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Biomedical subjects

G Leroux-Roels

Publications and source records attributed to G Leroux-Roels.

At least 73 records · Page 4Linked to original sources

Fibrinolysis and coagulation in patients with infectious disease and sepsis.

Sepsis is often associated with hemostatic dysfunction. This study aimed to relate changes in fibrinolysis and coagulation parameters to sepsis and sepsis outcome. Urokinase-type plasminogen activator (u-PA) antigen, tissue-type plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor (PAI) type 1 antigen, PAI activity, antithrombin (AT) III activity, and protein C activity were measured in 24 patients suffering from sepsis or septic shock and the results were compared with those observed in 30 non-sepsis patients with severe infectious disease. The u-PA level was markedly increased in plasma of sepsis patients as compared to non-sepsis patients (11.5 +/- 9.4 versus 1.6 +/- 1.5 ng/ml, p less than 0.0001). PAI-1 antigen and t-PA activity showed a significant increase in sepsis patients (320 +/- 390 ng/ml versus 120 +/- 200 ng/ml, and 3.0 +/- 3.6 IU/ml versus 1.0 +/- 0.7 IU/ml, respectively, p less than 0.01). AT III was decreased in sepsis patients (58 +/- 28% in sepsis versus 79 +/- 26% in severe infectious disease, p less than 0.01) as was protein C (30 +/- 18% versus 58 +/- 27%, p less than 0.001). No significant difference was found for t-PA antigen nor for PAI activity. Nonsurvivors of sepsis were distinguished mainly by a high u-PA antigen level and increased t-PA activity. It is concluded that plasma u-PA antigen showed the strongest significant difference, among the parameters evaluated, between sepsis and severe infection. u-PA antigen may be of prognostic value in patients admitted to the medical intensive care unit for severe infectious disease.

Adult↗

Evaluation of the automated haematology analyser Sysmex NE-8000.

The automated haematology analyser Sysmex NE-8000 was compared with the Technicon H-1, the automated analyser routinely used in our laboratory, and with manual cell differentiation results. One hundred and seventy samples from the daily routine workload, comprising specimens from healthy adults and patients with various ailments, were analysed on the Sysmex NE-8000 and the Technicon H-1. A manual-400 leukocyte differential count was performed on each specimen. Comparison of the results from the two blood cell counters showed good correlation (r greater than 0.9) for the white blood cell count, haemoglobin, haematocrit and platelet count. For the red blood cell count and mean cellular volume, the correlation coefficients were greater than 0.8. In the leukocyte differential count, Sysmex NE-8000 and Technicon H-1 showed good correlations for the neutrophil (r = 0.953), lymphocyte (r = 0.763), and eosinophil counts (r = 0.904). Correlation coefficients were very low for monocyte (r = 0.130) and basophil counts (r = 0.006). Correlation between the manual-400 method and the electronic leukocyte differential count showed similar results. Two hundred and twenty six normal and abnormal samples were compared with respect to morphology flagging with the two analysers, using the manual differentiation as the reference method. The abnormal specimens were representative of the range of leukocyte abnormalities seen in our laboratory. Sensitivity for detecting blasts was equal for both analysers. Sysmex NE-8000 was much more sensitive for detecting immature granulocytes than Technicon H-1. Low ranges of atypical lymphocytes were missed by Sysmex NE-8000. Left shift was also frequently missed.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Cell Count↗

Serum tumor necrosis factor levels in patients with infectious disease and septic shock.

The role of tumor necrosis factor (TNF-alpha) in the pathogenesis of septic shock has been assessed by daily measurements of serum TNF-alpha levels in 60 patients admitted to the medical intensive care unit. All patients in the study had infectious disease and were at risk for the development of sepsis and septic shock. Sepsis was diagnosed in 34 patients, 24 of whom died (six within the first 24 hours). The 26 patients who did not evolve toward sepsis served as a control group. The clinical condition of all patients was monitored by daily APACHE II scoring. Blood was drawn once a day and additional samples were taken in patients whose clinical condition underwent sudden deterioration. TNF-alpha levels were measured with a commercially available immunoradiometric assay. At time of patient admission, TNF-alpha levels were higher in the group with sepsis than in the control group (median 79 iqr 329 vs median 0.5 iqr 5; p less than 0.001). In the group with sepsis, extremely high TNF-alpha levels were found in patients who died within 24 hours. These patients had TNF-alpha levels of 917 iqr 755 pg/ml, whereas the patients who died more than 24 hours after admission had TNF-alpha levels of 58 iqr 59 pg/ml. Survivors had lower TNF-alpha levels (26 iqr 347 pg/ml). APACHE II scores correlated with TNF-alpha levels in the total sepsis group (Spearman rank correlation coefficient 0.477; p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗

Specific suppression elicited by EL4 lymphoma cells in syngeneic mice. Specificity includes self-antigens on EL4.

In vivo, subclones derived from EL4 lymphoma cells generate suppressor T lymphocytes specific for anti-EL4 immune responses. Spleen cells of EL4-sensitized C57BL/6 mice down-regulate the in vitro induction of EL4-specific cytolytic T lymphocytes (CTL). In addition, EL4-sensitized spleen cells interfere with the antigen response of two T lymphocyte clones. These recognize, in an H-2b context, a self-antigen on spleen cells that is also expressed by transformed cells, including EL4. The simultaneous anti-self and anti-EL4 specificity of the helper and suppressor activities suggests, therefore, that they are the product of an in vivo autoimmune reaction to EL4. The anti-self suppression might aim to re-establish self-tolerance, at the same time down-regulating responses against immunogenic epitopes that are co-expressed with the self-antigen on the EL4 cells. This agrees well with our observation that suppressor T cells, apparently elicited by suppressogenic epitopes on non-immunogenic EL4 subclones, down-regulate the CTL response elicited by immunogenic EL4 subclones. The additional self-specificity of this suppression indicates that the suppressogenic epitopes at least in part represent EL4 self-antigens.

Animals↗

Alloinduced suppression and cytotoxicity: two functions of a single cell.

Using different experimental approaches we here show that the suppression and cytotoxicity generated during a one-way mixed lymphocyte culture (MLC) are mediated by a single cell population, in this case the cytotoxic T lymphocyte (CTL). Results of limiting-dilution analysis of cells from a 4-day MLC demonstrate the coexpression of both functions and argue against the existence of a separate suppressor cell population that regulates the in vitro alloresponse. The suppressive quality of CTL is also exemplified in cells with a clonal origin, such as cloned cytotoxic T lymphocytes and the mouse X rat hybridoma PC60. Further experiments demonstrate that this suppression is not primarily mediated through lysis of the stimulator cells, and studies in the PC60 model suggest that lysis and suppression may have different induction requirements.

Animals↗

Glycylprolyl-diaminopeptidase in human leukocytes: selective occurrence in T lymphocytes and influence on the total serum enzyme activity.

Using biochemical methods glycylprolyl-diaminopeptidase (GP-DAP, EC 3.4.14.5) was measured in purified leukocyte subpopulations and found selectively in T lymphocytes. In 129 subjects with normal hepatic function a significant correlation was observed between the serum GP-DAP activity and the peripheral blood lymphocyte count. In four patients suffering from rheumatoid arthritis, four weeks of thoracic duct drainage resulted in a reduction of the peripheral blood lymphocyte count and a concomitant decrease of the serum GP-DAP activity. These observations suggest that lymphocytic GP-DAP may contribute to the total serum GP-DAP activity.

Arthritis, Rheumatoid↗

[Green urticaria].

A few minutes after a subcutaneous injection of patent blue dye, two patients developed acute urticaria with a characteristic blue green hue.

Female↗

Impairment of phagocytic activity of macrophages as studied by the skin window test in patients on regular hemodialysis treatment.

In 7 patients with less than 4 months of regular hemodialysis treatment (RDT), in 28 patients with more than 4 months RDT and in 9 normal subjects, the skin window technic of Rebuck and Crowley was used to study the cellular response and the phagocytic activity of macrophages. Phagocytosis of carbon particles is decreased in the patients with less than 4 months dialysis, whereas it is not significantly different from the normals in those being dialyzed for longer periods.

Humans↗

Vaccine- and hepatitis B immune globulin-induced escape mutations of hepatitis B virus surface antigen.

Hepatitis B virus surface antigen (HBsAg) vaccination has been shown to be effective in preventing hepatitis B virus (HBV) infection. The protection is based on the induction of anti-HBs antibodies against a major cluster of antigenic epitopes of HBsAg, defined as the 'a' determinant region of small HBsAg. Prophylaxis of recurrent HBV infection in patients who have undergone liver transplantation for hepatitis B-related end-stage liver disease is achieved by the administration of hepatitis B immune globulins (HBIg) derived from HBsAg-vaccinated subjects. The anti-HBs-mediated immune pressure on HBV, however, seems to go along with the emergence and/or selection of immune escape HBV mutants that enable viral persistence in spite of adequate antibody titers. These HBsAg escape mutants harbor single or double point mutations that may significantly alter the immunological characteristics of HBsAg. Most escape mutations that influence HBsAg recognition by anti-HBs antibodies are located in the second 'a' determinant loop. Notably, HBsAg with an arginine replacement for glycine at amino acid 145 is considered the quintessential immune escape mutant because it has been isolated consistently in clinical samples of HBIg-treated individuals and vaccinated infants of chronically infected mothers. Direct binding studies with monoclonal antibodies demonstrated a more dramatic impact of this mutation on anti-HBs antibody recognition, compared with other point mutations in this antigenic domain. The clinical and epidemiological significance of these emerging HBsAg mutants will be a matter of research for years to come, especially as data available so far document that these mutants are viable and infectious strains. Strategies for vaccination programs and posttransplantation prophylaxis of recurrent hepatitis need to be developed that may prevent immune escape mutant HBV from spreading and to prevent these strains from becoming dominant during the next decennia.

Hepatitis B↗

Evaluation of graft viability in heterotopic auxiliary liver transplantation in the rat.

In the rat model of heterotopic auxiliary liver transplantation, the coexistence of the engrafted liver and the recipient's native liver makes it difficult to evaluate the posttransplant graft viability. In this study, auxiliary liver transplantation was performed in Wistar rats, in which the recipient's native liver was handicapped with a 68% partial hepatectomy and a common bile duct ligation. Serum biochemistry of the liver was analyzed and compared with that of the selected control group. The surgical handicap of the liver showed severe damaging effects: the handicapped native livers appeared atrophic at autopsy, and no long-term animal survival could be achieved without an auxiliary liver transplantation. As the engrafted liver corrected the cholestasis of the handicapped native liver, significant differences of serum biochemistry were found between the transplanted group and the control group: for bilirubin concentration and gamma glutamyl transferase activity from postoperative day 3 to 28 (p < .05); for alkaline phosphatase on days 3, 7, 14, and 28 (p < .05); for alanine aminotransferase activity on days 3 and 14 (p < .05); and for aspartate aminotransferase activity on day 14 (p < .05). The efficiency to induce hepatic failure and to hamper its regeneration capacity in the native liver makes animal survival and liver biology as reliable parameters to evaluate the posttransplant graft viability in this rat model.

Alanine Transaminase↗

Comparison of a recombinant thromboplastin with Thrombotest for oral anticoagulant control.

Thrombotest results expressed in international normalized ratio (INR) values, obtained in 108 patients on oral anticoagulant treatment, were compared with prothrombin time (PT) results with a recombinant thromboplastin. The former results were obtained on an Amelung coagulometer, the latter on a photo-optical instrument. Using the Thrombotest method, performed within 2 h after sampling as the reference method, a first group of 63 patients had an INR value between 2 and 4. This group was considered as adequately anticoagulated and served as a true positive population in further analysis. The remaining 45 patients (true-negative group) had an INR value below 2 or higher than 4 and could thus be considered as inadequately anticoagulated. Using these definitions, a sensitivity of 86% and a specificity of 96% could be calculated for the PT with the recombinant thromboplastin. All tests from patients on oral anticoagulant treatment were also performed after 24 h storage of the blood or plasma samples at room temperature. When we compared the reference Thrombotest results with those of the late Thrombotest and the late PT recombinant thromboplastin, sensitivities of 86 and 86% as well as specificities of 91 and 96% were found, respectively. In conclusion, PT with a recombinant thromboplastin on a photo-optical instrument, even after prolonged storage of the plasma samples at room temperature, can be considered as suitable for oral anticoagulation control.

Administration, Oral↗