[Partial thrombosis of the corpus cavernosum: A new case with good outcomes under non-steroidal anti-inflammatory drugs]. / Thrombose partielle des corps caverneux : un nouveau cas avec évolution favorable sous anti-inflammatoires non stéroïdiens.

Partial priapism is a rare pathology with less than 60 cases published in the literature; the etiology remains unknown, although certain favorable factors are identified as having in relation a prolonged perineal compression or a thrombopathy. The symptomatology is characterized by the appearance of pain, perineal edema and an induration of the root of the penis, which do not concern the distal part of the penis or the glans. MRI is the best complementary examination. The first-line surgical treatment is abandoned. Medical treatment with non-steroidal anti-inflammatory drugs or low molecular weight heparins combined with platelet aggregation inhibitors give good results with complete resolution of symptoms in 82% of cases; first-line medical treatment should be favored. We report a case of idiopathic partial priapism, successfully treated with non-steroidal anti-inflammatory without recurrence after 10 years.

Postauthorization safety study of Clottafact® , a triply secured fibrinogen concentrate in acquired fibrinogen deficiency: a prospective observational study.

BACKGROUND AND OBJECTIVES: A postauthorization safety study was performed between 2009 and 2012 to describe the use of Clottafact® in acquired fibrinogen deficiency in real-life medical practice in France. MATERIALS AND METHODS: One hundred and fifty patients were planned for 28 days of prospective follow-up after infusion. The analysis of this observational study was descriptive and performed according to the type of treatment (curative or preventive) and the origin of the bleed. RESULTS: One hundred and fifty-six patients (16-87 years) were included in 13 centres and treated in five different medical bleeding situations: postpartum (59), other gynaecological/obstetrical (6), trauma (34), liver (13), cardiovascular (23) and other various bleeding situations (21). The mean follow-up time was 18·9 ± 12·3 days. Two patients presented adverse drug reactions: one a pulmonary embolism and the other a four-site venous thromboembolic episode. All were serious with a dubious causal relationship with the study treatment. Efficacy data were collected as a secondary objective. In 150 patients receiving curative treatment, 117 of 159 infusions (73·6%) were considered as successful by the investigators, 35 as moderate (22%) and seven as no response (4·4%). CONCLUSION: The Clottafact® safety profile observed during the study matched the known profile of fibrinogen during use.

Post-authorization safety study of Clottafact® , a triply secured fibrinogen concentrate in congenital afibrinogenemia. A prospective observational study.

BACKGROUND AND OBJECTIVES: A new fibrinogen concentrate Clottafact® was developed according to European guidelines on plasma-derived products. A post-authorization safety study was set up in 2009 as part of the risk management plan. This was a non-interventional, prospective, non-comparative, multicenter study of the use of fibrinogen concentrate for congenital afibrinogenemia in real-life medical practice in France. MATERIALS AND METHODS: The analysis was descriptive and performed on 3 subgroups: prophylaxis vs. on-demand treatment, age (<6, <12 and ≥12) and severity of the deficiency. RESULTS: Fourteen patients [1-78 years] were included in 7 centres and followed for 1 year. Twenty-one adverse drug reactions (ADRs) classically reported with fibrinogen (pallor, chills, cough, vomiting, headache, urticaria and erythematous rash) were reported in 5 of 14 patients. Two ADRs were serious: an anaphylactic shock and a subclavian venous thrombosis with a favourable outcome without sequelae. In the nine patients under prophylaxis, 365 of 367 infusions were considered as successful (99·5%) and 2 as failures. For the five patients treated on-demand, the efficacy was rated as excellent for 27 of 48 infusions and good for the 21 others. CONCLUSION: This study confirms that the benefit/risk balance for this fibrinogen concentrate is favourable.

Differential investigations from plasma-derived and recombinant Factor IX revealed major differences in post-translational modifications of activation peptides.

Post-translational modifications (PTMs) located on the activation peptide (AP) of recombinant FIX (rFIX, BeneFIX(®) ) and plasma-derived FIX (pdFIX, Betafact(®) ) have been investigated by mass spectrometry to review the structural differences between these two products. Three major structural differences were pointed out. rFIX contains a low amount of phosphorylated and sulphated AP (4% for rFIX vs. 70% for pdFIX); rFIX N-glycans are only sialylated in the α2-3 linkage, whereas pdFIX N-glycans contain both type of α2-3 and α2-6 linkages, and rFIX does not contain any sialyl Lewis(X) glycoantigens contrary to pdFIX. These variations might participate in the in vivo potential different behaviours of the two molecules.

A qualitative and quantitative analysis of von Willebrand factor contained in a very high-purity plasma-derived FVIII concentrate.

BACKGROUND AND OBJECTIVES: We studied the structural and functional properties of von Willebrand factor (VWF) molecules present in a very high-purity plasma-derived factor VIII concentrate (VHP pdFVIII - Factane® ) because several observations suggest that the presence of VWF in factor VIII (FVIII) preparations may decrease their immunogenicity. MATERIALS AND METHODS: Ten marketed batches of VHP pdFVIII (Factane® ) with levels of VWF ranging from 15 to 39 IU/100 IU FVIII were analysed. The VWF multimeric pattern was studied by agarose gel electrophoresis. The binding of VWF to FVIII was studied by gel filtration and ELISA. The binding of VWF to GPIb was analysed by ELISA. RESULTS: The results showed that high-molecular-weight multimers of VWF were present in VHP pdFVIII (Factane® ). VWF subunits maintain a triplet structure similar to that of normal plasma. Regardless of the VWF content, all FVIII molecules of each batch were co-eluted with VWF, and no free FVIII was detectable. By immunoassays, VWF was found to be able to bind to FVIII and platelet GPIb in a similar manner to that of VWF in normal plasma. CONCLUSIONS: In all the VHP pdFVIII (Factane® ) batches studied, regardless of the level of VWF, the structure and capacity of VWF binding to FVIII and to platelet GPIb were fully preserved.

Glycation of polyclonal IgGs: Effect of sugar excipients during stability studies.

A number of intravenous immunoglobulin preparations are stabilized with sugar additives that may lead over time to undesirable glycation reactions especially in liquid formulation. This study aimed to evaluate the reactivity of sugar excipients on such preparations in condition of temperature, formulation and concentration commonly used for pharmaceutical products. Through an innovative LC-MS method reported to characterize post-translational modifications of IgGs Fc/2 fragments, a stability study of IVIg formulated with reducing and non-reducing sugars has been undertaken. The rate of polyclonal IgGs glycation was investigated during 6months at 5, 25, 30 and 40°C. High levels of glycation were observed with reducing sugars such as glucose and maltose in the first months of the stability study from 25°C. Non-reducing sugars presented a low reactivity even at the highest tested temperature (40°C). Furthermore, a site by site analysis was performed by MS/MS to determine the glycation sites which were mainly identified at Lys246, Lys248 and Lys324. This work points out the high probability of glycation reactions in some commercialized products and describes a useful method to characterize IVIg glycated products issued from reducing sugar excipients.

Circadian phase dependent pharmacokinetics of L-dopa, its main metabolites (3-OMD, HVA, DOPAC) and carbidopa in rats.

This study aims to evaluate whether or not the kinetics of L-dopa, its main metabolites (3-O-methyldopa, 3-OMD, homovanilic acid, HVA and 3,4-dihydroxyphenylacetic acid, DOPAC) and carbidopa, vary according to the 24-hour scale in rats. Four groups of seven adult male Wistar AF EOPS rats were used for these experiments; each group received L-dopa (200 mg.kg-1 ip) and carbidopa (20 mg.kg-1 ip) at 1000, 1600, 2200 or 0400 hours. L-dopa, 3-OMD, DOPAC, HVA and carbidopa were simultaneously determined by specific ion-pair reversed-phase high performance liquid chromatography with electrochemical detection. A temporal variation of the kinetics of both L-dopa and carbidopa was demonstrated with higher plasma clearance and lower area under concentration curve after the administration at 2200 hours. Moreover, a temporal variation of the metabolism of L-dopa was indirectly documented by temporal variation in kinetics of 3-OMD, DOPAC and HVA.

Favorable outcome of gemcitabine-induced respiratory distress syndrome.

Gemcitabine, a deoxycytidine analog, is used to treat solid tumors, like non-small-cell lung carcinoma. The most commonly reported adverse effects are reversible and generally not fatal. However, among the five cases of acute respiratory distress syndrome (ARDS) secondary to gemcitabine treatment reported since 1997, four were fatal despite corticosteroid therapy. We describe here a patient who received gemcitabine for bronchial epidermoid carcinoma and developed ARDS which spontaneously regressed after gemcitabine withdrawal.

Concomitant polymyositis and myasthenia gravis reveal malignant thymoma. A case report and review of the literature.

The frequency of thymona associated with autoimmune diseases has been reported to be increased, with 50% of thymoma patients also having myasthenia gravis (MG). Other autoimmune disorders, such as autoimmune erythroblastopenia and polymyositis (PM), have been less frequently associated with thymoma. The association of MG and PM with thymoma is rare. We here report the case of a 66-year-old woman whose concomitant MG and PM revealed malignant thymoma and review the other published cases of this association.

Risk factors and prognostic influence of infection in a single cohort of 87 adults with systemic lupus erythematosus.

OBJECTIVES: To describe infectious complications and analyse their risk factors and prognostic role in adults with systemic lupus erythematosus (SLE). METHODS: A monocentric cohort of 87 adults with SLE (1960-1997) was studied to determine the risk factors for infection (disease activity evaluated by SLAM and SLEDAI scores, type of organ(s) involved or any biological abnormality, specific treatments) by comparing patients who had suffered at least one infectious episode (n=35; 40%) with non-infected patients (n=52; 60%). Prognostic indicators were assessed by comparing survivors at 10 years with non-survivors. RESULTS: Of the 57 infectious episodes, 47 (82%) were of bacterial origin, 16 (28%) were pneumonia, and 46 (81%) were community acquired. According to univariate analysis, significant risk factors for infection were: severe flares, lupus glomerulonephritis, oral or intravenous corticosteroids, pulse cyclophosphamide, and/or plasmapheresis. No predictors were identified at the time of SLE diagnosis. Multivariate analyses retained intravenous corticosteroids (p<0.001) and/or immunosuppressants (p<0.01) as independent risk factors for infection, which was the only factor for death after 10 years of evolution (p<0.001). CONCLUSION: In adults with SLE, infections are common and most often caused by community acquired bacteria. Intravenous corticosteroids and immunosuppressants are independent risk factors for infection, which is the only independent risk factor for death after 10 years of SLE evolution.

Are antineutrophil cytoplasmic antibodies a marker predictive of relapse in Wegener's granulomatosis? A prospective study.

OBJECTIVES: To investigate the predictive value of testing for antineutrophil cytoplasmic antibodies (ANCA) in 55 patients with systemic Wegener's granulomatosis (WG) included in a randomized, prospective trial comparing corticosteroids and oral or pulse cyclophosphamide. METHODS: All 55 patients received corticosteroids. A cyclophosphamide pulse of 0.7 g/m2 was given at the time of diagnosis. After the first pulse, the patients were assigned at random to receive either pulse or oral cyclophosphamide (2 mg/kg/day), independently of ANCA results. ANCA were sought using an immunofluorescence assay and an attempt was made to correlate them with relapse of WG. ANCA were monitored throughout the study. RESULTS: At the time of diagnosis, ANCA were detected in 48 (87%) patients, with a cytoplasmic labelling pattern in 44 and a perinuclear pattern in four. ANCA follow-up was available for 50 patients. ANCA disappeared in 34 patients and persisted in nine. For 79% of the patients, the clinical course improved with the disappearance of ANCA and deteriorated with their persistence or increased titre. Among the patients who were initially ANCA-positive, 23 relapses occurred. Relapses were more frequent when ANCA remained positive or reappeared [13/19 ANCA-positive patients vs 3/29 ANCA-negative patients (P<0.01)]. Nine relapses (39%) occurred in patients with persistent ANCA, and ANCA reappearance preceded relapse in eight (35%). The mean time between inclusion and relapse did not differ between the patients who became ANCA-negative and those who were persistently ANCA-positive (14.6+/-13.2 vs 14.4+/-8.2 months). The mean time to ANCA disappearance was similar for the patients who relapsed and those who did not. Corticosteroids and pulse or oral cyclophosphamide did not significantly modify the time to ANCA disappearance. Throughout the study, seven patients were ANCA-negative. CONCLUSION: Although ANCA positivity was associated with relapse, discordance between cytoplasmic ANCA and disease activity was not unusual. In the absence of clinical manifestations, ANCA titres alone can serve as a warning signal but not indicate whether to adjust or initiate treatment.

[Intravenously administered gamma-globulins in reactive hemaphagocytic syndrome. Multicenter study to assess their importance, by the immunoglobulins group of experts of CEDIT of the AP-HP]. / Les immunoglobulines intra-veineuses dans les syndromes d'activation macrophagique secondaires. Etude multicentrique évaluant leur intérêt, pour le groupe d'experts sur les immunoglobulines du CEDIT de l'AP-HP.

Reactive hemophagocytic syndrome is characterized by systemic proliferation and activation of benign hemophagocytic cells of the monocyte-macrophage lineage. Treatment should be directed to the etiology, but successful treatment with high-dose gamma-globulin has been reported, especially in viral-associated hemophagocytic syndrome. We report 17 patients, of which 9 had infection-associated hemophagocytic syndrome, all treated with high-dose gamma-globulin. High-dose gamma-globulins appear to be more effective in infection-associated hemophagocytic syndrome, with a mean dose of 1.6gm/kg for one or two cycles. A multicentric randomized study is required to evaluate high-dose gamma-globulin in the treatment of reactive hemophagocytic syndrome.

[Common variable immunodeficiency: one or multiple illnesses? 3 clinical cases]. / Déficit immunitaire commun variable: une ou plusieurs maladies? Trois observations cliniques.

Common variable immunodeficiency (CVID) is a major antibody-deficiency syndrome, associated with increased risk of bacterial infection, as well as autoimmune and granulomatous disease. The clinical and immunological features are heterogeneous. This heterogeneity is expressed by the case reports of three selected patients. These observations will be discussed, with reference to a recent classification of CVID distinguishing four different clinical entities: i) CVID presenting with clinical and immunological features of X-linked agammaglobulinemia; ii) CVID presenting with clinical and immunological features of X-linked hyper-IgM syndrome; iii) CVID associated with systemic granulomatous disease; and iiii) CVID associated with autoimmune manifestations.

The spectrum of reactive hemophagocytic syndrome in systemic lupus erythematosus.

We address the relationship between reactive hemophagocytic syndrome (RHS), systemic lupus erythematosus (SLE) activity, and treatment in 4 female patients with SLE. Febrile pancytopenia was related to cytologically proven RHS in all patients. Followup was 45+/-7 months from RHS onset. No causal infection could be identified. Outcome could be classified as: (1) RHS onset during a SLE flare and complete efficacy of high dose steroids; (2) death despite therapy for concomitant severe RHS and active SLE; (3) severe RHS in inactive SLE under immunosuppressants, with remission after steroid tapering and cyclophosphamide withdrawal. Three patients were treated with intravenous IgG. We conclude that (1) when SLE is active, RHS should be considered a specific manifestation and treated with steroids; (2) RHS occurring in otherwise inactive SLE might be related to iatrogenic immunosuppression; (3) intravenous IgG treatment might be indicated in both situations.

Characteristics and outcome of 49 patients with symptomatic cryoglobulinaemia.

OBJECTIVE: To describe a population of patients with symptomatic cryoglobulinaemia, comparing manifestations and outcome as a function of hepatitis C virus (HCV) status. PATIENTS AND METHODS: A retrospective study on 179 patients who tested positive for cryoglobulins, seen between 1978 and 1998 in an internal medicine department. RESULTS: Among 179 cryoglobulin-positive patients, only 49 (18 men, 31 women; mean age 59.96+/-12 yr) had clinical manifestations attributable to cryoglobulinaemia. Thirty-three had HCV infection, 20 had systemic autoimmune diseases, two had haematological diseases, one had human immunodeficiency virus and HCV co-infection, one had HCV and HBV co-infection and six had essential mixed cryoglobulinaemia. The clinical manifestations and cryoglobulin levels in HCV(+) and HCV(-) patients did not differ significantly. Only arthralgias and elevated transaminases were significantly more frequent in HCV(+) patients (P<0.02 and <0.05, respectively). Five-year survival rates were comparable for HCV(+) and HCV(-) patients. Eight patients died (six HCV(+), two HCV(-)), with a median time between diagnosis and death of 38.7 months. CONCLUSION: Clinical manifestations of cryoglobulinaemia, except arthralgias, were comparable for HCV(+) and HCV(-) patients. When systemic manifestations are present, the prognosis is poor despite intensive or prolonged therapy.