Search PubMed⌕ Search

Biomedical subjects

J M Lusher

Publications and source records attributed to J M Lusher.

At least 55 records · Page 3Linked to original sources
PubMed1995

Characterization of autoantibodies against the platelet glycoprotein antigens IIb/IIIa in childhood idiopathic thrombocytopenia purpura.

The majority of children with idiopathic thrombocytopenia (ITP) have an acute self-limiting course and no diagnostic test has been identified which will predict the course of thrombocytopenia and detect those with the chronic autoimmune form. The detection of autoantibodies directed against the platelet glycoprotein complex IIB/IIIa, may identify patients with chronic ITP. Serum anti-GP IIb/IIIa antibodies were assessed by the indirect MAIPA assay in 54 children with immune thrompocytopenia at initial presentation along with an additional 7 children previously diagnosed with chronic ITP, to determine if there was a difference in antibody positivity between acute and chronic ITP patients, and whether the identification of antibodies could be used as a predictive test at diagnosis. There was no significant difference in the percentage of antibodies detected in children classified with acute ITP (27/40-68%) compared to children with chronic ITP (13/21-62%, P > 0.05). Patients with acute ITP had significantly lower mean platelet counts at diagnosis compared to the chronic ITP group (16,225/mm3 vs 32,250/mm3, P < 0.05), though there was no significant difference in the bleeding manifestations between the acute and chronic ITP groups. Serum anti-GP IIb/IIIa antibodies are detected in a high percentage of children with ITP and autoantibodies appear to be involved in the pathogenesis of both acute and chronic ITP. The detection of anti-GP IIb/IIIa antibodies at diagnosis, however, does not appear to be a useful prognostic test in childhood ITP.

Adolescent↗
PubMed1995

Congenital thrombocytopenias.

Congenital thrombocytopenias are rare bleeding disorders but must be included in the differential diagnosis when investigating a young infant with chronic thrombocytopenia. Several of these syndromes have associated defects of immune, renal, or skeletal systems in addition to thrombocytopenia. These can be categorized into two groups depending on the presence or absence of bone marrow hypoplasia. The majority of these disorders are associated with a mild bleeding tendency and thus may be missed until the affected individuals experience excessive postoperative or posttraumatic hemorrhage. In adults, this entity must be considered when evaluating a patient with thrombocytopenia who is unresponsive to the medical management of immune thrombocytopenia. Other than platelet transfusion, no specific therapy is available for these disorders. A test dose of desmopressin may be attempted in a nonbleeding patient (to see if it will shorten the bleeding time) prior to using it for treatment of a bleeding episode or surgical prophylaxis. Bone marrow transplantation may prove curative in a select group of thrombocytopenic syndromes.

Albinism↗
PubMed1995

Comparison of six commercial plasma references for factor VIII, factor IX and von Willebrand factor. On behalf of the Subcommittee for Factor VIII and IX of the Scientific and Standardization Committee of the ISTH.

Six brands of normal reference plasma produced in the United States, with assigned assay values for factor VII and IX and, in four instances, ristocetin cofactor and van Willebrand antigen, were assayed in nine coagulation laboratories in academic institutions in the same country. Differences in mean assays of reference plasmas, as a percent of labelled potency, were significant and were greater than differences among laboratories. Standard methods of assigning potency to commercial reference plasmas are recommended.

Antigens↗
PubMed1994

Immune status of human immunodeficiency virus seropositive and seronegative hemophiliacs infused for 3.5 years with recombinant factor VIII. The Kogenate Study Group.

Recent studies suggest that treatment of hemophiliacs with highly purified factor VIII concentrates may preserve immune function. To test this hypothesis, we prospectively studied 51 hemophilic patients (21 human immunodeficiency virus [HIV] seropositive and 30 seronegative) who were on home therapy exclusively with recombinant factor VIII (Kogenate, Miles Laboratory, Berkeley, CA) for 3.5 years. Patients, all of whom had been previously treated with plasma-derived factor VIII concentrates, were monitored every 6 months with T-lymphocyte subsets and beta 2-microglobulin levels. Mean rate of change in absolute CD4 cell counts, calculated from regression slopes for individual patients, showed a small but statistically significant decrease over the 3.5-year study period for HIV seropositive hemophiliacs. No decrease in CD4 cell counts was seen in HIV seronegative hemophiliacs when the data for children under age 6 years were excluded from the analysis. beta 2-microglobulin levels and CD8 cell counts remained unchanged. These data show stability of immunologic parameters in HIV seronegative hemophiliacs, and a small decrease in CD4 cell counts in HIV seropositive hemophiliacs treated with recombinant factor VIII.

CD4-Positive T-Lymphocytes↗
PubMed1994

Transfusion therapy in congenital coagulopathies.

Transfusion therapy for the congenital coagulopathies has changed considerably in recent years. Improved donor screening, purification, and virucidal methodologies have resulted in much safer plasma-derived clotting factor concentrates. Additionally, synthetic products such as rF VIII and DDAVP are licensed and available. For persons with hemophilia B, nonthrombogenic coagulation F IX concentrates are available. Treatment recommendations for each of the congenital coagulopathies are discussed.

Autoantibodies↗
PubMed1994

Use of prothrombin complex concentrates in management of bleeding in hemophiliacs with inhibitors--benefits and limitations.

In summary, PCCs and APCCs are moderately effective in controlling bleeding in inhibitor patients. However, they are not as effective in controlling or preventing bleeding as factor VIII (or factor IX) concentrates in hemophiliacs who do not have inhibitors. Their precise mechanism of action is still poorly understood, and there is no readily available laboratory test for monitoring patient response. While viral safety is far less of an issue with PCCs than it was a few years ago, and while thrombogenicity is far less of a problem in using PCCs and APCCs in inhibitor patients than it is in persons with hemophilia B, one must keep in mind the risk of acute myocardial infarction. Frequent, repetitive doses may be hazardous. PCCs and APCCs represent a valuable part of one's therapeutic armamentarium in managing bleeding in inhibitor patients. However, one must be aware of their limitations and potential complications, and use them appropriately.

Controlled Clinical Trials as Topic↗
PubMed1993

Recombinant factor VIII for the treatment of previously untreated patients with hemophilia A. Safety, efficacy, and development of inhibitors. Kogenate Previously Untreated Patient Study Group.

BACKGROUND: Although methods of viral attenuation in plasma-derived clotting-factor concentrates have improved, there is still a possibility that such concentrates may transmit certain blood-borne viruses. For this reason, the use of recombinant DNA-derived factor VIII (which is virus-free) to treat hemophilia A has generated considerable interest. METHODS: We conducted a multicenter trial in previously untreated children with hemophilia A. They received recombinant factor VIII for all treatment or for prophylaxis and were evaluated at their respective clinics at intervals of no more than three months. RESULTS: Between January 1, 1989, and July 1, 1992, 95 patients who could be evaluated received recombinant factor VIII. By September 1, 1992, they had received the concentrate exclusively for 2.4 months to 3.5 years (median, 1.5 years). All responded well, with no treatment failures. A total of 3315 infusions were administered; there were three reports of minor adverse reactions. Inhibitor antibodies to factor VIII developed in 16 of 81 patients tested for them, after a median of nine days of exposure to factor VIII treatment. Inhibitor titers were or became low in 9 of the 16 patients despite continued episodic treatment with the concentrate. Inhibitors disappeared completely in 4 patients and remained at a low level (< 10 Bethesda units) in 5 patients receiving episodic treatment. CONCLUSIONS: Transient or low levels of inhibitor, as observed in this study, may represent part of the natural history of hemophilia in infants. In view of the transient nature and lower concentration of the inhibitors detected and the generally satisfactory response to treatment, the benefits of recombinant factor VIII for the treatment of hemophilia seem to outweigh the risks.

Antibodies↗
PubMed1993

Prediction and management of adverse events associated with the use of factor IX complex concentrates.

Among the adverse events that have been associated with the use of F IX CC in inhibitor patients, the likelihood of transmission of blood-borne pathogens is now greatly reduced. However, one must be aware of the possibility of thrombotic complications and acute myocardial infarction when using large, repetitive doses of F IX CC. A greater awareness of such potentially life-threatening complications, and avoidance of frequent, repetitive large doses, should decrease the risk. F IX CC are not always effective in achieving or maintaining hemostasis in hemophiliacs with inhibitors. Thus, in subjects who are responding suboptimally, in those in need of surgical intervention, or in those who have large intramuscular hemorrhages and/or will require a prolonged period of treatment, alternative therapeutic approaches should be considered.

Blood Coagulation Disorders↗
PubMed1992

Effect of age on human immunodeficiency virus type 1-induced changes in lymphocyte populations among persons with congenital clotting disorders. Transfusion Safety Study Group.

Children other than neonates infected with human immunodeficiency virus type 1 (HIV-1) have low rates of progression to acquired immunodeficiency syndrome (AIDS). Through 1989, 5.3% of 95 infected hemophiliacs aged 5 to 13 years developed AIDS, compared with 20.3% of 364 aged greater than or equal to 25 years. We asked whether the HIV-1 impact on peripheral blood mononuclear cell subpopulations differed with age using pairwise comparisons of uninfected and infected male children and adult hemophiliacs. Infected children had lesser reductions of total lymphocytes than adults, but proportionately lower numbers of CD2+, CD4+, CD2+CD26+, and CD4+CD29+ counts. CD4+CD45RA+ cell counts were greater than twofold higher in uninfected and infected children than adults; with infection, the CD4+CD45RA+/CD4+ proportion increased by 1.4-fold in adults, but was unchanged in children. Infected adults had highly significantly increased total CD8+ counts; both age groups had elevated CD8+HLA-DR+ counts. Infected children had significantly higher total B-cell counts than infected adults, with a disproportionately lower number of resting B cells (CD20+CD21+). During 2 years of follow-up, infected children and adults had lymphocyte changes in the same directions and these were proportionately equal. The lower rate of HIV-1 progression in children may be partly associated with differences in lymphocyte populations compared with adults; functional properties of immune cells may be equally or more important.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Variability in serial CD4 counts and relation to progression of HIV-I infection to AIDS in haemophilic patients. Transfusion Safety Study Group.

OBJECTIVE--To examine the CD4 count and its near term changes relative to progression to AIDS within 30 months and to subsequent CD4 counts. DESIGN--Longitudinal clinical and laboratory study. SETTING--Haemophilia treatment centres in six large American cities. PATIENTS--555 people with congenital clotting disorders who were infected with HIV, initially without AIDS, and seen at follow up for 6-30 months in 1986-9. MAIN OUTCOME MEASURES--Absolute CD4 counts and incidence of AIDS. RESULTS--Outset CD4 count and age were independently related to progression to AIDS (p less than 0.0001 and p less than 0.005 respectively). Patients with CD4 counts of 0.30-0.49 x 10(9) cells/l had an age adjusted risk of AIDS within 30 months of only 9% that of patients with counts less than 0.20 x 10(9)/l. Children under 10 years old had only 16% of the CD4 adjusted risk of AIDS of people aged greater than or equal to 45 years. Analysis of 149 patients' CD4 counts at the beginning and end of two successive six month intervals showed an average decrease of 11% in each six months regardless of the outset count (greater than or equal to 0.20 x 10(9)/l). For individual patients the decrease in the second six month period was unaffected by the decrease in the first six month period. CONCLUSIONS--Antiviral treatment of asymptomatic people, particularly children, with CD4 counts greater than or equal to 0.3 x 10(9)/l is questionable if predicted on near term progression to AIDS. Because of individual CD4 count variability and the low rate of progression to AIDS near term declines in individual CD4 counts are a poor index for identifying people who will rapidly progress to AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Hemophilia A.

Over the past few years considerable progress has been made in elucidating the molecular genetics of hemophilia A, in carrier detection and prenatal diagnosis, and in the production of safer clotting factor concentrates. Recombinant FVIII, shown to be safe and effective in ongoing prelicensure clinical trials that began in the spring of 1987, should soon be licensed and commercially available. There is now considerable interest in beginning prophylactic therapy regimens at 1 or 2 years of age, in an attempt to prevent chronic joint disease and other complications of serious bleeding episodes. The possibility of gene insertion therapy for persons with hemophilia now seems to be a realistic one--perhaps achievable in the 1990s. Although many problems remain--major problems resulting from HIV, HCV, and HBV infections; how to deal with existing musculoskeletal problems; how to pay for the higher-priced new technologies; high titer inhibitors; just to name a few--the many recent scientific advances and their clinical applications make this an exciting time. This is truly, as indicated in the title of the proceedings of the XIX Congress of the World Federation of Hemophilia, a new decade of hopes and challenges.

Child, Preschool↗