The average cycle intervals were 853 +/- 152 ms predialysis and 830 +/- 173 ms postdialysis; the difference was not significant. The maximal QT interval changed significantly from 449 +/- 43 to 469 +/- 41 ms (P < 0.01). The corrected maximal QT interval increased significantly from 482 +/- 42 to 519 +/- 33 ms (P < 0.01). The QT dispersion changed from 56 +/- 15 to 85 +/- 12 ms (P < 0.001) and the corrected QT interval dispersion from 62 +/- 18 to 95 +/- 17 ms (P < 0.001). During hemodialysis, the serum potassium and phosphate levels decreased from 5.5 +/- 0.8 to 3.9 +/- 0.5 (mM) and from 2.3 +/- 0.5 to 1.6 +/- 0.4 (mM), respectively, whereas calcium increased from 2.2 +/- 0.23 to 2.5 +/- 0.22 (mM). It is concluded that hemodialysis increases the QT and QTc interval and QT and QTc dispersion in patients with end-stage renal failure. Thus, it may be stated that the nonhomogeneity of regional ventricular repolarization increases during hemodialysis. Measurement of QT and QTc dispersion is a simple bedside method that can be used for analyzing ventricular repolarization during hemodialysis.

[Effect of hemodialysis on QT dispersion in chronic uremia]. / A hemodialízis hatása a QT diszperzióra krónikus uraemiás betegekben.

Interlead variability of the QT interval in surface 12-lead ECG (i.e. QT dispersion) reflects regional differences in ventricular recovery time and it has been linked to the occurrence of malignant arrhythmias in different cardiac diseases. The purpose of the study was to assess the effect of hemodialysis on QT dispersion in chronic hemodialyzed patients. The data of 34 patients (Male/Female = 21/13, mean age 54 +/- 15 years) on chronic hemodialysis were studied. Simultaneous 12 lead ECGs were recorded pre- and post-hemodialysis in a standard setting. The QT intervals for each lead were measured manually by one observer. Each QT interval was corrected for patient's heart rate: QTc = QT/square route of RR (sec). The maximal QT interval changed from 449 +/- 43 to 469 +/- 41 ms (p < 0.01). The maximal QTc interval increased from 482 +/- 42 to 519 +/- 33 ms (p < 0.01). The QT dispersion changed rom 56 +/- 15 to 85 +/- 12 ms (p < 0.001), and the QTc interval from 62 +/- 18 to 95 +/- 17 ms (p < 0.001). During hemodialysis the serum potassium and phosphate decreased from 5.5 +/- 0.8 to 3.9 +/- 0.5 (p < 0.001), and from 2.3 +/- 0.5 to 1.6 +/- 0.4, respectively, whereas calcium level increased from 2.2 +/- 0.23 to 2.5 +/- 0.22 (p < 0.001). It can be concluded that the hemodialysis increased the inhomogeneity of regional ventricular repolarization. Measurement of QT and QTc dispersion by a cheap and simple bedside method could predict the increased myocardial inhomogeneity in dialyzed patients.

[Prevention of atrial fibrillation by atrial-based pacemaker implantation]. / A pitvari fibrilláció megelözése pitvari vagy pitvar-kamrai szekvenciális pacemaker-beültetéssel.

A large number of studies have demonstrated the long term disadvantage of single lead ventricular pacing in sick sinus syndrome. Ventricular pacing mode predicts chronic atrial fibrillation in patients with preimplant paroxysmal atrial fibrillation. The goal of the report was to study the effectiveness of single atrial and dual chamber (atrio-ventricular sequential) pacemaker treatment in the prevention of atrial fibrillation for patients with sick sinus syndrome complicated with paroxysmal atrial fibrillation. In our university hospital 16 atrial based 5 and dual chamber 11 pacemaker were implanted for treatment of patients with sick sinus syndrome (with or without AV conduction disturbances) complicated with paroxysmal atrial fibrillation. The mean age were 61 (24-78), nine males and seven females. Before or during pacemaker implantation sinus node and AV node function analysis, and echocardiography were performed. There were no surgical complications, lead and/or generator failure. All patients had routine follow-up performed at 4 weeks, 3 months, 6 months. Mean follow up was 31 +/- 8 months (range 3 to 93 months). The atrial based and dual chamber pacing were effective in 90% of our cases. In one patient the treatment had to be combined with propafenone. According to our result, the atrial based pacing may be used to reduce the incidence of atrial fibrillation with careful programming of the base atrial pacing rate, and it is associated with lower frequencies of thromboembolic complications and pacemaker syndrome.

Allosamidin inhibits the fragmentation of Acremonium chrysogenum but does not influence the cephalosporin-C production of the fungus.

The pseudotrisaccharide allosamidin, a potent inhibitor of chitinases, retarded the fragmentation of hyphae but did not affect the fungal growth and cephalosporin-C production in Acremonium chrysogenum. In vitro inhibition of A. chrysogenum cell-bound chitinase(s) by allosamidin revealed that about 47% of the soluble intracellular chitinase activity was resistant to the inhibitory effect of allosamidin. On the other hand, about 76% of the total chitinase activity localised in both the soluble and insoluble enzyme fractions was effectively inhibited by allosamidin. All the chitinase activities were measured using a new procedure based on purified A. chrysogenum chitin as substrate.

[Efficacy of benazepril monotherapy in moderate essential hypertension studied by automatic ambulatory blood pressure monitoring]. / Benazepril monoterápia hatékonyságának vizsgálata automata ambuláns vérnyomás-monitorozással enyhe és középsúlyos essentialis hypertoniában.

Authors examined the effects of benazepril, regarding the length of effectiveness by ambulatory blood pressure monitoring (ABPM), drug tolerable, and the compliance of patients in mild to moderate essential hypertension. 14 patients were treated with benazepril monotherapy. Six of them were newly diagnosed, and the rest had already been treated for hypertension. At the start, after six and 12 weeks, 24-hour monitoring was performed. Casual blood pressure (BP) measurements and detection of side-effects were also performed at 3rd and 9th-week. Prior the study the average daytime BP measured by ABPM was 149.1 +/- 7.7/96.6 +/- 4.7 mmHg. 10 mg of benazepril was first administered in the morning. By the end of the sixth week the average BP was significantly decreased (daily average: 139.1 +/- 9.9/88.2 +/- 7.6 mmHg). The daytime diastolic average BP of 8 patients was lower than 90 mmHg and the other's daily dose was raised to 20 mg. During the 12th-week we found optimal tension in 11 patients, while in two others there was also a significant decrease. The daily average BP was 134.7 +/- 7.5/85.6 +/- 6.6 mmHg. In comparison the data at the beginning of the study here was significant decrease in the 24-hour, daytime and night-time BP, in the hypertension time-index and the hyperbaric impact, both in systolic and diastolic levels. During the 12th-week period the diurnal index was unchanged. The early morning BP decreased by the end of the 3rd month from 148.6 +/- 14.1/98.5 +/- 11.7 mmHg to 135.2 +/- 13.5/93.4 +/- 11.2 mmHg. Sustained side-effect did not occur. The patient's compliance to benazepril was excellent. Authors conclude that benazepril monotherapy lowered in 92.8%, and normalized in 78.5% the blood pressure of patients suffering from mild to moderate essential hypertension. The unchanged diurnal index, and the decrease in the early morning blood pressure suggest the 24-hour effect of benazepril.

[Local treatment of rheumatic diseases with propolis compounds]. / Mozgásszervi betegségek helyi kezelése propolisz készítményekkel.

The authors conducted a single blind, placebo controlled local therapy trial on a total of 190 patients involving the use of materials (i) topically and (ii) by iontophoresis for pain and/or inflammation of the organs of movement. The materials used comprised of the following: (i) purified propolis and propolis saturated with antiinflammatory trace metal elements and (ii) propolis saturated with trace metal elements and poplar bud ointment saturated with trace metal elements also. Both methods of application using all the three preparations significantly improved symptoms. The preparations saturated with metallic ions were more effective. The mild effect of the placebo treatment is explained by the treatment procedure itself. Side effects were not observed.

Changes in superoxide anion production and phagocytosis by circulating neutrophils during tumor progression in a rat model.

The functional state of circulating neutrophils was monitored in a rat model of mesoblastic nephroma during tumor progression. Superoxide anion (O2.-) production in response to PMA and phagocytosis of yeast particles (Saccharomyces cerevisiae) were measured every second day after tumor cell implantation. Both phagocytosis and PMA-induced 02.- generation were found to be enhanced in the first period (on Days 6, 8, and 10), while they became significantly reduced in the advanced stage of cancer (on Days 12, 14, 16, and 18). The suppression of PMNL functions was accompanied with tumor progression and an increased number of neutrophils in the peripheral blood. Studies were also carried out on PMNLs isolated from normal rats and the cells were treated with plasma samples obtained from tumor-bearing animals at different stages of nephroma. Incubation of the normal cells with plasmas separated on the 2nd and 8th days of tumor growth influenced neither the 02.- generation nor the phagocytosis. In contrast, plasma preparations obtained on the 14th day significantly inhibited both 02.- production and phagocytosis by normal neutrophils. The alterations in 02'- generation and phagocytosis by PMNLs were observed in close association with tumor growth, thus they could be considered as indicators of tumor progression. However, further studies are required to see whether the granulocyte dysfunctions observed in our animal model could provide additional prognostic information in the case of human malignancies as well as to clarify the origin of inhibitory factor(s) present in the blood of tumorous animals.

[Cilazapril replacing captopril in the therapy of medium-severe essential hypertension]. / Captopril kezelés felváltása cilazapril terápiával enyhe és középsúlyos essentialis hypertoniában.

Authors performed an open, crossover, multicenter study of oral cilazapril versus previous captopril treatment in mild to moderate hypertension. The treatment of the 100 outpatients on daily three or four times captopril was found ineffective, or in some cases side effects or non compliance necessitated a switch to a once daily dose of cilazapril. Reasons of ineffectivity were compliance problems in 76% of the patients during long term captopril therapy. Blood pressure decreased from 163.28 +/- 14.5/97.5 +/- 9.35 mmHg on captopril therapy to 136.67 +/- 12/83.49 +/- 7.77 mmHg at the end of a 12 week cilazapril treatment (p < 0.001). 80 patients received cilazapril monotherapy (with doses of 2.5 mg in 54 cases, 5 mg in 18 patients). 7.5 mg in 4 cases, 1 and 1.25 mg in 2 patients. In 20 patients an adjunctive diuretic was also added, while the cilazapril treatment was ineffective in 3 patients. In respect of the global evaluation and scoring of cilazapril versus captopril therapy, a clear and statistically significant improvement could be demonstrated in efficacy, tolerability and compliance after a 12 week cilazapril treatment. The 24 hour ambulatory blood pressure measurement performed in 13 patients also verified a decrease in blood pressure achieved by cilazapril therapy. Authors conclude that in case of ineffectivity of three or four times daily captopril treatment (caused most likely by non-compliance), a switch to a once daily dose drug like cilazapril is indicated.

Detectability of thyroid anti-microsomal antibodies, changes in thyroid-stimulating immunoglobulins (TSI) and thyrotropin-binding-inhibiting immunoglobulins (TBII) during methimazole treatment of Graves' disease patients.

The prognostic value of determination of different antibodies in Graves' disease patients is questionable. The authors simultaneously assessed the generation of cAMP, the TSH-receptor binding inhibitory assay and the detectability of anti-microsomal antibodies by indirect immuno-fluorescence. The tests were performed before, during and after methimazole treatment. During a 12 months' medication all 22 patients became euthyroid. Six months after withdrawal of the drug, 15 patients were still euthyroid (Group A); 7 relapsed (Group B). Patients showing enhanced activities by all three methods, relapsed (5 out of 7 cases of Group B). The results indicate that simultaneous determination of TSI, TBII and anti-microsomal antibodies are of high prognostic value for relapses. These data should be taken into consideration for the further therapy.