Antibody against mutated citrullinated vimentin: a new sensitive marker in the diagnosis of rheumatoid arthritis.

The aim of this study was to determine the performance of antibodies against mutated citrullinated vimentin (anti-MCV) in comparison with antibodies to cyclic citrullinated peptides (anti-CCP) in patients with rheumatoid arthritis (RA). Serum levels of anti-MCV and anti-CCP were determined in 193 patients with RA and 332 controls, and sensitivity and specificity were calculated. In a separate analysis of 86 patients, the anti-MCV levels were compared to disease activity. Sensitivity of anti-MCV versus anti-CCP was 71.5 and 69.4%, specificity was 81.3 and 97.6%, respectively. The ROC curves showed higher specificity and an advantage of anti-CCP. In seronegative RA patients the sensitivity of anti-MCV was superior over anti-CCP. Anti-MCV positivities also occurred in systemic lupus erythematosus and Sjoegren's syndrome. In a subgroup of 86 RA patients we found a significant correlation between anti-MCV and disease activity. Anti-MCV appears to be an important marker for the diagnosis of RA, and correlates also with disease activity.

Vascular endothelial growth factor in patients with psoriatic arthritis.

OBJECTIVE: To determine the levels of vascular endothelial growth factor (VEGF) in patients with active psoriatic arthritis, patients with inactive psoriatic arthritis, and healthy controls. Serum VEGF levels were correlated with clinical and laboratory features in patients with active psoriasis arthritis. METHODS: Serum samples from 14 patients with active psoriatic arthritis, 14 patients with inactive psoriatic arthritis, and 9 healthy controls were investigated. VEGF levels in the serum were measured using a sensitive sandwich ELISA. RESULTS: The mean serum VEGF concentration in patients with active PA was 394.4 pg/ml (394 +/- 171.8), in patients with inactive PA 200.4 pg/ml (200.4 +/- 115.7), and in healthy subjects 214.3 pg/ml (214.3 +/- 162.1). Patients with active psoriasis arthritis had significantly higher levels of VEGF compared to patients with inactive psoriasis arthritis and healthy individuals (p > 0.001). In contrast, VEGF levels were comparable in patients with inactive psoriatic arthritis and controls (p =0.659). Furthermore, in patients with psoriatic arthritis, VEGF levels were positively correlated with ESR, HAQ, PASI and VAS. CONCLUSION: VEGF levels may be regarded as a good indicator of active psoriasis arthritis.

A simple method for measurement of CD14weak CD16strong monocytes in peripheral blood.

Mounting evidence for the clinical significance of the CD 14weak CD16strong monocyte subpopulation in peripheral blood induced the demand for an efficient method for its determination. We propose a simple, fast, no-wash flow cytometric method using fluorescence-labelled anti-CD14, anti-CD16, and anti-HLA-DR antibodies and ammonium chloride-based erythrocyte lysis. This type of analysis can be performed on a standard three-colour flow cytometer. The method avoids interference by NK-cells and neutrophil granulocytes without defining monocytes by stringent light scatter criteria that might lead to a loss of CD14weak CD16strong monocytes. It, therefore, offers high reliability and accuracy. Its performance recommends the method to be used for routine clinical measurements of CD14weak CD16strong monocytes.

Value of neutrophil CD16 expression for detection of left shift and acute-phase response.

Fc gamma RIII (CD16) expression of neutrophil granulocytes was measured in 156 patients by means of fluorescence-labeled antibodies with a flow cytometer. Results were compared with (1) 400-cell manual differential count; (2) left shift flagging on hematology analyzers; (3) absolute neutrophil count; and (4) acute-phase protein levels. Asynchrony was noted between neutrophil CD16 expression and microscopically defined neutrophil stage, particularly in heavily left-shifted samples, which made it impossible to reliably enumerate immature neutrophils on the basis of CD16 expression. According to receiver operating characteristics, the absolute count of CD16-negative neutrophils was highly discriminatory for detection of left shift, with an area under the curve (AUC) of 0.842 +/- 0.03 (SE) and maximum efficiency of 81% +/- 3%, but absolute neutrophil count was not significantly inferior (0.821 +/- 0.03 and 76% +/- 3%). STKS and SE9000 flagging demonstrated efficiency of 76% +/- 3% and 81% +/- 3%, respectively. For detection of acute-phase response, absolute neutrophil count (AUC, 0.836 +/- 0.04; maximum efficiency, 80% +/- 4%) outperformed both quantitative neutrophil CD16 expression (0.760 +/- 0.05; 75% +/- 4%) and absolute CD16-negative neutrophil count (0.757 +/- 0.05; 71% +/- 4%); absolute band count performed similarly (0.853 +/- 0.04; 79% +/- 4%) and showed high efficiency at high sensitivity and specificity. Efficiency of analyzer flagging for detection of acute-phase response was not superior to absolute neutrophil count (STKS, 77% +/- 4%; SE9000, 78% +/- 4%). In conclusion, the diagnostic value of measuring neutrophil CD16 expression was generally similar to that of less complicated analytes.

Precision and accuracy of monocyte counting. Comparison of two hematology analyzers, the manual differential and flow cytometry.

The Coulter STKS (Coulter, Hialeah, FL), the Abbott CD3500 (Abbott Diagnostics, Abbott Park, IL), a 400-cell manual differential, and flow cytometry using double-staining with fluorescence-labelled monoclonal antibodies (CD45-FITC and CD14-PE) on a Coulter Epics Profile II were evaluated for precision and accuracy in relative monocyte counting. STKS, CD3500, and Profile II achieved a precision analogous to a 3,542-, 1,835-, and 11,998-cell differential, respectively, demonstrating the superiority of automated methods. Analysis of 156 normal and abnormal samples revealed that the mean relative monocyte counts of the manual differential, CD3500 and Profile II were not significantly different. Only the STKS results showed a positive bias (0.79% +/- 1.65), which was increased in lymphocytic samples. Linear regression between the Profile II as independent viable, and the other techniques yielded acceptable correlation coefficients (STKS: 0.861, CD3500: 0.844, manual differential:0.833). Profile II results were also compared to those of a Becton Dickinson FACScan (Becton Dickinson, Mountain View, CA), which yielded an excellent correlation (r = 0.991) but a slightly smaller relative monocyte count (bias-0.39% +/- 0.60) of the latter. On the basis of these data, the authors recommend the use of monoclonal antibodies as a new reference method, but also indicate the need for further methodological investigations.

Immunoreactive trypsin, alpha-amylase and lipase in serum--is there an age-dependence?

A strong age-dependence of IR trypsin was found in 424 healthy controls suggesting the need for age-matched reference values. A possible relation of other exocrine pancreatic enzymes like alpha-amylase and lipase to age was investigated in 185 apparently healthy persons undergoing a preventive health check. Only alpha-amylase showed a weak correlation with age, but not lipase. Both enzymes correlated with IR trypsin. Whilst alpha-amylase and lipase activities were within the normal range, approximately 25% of IR-trypsin concentrations were above age-matched control values. It is suggested that these apparently healthy persons already have disease of the exocrine pancreas, and IR trypsin is a more sensitive diagnostic tool for screening than alpha-amylase or lipase.

The action of somatostatin on intestinal alkaline phosphatase stimulated by secretin and cholecystokinin-pancreozymin.

The action of somatostatin on intestinal alkaline phosphatase activity (IAP) in the duodenal juice was examined in 22 subjects undergoing diagnostic secretin-CCK-PZ-tests. Under continuous secretin-CCK-PZ-stimulation there is an increase of IAP which is followed by a period of exhaustion after 1 h of stimulation. The intravenous administration of somatostatin induces a distinct inhibition of IAP which cannot be due to the exhaustion of the enzyme synthesis. As there is a functional relationship between fat absorption and alkaline phosphatase, it is suggested that this inhibition of IAP is one of the mechanisms of the somatostatin-induced inhibition of intestinal fat absorption.

Intestinal alkaline phosphatase and the ABO blood group system--a new aspect.

The influence of erythrocytes of different blood groups on the intestinal isoenzyme of alkaline phosphatase (EC 3.1.31.1) was investigated. Binding of the enzyme to erythrocyte membranes was demonstrated by sedimentation experiments, by enzyme electrophoresis, by gel chromatography and immunologically using a modified Coombs technique. We found that red cells of blood group A bind almost all intestinal alkaline phosphatase; erythrocytes of blood group B or O to a much lesser degree. This is in accordance with the fact that intestinal alkaline phosphatase is found more frequently in the serum of individuals of blood group O or B than in serum of persons of blood group A. We conclude that underlying the described blood group dependent differences in synthesis of intestinal alkaline phosphatase lies a mechanism involved in the regulation of the activity of intestinal alkaline phosphatase in human serum.

Serum-induced changes in electrophoretic mobility of creatine phosphokinase isoenzymes?

BB isoenzyme of creatine phosphokinase (CK-BB) obtained from human brain-extract changes its electrophoretic mobility after incubation in human serum at 37 degrees C. No change of electrophoretic mobility of CK-BB is observed after incubation in isotonic saline. We have shown by means of immunoprecipitation with specific antibodies that the structure of CK-BB is not changed. These findings are supported by other authors and make the diagnostic value of electrophoretic separation of CK isoenzymes doubtful as after a 3-h incubation CK-BB migrates similarly to CK-BB and consequently may be misinterpreted.

[Isoenzymes of alkaline phosphatase in pleural effusions (author's transl)]. / Isoenzyme der alkalischen Phosphatase in Pleuraergüssen

By separation of alkaline phosphatase into isoenzymes, an isoenzyme fraction corresponding to the intestinal isoenzyme was isolated in a case of chylothorax. Since this fraction is transported from the intestine through the thoracic duct, the appearance of this fraction in a pleural effusion is typical of chylothorax.

[Long-term results after therapeutic starvation (author's transl)]. / Langzeitergebnisse nach Nullkalorien-Diät

19 Persons with gross refractory obesity (7 men and 12 women) were treated by therapeutic starvation. The patients were controlled after 32 months, on average (range: 7 to 58 months), following completion of treatment. The study shows that 8 of the females gained weight, one of these attaining her pretreatment weight and another even exceeding the pretreatment figure. None of the males had regained his pretreatment weight but 4 showed an increase in comparison with the weight at the time of hospital discharge. During starvation the serum lipids showed a marked decrease, which was statistically significant in the case of cholesterol, but not triglycerides. At the time of follow-up examination the serum lipid values were about the same as before treatment. It is concluded that the long-term results of therapeutic starvation are beter in men than in women and yet this method of treatment should be attempted, when indicated according to strict criteria, in refractory cases of extreme obesity.

[Inhibition of postprandial increase in serum triglycerides by somatostatin in man (author's transl)]. / Hemmung des postprandialen Triglyzeridanstiegs im Serum durch Somatostatin beim Menschen

A test meal containing 100 g neutral fat was administered to 10 healthy subjects. Serum concentrations of triglycerides, cholesterol, free fatty acids and gastrin were determined during an infusion of 1000 microng somatostatin/h over 3 hours. In comparison with a control group (infusion of normal saline solution), somatostatin caused almost complete suppression of the triglyceride increase. The free fatty acids showed a slight increase under somatostatin while there was no change in the cholesterol levels. Gastrin release was also completely blocked by somatostatin. The suppression of the serum triglycerides may be explained by the inhibition of digestion and absorption of fat in the small intestine under the influence of somatostatin which suppresses exocrine pancreatic secretion.

[The detection of hyperlipidaemia during routine preventive medicine investigations. Serum lipid values in 3006 viennese adults (author's transl)]. / Vorsorgeuntersuchung Hyperlipidämie. Serumlipidwerte bei 3006 Erwachsenen aus dem Bereich von Wien

1. 3006 adult volunteers (1001 women after an overnight fast of at least 12 hours and 2005 women and men, 6 to 8 hours after a light breakfast) were investigated in regard to serum cholesterol and triglyceride levels, body weight and height. 2. 73.8% of the men and 75.2% of the women were overweight. The degree of overweight increased with increasing age and only decreased in the advanced age groups. 3. Serum triglyceride and cholesterol values increased with increasing age and showed a decrease in the older groups. 4. Serum triglyceride and cholesterol levels increased with increasing weight, also within each single decade. 5. 21.7% of the 1001 fasting women showed values for TG over 200 mg/dl and/or Chol over 300 mg/dl.

[Diagnostic value of the combined determination of carcinoembryonic antigen (CEA) in pleural effusion and serum with an enzyme immunoassay (EIA). Sensitivity, specificity and relation to tumor type]. / Diagnostischer Stellenwert der kombinierten Bestimmung des karzinoembryonalen Antigens (CEA) in Pleuraerguss und Serum mit einem Enzymimmunoassay (EIA). Sensitivität, Spezifität und Abhängigkeit vom Tumortyp.

Measurement of carcinoembryonal (CEA) levels in pleural fluid are suggested to improve the unsatisfactory sensitivity of pleural cytology in the differential diagnosis of malignant pleural effusions. We evaluated simultaneously determined pleural and serum CEA levels in 117 patients with pleural effusions of different aetiology (74 malignant, 30 inflammatory exudates and 13 transudates) by use of an enzyme immunoassay (EIA). Despite considerable scatter, pleural levels of CEA in malignant effusions were significantly higher (p less than 0.001) than the values in benign effusions. Using a cut off level of 5 ng/ml, 41% (= sensitivity) of malignant pleural effusions showed elevated concentrations of CEA. Only one out of 43 benign effusions showed a level of 5 ng/ml, which is equivalent to a specificity of 98%. However, malignant effusions due to small cell lung cancer, pleural mesothelioma and metastasising ovarian carcinoma never showed elevated levels of CEA. Highest pleural values of CEA were observed in cases of alveolar cell or adenocarcinoma of the lung or metastasising breast cancer. Although pleural and serum CEA levels correlated significantly (rs = 0.77), the evaluation of serum CEA levels alone yielded a lower sensitivity (36%) and specificity (93%) than pleural levels. 77% of cases with malignant pleural effusions showing elevated pleural CEA levels were characterized by an increased ratio Pleura/Serum greater than 1, particularly in effusions due to lung cancer. The CEA ratio was significantly higher (p less than 0.05) in patients with malignant than with benign effusions. EIA appears to be more specific by avoiding false positive results in benign effusions as compared with determination by conventional RIA. In conclusion, evaluation of pleural CEA levels in patients with malignant effusions by using an EIA because of its high specificity is a valuable adjunct to pleural cytology in improving the diagnosis of malignant effusions. However, a normal CEA level in either pleural effusion or in serum is of no clinical significance. Simultaneous measurement in pleural effusion and serum is of greater value.

[Results of screening for diabetes within the health-care program of vienna (author's transl)]. / Ergebnisse des Diabetessuchprogramms im Rahmen der Gesundenuntersuchung der Stadt Wien.

Within the health-care program of Vienna 1577 volunteers (1203 female, 374 male persons) were screened for diabetes mellitus during 1975/76. Besides measurement of glucose tolerance one hour after the ingestion of 100 g glucose the following parameters were analyzed: cholesterol, triglycerides, uric acid and blood pressure. Male persons had a slightly decreased glucose tolerance; a distinct relationship with age was found in both sexes. After elimination of volunteers in whom pathological results were obtained with respect to other examined parameters, a significantly greater glucose tolerance was found in the remaining "normal" group. There are no parameters which are closely correlated with glucose tolerance although it was possible to reject the null-hypothesis in several cases due to the large sample involved. For statistical reasons (test sensitivity, test specificity, prevalence of disease) single glucose-tolerance measurements do not give enough evidence for diagnosing diabetes mellitus. Depending on the aims of the screening program one has to define the detection limits as well as frequency of retesting.

[Exocrine pancreatic function in chronic alcoholics in Austria (author's transl)]. / Untersuchungen der exokrinen Pankreasfunktion bei chronischen Alkoholikern in Osterreich.

97 chronic alcoholic patients were investigated with regard to exocrine pancreatic function. Chronic calcifying pancreatitis was radiologically established in 7.2% of the cases. Secretin-pancreozymin tests were performed in 30 patients. Pancreatic insufficiency was found in 8 patients, while 8 patients showed marked hypersection. The daily faecal fat excretion in 10 other patients with partial gastrectomy and Billroth II operation was 5.3 g. Pancreatic disorders were, thus, detected in 53.2% cases of chronic alcoholism. This is higher than expected for Austria.

[The isoenzyme pattern of serum alkaline phosphatase in patients on intermittent haemodialysis and kidney transplant recipients (author's transl)]. / Isoenzymmuster der alkalischen Phosphatase bei dialysierten und nierentransplantierten Patienten

The total activity and the isoenzyme fractions of alkaline phosphatase were determined in the serum of 15 patients on intermittent haemodialysis and 32 kidney transplant recipients. The isoenzymes of alkaline phosphatase were separated by polyacrylamide gel disc electrophoresis. It was apparent that the increased activity of serum alkaline phosphatase in these patients was not limited to a distinct isoenzyme fraction. 5 of the 15 dialysis patients and 19 (59%) of the 32 kidney transplant patients showed a bone-type isoenzyme pattern. The possible causes for the presence of a bone-type alkaline phosphatase pattern are discussed. The fractionation of alkaline phosphatase gives a valuable indication as to the organ of origin of the particular fraction and is also of diagnostic value when the total activity of alkaline phosphatase lies within the normal range.

[Disturbances of lipid metabolism following renal transplantation (author's transl)]. / Fettstoffwechstörungen nach Nierentransplantation

The serum cholesterol and triglyceride levels and the lipoprotein electrophoretic pattern were investigated in 33 kidney transplant recipients. These patients showed elevated serum cholesterol and triglyceride levels in comparison with a group of healthy control subjects. Lipoprotein electrophoresis showed a predomination of types II a, II b and IV, according to Frederickson. The causes of the disturbances in lipid metabolism are discussed. There is a definite risk of cardiovascular disease in kidney transplant patients as a consequence of the altered lipid metabolism.

[A comparison of serum phosphohexose isomerase and sialyl transferase activities in patients with malignant disease]. / Phosphohexose-Isomerare- Enzymaktivitäten bei malignen Erkrankungen und Vergleich zu Serum-Sialytransferase

The diagnostic value of serum sialyl transferase, phosphohexose isomerase and lactate dehydrogenase determinations is discussed in respect to patients with malignant diseases. It was found that 80 % of the investigated cases showed an increase in serum sialyl transferase activity. Phosphohexose isomerase was elevated in 46.6 % and lactate dehydrogenase in 23.3% of the cases. The serum sialyl transferase activity was within the normal range in 13.3% of the patients. It is concluded that although the serum sialyl transferase activity is of great diagnostic significance in cases of suspected malignancy, total reliance cannot be placed on the determination of this sole parameter, but only in conjunction with others.

[Serum lactate dehydrogenase activity after renal transplantation (author's transl)]. / Serum-Laktatdehydrogenase-Aktivität nach Nierentransplantation.

Regular 4-weekly follow-up controls of serum lactate dehydrogenase activity in 23 renal transplant recipients revealed a constant rise in serum LDH activity during the early postoperative months. During the first post-transplant month serum LDH activity increased from 150.0 +/- 48.2 mE/ml to 195.5 +/- 84.8 mE/ml, serum enzyme activity being highest (329.1 +/- 143.2 mE/ml) 6 months after surgery. Since serum creatinine levels remained relatively constant, it seems unlikely that renal rejection played a major pathogenic role in the production of increased LDH activity. Since the pattern of lactate dehydrogenase isoenzymes was ithin normal limits, the pathogenesis of increased LDH serum activity following renal transplantation is not yet clear. Possible causes such as liver damage due to hepatitis B, macrocytosis induced by immunosuppressive therapy and myopathy to steroids are discussed.