Optimisation of vasculitis disease assessments in clinical trials, clinical care and long-term databases.

The systemic vasculitides are a group of rare, chronic, relapsing, but often progressive inflammatory conditions. They are associated with a significant burden of morbidity both due to scarring from the disease itself and as a consequence of treatment with glucocorticoids and other potent immunosuppressive agents. Careful assessment of disease activity is critical to guide appropriate use of these potentially toxic therapies. It is also important to differentiate features of active disease from those attributable to damage, which will not respond to immunosuppression. As these are chronic complex conditions, the impact on a patient's functional ability and quality of life are also important considerations. Given the lack of a reliable biomarker for assessment of disease activity or damage in systemic vasculitis, clinical tools developed and validated for use initially in clinically trials are key outcome measures in the evaluation of these patients. While the conduct of randomised clinical trials in vasculitis has been significantly enhanced by the development and use of validated outcome measures, regular use of validated disease activity and damage measurements as part of routine care offers a structured approach, which can serve as the basis of justifying treatment decisions. The authors review the concepts of clinical assessment tools used in the evaluation of patients with systemic vasculitis in the setting of clinical practice, clinical trials and long term databases with particular emphasis on disease activity, damage, prognosis and function.

Clinical characteristics of Polish patients with ANCA-associated vasculitides-retrospective analysis of POLVAS registry.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small to medium-size vessel systemic diseases. As their clinical picture, organ involvement, and factors influencing outcome may differ between countries and geographical areas, we decided to describe a large cohort of Polish AAV patients coming from several referral centers-members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS). METHODS: We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 to analyze their clinical picture, organ involvement, and factors influencing outcome. Patients were enrolled to the study by nine centers (14 clinical wards) from seven Voivodeships populated by 22.3 mln inhabitants (58.2% of the Polish population). RESULTS: Participating centers included 625 AAV patients into the registry. Their distribution was as follows: 417 patients (66.7%) with GPA, 106 (17.0%) with MPA, and 102 (16.3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA was twice more frequent among women (34/68). Clinical manifestations and organ involvement were analyzed by clinical phenotype. Their clinical manifestations seem very similar to other European countries, but interestingly, men with GPA appeared to follow a more severe course than the women. Fifty five patients died. In GPA, two variables were significantly associated with death: permanent renal replacement therapy (PRRT) and respiratory involvement (univariate analysis). In multivariate analysis, PRRT (OR = 5.3; 95% confidence interval (CI) = 2.3-12.2), respiratory involvement (OR = 3.2; 95% CI = 1.06-9.7), and, in addition, age > 65 (OR = 2.6; 95% CI = 1.05-6.6) were independently associated with death. In MPA, also three variables were observed to be independent predictors of death: PRRT (OR = 5.7; 95% CI = 1.3-25.5), skin involvement (OR = 4.4; 95% CI = 1.02-19.6), and age > 65 (OR = 6.3; 95% CI = 1.18-33.7). CONCLUSIONS: In this first multicenter retrospective study of the Polish AAV patients, we have shown that their demographic characteristics, disease manifestations, and predictors of fatal outcome follow the same pattern as those from other European countries, with men possibly suffering from more severe course of the disease.

Linear perturbation renormalization group for the two-dimensional Ising model with nearest- and next-nearest-neighbor interactions in a field.

The linear perturbation renormalization group (LPRG) is used to study the phase transition of the weakly coupled Ising chains with intrachain (J) and interchain nearest-neighbor (J_{1}) and next-nearest-neighbor (J_{2}) interactions forming the triangular and rectangular lattices in a field. The phase diagrams with the frustration point at J_{2}=-J_{1}/2 for a rectangular lattice and J_{2}=-J_{1} for a triangular lattice have been found. The LPRG calculations support the idea that the phase transition is always continuous except for the frustration point and is accompanied by a divergence of the specific heat. For the antiferromagnetic chains, the external field does not change substantially the shape of the phase diagram. The critical temperature is suppressed to zero according to the power law when approaching the frustration point with an exponent dependent on the value of the field.

Oxidation of amino acids and peptides in reaction with myeloperoxidase, chloride and hydrogen peroxide.

Oxidation was studied of N-acetyl derivatives of cystine, cysteine, methionine and glycyltryptophan employing the myeloperoxidase-Cl--H2O2 system at pH 4.5, 6.0 and 7.0. Moreover, oxidation of pentapeptide composed of Leu-Trp-Met-Arg-Phe-COOH with myeloperoxidase (donor:hydrogen-peroxide oxidoreductase, EC 1.11.1.7) and hypochlorite was also studied. It was found that amino-acid derivatives having an amino group bound to an acetyl residue react with functional groups of the side-chain. The -SH groups of N-acetylcysteine and the -SS- group of cystine oxidize to cysteic acid. Methionine residues oxidize to methionine sulphoxide, and tryptophan residues to a derivative of 2-oxoindolone. The same reaction products were obtained when respective amounts of hypochlorous acid were used instead of myeloperoxidase, Cl- and H2O2. Differences in the stoichiometry of reactions of myeloperoxidase-mediated oxidation and hypochlorite oxidation suggest differences in the reaction mechanisms of both studied systems. Interaction of the studied pentapeptide with myeloperoxidase-Cl(-)-H2O2 system as well as with hypochlorite showed that in the peptide molecule individual amino acids oxidize consecutively according to their susceptibility to oxidation. No splitting of peptide bonds was observed. Therefore, a modified peptide with methionine sulphoxide and and oxidized tryptophan incorporated into the molecule was obtained.

Poland-US collaborative study on cardiovascular epidemiology: classification agreement between US National Cholesterol Education Program and European Atherosclerosis Society hyperlipidemia guidelines in selected Polish and US populations.

Data from two epidemiological studies are used to measure the degree to which two well-known guidelines agree in measuring hyperlipidemia in population samples in the US and Poland. The epidemiological studies are the US Lipid Research Clinics Program Prevalence Study and the Pol-MONICA project in Poland and the guidelines are those adopted by the US National Cholesterol Program (USNCEP) and by the European Atherosclerosis Society (EAS). EAS guidelines were analyzed in two ways: Method 1 used triglycerides and total cholesterol only in classifying persons as hyperlipidemics or non-hyperlipidemics; Method 2 used triglycerides, total cholesterol and nine additional risk factors in the classification process. USNCEP guidelines used total cholesterol, low density lipoprotein cholesterol and the same additional nine risk factors used in EAS Method 2 in classifying hyperlipidemics. Classification differences between the two sets of guidelines were high when EAS Method 1 guidelines were compared with USNCEP guidelines. However, EAS Method 2 which included risk factors, compared favorably with USNCEP guidelines in all three populations under study.

Action of myeloperoxidase-hydrogen peroxide-chloride system on the egg white lysozyme.

The enzyme system composed of human neutrophilic myeloperoxidase (H2O2-oxidoreductase, EC 1.11.1.7), H2O2 and Cl-, at pH 4.5 interacts with egg white lysozyme (EC 3.2.1.17) in several stages. In the first stage, occurring at lysozyme to H2O2 molar ratio of 1:1.4-1.8, the lysozyme loses its enzyme activity but does not yield any derivative distinguishable from the native protein on polyacrylamide gel electrophoresis (PAGE). The second stage of oxidation begins at lysozyme to H2O2 molar ratio above 1:5, producing a change in the lysozyme spectrum at 260-290 nm, and yielding protein derivatives with molecular masses equal to multiples of 14.3 kDa, i.e. the lysozyme molecular mass. This implies that an excessive oxidation of lysozyme by the myeloperoxidase-H2O2-Cl- system produces cross-linking of lysozyme molecules to di-, tri-, tetra-, and pentameric structures. At lysozyme to H2O2 molar ratio exceeding 1:12 a water insoluble white product, which consists of a set of lysozyme cross-linked derivatives, is obtained.

Ribonuclease from cytosolic fraction of human erythrocytes.

Ribonuclease (RNase) activity is detectable in only one third of specimens of human erythrocyte haemolysates. On the other hand, treatment of erythrocytic cytosoles with sulphosalicylic acid reveals an inhibitor-bound RNase activity which is present in all erythrocyte specimens studied. The level of the erythrocyte inhibitor-bound RNase activity is comparable to that in human lymphocytes. Isolated RNase from the cytosolic fraction of human erythrocytes is poly-C avid RNase with maximum activity at pH 6.5. The enzyme is resistant to treatment with strong acids and heating up to 95 degrees C. Molecular filtration of the erythrocyte RNase shows that it is composed of two fractions differing in molecular mass, 19 000 and 15 000. No difference in enzymic properties between these fractions was found. The general properties of erythrocyte cytosolic RNase are much like those of acid RNases of human granulocytes and lymphocytes. As the erythrocytes do not metabolize RNA no function for the inhibitor-bound RNase can be suggested. Assuming that the observed erythrocyte RNase is the residual enzyme, persisting in the cell since it was functioning in the nucleated erythrocyte precursors, one may surmise that levels of free and inhibitor-bound erythrocyte RNase activity may be related to the normality or abnormality of erythrocyte maturation.

Results from a comparative dietary assessment in Europe: I. Comparison of dietary information derived from concurrently applied frequency questionnaires and quantitative measurement instruments.

Data from four central European dietary investigations carried out between 1982 and 1984 in the German Democratic Republic, Poland and the Federal Republic of Germany applying both a food frequency questionnaire (FFQ) and a quantitative recording instrument (24-h recall, 3-d record or 10- to 14-d record) were analysed to compare frequency of food consumption as reported by the FFQ with the corresponding information as derived from the quantitative instrument. The actual intake was found to be overestimated by the FFQ for categories of frequent consumption and underestimated for categories of rare consumption. Categories for which both instruments yielded similar estimates of frequency were found to vary between food items and to depend on the overall frequency of consumption of an item. This indicates that when using unvalidated FFQs and taking their FFQ-categories literally artificial differences of food consumption within the population(s) under study can be introduced. This implies also the tendency that the average food intake estimated through FFQs can yield unrealistically high values for items consumed frequently.

Results from a comparative dietary assessment in Europe: II. Feasibility of pooling individual-based dietary data between countries.

Dietary investigations in four central European survey populations carried out in the German Democratic Republic, Poland and Denmark between 1982 and 1984 using different methodologies were analysed in order to assess the possibilities of characterizing the dietary habits of individual survey participants in a comparable fashion. This was done with the view of assessing the feasibility of a pooled cancer cohort study. For this purpose a method has been devised to combine dietary information derived by food frequency questionnaires and quantitative recording methods into a quantitative characterization of individuals' habits. A comparable characterization between different cultural settings could be demonstrated for a selected list of food items. The selection was determined by the food items considered in common in the different food frequency questionnaires and yielding sufficient and comparable variation as well as absolute amounts of intake. This was more clearly found for food items such as 'fruit' which experience a concise role in dietary habits. However, the observed discrepancies of the different dietary methods within the countries, and, most importantly, between the countries, result in distributions of average daily consumption values which are not deemed to be comparable.

Comparative data on diet and risk factors from five Eastern European communities.

Starting from large differences in rates and trends of mortality between European countries, an ecological type of comparative study was launched between five population samples in so-called Eastern European countries: Krakow, Warsaw, Novosibirsk, Kaunas, and the German Democratic Republic (GDR). The purpose was to look into dietary data as a possible explanation for varying risk factor and mortality data. It was found that high energy and fat consumption but low carbohydrate intake are common in these populations. The sources of energy and fat however vary markedly. An association was found between diet-related cardiovascular risk factors like the mean total cholesterol value and excess energy or fat intake both in males and in females. It was concluded that changes in diet might be the most important prerequisite for a number of lifestyle changes in these communities, and that those diet changes need to be monitored on a regular basis as part of the national health reports.

[Utilization of risk factors in medical practice for ischemic heart disease evaluation]. / Uzyteczny w praktyce lekarskiej wskaznik ryzyka zachorowania na chorobe niedokrwienna serca.

The Multivariate risk of developing Ischaemic Heart Disease (IHD) during period of 6 years was estimated for men aged 40-59 years on the basis of 2 Polish populations. Coefficients of multivariate logistic function (MLF) were calculated using sample of 4831 men with 240 cases of IHD. The significant risk factors were: age, total serum cholesterol level, diastolic blood pressure, number of cigarettes smoked, familial history of IHD. For these five significant factors new MLF coefficients were calculated. Discriminant power and goodness of fit for both functions were analysed and no significant differences found. The reduced MLF was applied to construct a simple questionnaire of IHD risk test.

[Gastric neurofibroma--still a diagnostic problem]. / Neurofibroma zoladka--nadal aktualny problem diagnostyczny.

We report a case of gastric neurofibroma encountered in 41-year-old woman who complained of dyspepsia and physical examination revealed palpable mass in her abdomen. It was not possible to determine the nature and origin of the tumor by radiological and endoscopic investigations. At laparotomy the tumor was found to be pendiculated and growing extramurally from the anterior wall of the stomach. Wedge gastric resection, including the mass, was performed. Histological examination revealed a spindle cell gastric tumor, immunohistochemically differentiated as a neurofibroma.

[Beclobrate (Turec) in the treatment of primary hyperlipoproteinemia. I. Effect on cholesterol, lipid and apoprotein levels]. / Beklobrat (Turec) w leczeniu pierwotnej hiperlipoproteinemii. Czesc I: Wplyw na stezenie cholesterolu, lipidy i apoproteiny.

The effects of a new fibric acid derivative--beclobrate (Turec, Zyma) on serum lipid and apoprotein concentrations in 63 patients with primary hyperlipoproteinemia were examined. Beclobrate was given in the evening, 100 mg, once daily. After 3 months of beclobrate treatment mean total cholesterol concentration in serum decreased from 9.35 to 7.73 mmol/l (17.3%), mean LDL-cholesterol concentration from 6.32 to 5.38 mmol/l (14.9%), mean HDL-cholesterol concentration increased by 0.21 mmol/l (15.3% of initial value). The greatest decrease was observed in triglyceride concentration--by 50% of the initial value. Apoprotein B concentration decreased by 19.7%, apoprotein A1 and A2 concentration increased by 20.3% and 26.8% respectively. Higher initial values of total cholesterol and triglyceride concentration in serum were associated with greater concentration decrease after beclobrate treatment.

[Beclobrate (Turec) in the treatment of primary hyperlipoproteinemia. II. Results of the treatment in relation to the type of hyperlipoproteinemia]. / Beklobrat (Turec) w leczeniu pierwotnej hiperlipoproteinemii. Czesc II: Zaleznosc wyników leczenia od postaci hiperlipoproteinemii.

After three months of beclobrate treatment (100 mg once daily) of 63 patients with primary hyperlipoproteinemia (HLP) significant decrease of total cholesterol concentration was found in type IIa by 12.9%, IIb by 23.7%, IV by 20.8%. LDL cholesterol concentration decreased in type IIa by 15.4%, IIb by 8.3%, in type IV non significant increase of LDL cholesterol by 21.6% was observed. Decrease of initial triglyceride level in type IIa by 36.1%, IIb by 41.2%, in type IV by 56.6% was found. HDL-cholesterol concentration increased in all examined HLP types in IIa by 19.5%, IIb by 19.3%, IV by 14.5%. Also initial apolipoprotein A1 and A2 levels increased in all HLP types examined, namely in type IIa respectively by 21.2% and 12.4%, IIb by 25.1% and 11.0%, in type IV by 23.6% and 34.9%. Serum apolipoprotein B concentration decreased significantly in type IIa by 20.5%, IIb by 28.4%, however in type IV a slight increase of apoprotein B level was observed. Comparison of HLP types response to beclobrate treatment revealed that the HLP types examined are significantly different in change size of LDL cholesterol concentration, triglyceride concentration and apoprotein B concentration after treatment.

[Hypersensitivity to house dust mites and incidence of acute respiratory tract infections in children with bronchial asthma]. / Uczulenie na roztocza kurzu domowego a czestosc wystepowania ostrych zakazen ukladu oddechowego dzieci z astma oskrzelowa.

The aim of the study was to evaluate the relationship between h.d.m. allergy and incidence of respiratory tract infections in children with episodic, mild and moderate asthma. 32 children with bronchial asthma being followed up at the I. Department of Children Diseases P.A.I.P. CMUJ in Cracow were included into the study. The positive skin prick test (SPT) with H.D.M. allergens was confirmed in 18 children. The negative SPT allergens were observed in 14 patients. All patients were examinated by the retrospective inquiry which included the degree of asthma, severity of therapy schedule and incidence of acute respiratory tract infections during the last 6 months. The anthropometric measurement (length, weight, body mass index, thorax circumference) and spirometric parameters with physical examination challenge were introduced. The mean number of infections in group of patients sensitive to H.D.M. was 6.8; in non sensitive group-4.6. There was no significant difference in incidence of acute respiratory tract infections between both groups. It seems likely that small number of patients may influence the statistics. To verify the results, prospective observation of wider group of patients is planned in forthcoming winter.

[12-year trends in cardiovascular disease mortality]. / Dwunastoletnie trendy umieralnosci z powodu chorób ukladu krazenia.

The coefficients and trends of mortality in years 1976-1987, based on data of Central Statistical Office, has been estimated in population of men and women aged 25 to 64 years, inhabitants of the Warsaw city region or the county region of Tarnobrzeg province . The trend of decrease of general mortality due to diseases of circulatory system has been statistically significant one similarly as that of mortality due to other heart diseases or ischaemic heart disease in men (group aged 25-34 or 35-44 years) in the Tarnobrzeg province . The analogously significant trend of mortality due to diseases of circulatory system or ischemic heart diseases in men aged 35-44 years has been stated in the Warsaw inhabitants. In the group of women an increase of general mortality has been noted in the youngest age group in Warsaw. In Warsaw and the Tarnobrzeg province in 1987 deaths due to diseases of circulatory system represented 33.2% and 39.9%, respectively, of total death pool among subjects aged 25 to 64 years. The respective percentages in the group of women were 29.1% and 39.4%.

[Myocardial infarction incidence and mortality among urban and rural populations during the 3-year period]. / Zachorowalnosc i smiertelnosc spowodowana zawalem serca populacji wielkomiejskiej i rolniczej w okresie 3-letniej obserwacji.

In years 1984-1986 3639 men and 1885 women were registered with suspected myocardial infarction from right-side Warsaw, simultaneously 2371 men and 917 women with the same suspected disease were registered from the Tarnobrzeg province population. The myocardial infarction diagnosis was confirmed in 54% of men and 43% of women from the Warsaw population as well as in 77% of men and 66% of women from Tarnobrzeg province population. In Warsaw the standardized incidence due to myocardial infarction increased during years of study from 466 to 588/100,000 among men and from 178 to 206/100,000 among women. The analogous increase among the Tarnobrzeg province population was 302 to 559/100,000 among men and 64 to 195 among women. Fatality during 28 days from the onset of the disease did not show any relationship with year of study and corresponded yearly among men to 45% and among women to 37% in Warsaw and to 42% among men and 33% among women in the Tarnobrzeg province . High fatality was noted during first 24 hours of hospitalization (Warsaw: 36% among men and 26% among women, Tarnobrzeg: 39% among men and 32% among women). The highest fatality was noted in the youngest of analysed groups.

[Stroke incidence and mortality among urban and rural populations during the 3-year period]. / Zachorowalnosc i smiertelnosc na udar mózgu w populacji wielkomiejskiej i rolniczej w okresie trzyletniej obserwacji.

In years 1984-1986 582 men and 338 women have been registered with clinical diagnosis of cerebral stroke. The respective numbers in the Tarnobrzeg province were 340 and 263. Preliminary diagnosis of cerebral stroke was confirmed according to criteria of registration in 82% of men or women from Warsaw and in 81% of men and 84% of women in the Tarnobrzeg province . Standardized incidence due to cerebral stroke was significantly higher in every of analysed years in the Warsaw population both among men and women in compare with that in the Tarnobrzeg province . In both population studied the incidence was significantly higher among men than among women. Standardized fatality during 28 days from the start of sickness was higher in the Tarnobrzeg province population than in the Warsaw population so far as both men and women are concerned. In both populations among men and women the most frequently diagnosis was acute disease of cerebral vessels.

[Characteristics of the main risk factors of coronary disease among the population of Warsaw and rural agricultural population of the Tarnobrzeg province]. / Charakterystyka glównych czynników ryzyka choroby niedokrwiennej serca w populacji wielkomiejskiej Warszawy i rolniczo-przemyslowej województwa tarnobrzeskiego.

Basing on results of first screening of the Pol-MONICA Project in 1984 in two centres that is the Tarnobrzeg province and two districts of Polish capital Warsaw (Praga South and Praga North) the level of 11 main coronary disease risk factors was compared in 2469 men and 2729 women. The following 5 risk factors were statistically significant for both men and women: the Durnin index of body fat content, the total cholesterol concentration in the plasma, triglyceride level, numbers of daily meals. The mean level of two factors that is the HDL-cholesterol concentration and the HDL-cholesterol/total cholesterol ratio was lower in the Warsaw sample what speaks in favor of concept that the ischemic heart disease threat is greater in that population. Among men the Warsaw population exhibited moreover the significantly higher value of diastolic blood pressure as well as of Quetelet body mass index; age and numbers of cigarettes smoked daily has also been higher in that population. In women from the Tarnobrzeg province ++ the diastolic blood pressure was higher than that in the Warsaw population. The two populations studied showed also highly significant differences so far as the complex of all 11 features is concerned what enabled the qualification of 72.3% of men, and 68.4% of women as belonging to the big city population or to the agricultural-industrial population using the discriminant Fisher function.

[Effect of inter-population differences in the levels of selected factors on the differences in arterial blood pressure]. / Wplyw miedzypopulacyjnych róznic w poziomie wybranych czynników na róznice w cisnieniu tetniczym krwi.

According to the Pol-MONICA program the random selected population samples were studied in inhabitants of Warsaw or the Tarnobrzeg province . After excluding from analysis the subjects treated with the hypotensive++ or hypolipemic drugs the differences between populations studies with regard to range of mean pressure value, except systolic pressure (RRs) in women, appeared significant ones. In populations studied the arterial blood pressure (CTK) was influenced by: age, sex, education, family history with regard to the circulatory system, the alcohol intake, smoking, heart action frequency the Quetelet coefficient value, triglyceride concentration and daily sodium intake. After analysis of inter-population differences in values of above factors the mean RRs values in populations studied did not differed significantly whereas differences in mean values of diastolic pressure (RRr) were highly statistically significant.