Human immunodeficiency virus-associated thrombotic microangiopathies: clinical characteristics and outcome according to ADAMTS13 activity.

Human immunodeficiency virus (HIV) infection is a risk factor for thrombotic microangiopathy (TMA). We sought whether a severe deficiency in ADAMTS13, the enzyme specifically involved in the cleavage of von Willebrand factor, was associated with specific presenting features and outcome in HIV-associated TMA. In this prospective, multicentre, case-control study, 29 patients of 236 in the French Network on TMA had an HIV-associated TMA. Seventeen patients with severe ADAMTS13 deficiency (ADAMTS13 <5% HIV(+) group) were compared to 12 patients with a detectable ADAMTS13 activity (ADAMTS13 >or=5% HIV(+) group). HIV(+) patients were also compared to 62 patients with idiopathic TMA, either with (45 patients, ADAMTS13 <5% idiopathic group) or without (17 patients, ADAMTS13 >or=5% idiopathic group) severe ADAMTS13 deficiency. ADAMTS13 <5% HIV(+) patients had less AIDS-related complications than ADAMTS13 >or=5% HIV(+) patients (23.5% versus 91.6%, respectively, P = 0.0005) and their median CD4(+) T cell count was higher (P = 0.05). TMA-associated death rate was higher in ADAMTS13 >or=5% HIV(+) patients than in ADAMTS13 <5% HIV(+) patients (50% versus 11.7%, respectively, P = 0.04). In ADAMTS13 <5% patients, TMA-associated death rate was comparable between HIV(+) and idiopathic patients (15.5% in idiopathic patients, P-value was non-significant). By contrast, TMA-associated death rate in ADAMTS13 >or=5% HIV(+) patients was higher than in idiopathic patients (11.7% in idiopathic patients, P = 0.04). In conclusion, HIV-associated TMA with severe ADAMTS13 deficiency have less AIDS-related complications and a higher CD4(+) T cell count. TMA prognosis is better and comparable to this of idiopathic forms.

Human fear-related motor neurocircuitry.

Using functional magnetic resonance imaging and an experimental paradigm of instructed fear, we observed a striking pattern of decreased activity in primary motor cortex with increased activity in dorsal basal ganglia during anticipation of aversive electrodermal stimulation in 42 healthy participants. We interpret this pattern of activity in motor neurocircuitry in response to cognitively-induced fear in relation to evolutionarily-conserved responses to threat that may be relevant to understanding normal and pathological fear in humans.

Circulating malignant lymphocytes from Sezary syndrome express high level of glycoproteins carrying beta (1-6)N-acetylglucosamine-branched N-linked oligosaccharides.

The circulating forms of malignant cells from patients with Sezary syndrome exhibit on their glycoproteins a high level of beta (1-6)GlcNAc-branched N-linked oligosaccharides, a particular species of glycans related to the metastatic potential of several tumors and T lymphocytes activation. An increased activity of the N-acetylglucosaminyltransferase V and of the beta (1-4)galactosyltransferase, two enzymes implicated in beta (1-6)GlcNAc-branching is also found. Nevertheless, contrary to activated normal T lymphocytes, Sezary lymphocytes in agreement with their non-proliferating state, do not exhibit increased thymidine uptake. This result suggests that expression of the beta (1-6)GlcNAc-branched N-linked carbohydrates could be related to some of the malignant properties of Sezary lymphocytes.

A CD2+ subset of non-malignant peripheral blood lymphocytes from patients with Sézary syndromes overexpress the low-molecular-weight GTP-binding protein Rab2.

The Rab branch of the Ras-related GTP/GDP-binding proteins currently includes at least 25 related members which are involved in the intracellular vesicular transport along the secretory and endocytic pathways in eukaryotic cells. The overexpression of the Rab2 protein in peripheral mononuclear cells is demonstrated from 13 out of 17 patients exhibiting a Sézary syndrome. Moreover, this phenomenon is detectable in other lymphoid and myeloid malignancies. Several lines of evidence are shown suggesting that the Rab2 overexpression can be related not to leukemic cells but to a subset of peripheral lymphocytes with a CD2+ phenotype. Our results provides strong evidence for the implication of a small GDP/GTP-binding protein in immunological events associated with neoplastic states. The precise cellular population involved in this process remains to be determined.

p53 antibodies in patients with various types of cancer: assay, identification, and characterization.

Alteration of the p53 gene is the most frequent genetic alteration in human cancer and leads to the accumulation of mutant p53 in the nucleus of tumor cells. In addition, it has been shown that patients with various types of neoplasia have p53 antibodies in their sera which could be used as an indirect diagnostic procedure for p53 alteration. Using a new ELISA, we have analyzed the sera from more than 1000 patients with various types of cancer and from healthy blood donors. We demonstrate that p53 antibodies are detected mainly in cancer patients and are strictly proportional to the occurrence of p53 mutations. Using various immunological approaches, these antibodies were unambiguously demonstrated to be directed toward the human p53 protein. Isotyping analysis of these antibodies strongly suggested that they correspond to a humoral response to the p53 protein which accumulates in the tumor cell. This finding suggests that serological analysis, combined with histochemistry, is suitable for assessing the integrity of the p53 gene in cancer patients.

Late-onset rod myopathy associated with monoclonal gammopathy.

A 31-yr-old woman presented with a severe and rapidly progressive myopathy affecting proximal limbs, neck flexors and respiratory muscles. Muscle biopsy revealed numerous atrophic fibres with marked structural alterations, without inflammatory infiltrate. By electron microscopy, atrophic fibres displayed many rods. A benign monoclonal gammopathy (IgG, lambda chain) was evident in serum. A sarcolemmal deposit of IgG, lambda chain was found by immunostaining. Plasmapheresis and immunosuppressive therapies produced a decrease in paraproteinemia and a partial clinical improvement. This observation is the third to associate monoclonal gammopathy with "late-onset rod myopathy". The pathogenetic role of paraproteinemia remains unclear.

t(8;21) prior to acute leukemia.

A t(8;21)(q22;q22) without blood and bone marrow invasion by immature myeloid precursor cells occurred in a patient previously treated for polycythemia vera. The presence of a molecular rearrangement confirmed that the chromosomal abnormality was identical to that observed in acute leukemia with t(8;21). This case shows that the translocation, t(8;21), may occur in myelodysplasia and suggests that it can precede the appearance of overt leukemia.

A low-cost automated device incorporating a hollow fiber filtration cartridge for large-scale production of ghosts from human erythrocytes.

Readily available elements were used to build an automatic apparatus dedicated to the preparation of erythrocyte ghosts. The apparatus is designed around a low-cost re-usable hollow-fiber filtration cartridge (marketed for therapeutic plasmapheresis). The apparatus is controlled by a simple programmer (based on a diode matrix and low cost timers and liquid level sensors): once the apparatus is loaded with whole red blood cells, washing of cells, as well as hemolysis and washing of ghosts, is performed by the machine in about 4.5 h without any operator intervention. Automatic filter cleaning takes a further 110 min.

Allogeneic bone marrow transplantation in aplastic anemia--report of 25 cases.

Bone marrow transplantation using an HLA-MLC-identical sibling is the most valuable treatment of severe aplastic anemia.2,6,7 Between November 1973 and March 1977, 25 consecutive patients have been treated by marrow transplantation in our unit. Nine patients are alive with complete hematologic restoration between 3 months and 3 years. The high mortality can be largely accounted for by marrow graft rejection (14 patients). Despite the small number of patients, we have tried to identify prognostic factors associated with marrow graft rejection. They are mainly the existence of anti-HLA antibodies, the sex difference, and the normal PHA and MLC response before grafting. After the graft, the disappearance of anti-HLA antibodies has a good prognostic value. The appearance of autolymphocytotoxins seems to correlate strongly either with rejection or graft-versus-host disease.

Plasma exchange in severe erythema nodosum leprosum.

Four patients with severe erythema nodosum leprosum were treated by plasma exchange and/or fresh frozen plasma infusions after failure of classical therapy. After the procedures, the patients improved rapidly; with a follow-up between 4 and 7 years after the last plasma exchange, no clinical relapse was noted. The replacement fluids were variable; the most beneficial procedure seemed to be plasma exchange replaced with fresh frozen plasma. Elimination of circulating immune complexes, replacement of a lacking plasma factor are possible mechanisms of action. Plasma exchange may also work like a regulator of immune mechanisms, since it has been shown that there is a depression of suppressor cells in erythema nodosum leprosum.

Treatment of progressive systemic sclerosis by plasma exchange: long-term results in 40 patients.

The efficacy of plasma exchanges (PE) during the course of scleroderma has only been investigated for short periods. The aim of this study was to follow patients over a long enough period to observe the course of the clinical and paraclinical symptoms in the short, medium, and long term. Forty patients, 24 women and 16 men, were treated by PE and observed for 1-3, 3-12 and over 12 months. Immunological, biological and clinical course and any undesirable side effects were evaluated using a detailed questionnaire. Concomitant therapies were reported and most frequently consisted of corticosteroids, colchicine, factor XIII or vasodilators (nifedipine, captopril). The therapeutic effectiveness of PE was assessed on the basis of improvements in cutaneous, digestive, joint, muscular, lung, cardiovascular and renal lesions. Our findings confirmed the effectiveness of short-term PE on scleroderma (52% of the patients improved during the first 3 months). However, this improvement was transient (5% improvement between 3 and 12 months and only 2.5% over 12 months) and limited to the cutaneous and muscular lesions. Thus, PE cannot be recommended for the treatment of progressive systemic sclerosis.

[Resistant acquired bullous epidermolysis with severe ocular involvement: the success of extracorporeal photochemotherapy]. / Epidermolyse bulleuse acquise résistante avec atteinte oculaire sévère: succès de la photochimiothérapie extracorporelle.

BACKGROUND: Epidermolysis bullosa aquisista can leave several functional sequelae. The lesions sometimes resist treatment. CASE REPORT: We report a case of a 25-year-old young man presenting with a severe epidermolysis bullosa acquisita confirmed by the electronic immunomicroscopy. He had a major ocular involvement with symblepharon and cicatricial synechial lesions. He was almost blind because of corneal scars. All immunosuppressive treatments had failed: systemic corticoids, cyclosporin, azathioprine. The introduction of extracorporeal photochemotherapy resulted in the healing of the lesions, after a total of 32 procedures. All treatment are now stopped, and the lesions are purely cicatricial, without any relapse of the disease since 9 months. Corneal grafts are now under process, to try to recover a part of the lost visual acuity. DISCUSSION: This case demonstrates the efficacy of extracorporeal chemotherapy to be tried in case other treatments failed.

[Indications of plasma extraction during the treatment of monoclonal gammopathies]. / Indications des épurations plasmatiques au cours du traitement des gammapathies monoclonales.

Data from the french national registry show that about 20% of plasma exchange are performed to alleviate clinical manifestations related to a monoclonal Ig. Plasma removal has to be only considered as a part of therapy, the disease being controlled by cytotoxic drugs. However, owing to its delayed effect plasma exchange are useful to preserve the functional or vital prognosis. Technical aspects such as plasma volume removed or frequency of procedures will be scheduled according to monoclonal Ig specification: repartition between intra and extravascularly pools-allotypes-efficiency of chemotherapy. Hyperviscosity syndrome, interferences with hemostasis and vascular manifestations of cryoglobulins are the main established indications. Renal insufficiency of myeloma, peripheral neuropathies and unusual clinical symptoms associated with monoclonal gammapathy of undetermined significance should also be considered as possible indications. In contrast regression of amyloidosis deposits has not been reported.