Search PubMed⌕ Search

Biomedical subjects

J B Bussel

Publications and source records attributed to J B Bussel.

At least 37 records · Page 2Linked to original sources
PubMed2000

Serum granulocyte colony-stimulating factor levels are not increased in patients with autoimmune neutropenia of infancy.

OBJECTIVE: To assess the role of granulocyte colony-stimulating factor (G-CSF) in autoimmune neutropenia (AIN). DESIGN: Serum G-CSF levels were measured in 57 children with AIN. Two different G-CSF-dependent assays were used: a solid-phase "sandwich" enzyme-linked immunosorbent assay and a proliferation assay. Sera from healthy persons and from patients with severe congenital neutropenia were used for negative and positive controls. RESULTS: The median G-CSF level in healthy persons (n = 13) was low, 45.6 pg/mL (range <39 to 141 pg/mL). The median G-CSF level in patients with AIN (n = 57) was very similar, 45.5 pg/mL (range <39 to 2500 pg/mL). Forty-five (79%) of 57 patients with AIN had levels within the range of the control group. Seven (12%) had marginally increased G-CSF levels (141 to 400 pg/mL), and only 5 (9%) had levels higher than 400 pg/mL. The G-CSF levels measured by enzyme-linked immunosorbent assay correlated well with levels measured by the proliferation assay, thus demonstrating that antibodies present in patient sera did not affect the biologic activity of G-CSF. CONCLUSION: G-CSF production in AIN is not increased despite the low neutrophil count, similar to thrombopoietin in immune thrombocytopenic purpura.

Autoimmune Diseases↗
PubMed2000

Thrombocytopenia with absent radii: frequency of marrow megakaryocyte progenitors, proliferative characteristics, and megakaryocyte growth and development factor responsiveness.

Congenital thrombocytopenia with absent radii (TAR syndrome) is characterized by defective thrombopoiesis and bleeding in early infancy. To determine the frequency and responsiveness to cytokines of megakaryocyte progenitors (CFU-Meg) in TAR syndrome, the authors studied marrow samples from 3 patients and 6 normal controls, using optimally standardized megakaryocyte growth media incorporating interleukin-3, interleukin-6, stem cell factor, and granulocyte-monocyte colony-stimulating factor, with and without pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF). CFU-Meg was identified with a specific staining system utilizing monoclonal antibodies to glycoprotein IIb/IIIa. Growth of small CFU-Meg colonies (3-20 cells/colony) was observed in all patients in cultures without PEG-rHuMGDF, with a mean frequency of 8 (range 5-12) per 2.25 x 10(5) mononuclear cells plated (control mean 23; range 2-70). Identical cultures of marrow cells from patients and controls with added PEG-rHuMGDF produced more colonies per dish (mean 17, range 8-23; control mean 30, range 6-62). Except for 1 case, however, patients' colonies in response to PEG-rHuMGDF remained smaller than those of controls. Two patients tested had higher plasma thrombopoietin levels than 6 normal subjects. The findings demonstrate proliferative and PEG-rHuMGDF-responsive megakaryocytic progenitors in TAR syndrome. The modest reduction in frequency of megakaryocyte progenitors and the suboptimal size of colonies in response to PEG-rHuMGDF are compatible with the reported defective signal transduction in the c-mpl pathway in TAR syndrome.

Adolescent↗
PubMed2000

Overview of idiopathic thrombocytopenic purpura: new approach to refractory patients.

Idiopathic thrombocytopenic purpura is a disorder in which autoantibodies are made to platelets, resulting in accelerated platelet destruction. The diagnosis may be made in outpatients who are previously well or in patients with multiple medical conditions and medications. There are no unequivocal ways to distinguish immune thrombocytopenias from other thrombocytopenias, even with state-of-the-art tests including anti-platelet antibodies, thrombopoietin, glycocalicin, and platelet reticulocyte counts. Clinical evaluation includes ruling out a systemic process such as a viral infection or leukemia. Treatment of idiopathic thrombocytopenic purpura should be individualized. Substantial platelet increases are seen in more than 50% of patients who receive intravenous IgG, intravenous anti-D, steroids, or splenectomy. Two additional agents showing promising clinical trial experience are anti-CD40 ligand and rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA).

Antibodies, Monoclonal↗
PubMed1999

Alloimmune thrombocytopenia.

For the fetuses who are at risk for antenatal or postnatal sequelae from AIT, prevention and treatment are now possible. This requires the attention of the obstetrician to factors in the patient's history and early referral to a center experienced in the diagnosis and management of fetal AIT.

Antibodies↗
PubMed1998

Clinical experience with anti-D in the treatment of idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP), an autoimmune disease of children and adults, is characterized by low platelet counts and bleeding through mucous membranes. While not uncommon among otherwise healthy adults and children, ITP is a frequent complication of human immunodeficiency virus (HIV) infection. Anti-D is a gamma globulin (IgG) fraction containing a high proportion of antibodies to the Rh0 (D) antigen of the red blood cells. Clinical studies over the past 10 years have shown intravenous anti-D to be a safe and effective treatment for Rh-positive, nonsplenectomized patients with ITP (classic or HIV-related). While it is unlikely that anti-D is a curative treatment for ITP, repeated infusions can be used to maintain the platelet count at a level sufficient to provide adequate hemostasis (>30,000/microL) and may enable patients to postpone or even avoid splenectomy.

Adolescent↗
PubMed1998

Idiopathic thrombocytopenia purpura: Treatment patterns and an analysis of cost associated with intravenous immunoglobulin and anti-D therapy.

A retrospective study was conducted to determine treatment patterns for idiopathic thrombocytopenia purpura (ITP) across the US and to determine the cost of its treatment with high-dose intravenous immunoglobulin (IVIg) and anti-D therapy. Information on the incidence, treatment patterns, hospital care, and costs for ITP was derived from three data bases and supplemented by in-depth case studies from five hospital centers in the US. Data collection forms were developed to collect data on treatment patterns and costs at the five hospital centers. Treatment patterns were analyzed and used to model the comparative costs of IVIg and anti-D therapy. Cost estimations were based on a process and cost-finding analysis reflecting current practice patterns for the use of IVIg and anti-D therapy in an outpatient clinic. The incidence of ITP was estimated at 65 per 10,000 in human immunodeficiency virus (HIV)-positive individuals and 1.5 per 10,000 in HIV-negative individuals. Hospital discharge data from all 1991 and 1992 hospital discharges in Maryland revealed that both Medicare patients and patients who had other payment options spent less time in hospital compared to Medicaid patients. The limited case study data indicate that anti-D therapy increased platelet counts to greater than 25,000/microL in 82% of evaluable episodes and that IVIg-treated patients reached 25,000/microL in 48% of treated episodes. The estimated cost per treated episode of ITP was $4,269 for IVIg and $2,716 for anti-D therapy, reflecting a cost savings of $1,553 per episode. This retrospective study has shown that the use of anti-D therapy is associated with lower costs compared with IVIg treatment in patients with ITP. The shorter infusion time required for anti-D therapy may also contribute to a better quality of life for patients.

Costs and Cost Analysis↗
PubMed1997

Immune thrombocytopenia in pregnancy: autoimmune and alloimmune.

Auto- and alloimmune thrombocytopenias in pregnancy may seriously impact on both mother and fetus. Autoimmune thrombocytopenia (ITP) affects both mothers and fetuses but is considered to be quite benign for both groups. The 'facts' are that: 1) ITP occurs commonly in pregnancy; 2) there has been no reported maternal mortality in more than 20 years; 3) management, except at delivery, is similar to management in the non-pregnant state; 4) splenectomy is virtually never required during pregnancy; 5) significant neonatal thrombocytopenia occurs in approximately 10% of cases and intra-cranial hemorrhage (ICH) 1%; 6) the course of the first sibling predicts that of the next sibling; and 7) the fetal platelet count can be successfully determined (if desired) by either fetal blood sampling (FBS) or by fetal scalp sampling. Many other important considerations remain undetermined: 1) non-invasive prediction of severe fetal thrombocytopenia; 2) the appropriate mode of delivery for a thrombocytopenic fetus; 3) the role of anti-platelet antibody testing; and 4) the effects on the fetal platelet count of maternal therapy. Alloimmune thrombocytopenia (AIT) is easier to outline because it is a far more serious fetal disorder: 1) neonatal platelet counts < 20,000/microliter are common in AIT; 2) there is a 10-30% ICH rate in first affected newborns, some of which occur antenatally; 3) there is no universal prenatal screening although this would be scientifically feasible; 4) testing is complex and requires an experienced laboratory that can test at least five platelet antigens and has sufficient typed controls to confirm the specificity of any anti-platelet antibodies detected; 5) the second affected sibling in a family is usually more severely affected than the first; 6) treatment of the thrombocytopenic neonate can be accomplished with intravenous (i.v.) gammaglobulin and/or platelet transfusions; and 7) treatment of the fetal platelet count can be accomplished in most instances by infusing the mother with i.v. gammaglobulin with or without steroids; platelet transfusions to the fetus is another option.

Autoimmune Diseases↗
PubMed1997

Fetal alloimmune thrombocytopenia.

BACKGROUND: Alloimmune thrombocytopenia is a serious fetal disorder resulting from platelet-antigen incompatibility between the mother and fetus. The diagnosis is usually made after the discovery of unexpected neonatal thrombocytopenia. Approximately 10 to 20 percent of affected fetuses have intracranial hemorrhages, one quarter to one half of which occur in utero. We studied the correlates of thrombocytopenia in affected fetuses. METHODS: We studied 107 fetuses with alloimmune thrombocytopenia at a mean (+/-SD) gestational age of 25+/-4 weeks, before their entry into one of three treatment protocols. The fetuses were initially evaluated because an older sibling had been given this diagnosis at birth. We compared the initial platelet counts in utero in these 107 fetuses with the platelet count at birth and the history of intracranial hemorrhage in the affected sibling. RESULTS: The initial platelet count was < or =20,000 per cubic millimeter in 53 of the 107 fetuses (50 percent), including 21 of 46 fetuses (46 percent) studied before 24 weeks of gestation. The 97 fetuses with PI(A1) incompatibility had more severe thrombocytopenia than the 10 fetuses with other antigen incompatibilities. Among seven fetuses with platelet counts of more than 80,000 per cubic millimeter that were not treated initially, the counts decreased by more than 10,000 per cubic millimeter per week. Although 41 fetuses had initial platelet counts that were lower than those measured at birth in an older affected sibling, only a history of antenatal intracranial hemorrhage in the sibling predicted greater severity of thrombocytopenia in the fetus. Only one treated fetus had an intracranial hemorrhage, and the thrombocytopenia resolved after birth in all cases. CONCLUSIONS: Fetal alloimmune thrombocytopenia occurs early in gestation, is severe, and is more severe in fetuses with an older affected sibling who had had an antenatal intracranial hemorrhage.

Fetal Blood↗
PubMed1997

Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients.

We report the results of intravenous anti-D (WinRho, WinRho SD) therapy in 261 non-splenectomized patients treated at the New York Hospital-Cornell Medical Center over the period from 1987 to 1994. Children (n = 124) and adult patients (n = 137) with classic immune thrombocytopenic purpura (ITP; n = 156) or human immunodeficiency virus (HIV) related thrombocytopenia (n = 105) and acute (n = 75) or chronic (n = 186) disease at the time of the initial anti-D treatment were studied. In addition, 11 previously splenectomized patients were treated as a separate group. Our objectives were to evaluate the following. (1) Efficacy of anti-D: The response after the initial infusion was analyzed according to clinical parameters, such as patient's age, HIV status, gender, disease duration, pretreatment platelet count, and hemoglobin value, as well as treatment-related factors, including the dose of anti-D, the solvent detergent treatment of the preparation, and the type of administration. (2) Use of anti-D as maintenance therapy: The duration of response after the initial infusion and the results of subsequent treatments were evaluated. (3) Safety/toxicity of anti-D: Postinfusion reactions and hemoglobin decrease after treatment were studied. Anti-D is a safe treatment providing a hemostatic platelet increase in greater than 70% of the Rh+ non-splenectomized patients. The group with the best results is HIV- children, but all patient groups respond and the effect lasts more than 21 days in 50% of the responders. Duration of response is not influenced by HIV status; furthermore, HIV+ patients show no adverse effects on hemoglobin decrease or HIV disease progression. Patients with chronic ITP after splenectomy have minimal or no response to intravenous anti-D.

Adult↗
PubMed1997

Comparison of platelet counts in first and second newborns of mothers with immune thrombocytopenic purpura.

OBJECTIVE: This study was designed to estimate the predictive value of the first neonatal platelet count for the second neonate in women with immune thrombocytopenic purpura (ITP). METHODS: Data of 34 patients, repeatedly pregnant while they had ITP, were prospectively collected in two study centers between 1984 and 1995. The main outcome measure was neonatal thrombocytopenia. RESULTS: Early neonatal platelet counts (i.e., umbilical cord count or count during the first 24 hours of life) between siblings were correlated (r = .73; 95% confidence interval (CI) for the correlation coefficient 0.52, 0.86). Severe thrombocytopenia (less than 50 x 10(9)/L) at birth did not occur in any of the 27 siblings of infants with birth platelet levels above 50 x 10(9)/L. Also the second sibling's nadir neonatal platelet counts during the first 2 weeks of life were correlated with those of the first sibling (r = .76; 95% CI for the correlation coefficient 0.58, 0.88). In those cases in which the first sibling had a lowest platelet count above 100 x 10(9)/L (n = 19), the second sibling never became thrombocytopenic. CONCLUSION: The platelet count of the first sibling can be used to counsel women with ITP, and may be helpful in their management.

Female↗
PubMed1996

Antiplatelet antibody testing in thrombocytopenic pregnant women.

OBJECTIVE: The purpose of the study was to attempt to distinguish pregnant women with gestational thrombocytopenia from those with idiopathic immune thrombocytopenia by eight different platelet antibody assays. STUDY DESIGN: Sera from pregnant women with presumed gestational thrombocytopenia (n = 160) and idiopathic immune thrombocytopenia (n=90) were prospectively tested for indirect and platelet-associated immunoglobulins G and M and complement C3, as well as for serotonin release. After the results were analyzed, a subset of patients were subsequently analyzed for circulating antiplatelet antibody directed against platelet membrane glycoprotein GPIIb/IIIa. RESULTS: Indirect immunoglobulin G was significantly greater in the 85 women with idiopathic immune thrombocytopenia than in the 129 women with gestational thrombocytopenia (p<0.001). Platelet-associated immunoglobulin G was elevated in the majority of women, both those with gestational thrombocytopenia and those with idiopathic immune thrombocytopenia. There were also no statistically significant difference in the values for platelet-associated C3 or indirect immunoglobulin M and C3. Levels of platelet-associated immunoglobulin M showed a tendency to be higher in women with gestational thrombocytopenia (p=0.04), as did the values in the serotonin release assay (p=0.06). CONCLUSION: Our data demonstrate that patients with gestational thrombocytopenia had surprisingly high levels of platelet-associated immunoglobulin despite mild thrombocytopenia. Comparison of a relatively large number of patients with idiopathic immune thrombocytopenia and gestational thrombocytopenia indicates that women with idiopathic immune thrombocytopenia cannot be distinguished from those with gestational thrombocytopenia by means of one or more of the prototypic platelet antiglobulin tests currently in use. Our preliminary data with glycoprotein-specific assays indicate that they may be more useful.

Autoantibodies↗
PubMed1996

Antenatal management of alloimmune thrombocytopenia with intravenous gamma-globulin: a randomized trial of the addition of low-dose steroid to intravenous gamma-globulin.

OBJECTIVES: Our purposes were to investigate maternal infusions of intravenous gamma-globulin, to prevent intracranial hemorrhage, and to determine whether 1.5 mg dexamethasone and 60 mg prednisone per day add to the effect of intravenous gamma-globulin. STUDY DESIGN: Fifty-four women with alloimmune thrombocytopenia and thrombocytopenic fetuses were randomized to intravenous gamma-globulin 1 gm/kg per week with or without dexamethasone. Nonresponders after 4 to 6 weeks received continued intravenous gamma-globulin plus 60 mg of prednisone per day ("salvage"). RESULTS: Dexamethasone did not add to the effect of intravenous gamma-globulin. Overall, there was a mean platelet increase from the first to the second fetal blood sampling of 36,000/microliters (n = 47) and from the first fetal blood sampling to birth of 69,000/microliters (n = 54). A total of 62% to 85% of fetuses responded. There were no intracranial hemorrhages. "Salvage" increased the platelet count in 5 of 10 nonresponders to intravenous gamma-globulin. CONCLUSION: Intravenous gamma-globulin treatment is appropriate for thrombocytopenic fetuses with alloimmune thrombocytopenia before use of weekly in utero platelet transfusions, even in severe thrombocytopenia.

Cerebral Hemorrhage↗