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Biomedical subjects

D Brohée

Publications and source records attributed to D Brohée.

At least 19 recordsLinked to original sources

Diagnosis and prognosis of overt disseminated intravascular coagulation in a general hospital -- meaning of the ISTH score system, fibrin monomers, and lipoprotein-C-reactive protein complex formation.

The meaning, the utility, and the prognostic significance of the International Society of Thrombosis and Hemostasis overt disseminated intravascular coagulation (DIC) score and other parameters of coagulation activation including soluble fibrin monomer complexes (SFMC), antithrombin and protein C consumption, and formation of lipoprotein-C-reactive protein (LP-CRP) complexes (MDA slope 1 and flag A2) were evaluated in 165 inpatients from a general hospital for whom DIC testing was required by the attending physicians. Of these 165 patients, 148 had an underlying disease that clearly justified the laboratory request from our systematic post hoc review of the clinical charts. Of these 148 patients, 28 had a positive overt DIC score, 19 had an A2 flag, and 4 had both. The DIC score was strongly related to several major markers of coagulation activation such as D-dimers, thrombin-antithrombin complexes, and soluble fibrin and was inversely related to antithrombin and protein C levels, which began to fall from DIC score 4 or higher. The formation of LP-CRP complexes was only related to Gram-negative sepsis and these patients had a strong inflammatory reaction. Independent risk factors for death were high creatininemia, positive overt DIC score, and/or presence of SFMC. In patients with positive DIC score, SFMC positivity and low levels of antithrombin and/or protein C were additional risk factors. The ISTH overt DIC score proves useful and adequate as a marker for clinically significant DIC. Illness severity is further defined by SFMC, antithrombin, and protein C levels. LP-CRP complexes are related to sepsis but not to actual overt DIC and lethal prognosis.

Biomarkers↗

A new device for measurement of fibrin clot lysis: application to the euglobulin clot lysis time.

BACKGROUND: Determination of clot lysis times on whole blood, diluted whole blood, plasma or plasma fraction has been used for many years to assess the overall activity of the fibrinolytic system. We designed a completely computerised semi-automatic 8-channel device for measurement and determination of fibrin clot lysis. The lysis time is evaluated by a mathematical analysis of the lysis curve and the results are expressed in minute (range: 5 to 9999). We have used this new device for Euglobulin Clot Lysis Time (ECLT) determination, which is the most common test used in laboratories to estimate plasma fibrinolytic capacity. RESULTS: The correlation between ECLT and manual method is very tight : R = 0,99; p < 10(-6). The efficiency scores of the method are <4% in intra-assay and <7% in inter-assay. It allows to achieve the tests on hyperlipaemic samples. This new device has been easily integrated in laboratory routine and allows to achieve several ECLT every day without disturbance of laboratory workflow. CONCLUSIONS: The routine use of this new device could be useful in various situations such as assessment in atherosclerosis and arteriosclerosis associated diseases, coagulation survey of liver transplantations, cardiovascular surgery or pharmacological research.It has already provided highly promising results in preliminary studies on the relation between fibrinolysis and cardiovascular risk factors.

Adult↗

Frequent discordance of the light-chain isotypes expressed by serum monoclonal components and leukaemic B-cells.

In B-cell malignancies, it is generally held that the monoclonal components (MC) are produced by the malignant clones. Genetic relatedness implies the concordant expression of light-chain (LC) isotypes in the MC and at the surface of the malignant lymphocytes. We reviewed a series of 91 B-cell leukaemias, immunophenotyped by flow cytometry in our laboratory. A serum MC had been sought in 75 of these patients, and had been found in 23 (31%). Biclonal serum components were detected in three cases. LC concordance could not be assessed in three cases of surface LC-null lymphocytes. Of the 23 MC studied in 20 patients, light-chains were discordant in 39%, mostly due to kappa MC in lambda leukaemias. The origin of LC discordance remains speculative. It could be due to the emergence of subclones with the same primal VDJ gene rearrangement or, alternatively, to the development of new B-cell clones escaping immune surveillance from deregulated T-cells.

Aged↗

[Acute portal thrombosis revealing hereditary hemochromatosis: report of a case].

The authors report the case of a 49-year old man in whom an inaugural portal vein thrombosis led to the diagnosis of hereditary hemochromatosis. In this case, the increase in ferritinemia and the T2-weighted MRI hepatic segmental hyposignal were considered as consequences of tissular necrosis while they did probe a real iron overload. Genetic testing, revealing C282Y/H63D compound heterozygoty, provided evidence for a diagnosis of hereditary hemochromatosis. Weekly venesections induced a calculated iron depletion of 3.5 g without occurrence of anemia, further supporting the diagnosis. We suggest that hemochromatosis should be considered in the differential diagnosis of idiopathic portal vein thrombosis when signs of abnormal iron accumulation exist.

Acute Disease↗

Adjuvant intraportal chemotherapy for Dukes B2 and C colorectal cancer also receiving systemic treatment: results of a multicenter randomized trial. Groupe Régional d'Etude du Cancer Colo-Rectal (Belgium).

In a randomized trial, the authors evaluated the possible adjuvant activity of intraportal chemotherapy (with 5-fluorouracil 500 mg/m2/day in continuous infusion for 7 days and mitomycin C 10 mg/m2 at day 7) administered after surgery to half of the patients who underwent a full resection for Dukes B2 or C colorectal cancer. The procedure appeared manageable and safe. Two hundred and sixty patients were initially randomized, among whom 173 were finally considered as fully evaluable after having completed six courses of systemic chemotherapy. The reasons for withdrawal were basically tumoral ones and patients or doctors compliance. After a median follow-up of 4.5 years, no difference could be observed in the patients evolution assessed as relapses or deaths rate, or as relapse-free (at 5 years: 68% in the portal treatment group versus 70% in the control group) or overall survival (at 5 years: 76 versus 74%). The frequency of hepatic metastases (21 versus 18%) was also similar in both groups.

Adult↗

Effect of dietary high doses of vitamin E on the cell size of T and B lymphocyte subsets in young and old CBA mice.

Using anti-CD5 and anti-SIgM fluorescent monoclonal antibodies, four subsets of lymphocytes can be distinguished in CBA mice, SIgM+ (T2) and SIgM- (T1) T lymphocytes and, CD5+ (B1) and CD5- (B2) B lymphocytes. L3T4 anti-CD4 and Lyt2 anti-CD8 positivities delineate two major T lymphocyte subsets. The cell size of these subsets has been evaluated by their forward light scatter in flow cytometry after cell fixation. The mean cell size of the different subsets differs, according to subset, age and vitamin E treatment. Globally, there is an age-related increase in size for all subsets. In vitamin-E treated young animals, all subsets are smaller, and the percentages of the biggest B1 and B2 cells decrease. In old mice, the vitamin-E effect is far more variable. B2 cells tend to increase in size but the percentage of the biggest cells diminishes. On the contrary, there is a marked expansion of the large B1 cells. No effect is discernible on CD5+ T lymphocytes, but L3T4 and Lyt2 subpopulations increase in size. This study is a retrospective one and the mechanisms affecting cell size are speculative. Since the lymphocyte cell size was measured after fixation in an hypertonic medium devised for human blood processing, we cannot differentiate a real size modification from a differential volume resistance to experimental conditions. Whatever the case, the changes in cell volume argue for age-related changes in cell membrane permeability and volume homeostasis. For some subsets, cell activation and consequent size increase must also be considered. As far as vitamin E has marked anti-oxidant properties, its effect on cell size provides indirect evidence for a role of free radicals in the observed changes and gives support to the oxidant stress theory of ageing in immune senescence.

Aging↗

Effect of dietary high doses of vitamin E on lymphocyte subsets in young and old CBA mice.

Different theories of ageing exist. Oxidative stress by generating neo-antigens and affecting cellular communications may precipitate immune disregulation, and both may concur in the whole ageing process. In the present study, we have analysed the effect of dietary high doses of vitamin E, a free radical scavenger, on blood and spleen leukocytes and lymphocyte subsets, in young (3-month-old) and old (23-month-old) CBA mice. Age per se induced an increase in blood leukocytes, especially phagocytic cells, and a splenic atrophy, affecting both weight and cellularity. A differential effect of age on blood or spleen lymphocyte subsets was observed. In blood, there was a decrease in T cells, particularly CD4+ cells (T helper cells) and CD5+ cells without surface IgM (conventional T cells), along with a corresponding increase in B cells, principally B1 CD5+ cells (polyreactive autoimmunity-prone B cells). In the spleen, the relative percentage of each subset remained unchanged. Vitamin E supplementation for 7 weeks before sacrifice in young animals resulted in a decrease in CD4+ and CD5+ SIgM+ (putative Fc-receptor positive) T cells and B1 cells in blood. Similar changes in the splenic lymphocyte subsets were found, while more leukocytes could be recovered from less weighty spleens. Considering the free radical scavenging properties of vitamin E, it was assumed that oxidative stress might play some role in the ontogenesis of the immune system in young adulthood. Vitamin E for 20 months before sacrifice in old animals did not prevent splenic atrophy and had no effect on splenocytes. In blood, the ratio of SIgM+ (assumed Fc-R+) to SIgM- CD5+ T cells decreased and the B1:B2 B-cell ratio increased. In this setting, oxidative stress seemed to play a lesser role in post-adulthood immune senescence. It must be stressed that no functional test was realized that could have uncovered qualitative changes in immune reactivity. Vitamin E supplementation had complex effects on the weight of our animals, so that influences on physical activity, energy metabolism and hormonal status should be considered in interpreting its impact on the immune system. However, the observed age-related changes in T-cell and B-cell subsets are consistent with diminished immune function and increased autoimmunity in senescence. Vitamin E, by a direct anti-oxidant effect or some other mechanisms, can prevent some changes and seems to decrease the potential for autoimmune reactivity.

Aging↗

Co-expression of CD2 or CD8 antigens in B-cell chronic lymphocytic leukaemia. A flow cytometry analysis of 3 cases.

Three cases of biphenotypic CD2 or CD8 positive chronic lymphocytic B-cell leukaemias are reported. This represents an incidence of 15% in the authors' series, a frequency never mentioned previously. CD2 expression could be an example of asynchronous expression of an early pre-B antigen. CD8 expression might probe a true mixed lineage phenotype. These aberrant phenotypes were not associated with any peculiar clinical presentation.

Aged↗

Pineal body metastasis.

We present a rare case of a pineal body metastasis developed from an oat cell carcinoma of the lung. Diagnosis by CT brain scan was easy but could have been difficult if the metastasis was solitary with the primary focus of tumor unknown. This lesion was temporarily radiosensitive but non-responsive to cytotoxic drugs and the patient died after other metastases developed.

Brain Neoplasms↗

[Fulminant hepatic failure of neoplastic origin].

The case of a 59-year-old woman, hospitalised for a degradation of her health status which evolved within 10 days in fatal liver failure is reported. Although acute yellow atrophy was diagnosed, its origin remained elusive. Post-mortem examination of the liver disclosed massive hepatic infiltration by a breast adenocarcinoma. The causes of acute hepatic failure are reviewed and, particularly, the neoplastic ones.

Adenocarcinoma↗

Differential effect of dipyridamole upon thymidine incorporation and expression of surface activation antigens by in vitro stimulated lymphocytes.

Dipyridamole inhibits, by 50% at 10(-6) M and 100% at 10(-5) M, the incorporation of tritiated thymidine by lymphocytes stimulated with 1 microgram/ml phytohaemagglutinin A for 72 h. At the latter concentration, a clinically relevant one, dipyridamole fails to inhibit lymphocyte proliferation and expression of the cell surface stimulation markers, CD25 and HLA-DR, or differential regulation of the CD45 -RA and -RO isoforms, as determined by single laser two-colour flow-cytometry. No significant immunodepressant effect of dipyridamole can be demonstrated in vitro.

Adult↗

In vitro stimulation of peripheral blood mononuclear cells by phytohaemagglutinin A induces CD45RA expression on monocytes.

Following phytohaemagglutinin A stimulation, CD45RA positive monocytes increased from 12.2 +/- 8.9% to 63.5 +/- 8.8% (p < 0.001), without a significant change in cell surface antigen density. In contrast, HLA-DQ antigen, also expressed in 76.8 +/- 10.5% of the monocytes after PHA stimulation for 48 h, revealed a marked enhancement in fluorescence intensity (p < 0.001). This up-regulation is already evident in unstimulated cultures. The percentages of CD45RA and HLA-DQ positive monocytes were correlated (r = 0.80, p < 0.001), substantiating a previous clinical observation. CD45RA expression may probe activated mono/macrophages.

Adult↗

5-Fluorouracil (5FU) with or without folinic acid (LV) in human colorectal cancer? Multivariate meta-analysis of the literature.

This meta-analysis is based on 106 evaluations of response from 77 clinical studies about 5-fluorouracil (5FU) treatment with or without leucovorin (LV) in metastatic colorectal carcinoma. Overall, in naive patients, LV is associated with a median response rate of 31% as compared with a 12% figure with 5FU alone. Using a forward stepwise multilinear regression analysis, it is shown that as much as 44% of the variance in the reported response rates in naive patients can be accounted for by treatment-related variables (P less than 0.001). The significant parameters are LV adjunction (partial R = 0.636), cumulative total 5FU dose (R = 0.344), and 5FU weekly schedule (R = 0.246). In pretreated patients, the latter parameter is the only significant one (R = 0.443). Unexpectedly, LV administration behaves like an all-or-nothing governor, without any obvious dose-effect relationship. Protracted 5FU infusion over weeks allows a mean cumulative drug delivery, 3 times higher than bolus regimens (21.3 vs 7.02 g m-2, P less than 0.001) and may represent the best clinical approach to influence the 5FU-related variables. Accordingly, it is suggested that 5FU protracted infusion, titrated to the highest tolerable doses and potentiated with low doses of leucovorin, could represent the most efficacious way for using 5FU in colorectal disseminated cancer. This hypothesis and its eventual impact on survival should be tested in randomized trials.

Colorectal Neoplasms↗