[Sweet's syndrome induced by pegfilgrastim during a myelodysplastic syndrome AREB2: A case report]. / Syndrome de Sweet induit par le pegfilgrastim au cours d'un syndrome myélodysplasique AREB2 : à propos d'un cas clinique.

INTRODUCTION: Sweet's syndrome is an acute neutrophilic dermatosis characterized by abrupt onset of skin lesions accompanied by fever, arthralgia, leukocytosis and diffuse neutrophilic infiltration of the dermis, as well as an excellent response to corticosteroid therapy. CASE REPORT: A 46-year-old patient with myelodysplastic syndrome was admitted for chemotherapy. On the eighth day of chemotherapy, he received a single dose of pegfilgrastim. Three days later, he developed pyrexia, conjunctivitis, arthralgia and erythematous and painful papulo-nodular lesions. Broad-spectrum empiric antibiotic therapy was started but the patient's condition deteriorated. Biology showed pancytopenia and inflammatory syndrome. Microbiological tests, autoimmune serologies and chest-computed tomography were negative. Cutaneous biopsy was compatible with Sweet's syndrome. A diagnosis of Sweet's syndrome induced by pegfilgrastim was made and intravenous corticosteroid therapy was started with a rapid favorable outcome. CONCLUSION: Sweet's syndrome is a rare adverse effect of G-CSF.

[Tamoxifen induced thromboembolic events in breast cancer. Some possible mechanisms]. / Evénements thromboemboliques induits par le tamoxifène dans le cancer du sein. Certains mécanismes potentiels.

Tamoxifen is an antagonist of the oestrogen receptor, used in the treatment of breast cancer. It is known to reduce osteoporotic bone fractures, but it increases the risk of endometrial tumors and venous thromboembolic events (VTEs). VTEs increased significantly during tamoxifen therapy within 3 months of major surgery, immobilization or fracture. Their incidence is associated with patients' risk factors, tumor and tissue induced procoagulation. The mechanisms are still not well known. There is a need for a better understanding in order to develope a prophylactic and therapeutic strategy.

Le tamoxifène est un antagoniste du récepteur de l'oestrogène, utilisé dans le traitement du cancer du sein. Le rôle du tamoxifène dans la réduction du risque de fractures osseuses ostéoporotiques est connu. Par contre il augmente le risque d'apparition de tumeurs de l'endomètre et des événements thromboemboliques veineux (ETEV). L'incidence d'ETEV augmente de manière significative au cours du traitement par le tamoxifène dans les 3 mois d'une chirurgie majeure, suite à une immobilisation ou une fracture. L'incidence est associée aux facteurs de risque des patients et à une hyper coagulabilité tumeur ou tissu induite. Les mécanismes thromboemboliques liés au tamoxifène ne sont pas encore bien connus. Il est nécessaire de mieux les connaître pour développer une stratégie prophylactique et thérapeutique.

[Sickle cell disease patients, sickness and medical accompanying questioning related to specific adolescent period]. / Patients drépanocytaires: quel accompagnement médical spécifique lors de l'adolescence?

The sickle cell disease is a genetic disease of the hemoglobin, also called sickle-cell anemia. It is the most common genetic disease in the world. It is nevertheless still enough underestimated by the general public and even sometimes by the medical world. The patients who are affected suffer, besides a chronic anemia, extremely painful vaso-occlusive crises and possibly diverse complications. Because of the extension of their life expectancy, due to important medical progress, the patients are required to go to the hospital for adults. The object of this article is to try to draw a portrait of these patients and the multiple obstacles with wich they are confronted. These teenagers or grown-up young people have indeed to face important physical problems wich have significant psychological impact. How do they reconcile adolescentaire crisis and management of the disease? How can the hospital welcome at the best these "new" patients?

[Refractory anemias]. / Les anemies réfractaires.

Refractory anemia, also known as myelodysplastic syndromes, forms a group of clonal diseases characterized by cytopenias with mostly rich bone marrow. Preferentially reaching an older population, the prognosis depends on both comorbidities and characteristics of the disease, which have been grouped into a score established in 1997 ("IPSS = International Prognostic Scoring System") and revised in 2012 ("R-IPSS = Revised IPSS"). Overall survival and risk of transformation into acute nonlymphoblastic leukemia can now be estimated fairly accurately. Based on these characteristics, the treatment will be mainly supportive or will use several new molecules: growth factors, lenalidomide, 5-azacitidine, etc. A minority of patients may also benefit from allogeneic BMT or sometimes immunosuppressive therapy.

A phase II randomized study of combined infusional leucovorin sodium and 5- FU versus the leucovorin calcium followed by 5-FU both in combination with irinotecan or oxaliplatin in patients with metastatic colorectal cancer.

BACKGROUND: Leucovorin Sodium (LV/Na) has a high solubility, and is stable when given with continuous infusion of 5-FU. It could maintain significant plasma concentration of 5, 10-meTHF during the whole 5-FU perfusion with the potential of increasing 5-FU cytotoxicity. We conducted a randomized phase II clinical trial on leucovorin calcium (LV/Ca) and LV/Na in metastatic colorectal cancer patients (mCRC). Main objectives were to assess efficacy and safety. PATIENTS AND METHODS: Fifty seven patients with mCRC and no previous chemotherapy for metastatic disease were randomized to receive LV/Na or LV/Ca with irinotecan or oxaliplatine combined with infusional 5-FU. LV/Na was defined as warranting further evaluation in phase III if true overall response rate (ORR) > 35% (α=5%, ß=10% in case of true ORR >55%, 51 evaluable patients planned/arm). RESULTS: Results for LV/Ca and LV/Na arm respectively were: observed ORR, 55% (significantly higher than 35%, p = 0.02) and 61% (p = 0.004). Median overall survival durations were 11.9 months and 22.9 months (p = 0.02) and PFS 8.0 vs. 11.5 months (ns). Grade 3 events were 64% and 46% (p = 0.28). CONCLUSION: Both LV/Na and LV/Ca disclosed an ORR > 35% with comparable safety.

[May still in 2010 a surgeon decide alone to operate a digestive cancer?]. / Un chirurgien peut-il en 2010 décider seul d'opérer un cancer digestif?

The authors raise the question whether a surgeon in 2010 may still decide by himself to operate a digestive cancer. Progresses in oncology and surgery have been considerable over the past 50 years. The appearance of laws over the past decade and the emergence of the concept of Evidence Based Medicine (EBM) have refocused the role of the surgeon in the care of digestive cancers. The emergence of quality systems such as peer review, 150 certification to analyze surgical procedures and results place the surgeons in the very front. The evolution of the surgical and oncological disciplines will change the role of the surgeon again in the future. The surgeon may always decide to operate a cancer in a coordinate way with the other care givers.

Interferon alpha prevents spontaneous apoptosis of clonal Th2 cells associated with chronic hypereosinophilia.

A recent study identified a clonal expansion of CD3(-)CD4(+)cells secreting Th2-type cytokines in 4 patients with chronic hypereosinophilia. Because interferon alpha (IFN-alpha) is used in the therapy of the idiopathic hypereosinophilic syndrome, the effects of this cytokine on the survival of clonal Th2 cells isolated from the blood of 2 patients were determined. First, these cells displayed a high rate of spontaneous apoptosis on culture in cytokine-free medium and were also sensitive to Fas-mediated apoptosis induced by soluble Fas ligand. Addition of IFN-alpha or interleukin-2 (IL-2) to culture medium resulted in significant protection against spontaneous but not Fas-induced apoptosis. Although spontaneous apoptosis of the clonal Th2 cells was clearly associated with down-regulation of both bcl-2 and bcl-x(L) levels, IFN-alpha had no significant effect on the expression of these antiapoptotic proteins, whereas addition of IL-2 resulted in higher levels of bcl-2. On the other hand, IFN-alpha decreased the numbers of cells with disrupted mitochondrial transmembrane potential both during spontaneous apoptosis and after exposure to protoporphyrin IX. Thus, IFN-alpha might promote the survival of clonal Th2 cells, an effect that could be relevant to the therapeutic approach for patients with chronic hypereosinophilia caused by clonal expansion of Th2-type cells. (Blood. 2000;96:4285-4292)

[What is the role of internal medicine in the collective of a general hospital?]. / Quelle place pour la Médecine Interne d'ensemble dans un Hôpital général?

General internal medicine tends to decrease in many Belgian hospitals. On the opposite, United States are now clearly engaged in a reform of their health system, with a drastic augmentation of the number of general internists. This reflection recognizes the specificities of general internal medicine: the first contact, the longitudinal follow-up, the comprehensive approach and the coordination with other medical participants. The need for subspecialists would be reduced and the need for primary comprehensive care physicians would be increased. The development of a performent sector of general internal medicine is able to respond to the demand of the patients and also of the general family practitioners. This model has positive impacts for the whole hospital community. We are all weary of discussions of state medicine, of the high cost of medical care, of the adequacy of medical care for the indigent, of the shortage of hospital beds for those who can pay, of the shortage of nurses, and so on. But these are, in part our problems; if their solution is to be to our liking, we must be active in them. The spector of state medicine is continually raised before us. Greater participation, by the federal, state and local governments in matters of health seems inevitable although most of us think it is important to retain in some manner or other the principle of private enterprise. Change of some sort will come; it is evident that unless we ourselves reorganize the practice of medicine, it will be reorganized for us.

Clonal Th2 lymphocytes in patients with the idiopathic hypereosinophilic syndrome.

Idiopathic hypereosinophilic syndrome (HES) and Gleich's syndrome are related disorders characterized by persistent or recurrent hypereosinophilia of unknown origin. Elevated IgE levels and polyclonal hypergammaglobulinaemia are considered as markers of benign outcome in this setting as they are generally associated with predominant cutaneous manifestations and favourable response to glucocorticoid therapy. In a previous study, we identified a clonal population of CD3-CD4+ Th2-like lymphocytes secreting interleukin (IL)-5 and IL-4 in peripheral blood of a patient fulfilling the diagnostic criteria of HES with associated serum hyper-IgE. We now extend this observation by describing identical findings in three additional patients, and we compare their clinical and biological parameters with five other patients with HES. Chromosomal abnormalities were detected in purified CD3-CD4+ Th2 cells from three patients, among whom one developed anaplastic null cell lymphoma. We therefore suggest that a careful search for T-lymphocyte clonality and cytogenetic changes should be included in the work-up of HES for adequate management.

T-cell receptor-independent activation of clonal Th2 cells associated with chronic hypereosinophilia.

We recently observed a clonal expansion of CD3(-)CD4(+) T cells secreting Th2-type cytokines in patients presenting chronic hypereosinophilia. As clonal T cells isolated from such patients did not spontaneously secrete cytokines in vitro, we reasoned that costimulatory signals delivered by antigen-presenting cells might be required to induce their full activation. To address this question, we investigated in two such patients the responses of CD3(-)CD4(+) T cells to dendritic cells (DC). DC elicited proliferation and production of interleukin-5 (IL-5) and IL-13 by clonal cells from patient 1 and upregulated their expression of CD25 (IL-2R-alpha). These effects were abolished when blocking monoclonal antibodies (MoAbs) against IL-2R-alpha and IL-2 were added to cocultures, indicating critical involvement of an autocrine IL-2/IL-2R pathway. Cells from patient 2 were stimulated by DC to produce Th2 cytokines only when rIL-2 or rIL-15 was added to cocultures. In both patients, addition of inhibitory MoAbs against B7-1/B7-2 or CD2 to cocultures resulted in dramatic reduction of cytokine production and inhibited CD25 upregulation. Thus, TCR/CD3-independent activation of clonal Th2 cells by DC is an IL-2-dependent process, which requires signaling through CD2 and CD28.

Intracardiac thrombi associated with antiphospholipid antibodies.

Two cases of intracardiac thrombi associated with antiphospholipid antibodies are presented, one in the right atrium and the other in the left ventricle, the latter occurring in the presence of normal left ventricular function. In each, the diagnosis was made by transthoracic echocardiography. Both patients had contraindications to thrombolytic therapy and underwent successful surgical thrombectomy. We suggest that serial transthoracic echocardiography may be warranted in the follow-up of patients with primary hypercoagulable states.

[A case of thrombotic thrombopenic purpura. Literature review]. / Un cas de purpura thrombotique thrombocytopénique. Revue de la littérature.

We report the case of a 70 years old woman who developed a thrombotic thrombocytopenic purpura. Despite a treatment with corticoids and high doses IV gammaglobulins, the patient developed seizures. Treatment with plasma exchanges combined with plasma infusions allowed recovery. The authors review the clinical and biological aspects as well as the pathogeny of the disease. The authors insist on the importance of the plasma exchanges in the treatment of this disease.

[Intravenous corticosteroid megadose treatment in ocular Behçet disease]. / Traitement par mégadoses intraveineuses de corticoides dans l'atteinte oculaire de la maladie de Behçet.

Ocular Behçet's disease is characterized by a very poor visual prognosis. Twelve patients which had a maintenance treatment with immunosuppressors received 30 intravenous i.v. bolus of corticoids for uncontrolled severe retinal vasculitis (macular edema 58% of cases) and papillitis (100% of cases) (1 bolus treatment = 0.5-2 g of i.v. methylprednisolone once a day, for 3 days). In addition, oral immunosuppression was moderately increased in order to prevent further recurrences. Tolerance was good in all cases. Visual acuity (VA) remained stable or improved after one month in 87% of cases following the bolus treatment. In 92%, the VA remained stable or improved for a mean follow-up of 6 years. These good results suggest that intravenous bolus of steroids is a safe and efficient therapy which may prevent further decrease of the visual acuity and may reduce the side effects of the immunosuppressive treatment needed to control severe posterior uveitis in Behçet's disease.

[Churg-Strauss syndrome: personnel case report and literature review]. / Syndrome de Churg-Strauss: observation personnelle et revue de la littérature.

A 58-year-old male presented with a three years history of atopic asthma, fluctuating eosinophilia and, at the moment of diagnosis, systemic vasculitis of brutal onset affecting skin and peripheral nerves. Demonstration of eosinophilic infiltrates and granulomata in involved tissues confirmed the clinical diagnosis of Churg-Strauss syndrome. Therapy with high-dose methylprednisolone and cyclophosphamide was followed by normalization of blood cell count and partial recovery of clinical manifestations, with persisting damage to the peripheral nerves.

[Comparative study of 2 common tests for lupus anticoagulant determination: critical analysis of the results observed in 21 patients]. / Etude comparative de deux tests usuels de dépistage de l'anticoagulant du lupus: analyse critique des résultats observés chez 21 malades.

The Schleider and/or the Exner test have been found positive in twenty-one patients; five of these patients suffered of systemic lupus erythematosus (SLE). The Quick time and the activated partial thromboplastin time are normal in 52% of the cases. 40% have a minor haemorrhagic diathesis, without other significant clotting defect and 30% have thrombo-embolic complications. The Schleider index is more often strongly positive (greater than 2) in these two groups. 58% have an anemia, 25% a mild thrombocytopenia not deep enough to explain an haemorrhagic tendency (from 90.000 to 140.000/mm3). Several auto-immune tests are frequently positive even without SLE. The Schleider test is positive in 86% of the cases and appears a little more useful for the diagnosis than the Exner test, which has a 71% positivity.