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D Blockmans

Publications and source records attributed to D Blockmans.

At least 19 recordsLinked to original sources
PubMed1998

[Inflammation phenomena in vasculitis: from immune complexes to less immune forms].

Immune complexes are involved in the pathogenesis of Henoch-Schönlein purpura, essential mixed cryoglobulinemia, hepatitis B-associated periarteritis nodosa and hypersensitivity vasculitis (related to infection or medications). ANCA's probably play a pathogenic role in Wegener's Granulomatosis, microscopic polyangiitis and renal-limited vasculitis. Pathologic responses of T-lymfocytes and granuloma formation have been demonstrated in temporal arteritis, Takayasu arteritis, Wegener's Granulomatosis, Chürg-Strauss syndrome and Kawasaki syndrome. The eventual pathogenic role of AECA's is less clear, with the possible exception of rheumatoid arthritis and systemic lupus erythematosus. These four pathogenic factors are not mutually exclusive: several mechanisms may play in one disorder, as has been demonstrated for Wegener's Granulomatosis. From these new insights in the pathogenesis of vasculitis, new therapies with better efficacy and fewer side effects may arise.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1998

Clinical spectrum associated with positive ANCA titres in 94 consecutive patients: is there a relation with PR-3 negative c-ANCA and hypergammaglobulinaemia?

OBJECTIVE: To calculate the positive predictive value (ppv) of cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCAs) and anti-proteinase 3 (PR 3) antibodies for Wegener's granulomatosis (WG) and to evaluate their association with other diseases. METHODS: The clinical files of all 94 patients who had a positive c- or perinuclear (p)-ANCA test, or both, in the laboratory of the University Hospital, Leuven between April 1995 and March 1996 and who attended the Internal Medicine Department of the hospital were retrospectively studied. RESULTS: Of the 94 patients with ANCAs (fluorescence titre > or = 1/40), 57 were c-ANCA positive and 45 p-ANCA positive (eight were simultaneously c- and p-ANCA positive). Of the 57 c-ANCA positive patients, 23 had WG. The ppv for WG thus was 40%. This value did not increase by defining a higher threshold for a positive ANCA. There was not a good relation between ANCA titres and disease activity in the WG patients, nor was there a relation between anti-PR 3 antibody levels and WG disease activity. The ppv of anti-PR 3 antibodies for WG however was very high (85%). There was a positive correlation between the level of (hyper) gammaglobulinaemia and c-ANCA titres in those patients with final diagnoses not known to be associated with c-ANCA. Forty five patients had positive p-ANCAs. The largest group were those with inflammatory bowel disease (n = 20, of whom the majority had colitis ulcerosa or primary sclerosing cholangitis, or both); the great majority of these patients had no anti-myeloperoxidase antibodies. Vasculitis was present in eight patients, of whom two had WG (both were also c-ANCA positive). CONCLUSION: There is a low ppv of c-ANCAs for WG, caused by a high percentage of PR 3 negative, positive c-ANCA determinations, possibly related to hypergammaglobulinaemia. Anti-PR 3 antibodies have a high ppv for WG. However, neither c-ANCA titre, nor the level of anti-PR 3 antibodies correlated with the activity of the disease.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1997

Skewed X-chromosome inactivation in female carriers of dyskeratosis congenita.

In this study, we report on a family with X-linked dyskeratosis congenita (DC). Linkage analysis with markers in the factor VIII gene at Xq28 yielded a LOD score of 2 at a recombination of 0. Clinical manifestations of DC, such as skin lesions following the Blaschko lines, were present in two obligate carrier females. Highly skewed X inactivation was observed in white blood cells, cultured skin fibroblasts, and buccal mucosa from female carriers of DC in this family. This suggests a critical role for the DC gene in bone marrow-cell and fibroblast-cell proliferation.

Adult↗
PubMed1996

Predictive value of nailfold capillaroscopy in the diagnosis of connective tissue diseases.

We revised the clinical files of 326 patients who underwent nailfold capillaroscopy. These patients could be subdivided into 4 groups: I: patients with clinical suspicion of connective tissue disease, II: patients with isolated Raynaud's phenomenon, III: patients with existing connective tissue disease, IV: patients with acrocyanosis, chronic pernio or related disorders. The presence of megacapillaries was noted. The sensitivity of their presence for the various categories of connective tissue disease was as follows: systemic sclerosis (n = 11): 100%, CREST (n = 15): 73%, MCTD (n = 9): 56%, dermatomyositis (n = 7): 86%. Nineteen patients with megacapillaries had no final diagnosis of connective tissue disease (specificity 93.3%). The positive predictive value of the presence of megacapillaries for a scleroderma spectrum disorder (SSD) was 63.5% and the negative predictive value of a normal capillaroscopy 96.7%. We conclude that nailfold capillaroscopy can be advised to rule out SSD's.

Angioscopy↗
PubMed1995

Platelet activation.

This review article describes the different receptors, second-messengers and mechanisms involved in platelet activation. Several platelet agonists have well-defined receptors at the platelet membrane of which a number are single polypeptides with 7 hydrophobic transmembrane domains. These receptors are connected, via GTP regulatory proteins, with cytoplasmic second-messenger-generating enzymes. Phospholipase C and adenylate cyclase are the two best-known enzymes, generating inositol triphosphate (IP3) and diacyl glycerol from phosphatidylinositol biphosphate and cyclic AMP from ATP respectively. The intraplatelet free calcium level, which is critical for the activation status of the platelet, is increased by IP3 and is lowered in the presence of rising cyclic AMP concentrations. Shape-change occurs with small increases in intraplatelet calcium, while aggregation and secretion of granules take place at higher calcium, levels. The role of myosin and actin filaments and of transmembrane glycoproteins is further discussed.

Animals↗
PubMed1995

Linear IgA dermatosis: a new cause of fever of unknown origin.

We describe a 60-year-old patient who presented with prolonged fever, weight loss, adenopathies and malaise. Two months later, an aphthous stomatitis and pharyngitis developed, together with ulcerations bilaterally in the groin. Two separate skin biopsies revealed the diagnosis of linear IgA dermatosis. This entity, which is well known to dermatologists but not to internists, should be added to the extensive list of disorders than can provoke the syndrome of fever of unknown origin.

Autoimmune Diseases↗
PubMed1995

Platelet ultrastructural and functional studies in myelodysplasia.

We studied the platelets of 8 patients with myelodysplasia aged 49-77 years, using both ultrastructural and functional techniques. Five of the 8 patients were classified as having refractory anaemia, and 3 as refractory anaemia with excess of blasts (RAEB). Electron microscopically, the myelodysplastic patients had in addition to normal ones, platelets containing significantly less alpha-granules. In part of these hypogranular platelets, the dense tubular system was abundant, but in contrast with normal platelets, it was not dispersed between the other organelles, nor did it form a membrane complex with the open cannalicular system. From a functional point of view, collagen-induced shape change was the most frequently disturbed parameter: there was a total loss of collagen-induced shape change in 5 patients. In 2 patients, there was a complete lack of response to collagen in platelet-rich plasma (both shape change and aggregation); in one of them, there was also a total loss of adenosine triphosphate secretion in response to all inducers tested. After 4 years of follow-up, 5 patients had died, of whom 3 were RAEB patients. An initial complete absence of collagen-induced shape change was found in these 5 patients, while in the 3 patients who were still alive at the end of the follow-up period, collagen-induced shape change was normal in 2 and slightly diminished in one.

Aged↗
PubMed1994

Kaposi's sarcoma presenting as generalized lymphedema.

We present a HIV-1 seropositive patient with generalized lymphedema, due to a rare lymphangiomatous variant of Kaposi's sarcoma, successfully treated with interferon-alpha. The clinical presentation and treatment possibilities of Kaposi's sarcoma are reviewed.

Blotting, Western↗
PubMed1993

Nailfold capillaroscopy in connective tissue disorders and in Raynaud's phenomenon.

This article focuses on the value and the limitations of nailfold capillaroscopy in the differential diagnosis of certain connective tissue diseases and in the early recognition of secondary Raynaud's phenomenon. The finding of a "scleroderma-pattern" (apical enlargement and drop-out of capillaries) points almost certainly to an underlying progressive systemic sclerosis, mixed connective tissue disease or dermatomyositis.

Arthritis, Rheumatoid↗
PubMed1992

HIV-related thrombocytopenia.

HIV-related chronic ITP is caused by an accelerated platelet destruction due to adsorption of circulating immune complexes and to specific anti-platelet antibodies, but perhaps also by a defective thrombopoiesis resulting from invasion of the megakaryocytes by the retrovirus. Treatment is needed when platelet numbers drop beneath 20.10(9)/L or when severe bleeding symptoms occur. Steroids, commercially available immunoglobulins for IV use, AZT and anti-Rh immunoglobulins can be administered, although relapses are frequent after withdrawal of the drugs. Recurrences after splenectomy are far less common, but the progression towards AIDS might be accelerated.

Antigen-Antibody Complex↗
PubMed1988

Congenital macrothrombocytopenia, leucocyte inclusions, deafness and proteinuria: functional and electron microscopic observations on platelets and megakaryocytes.

We report a patient with a variant of Alport's syndrome: macrothrombocytopenia, leucocyte inclusions, deafness and proteinuria. Ultrastructural studies revealed giant spheroid platelets with a high density of organelles and a disorganized microtubular system. In addition, Fechtner inclusions were observed in neutrophils of the patient and her mother. In platelet rich plasma platelets aggregated normally for the low platelet number, although no shape change was visible. Platelet studies in whole blood using impedance aggregometry gave supernormal aggregation curves; this is not in agreement with the abnormally long bleeding time, showing the limited usefulness of this technique in patients with such large platelets. The megakaryocytes (MK) showed two different distribution patterns of the demarcation membrane system (DMS), which may explain the production of few large platelets. The formation of platelets occurred by fragmentation of the granular zone of the MKs, which seemed to be followed by expulsion of platelets through openings of the peripheral zone. The involvement of cytoskeletal structures in the organization of the DMS and the expulsion of platelets is discussed.

Adult↗
PubMed1988

Adenylate cyclase activation determines the effect of thromboxane synthase inhibitors on platelet aggregation in vitro. Comparison of platelets from responders and nonresponders.

The effect of five thromboxane-synthase inhibitors (UK-37248, UK-38485, UK-34787, CGS-13080 and OKY-1581) on arachidonic acid-induced platelet aggregation has been studied in vitro on platelets from 30 different healthy volunteers. The sensitivity of their platelets to adenylate cyclase stimulators or to dibutyryl cyclic AMP has been evaluated contemporarily. In 4 of the 30 volunteers tested no inhibition of platelet aggregation was obtained with any of the five thromboxane synthase inhibitors: these subjects were defined nonresponders; in 13 volunteers inhibition was observed with all the five drugs (responders). Significantly higher amounts of prostaglandin (PG)D2, prostacyclin and adenosine were required to suppress arachidonic acid-induced aggregation of platelets from nonresponders in vitro. No differences were instead observed between responders and nonresponders concerning platelet sensitivity to forskolin or dibutyryl cyclic AMP. The cyclic AMP rise obtained with exogenous prostacyclin was lower in platelets from nonresponders than in those from responders. PGE2 added in vitro to platelets from nonresponders exerted always a proaggregatory effect whereas this PG was antiaggregatory in most of the nonresponders. PGE2 blunted the antiaggregatory activity of PGD2 and limited the cyclic AMP increase induced by PGD2 in all the subjects tested. These data indicate that the unequal functional response of platelets from different subjects to thromboxane synthase inhibition depends essentially on adenylate cyclase function: a relative insensitivity of this enzyme to activating stimuli and the accumulation of substances (PGE2, PG endoperoxides, etc.) reducing the activity of adenylate cyclase may lead to continued platelet activation in some subjects despite the suppression of the synthesis of thromboxane A2.

Adenylyl Cyclases↗
PubMed1986

Heparin-induced thrombocytopenia platelet aggregation studies in the presence of heparin fractions or semi-synthetic analogues of various molecular weights and anticoagulant activities.

One case of heparin-induced thrombocytopenia is reported. Aggregation was observed in the platelet-rich plasma of this patient in the presence of two commercial standard heparin preparations (from a final concentration of 0.025 IU/ml upwards), of two semi-synthetic heparin analogues (0.1 APTT U/ml) and of three low-molecular weight heparin (LMWH) fractions (0.1 anti-Xa U/ml) but not in the presence of five other LMWH fractions. The patient's isolated platelets no longer aggregated in the The patient's isolated platelets no longer aggregated in the presence of heparin but the phenomenon recurred after addition of the patient's platelet poor plasma (PPP). Furthermore, addition of patient's PPP to control platelets led to heparin-induced aggregation. The phenomenon was associated with thromboxane generation and could be blocked by in vitro addition of aspirin, PGI2, and PGD2 whereas the lag phase was dose-dependently prolonged by adenosine. It is concluded that platelet aggregation may be induced in some patients by standard heparin and by certain LMWH fractions or semi-synthetic analogues, independently of their molecular weight and anticoagulant activity.

Adenosine↗
PubMed1986

Thrombosis and immune disorders.

The purpose of this review has been to draw the attention of clinicians towards the possibility that some of the patients they are treating for thrombosis may have an underlying immune disturbance. This could involve functional abnormalities of the complement system (as in acquired angioneurotic oedema or in paroxysmal nocturnal haemoglobinuria), or cell-mediated immunological damage to the vessel wall (as in Behcet's syndrome or Buerger's disease), or the presence of circulating antibodies (the lupus anticoagulant or antibodies to heparin). While obviously our knowledge on most aspects is still very incomplete, the awareness of the association of thrombosis with certain immune disorders should encourage further detailed studies of mechanisms and enhance our understanding of the role of blood constituents and the vessel wall in thrombogenesis.

Angioedema↗
PubMedDate not supplied

Assessment of the patency of deep leg veins with duplex.

To evaluate the accuracy of venous duplex, results obtained in 101 patients are compared with venography. A first group consisted of 48 patients with clinically suspected deep vein thrombosis. In 30 of them a positive duplex scan was obtained and all had subsequently a positive venography. Eighteen patients with a normal duplex scan had a normal venography. Another group of 53 patients were tested preoperatively for varicose vein surgery. No obstruction of the venous system was withheld with duplex but 3 patients had an old thrombosis on venography. Thus duplex is a highly reliable method to detect proximal thrombosis in clinically suspected patients but detection of late sequelae of thrombosis may be more difficult.

Adolescent↗