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J Lüdemann

Publications and source records attributed to J Lüdemann.

At least 19 recordsLinked to original sources
PubMed2000

[Methods for quality assurance of medical examination in epidemiological field studies: the "Study of Health in Pomerania" (SHIP)].

The aims of the population-based, cross-sectional survey "Study of Health in Pomerania" (SHIP) are to describe prevalences and distributions of a broad range of diseases, as well as environmental and behavioural risk factors in the region of Pomerania (North-eastern Germany). The examinations are performed in two study units by different physicians, technicians and interviewers and laboratory analyses in two separate laboratories. In addition, the study will take at least 3 years and approximately 7000 persons will be examined. Because of the design of the study a special concept of quality assurance is indispensable. In the present paper methods are presented for quality assurance and control in anthropometry, ECG, echocardiography, abdominal sonography, carotid ultrasound, sonography of the thyroid gland, blood pressure measurements as well as clinical laboratory analyses. The technical control protocols, the training programmes of the observers and methods to establish observer and method variabilities are presented by means of typical examples. The logistic, personal and technical measures for quality assurance and control require appropriate attention. The methods and procedures presented here are expected to provide an effective instrument to continually monitor the quality of medical examinations in the SHIP study.

Adult↗
PubMed2000

Evaluation of a sensitive immunoluminometric assay for the determination of C-reactive protein (CRP) in serum and plasma and the establishment of reference ranges for different groups of subjects.

A sensitive immunoluminometric assay originally designed to measure C-reactive protein (CRP) in neonates and minimal serum volumes was adapted to measure this protein in a routine method without prior sample dilution. The concentration range covered without prior dilution was 10 micrograms/l to 20 mg/l using a sample volume of 5 microliters serum and a total assay time of less than 2 h. Serum samples were assayed from participants in a community medicine programme (SHIP--Study of Health in Pomerania) of the University of Greifswald, Germany (n = 414), as well as from mother-child pairs at birth (n = 30) and women attending the infertility clinic (n = 36). The validation of the assay was compared with a commercial latex-enhanced turbidimetric immunoassay (Roche Diagnostics--Integra 700) using routine serum samples (n = 60) from hospital patients. Comparison was made with the routine assay used in the SHIP study (Roche Diagnostics--Hitachi 717/Tina Quant). From 414 SHIP samples measured in the immunoluminometric assay, 289 were below the detection level in the turbidimetric (Tina Quant) assay. A significant positive correlation (p < 0.01) between log C-reactive protein concentration with age was found, both in the non-screened (all CRP values) (n = 414, r = 0.222) and selected (CRP < 5.00 mg/l = 90th percentile) (n = 370, r = 0.242) SHIP participants. Women were found to have significantly higher CRP levels than men (women: median age 47 a, median CRP 1.29 mg/l; men: median age 55 a, median CRP 1.00 mg/l--p = 0.016) in the non-selected SHIP participants. The situation was different in the selected group, (median age: men 54 a, women 48 a) where no significant difference in median CRP values between the sexes was seen (men: 0.874 mg/l, women 0.951 mg/l, p = 0.206). The distribution of CRP values in a "Normal Healthy Population" is skewed (mean/median--SHIP: all--2.08; selected--1.49). From the 414 SHIP samples measured in the immunoluminometric assay, 289 were below the detection level (2.5 mg/l) in the turbidimetric (Tina Quant) assay. From the 125 remaining samples the correlation between both methods was acceptable (r = 0.813), the regression line y = a + bx being: CRP (ILMA) = 1.83 + 0.842*CRP (Tina Quant). The Tina Quant assay gave values significantly higher than the ILMA in the range 2.5-25 mg/l CRP (p < 0.001). The total information loss in 289/414 subjects with a CRP < 2.5 mg/l with the Tina Quant assay makes it no longer suitable for epidemiological studies in which CRP is to be studied as a risk factor for cardiovascular events. The comparison between the immunoluminometric assay and the latex-enhanced immunoturbidimetric assay (Roche Integra) was much better. The latter measured down to less than 0.3 mg/l, thus being more suitable for epidemiological studies than the Tina Quant assay from the same producer. The correlation and regression data between the ILMA (x) and the Roche Integra assay (y) were: r = 0.971; CRP (Roche Integra) = 0.635 + 0.984*CRP (ILMA); n = 50.10 sera with CRP levels between 25 and 460 mg/l showed no high-dose hook effect in either assay. The remaining 50 sera were measurable in both assays. The turbidimetric assay gave rise to marginally but significantly higher values than the immunoluminometric assay (p = 0.004). The mothers at birth had a median CRP of 3.64 mg/l (range 1.49-12.6 mg/l), the neonates a median CRP of 34 micrograms/l (range 4-288 micrograms/l). All births were without complications, with gestational periods between 38 and 42 weeks. There was no correlation between maternal and neonatal CRP at birth. Mothers at birth had significantly higher CRP levels than healthy non-pregnant women (p < 0.001). Women attending the infertility clinic had CRP-values similar to age-matched healthy non-pregnant women (median 0.698 mg/l, range 0.05-9.97 mg/l). Interassay coefficients of variation at CRP concentrations of 0.85 and 7.9 mg/l were 8.99 and 7.93%, respectively, for the immunoluminometric

Adolescent↗
PubMed2000

A simulation approach to study planning for large-scale epidemiological surveys.

In study planning for large-scale epidemiological studies with multi-type examinations, important resource questions have to be answered, e.g. study horizons, personnel and other resources and cost estimates are needed. A simulation approach for scheduling that uses relevant parameters to simulate examination times gives simulation distributions that can be utilised to answer planning questions.

Adult↗
PubMed1999

Hormone replacement therapy in postmenopausal women: carotid intima-media thickness and 3-D volumetric plaque quantification.

OBJECTIVE: The relationship between postmenopausal hormone replacement therapy (HRT) and the risk of stroke has been investigated in a number of epidemiological studies. However, data concerning the quantitative effects of HRT on carotid atherosclerosis, as measured by noninvasive ultrasound methods, are sparse. METHODS: In the present case, we examined 55 postmenopausal women (mean age 57.6 +/- 4.2 years) who were treated for 4.7 years with estrogens, either alone (n = 11) or in combination with progestins (n = 44). They were compared to 46 control subjects without HRT who were matched for age, hypertension, and various other vascular risk factors. At the study onset and 1.5 years later, all participants were examined by Doppler ultrasound and B-mode sonography, and plaque visualization, intima-media-thickness (IMT) and volumetric quantification of carotid plaques was performed. RESULTS: The HRT group had a significantly lower incidence of carotid plaques (18%) than the control group (61%). The mean TMT for the HRT subjects was 0.52 mm in the common carotid artery and 0.46 mm in the internal carotid artery, as compared to 0.68 and 0.62 mm, respectively, for the control subjects. No significant changes in IMT were found in either group. 3-D evaluation of carotid plaques showed increased plaque volume in women without HRT compared to women with HRT. CONCLUSION: We have obtained quantitative data using different noninvasive ultrasound techniques which demonstrate that women receiving HRT develop less severe carotid atherosclerosis, an effect which may be mediated by direct hormonal effects on the carotid wall and, in part, by the indirect influence of hormones on lipoproteins. HRT may, indeed, be more effective on existing atherosclerotic plaques.

Adult↗
PubMed1998

Shortening versus isometric contractions in isolated human failing and non-failing left ventricular myocardium: dependency of external work and force on muscle length, heart rate and inotropic stimulation.

BACKGROUND: For reasons of simplicity, studies on isolated human myocardium have been conducted using exclusively isometric contractions, although positive inotropic interventions may differently influence force development, extent of shortening and myocardial work performance. We investigated human left ventricular failing and non-failing preparations comparing isometric versus isotonic, i.e., shortening contractions. RESULTS: (1) When muscle length is increased from 90% to 100% lMAX, peak developed force increases by 36% and 43% (p < 0.05) in non-failing and failing human left ventricular myocardium, respectively. Maximum performed work increases similarly in non-failing but decreases in failing myocardium. It can be shown that this discrepancy is due to significantly higher resting tension and does not present an insufficient intrinsic shortening capacity in failing myocardium. (2) When stimulation rate is increased from 0.5 to 2.0 Hz, isometric force increases significantly by 59% in non-failing and decreases by 27% in failing myocardium, whereas maximum performed work increases by 98% and decreases by 46%, respectively. (3) Pharmacological positive inotropic interventions by 7.2 mM calcium (n = 9), 3 x 10(-8) M isoproterenol (n = 7), 3 x 10(-8) M ouabain (n = 5), and 10(-5) M EMD 57033 (n = 3) equally increased force development and extent of shortening: When the fractional effect on shortening (y) was correlated to the fractional effect on force (x), the following linear regression equation was obtained: y = 0.91x + 0.26 (r = 0.86; p < 0.001). CONCLUSIONS: The data presented are of clinical and pharmacological importance: (1) The Frank-Starling mechanism is demonstrated to be existent in the failing human myocardium regarding both isometric force developed and maximum work performed. (2) Both force-frequency relations and--to a greater extent--work-frequency relations are reversed in failing human myocardium. (3) Independent of the pharmacological mode of action, positive inotropic compounds increase developed isometric force to the same extent as isotonic shortening and therefore potentiate maximum performed work.

Adolescent↗
PubMed1998

Alterations of cross-bridge kinetics in human atrial and ventricular myocardium.

CONDENSED ABSTRACT: We analyzed actomyosin cross-bridge kinetics in human atrial and ventricular muscle strip preparations by using sinusoidal length changes from 0.1 to 60 Hz. The minimum stiffness frequency was higher in atrial than in ventricular human myocardium and lower in failing than in non-failing left ventricular human myocardium. beta-Adrenergic stimulation increased the minimum stiffness frequency by 18 +/- 3% (p < 0.05). Cross-bridge kinetics are temperature-dependent, with a Q10 of at least 2.7. BACKGROUND: Dynamic stiffness measurements have revealed acute and chronic alterations of actomyosin cross-bridge kinetics in cardiac muscles of a variety of different animal species. We studied dynamic stiffness in right atrial and left ventricular preparations of non-failing and failing human hearts and tested the influence of the temperature and beta-adrenergic stimulation on cross-bridge kinetics. METHODS AND RESULTS: Muscle strips were prepared from right atria and left ventricles from human non-failing and failing hearts. After withdrawal of calcium, steady contracture tension was induced by the addition of 1.5 mM barium chloride. Sinusoidal length oscillations of 1% muscle length were applied, with a frequency spectrum of between 0.1 and 60 Hz. Dynamic stiffness was calculated from the length change and the corresponding force response amplitude. The specific minimum stiffness frequency, which indicates the interaction between cross-bridge recruitment and cross-bridge cycling dynamics, was analyzed for each condition: (1) The minimum stiffness frequency was 0.78 +/- 0.04 Hz in left ventricular myocardium and 2.80 +/- 0.31 Hz in right atrial myocardium (p < 0.01) at 27 degrees C. (2) The minimum stiffness frequency was 41% higher in non-failing compared to failing left ventricular human myocardium. (3) Over a wide range of experimental temperatures, the minimum stiffness frequency changed, with a Q10 of at least 2.7. (4) beta-Adrenergic stimulation significantly (p < 0.05) increased the minimum stiffness to 18 +/- 3% higher frequencies and significantly (p < 0.05) lowered contracture tension by 7 +/- 1%. CONCLUSIONS: The contractility of human heart muscle is not only regulated by excitation-contraction coupling but also by modulation of intrinsic properties of the actomyosin system. Acute and chronic alterations of cross-bridge kinetics have been demonstrated, which play a significant role in the physiology and pathophysiology of the human heart.

Actomyosin↗
PubMed1998

Diagnostic value of standardized assays for anti-neutrophil cytoplasmic antibodies in idiopathic systemic vasculitis. EC/BCR Project for ANCA Assay Standardization.

Anti-neutrophil cytoplasmic antibodies (ANCA) are widely used as diagnostic markers for Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS) and idiopathic rapidly progressive glomerulonephritis (iRPGN). The objective of this study was to evaluate the diagnostic value of ANCA measurement by the indirect immunofluorescence (IIF) test, and by anti-PR3 and anti-MPO ELISA performed in different locations, in patients with idiopathic small vessel vasculitis. Fourteen centers participated in a standardization study of ANCA assays, and entered a total number of 169 newly diagnosed and 189 historical patients with idiopathic systemic vasculitis or iRPGN. Patients were classified according to a pre-defined diagnostic classification system. Results were compared with those of 184 disease controls and 740 healthy controls. The IIF test was performed according to standard methodology; ELISAs had been standardized among the participants in a previous phase of the study. The sensitivities of assays in patients were as follows. The sensitivity in WG was: cANCA 64%, pANCA 21%, anti-PR3 66%, anti-MPO 24%. In MPA the sensitivity was: cANCA 23%, pANCA 58%, anti-PR3 26%, anti-MPO 58%. Sensitivity in iRPGN was: cANCA 36%, pANCA 45%, anti-PR3 50%, anti-MPO 64%. The specificity of assays (related to disease controls) was: cANCA 95%, pANCA 81%, anti-PR3 87%, anti-MPO 91%. When the results of the IIF test were combined with those of the ELISAs (cANCA/anti-PR3 positive, pANCA/anti-MPO positive), the diagnostic specificity increased to 99%. The sensitivity of the combination of cANCA + anti-PR3 or pANCA + anti-MPO for WG, MPA or iRPGN was 73%, 67% and 82%, respectively. From this study we conclude that the value of the IIF test for ANCA detection can be greatly increased by the addition of a well standardized antigen-specific ELISA. In a significant number of patients with idiopathic small vessel vasculitis, however, the ANCA test results (either in IIF or ELISA) are negative.

Adolescent↗
PubMed1996

Development and standardization of solid phase assays for the detection of anti-neutrophil cytoplasmic antibodies (ANCA). A report on the second phase of an international cooperative study on the standardization of ANCA assays.

Anti-neutrophil cytoplasmic antibodies (ANCA) are diagnostic markers for systemic vasculitis. They are classically detected by an indirect immunofluorescence test using normal donor neutrophils as substrate. This assay lacks antigenic specificity and is not quantitative. The 'EC/BCR Project for ANCA Assay Standardization' is an international collaboration study with the aim to develop and standardize solid phase assays for ANCA detection. In this part of the study the isolation and characterization of proteinase-3 and myeloperoxidase, the two main target molecules for ANCA, and the development and standardization of ELISAs with these antigens are described. Six laboratories successfully isolated purified proteinase-3 preparations that could be used. Three of these preparations, together with one myeloperoxidase preparation, were subsequently used for ANCA testing by ELISA. The ELISA technique was standardized in two rounds of testing in the 14 participating laboratories. The coefficient of variation of these new assays decreased from values of approx. 50% in the first round to approx. 20% in the second round. We conclude that purified proteinase-3 and myeloperoxidase can be used in standardized ELISAs for ANCA detection. Whether such procedures offer advantages over the IIF test will be determined in a prospective clinical study.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1996

Existence of the Frank-Starling mechanism in the failing human heart. Investigations on the organ, tissue, and sarcomere levels.

BACKGROUND: The Frank-Starling mechanism is one of the most important physiological principles for regulation of contractile performance. We therefore studied the question of whether this mechanism may be absent or attenuated in end-stage failing human left ventricular myocardium. METHODS AND RESULTS: Different methodological approaches were used to analyze the effects of this mechanism on the organ, tissue, and sarcomere levels: (1) In excised human whole left ventricles (2 donor hearts, 5 failing hearts), diastolic and systolic pressure-volume relationships were obtained. (2) In isolated muscle strip preparations from the left ventricular wall of donor hearts (n = 14) and failing hearts from patients with idiopathic dilated cardiomyopathy (n = 21) and ischemic cardiomyopathy (n = 11), peak developed force was measured at different muscle lengths of the preparation. (3) Skinned fiber preparations were obtained from failing right and left ventricles (n = 12). In all three studies, we clearly observed the existence of the Frank-Starling mechanism: (1) In isolated failing human left ventricles, peak developed isometric pressure is increased when the preload is elevated. (2) Peak developed tension is increased by approximately 50% to 70% (P < .01) in left ventricular preparations of failing and nonfailing ventricles when the muscles are stretched from 90% to 100% optimum length. (3) An increase in sarcomere length leads to a sensitization of contractile proteins of ventricular skinned fiber preparations from failing human hearts. At 1.9-microns sarcomere length, the EC50 value was 5.56 +/- 0.06, and at 2.3 microns it was 5.70 +/- 0.05 (P < .01; n = 7). CONCLUSIONS: The Frank-Starling mechanism is maintained in end-stage failing human hearts, whereas significant alterations of diastolic myocardial distensibility are evident in chronic heart failure.

Analysis of Variance↗
PubMed1993

The value of indirect immunofluorescence and solid phase techniques for ANCA detection. A report on the first phase of an international cooperative study on the standardization of ANCA assays. EEC/BCR Group for ANCA Assay Standardization.

This study describes the results of phase I of an international effort to develop and standardize assays for the detection of anti-neutrophil cytoplasmic antibodies (ANCA). 12 sera, four of which were selected for their potential to cause problems in the detection of various ANCA specificities, were analyzed in the standard indirect immunofluorescence (IIF) test and in ELISAs for ANCA routinely performed in the seven participating laboratories. The IIF methodology differed with respect to the dilution of the serum being screened and the concentration of the conjugate used. Results from sera with high ANCA titers were similar, although the quantitative values could not be compared. In sera containing rheumatoid factor and anti-nuclear antibodies (ANA), ANCA-unrelated staining patterns were observed. Six antigen preparations were used in ELISA for the detection of cANCA. In ELISA with purified proteinase-3 all three cANCA sera were positive, but not anti-myeloperoxidase (MPO) or anti-lactoferrin (LF) positive sera. The other assays were less sensitive or gave inconsistent results. Various preparations of purified MPO and LF used in ELISA were readily recognized by anti-MPO and anti-LF positive sera. From this study it can be concluded that the IIF test, although performed with different methods, shows comparable results using strongly positive sera. In general solid phase assays for cANCA detection are not well standardized and need improvement although the purified proteinase-3 ELISA is possibly an exception. MPO and LF can be used in ELISA procedures for the detection of pANCA-related antibodies.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

Inhibition of proteinase 3 activity by peptides derived from human epidermis.

Elafin and antileukoprotease are potent peptide-like inhibitors of human leukocyte elastase and have been isolated from human skin and bronchial mucus. Elafin proved to be a potent inhibitor of proteinase 3, whereas other inhibitors of human leukocyte elastase such as antileukoprotease and eglin C proved to be much less effective.

Amino Acid Sequence↗
PubMed1992

[A new type of ANCA in sera of patients with ulcerative colitis: effects of therapy and disease severity on serum titer].

Sera of 108 patients with chronic inflammatory bowel disease (IBD) and 13 control sera were screened for antibodies against neutrophil cytoplasmic antigens (ANCA) by an indirect immunofluorescence test. 37 out of 64 sera (58%) from patients with ulcerative colitis (UC) produced a fine granular and perinuclear ANCA staining pattern (p-ANCA) clearly different from the typically diffuse and granular cytoplasmic ANCA fluorescence (c-ANCA) seen in active Wegener's granulomatosis (WG). Only 1 of the 44 sera from patients with Crohn's disease and none of the control sera showed positive p-ANCA reactions. Only 1 of the 64 CU sera was positive for antinuclear antibodies, and another one showed a positive reaction in the anti-proteinase-3 ELISA which is specific for WG. Antibodies against myeloperoxidase were negative in the CU sera. 31 out of the 37 p-ANCA-positive sera (84%) were obtained from patients with high disease activity. p-ANCA titers became negative after long-term steroid therapy and after complete colectomy. These preliminary data suggest that ANCA screening may be of value in differentiating IBD and in monitoring disease activity and drug effects in UC patients.

Adult↗
PubMed1990

Anti-neutrophil cytoplasm antibodies in Wegener's granulomatosis recognize an elastinolytic enzyme.

The target antigen of anti-neutrophil cytoplasm antibodies (ACPA; also known as ANCA) was isolated by affinity chromatography from supernatants of human neutrophils, stimulated with phorbol ester to induce degranulation. Sequence analysis of the antigen revealed 17 NH2-terminal amino acids (IVGGHEAQPHIRPIYMA), which have considerable sequence homology with known serine proteinases. Investigation of the enzymatic activity showed that the antigen is a neutral serine proteinase that is able to cleave elastin. Since the molecular weight of the antigen, its substrate specificity, and its inhibitor profile reported in this study are identical with those reported recently for proteinase 3, we conclude that ACPA are most probably directed against proteinase 3.

Amino Acid Sequence↗
PubMed1990

A new type of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in active ulcerative colitis but not in Crohn's disease.

Sera of 64 patients with chronic inflammatory bowel disease (IBD) were screened for antibodies against neutrophil cytoplasmic antigens (ANCA) using an indirect immunofluorescence technique on ethanol-fixed human neutrophil granulocytes. 20 of 34 sera (59%) from patients with ulcerative colitis (UC) produced a fine-granular and perinuclear ANCA staining pattern (p-ANCA) clearly different from the typical diffuse and granular cytoplasmic ANCA fluorescence (c-ANCA, synonym ACPA) seen in active Wegener's granulomatosis (WG). The majority of the 20 p-ANCA positive UC patients had a high inflammatory disease activity. Among the 14 p-ANCA negative UC patients nine were without steroids; five of them had active disease, two were inactive and two had previously undergone colectomy. The remaining five patients still had active disease but received steroids for more than 4 weeks. Only 3 of the 30 sera from patients with Crohn's disease (CD) showed positive p-ANCA reactions. To narrow the specificity of the p-ANCA reaction all 64 sera were tested by ELISA for antibodies against anti-proteinase-3 (WG specific) and on HEp-2 cells for antinuclear (ANA) and anticytoplasmic antibodies. Ten p-ANCA positive UC sera were also tested in a myeloperoxidase ELISA. Only one UC serum reacted positively in the proteinase-3-ELISA and another one produced a weakly positive anti-nucleolar ANA fluorescence on HEp-2 cells. None of the tested sera reacted with myeloperoxidase suggesting that the p-ANCA staining pattern of granulocytes is not restricted to anti-myeloperoxidase antibodies as reported in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Ultrastructural localization of proteinase 3, the target antigen of anti-cytoplasmic antibodies circulating in Wegener's granulomatosis.

To investigate the distribution of proteinase 3, the target antigen of anti-cytoplasmic antibodies (ACPA or C-ANCA), within the organelles of resting normal human polymorphonuclear leukocytes and monocytes, the authors used immunocytochemical techniques on thin frozen sections. To obtain valuable tools for immunolabeling, two murine monoclonal antibodies (MAbs) directed against the ACPA antigen were produced. In neutrophils, the authors observed immunogold label for the ACPA antigen, predominantly in myeloperoxidase-positive azurophil granules, and in smaller amounts on the plasma membrane. In monocytes, the ACPA antigen could be detected in small granules, which occasionally also contained myeloperoxidase, and rare labeling was found on the monocyte membrane. The finding that the ACPA antigen is expressed on the plasma membrane of neutrophils and monocytes, thereby becoming accessible to circulating autoantibodies, supports the supposition that ACPA are not only markers of disease activity, but also are involved in the pathogenesis of Wegener's granulomatosis.

Antibodies, Anti-Idiotypic↗