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Biomedical subjects

B Godeau

Publications and source records attributed to B Godeau.

At least 37 records · Page 2Linked to original sources

Lack of relevance of the acetylator status on dapsone response in chronic autoimmune thrombocytopenic purpura.

Dapsone provides an alternative treatment for patients with chronic autoimmune thrombocytopenic purpura (AITP) who had inadequate response to conventional therapy. However, the efficacy of this treatment is achieved in only 50% of patients. Dapsone is partly metabolized by the polymorphic N-acetyltransferase 2% and 50% of Caucasian patients show a genetically determined slow acetylator phenotype. The aim of our study was to investigate the influence of the acetylator status on dapsone efficacy in patients with chronic AITP. Nineteen caucasian adults with chronic AITP, previously treated by dapsone, were included in the study. Acetylator phenotype was determined by using a caffeine urinary test. Among the fourteen fast acetylator patients, eight patients exhibited positive response to dapsone and six patients did not. Among the five slow acetylator patients, one patient displayed a positive response to dapsone. Comparison of data by using the Fisher's exact test did not reach statistical significance. Our results do not support a relationship between dapsone efficacy and acetylator status in adults with chronic AITP.

Acetylation↗

[Intravenous immunoglobulins and autoimmune thrombopenic purpura].

OBJECTIVE: To determine the usefulness of intravenous immunoglobulin in the treatment of autoimmune thrombocytopenic purpura (AITP). RESULTS: IVIg infusion is an important agent in managing AITP because most patients experienced a rapid increased platelet count. Its precise place in the management of these patients is however controversial, particularly on account of its high cost and transient effect. It is indicated in the severe form of the disease or before surgery in corticoresistant patients. PERSPECTIVE: Prospective studied are mandatory to compare the efficacy of IVIg and high dose corticosteroids in this indication.

Anti-Inflammatory Agents↗

Acute swelling of the limbs: magnetic resonance pictorial review of fascial and muscle signal changes.

OBJECTIVE: This pictorial review analyzes the magnetic resonance (MR) fascial/muscular changes in 69 patients referred as emergencies with acute swelling of the limbs (ASL) from various causes. METHODS AND MATERIAL: A prospective MR imaging (MRI) study of 69 patients referred as emergencies for ASL was performed. Our population consisted of 45 patients with skin and soft-tissue infections (cellulitis and necrotizing fasciitis, and pyomyositis), six patients with soft-tissue inflammatory diseases (dermatomyositis, graft-versus-host disease), 11 patients with acute deep venous thrombosis, three patients with rhabdomyolysis, one patient with acute denervation and three other patients with rare diseases. Hematomas, tumorous or infectious bone involvement and soft-tissue tumors were excluded. All studies included spin echo T1-weighted images and spin echo T2-weighted images. Gadolinium-enhanced spin echo T1-weighted images were obtained when an abscess was suspected on T2-weighted images. Selective fat-saturated T1- and T2-weighted sequences were also used. MRI analysis was performed to obtain a compartmentalized anatomical approach according to the location of signal abnormalities in subcutaneous fat, superficial and deep fascia and muscle. RESULTS: In all patients with ASL, MRI demonstrated soft-tissue abnormalities involving subcutaneous fat, superficial fascia, deep fascia, or muscle. Although MR findings were non-specific, MRI appears sensitive for detecting subtle fascial and muscle signal changes. CONCLUSIONS: In skin and soft-tissue infections, MRI can be helpful for therapeutic management by determining the depth of soft-tissue involvement, particularly within fasciae and muscles, which is partly related to the severity of cellulitis with severe systemic manifestations. MRI can also aid the surgeon in diagnosing abscesses. In inflammatory diseases, MRI can determine the best site for biopsy and also monitor therapeutic response.

Adolescent↗

The response to high-dose intravenous immunoglobulin or steroids is not predictive of outcome after splenectomy in adults with autoimmune thrombocytopenic purpura.

The response to high-dose intravenous immunoglobulin (IVIg) was recently reported to be predictive of outcome after splenectomy in patients with autoimmune thrombocytopenic purpura (AITP). We analysed the records of 75 adults with chronic AITP who received IVIg and subsequently underwent splenectomy. There was no significant difference in the response rate to splenectomy according to whether or not patients had responded to IVIg (81% v 67%, P = 0.36). Age, the time from diagnosis to splenectomy, and the response to steroids were also not significantly associated with outcome after splenectomy. These results indicate that the response to IVIg or steroids is not predictive of the efficacy of splenectomy.

Adolescent↗

Intravenous immunoglobulin for adults with autoimmune thrombocytopenic purpura: results of a randomized trial comparing 0.5 and 1 g/kg b.w.

Since the first reports demonstrating the ability of a total dose of 2 g/kg body weight (b.w.) of intravenous immunoglobulin (IVIg) to increase the platelet count in patients with autoimmune thrombocytopenic purpura (AITP), the optimal dose has remained controversial. We report the results of a randomized study which compared two low doses of IVIg (0.5 g/kg b.w., group A, n = 19, and 1 g/kg b.w., group B, n = 18) in 37 adults with AITP and platelet count <50 x 109/l, in preparation for surgery or in a situation with a risk of bleeding. On day 4 the proportion of responses, defined by a platelet count > 80 x 109/l and at least twice the initial platelet count, was significantly higher in the group receiving 1 g/kg b.w. (12/18 in group B versus 4/19 in group A, P = 0.005). All but one of the day 4 responders had already responded on day 3. The daily changes in the platelet count from the beginning of IVIg treatment were larger in group B, with a significant difference relative to group A on day 3 (92 x 109/l in group B versus 50 x 109/l in group A, P = 0.03) and on day 4 (106 x 109/l in group B versus 55 x 109/l in group A, P = 0.03). Patients who had not responded by day 4 subsequently received 1.5 g IVIg/kg b.w. (group A) or 1 g IVIg/kg b.w. (group B). A response was observed in 11/13 initial non-responders in group A, and in 2/6 initial non-responders in group B. Finally, on day 8, the proportion of responders was 78% (29/37) in the entire group and was similar in the two subgroups. In conclusion, (1) initial treatment with 1 g/kg b.w. of IVIg appeared to be more effective than 0.5 g/kg b.w. in adults with AITP; (2) infusion of a low dose of IVIg did not jeopardize the efficacy of IVIg reinfusion; (3) some adults who did not respond to 1 g IVIg/kg b.w. responded to a higher dose.

Adult↗

CD36 deficiency is frequent and can cause platelet immunization in Africans.

BACKGROUND: CD36 is expressed on several cell lineages. About 5 to 10 percent of Asians lack platelet membrane CD36 (pCD36), but the frequency of pCD36 deficiency in other ethnic groups is not known. Persons who are pCD36-negative are apparently healthy but can develop CD36 isoimmunization. STUDY DESIGN AND METHODS: The pCD36 phenotype was studied in 1885 subjects belonging either to a group of 1127 healthy French blood donors (almost all of whom were white Europeans) or to a group of 758 patients of known ethnic origin. RESULTS: No pCD36-negative persons were found among the blood donors. Only 1 of the 301 white European patients was pCD36-negative. In contrast, 16 of the 206 sub-Saharan Africans was pCD36-negative, a proportion higher than that among that black Caribbeans (1/148, p<0.01). The frequency of pCD36-negative patients was similar in blacks with and without sickle cell disease. Monocyte CD36 (mCD36) expression was studied in 15 of 22 pCD36-negative individuals: it was <10 percent in 7 subjects (type I deficiency) and between 12 and 100 percent in 8 others (type II deficiency). Thirteen pCD36-negative individuals had risk factors for immunization, and 4 had anti-CD36. Some had a history resembling posttransfusion purpura (n = 2), platelet transfusion refractoriness (n = 1), and recurrent miscarriage (n = 1). No correlation was found between immunization and the amount of mCD36. Anti-CD36 from an immunized type II-deficient woman reacted with monocytes from normal controls but not with monocytes from type I- or type II-deficient individuals, and thus it is postulated that mCD36 could be structurally different in normal and type II CD36-deficient individuals. CONCLUSION: CD36 deficiency is frequent in sub-Saharan Africans; development of anti-CD36 can lead to serious complications in multiply transfused patients, such as those with sicke cell disease.

Adult↗

[Hemolysis and schizocytosis, malabsorption and the "folate trap": unusual semiological peculiarities associated with vitamin B12 deficiency].

INTRODUCTION: Hemolysis and red cell fragmentation accompanying vitamin B12 deficiency may misdirect the diagnosis. Signs of malabsorption and abnormalities related to folic acid metabolism characterized by discrepancies between folic acid normal serum levels and erythrocytic folic acid levels may also exist. EXEGESIS: We report the occurrence of hemolysis and red cell fragmentation mimicking microangiopathic hemolytic anemia, malabsorption and folic acid deficiency in the course of vitamin B12 deficiency. Appropriate replacement therapy corrected all abnormalities. CONCLUSION: An association between hemolysis, malabsorption and folic acid deficiency should lead physicians to search for signs of vitamin B12 deficiency.

Adult↗

Disseminated aseptic abscesses associated with Crohn's disease: a new entity?

Our purpose is to describe seven cases of disseminated aseptic abscesses with regard to clinical, biological, radiological, and histological information, treatment, and outcome. Data were collected on seven Caucasian patients who had proven sterile deep abscesses diagnosed in French university hospitals. The onset of the disease related to abscesses began at times from June 1988 to August 1994. Follow-up periods were 1 year, 7 months to 8 years, 2 months. The age of the patients ranged from 15 to 26 years old. At onset, all had fever and six had abdominal pain. Abscesses involved spleen and abdominal lymph nodes in six cases; liver in three; pancreas, brain, and chest in one. All had polymorphonuclear leukocytosis. Pathological examination showed granulomatous abscesses. Direct and indirect investigations failed to identify any causal microorganism. On six occasions, Crohn's disease was revealed 1 to 41 months later and in one case, it preceded the onset of abscesses. One subsequently developed Sweet's syndrome. Various antibiotic regimes were inefficient. Steroids, associated in three cases with immunosuppressive agents, resulted in a rapid improvement in six patients. In one case, splenectomy followed by 5-ASA therapy was used successfully. The dramatic effectiveness of steroids and immunosuppressive agents as well as follow-up suggest that disseminated aseptic abscesses might be an extraintestinal manifestation of Crohn's disease. Although the pathogenesis of this condition remains unknown, this entity may be related to neutrophilic dermatosis in which sterile deep abscesses have been reported.

Abdominal Abscess↗

Pulmonary hypertension in POEMS syndrome: a new feature mediated by cytokines.

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare variant of plasma cell dyscrasia with multiple systemic manifestations. We followed the progress of 20 patients with POEMS syndrome in our institution over a 10-yr period. Pulmonary hypertension (PH) was observed in five patients. All patients suffered dyspnea on exertion, which always appeared during an exacerbation of POEMS syndrome. The typical echocardiographic signs of PH were observed in all of these patients, and the median pulmonary-artery systolic pressure was 57 mm Hg (range, 50 to 65 mm Hg). Mean pulmonary-artery pressure during right side heart catheterization in two patients was 32 mm Hg. No other explanation for the PH could be found. Overproduction of cytokines was found in all cases, with high serum concentrations of interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and vascular endothelial growth factor. We suggest that PH should be added to the list of symptoms of POEMS syndrome. Cytokines may mediate POEMS syndrome-associated PH, as proposed for the other systemic manifestations of this disorder.

Adult↗

Pulmonary embolism; lung scanning interpretation: about words.

OBJECTIVE: To assess clinicians' agreement on how they interpret lung scan reports with regard to the diagnosis of pulmonary embolism. DESIGN: In this prospective study, nuclear medicine physicians provided two types of reports for each lung scan: a routine descriptive report and a short form with a standardized conclusion on the likelihood of pulmonary embolism: "high probability," "no conclusion," and "diagnosis excluded." Three independent blinded senior clinicians reviewed all routine reports and chose one of the following conclusions: "high probability," "no conclusion," or "diagnosis excluded." SETTING: An acute care teaching hospital near Paris. SUBJECTS: Eighty-two lung scans were studied. MAIN OUTCOME MEASUREMENTS: Inter-clinician agreement and agreement between clinicians' conclusions and the nuclear medicine physicians' standardized reports were analyzed using the kappa index. RESULTS: The distribution of the clinicians' conclusions from routine reports strongly differed (p < 0.001). Agreement among the three clinicians was observed in 40.2% of the routine reports, and the inter-clinician agreement was poor to moderate (kappa range, 0.28 to 0.52). A complete agreement among the three clinicians and the nuclear medicine physicians' standardized conclusions was observed for 32.9% of the reports. The agreement between each clinician and the standardized conclusions was also poor to moderate (kappa range, 0.32 to 0.55). CONCLUSION: Reading the same routine reports, clinicians reached different conclusions. Furthermore these differed greatly from the nuclear medicine physicians' standardized conclusions. These results support the notion that physicians should be given standardized reports.

Adult↗

Specific antiplatelet glycoprotein autoantibodies are associated with the thrombocytopenia of primary antiphospholipid syndrome.

Thrombocytopenia is a frequent complication of primary antiphospholipid syndrome (PAPL) and has been attributed to antibodies directed against platelet glycoproteins (Gp) and also to antiphospholipid antibodies. We tested patients with PAPL with and without thrombocytopenia for specific antiplatelet autoantibodies. Platelet autoantibodies were detected by means of platelet immunoassays which included MAIPA with a panel of monoclonal antibodies directed against all the platelet Gps known to be possible targets for platelet autoantibodies. A high prevalence of serum platelet antibodies was found in patients with thrombocytopenia (73%, 11/15 patients) whereas antiplatelet antibody was detected in only one of the 10 control patients (P < 0.01). The antibodies mainly recognized GpIIbIIIa (n = 7), but also CD9 (n = 5), GpIaIIa (n = 4). GpIbIX (n = 3) and GpIV (n = 3). Platelet-Gp antibodies eluted from the platelet surface had the same reactivity as those found in the original sera from three of the four patients tested, whereas no anticardiolipin activity was found in the platelet eluates, suggesting the absence of cross-reactivity between anticardiolipin and antiplatelet antibodies. The MAIPA assay was also performed with F(ab')2 fragments obtained by pepsin digestion of serum IgG from four patients. The same results were obtained with F(ab')2 fragments and the original serum, demonstrating that platelet antibodies specifically bind in vivo to platelet Gps via their F(ab')2 fragments. Our results suggest a link between specific platelet antibodies and the thrombocytopenia of PAPL.

Adult↗

Dapsone for chronic autoimmune thrombocytopenic purpura: a report of 66 cases.

Sixty-six adults with chronic autoimmune thrombocytopenic purpura AITP and platelet count <50 x 10(9)/l were treated with dapsone (75-100 mg orally). A response was observed in 33 patients. The median duration of treatment required to obtain a response was 21 d (range 8-90). The median maximal platelet count on treatment was 130 x 10(9)/l (range 71-355). Dapsone was continued in 20/33 responders for a median of 12.5 months (range 1-48) and the response persisted in 19. Treatment was intentionally withdrawn in the other 13 responders and thrombocytopenia immediately recurred in 12. Reversible side-effects required cessation of treatment in seven patients. These results demonstrate that dapsone is an effective, inexpensive, and well-tolerated treatment for chronic AITP.

Adult↗

Treatment of good-prognosis polyarteritis nodosa and Churg-Strauss syndrome: comparison of steroids and oral or pulse cyclophosphamide in 25 patients. French Cooperative Study Group for Vasculitides.

Twenty-five patients with good-prognosis polyarteritis nodosa or Churg-Strauss syndrome entered a prospective, randomized, multicentre study comparing two treatments: either oral corticosteroids and oral cyclophosphamide (CY; 2 mg/kg/day) for 1 yr (group A), or oral corticosteroids and monthly i.v. CY pulses (0.6 g/m2) (group B) for 1 yr. The objective was to determine the optimal CY regimen. Judgement criteria were the efficacy of the treatment in controlling the disease and the development of side-effects. Among the 25 patients who could be analysed, complete recovery was achieved with the experimental treatment in 9/12 patients in group A and 10/13 patients in group B. Two patients in each group relapsed after the end of therapy and were well controlled by corticosteroids or other drugs. One failure occurred in each group. The mean follow-up was 60.8 +/- 14.5 months after the beginning of the treatment. Side-effects associated with the administration of CY and steroids were noted 27 times in group A vs 14 times in group B (not significant). The oldest patient in these series (group B) died of pneumonia. No superiority in terms of efficacy could be established between the two regimens; however, the number of patients included was too small to conclude definitively. Toxic side-effects were significantly more frequent in women (P < 0.02). The high number of adverse effects leads us to recommend pulse over oral CY and an overall lowering of the doses of immunosuppression.

Adult↗

Short and longterm outcomes for patients with systemic rheumatic diseases admitted to intensive care units: a prognostic study of 181 patients.

OBJECTIVE: To determine short and longterm outcomes and prognostic factors for patients with systemic rheumatic diseases admitted to intensive care units in 4 teaching hospitals. METHODS: All adult intensive care unit admissions over a 12 year period for systemic rheumatic diseases were retrospectively assessed. One hundred and eighty-one patients with a mean age of 57 +/- 17 years were studied. RESULTS: The death rate in intensive care units was 33% (59/181) and in-hospital mortality was 43% (77/181). One hundred and four patients were discharged alive from hospital; 40 died during followup (mean 105 +/- 7 mo). The estimated 5 year survival rate for the discharged patients was 69%. The 4 factors significantly associated with in-hospital mortality by multivariate analysis were simplified acute physiologic score (p = 10(-4)), poor prior health status (p = 10(-4)), corticosteroid administration (p = 0.005), and the reason for admission; mortality was higher in the group admitted to intensive care for infectious complication (55 versus 34% for others; p = 0.006). In contrast, in-hospital mortality was not influenced by age or by systemic rheumatic diseases. Using Cox's model, only age over 60 years was a prognostic factor significantly associated with an increase in longterm mortality (p = 10(-4)). CONCLUSION: The short term outcome for patients with systemic rheumatic diseases in intensive care units was poor. The longterm prognosis after hospital discharge appeared fair, although the standardized mortality ratio was 5-fold that of a nonselected population. Short and longterm prognoses were similar for different systemic rheumatic disease groups.

Adult↗

[Patients with systemic disease admitted to intensive care units: course and prognostic factors].

Based on our experience, hospitalization in intensive care units of patients with systemic diseases occurs several years after diagnosis. Though mortality ranges from 30 to 45%, it is not statistically different from that in unselected patients. Outcome is clearly related to controllable infectious complications. Three other prognosis factors are the gravity of the patient's status at admission (APACHE or IGS scores), corticosteroid therapy and prior health status. Long-term prognosis for patients discharged from intensive care is good with a 30% mortality at 5 years despite the irreversible nature of their disease.

Connective Tissue Diseases↗