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Biomedical subjects

M Werner

Publications and source records attributed to M Werner.

At least 343 records · Page 19Linked to original sources

[The importance of active rosette-forming cells and specific antigen-binding cells in the diagnosis of rejection after allogeneic orthotopic kidney transplantation].

After allogeneic renal transplantation in 26 female pigs the kinetics of the immunological reactivity against the graft have been investigated with a specific test, the antigen specific rosette test and an unspecific test, the active E-rosette test. In acute and chronic rejection the level of antigen specific rosette forming cells reflects very well the clinical signs of rejection. Because of early occurrence of immunological reactivity in the case of frequent (daily) testing this test is suitable for a relative sure prediction of rejection episodes. In spite of their relative good correlations to the increase of serum creatinine, posttransplant increase and decrease of active rosette forming cells are not always in an uniform temporal relation to the rejection process. For that reason this test alone is not suitable for diagnosis of rejection. However, high preoperative values (greater than or equal to 18% active T cells) refer to an increased readiness to immunological reactivity of recipient against the graft and reflect contraindication to transplantation. If active rosette forming cells (greater than or equal to 18%) and antigen specific rosette forming cells show maxima at the same time, than follow in high significance strong cell mediated rejections. On this way the active E-rosette test completes the values of the antigen specific rosette test.

Animals↗

[Antigen-specific rosette inhibition test with autologous serum--a possibility for the detection of blocking factors in chronic rejection of allogeneic orthotopic kidney transplants].

After allogeneic renal transplantation in 26 female pigs the kinetics of the immunological reactivity have been investigated in order to diagnose a rejection crisis. The animals were not treated with immunosuppressive substances. The antigen specific rosette test is an useful parameter for estimation of immune reactions against a graft. Moreover, the inhibition of this test by autologous serum taken in the course of a chronic graft rejection is caused by blocking factors. Therefore this inhibition test would be suitable for an exact determination of specific immune reaction against the graft. By exclusion of false positive results by means of the rosette reaction test a high significant correlation between the antigen specific rosette formation and the clinical symptoms of the rejection could be observed. As long as blocking factors are protecting the graft against activities of immunocompetent cells respectively their effector molecules, recipient serum is able to inhibit the rosette formation. On the other hand a strong increase of rosette forming cells in a pig whose serum does not show an inhibitory activity is correlated with clinical symptoms of a rejection.

Animals↗

[Employment of the antigen-specific rosette test in the diagnosis of rejection following allogeneic orthotopic kidney transplantation in the pig].

Investigations of the course were performed by means of an antigenspecific rosette test using a poolantigen from tissue samples of approximately 100 pigspleens with the help of the model of allogenic renal transplantation in 26 female pigs. The animals received no immunosuppressive treatment. In our study with this test 75% all of the rejection episodes by clinical acute and chronic rejection were predictably. In acute rejection a maximum rosette forming cell response was examined in general 2-3 days before a pathological rise of serum creatinine or in the course of a bad clinical state. Under chronic rejection this reaction can be seen 5-14 days before the kidney function will go poor. In spite of the high individuality of original curves statistical analyses indicate a good correlation of the number of antigenbinding cells toward pathological deviation of serum creatinine, as long as blocking factors not protect the transplant against the attack of persisting immunocompetent cells or their effectors. These blocking factors can be monitored in a rosette inhibition test with autolog serum.

Animals↗

The biological role of enzyme attachment and immobilization.

The state of enzymes in the living cell is considered: it is not clear whether some, if any, enzymes are naturally present in the "soluble" state. The evidence for enzyme binding to cellular constituents, and its effects on function and properties of enzyme and isoenzymes, is reviewed.

Animals↗

Diagnostic performance of enzymes in the discrimination of myocardial infarction.

We apply rigorous statistical methods to assess the diagnostic value of creatine kinase, creatine kinase-MB, aspartate aminotransferase, lactate dehydrogenase, and alpha-hydroxybutyrate dehydrogenase in realistic circumstances. The trade-off between false positives and false negatives obtained with various decision rules is examined with the receiver-operator characteristic function and with discriminant analysis. During the three days after an infarction, lactate and alpha-hydroxybutyrate dehydrogenase can provide diagnostic thresholds of constant sensitivity and specificity. By contrast, sensitivity progressively decays for creatine kinase, creatine kinase-MB, and aspartate aminotransferase. The diagnostic uncertainty introduced by the infarction's varying age at hospitalization is evaluated by subjecting the mixed patient population to discriminant analysis. For some enzymes, repeating the same assay on the second day contributes to sensitivity, while adding a different assay on the first day enhances specificity. The effects of lower or higher infarction prevalences on sensitivity and specificity are most favorable when creatine kinase-MB is combined with lactate or alpha-hydroxybutyrate dehydrogenase. Adding a third assay is ineffective. The further differentiation according to infarction stage produces only 81% correct classifications, even when five different assays are used on two consecutive days. As a general strategy, we recommend the assay of two enzymes on two consecutive days.

Aspartate Aminotransferases↗

Cost effectiveness of multiphasic screening: old controversies and a new rationale.

The cost effectiveness of multiphasic screening is evaluated from a conceptual as well as from a practical viewpoint. Conceptual analysis includes a consideration of the technical sensitivity and specificity of the tests used, of the prevalences of the screened diseases, and of the costs and values associated with different outcomes of screening. Practical considerations include the potential of multiphasic screening for increasing productivity, for reassuring patients, and for reducing morbidity and mortality. Although all these issues can be cogently formulated, at present none can be documented by a comprehensive set of data leading to irrefutable conclusions. Therefore, the issue of who should be screened continues to be obfuscated by controversy and prejudice. To resolve this dilemma a new rationale for the use of multiphasic screening is developed. This is based on a small number of uncontroversial facts and leads to practical proposals relating to how standards for useful test batteries can be constructed.

Clinical Laboratory Techniques↗

Consultation in the coagulation laboratory. A conceptual analysis.

Physicians can play an important role as consultants in the utilization of laboratory data by providing interpretation, recommending action, and presenting rationale. These activities have been quantitated in 382 consecutive consultations provided by pathologists in the coagulation laboratory, and their statistical interrelationships have been analyzed. Quantitative characterization of the consultation is important, since the pathologist's professional role in patient care may no longer remain informal and undocumented. However, analogous evaluations can be applied to expose, evaluate, and improve the properties of clinical consultation in general.

Blood Coagulation Tests↗

Ultramicro determination of serum triglycerides by bioluminescent assay.

The ultramicro (1-microL samples) assay of serum or plasma triglycerides that we describe here is potentially applicable to 1-nL samples and to isolated cells. This technically simple method involves only three reactions: (a) enzymic hydrolysis with lipase and alpha-chymotrypsin; (b) conversion by glycerol kinase of the liberated glycerol and of adenosine triphosphate added in excess to glycerol-1-phosphate and to adenosine diphosphate; and (c) assay of the residual adenosine triphosphate by the luciferin-luciferase reaction. The assay was optimized with respect to glycerol kinase, buffer, pH, temperature, and adenosine triphosphate. Performance characteristics compare well with those of traditional triglyceride assays.

Drug Stability↗

Optimization of diagnostic discrimination applied to the amniotic fluid lecithin/sphingomyelin ratio.

An unrecognized disparity frequently separates the intuitive reliance placed on laboratory information by those who produce it and those who use it. To harmonize these dissimilar perceptions requires quantitative measures of the information contained in laboratory data. The assay of the lecithin/sphingomyelin ratio in amniotic fluid is used as an example to analyze the discriminatory ability of a test. This assay can be optimized from the different viewpoints of sensitivity, specificity, diagnostic effectiveness or value. In each case test results are interpreted in the light of different factors and so the optimal decision threshold to separate positive from negative results may vary. Appreciation of this concept would endow the interpretation of laboratory tests with the same flexibility traditionally available to other clinical information.

Amniotic Fluid↗