PubMed Health⌕ Search

Biomedical subjects

E D Gomperts

Publications and source records attributed to E D Gomperts.

At least 37 records · Page 2Linked to original sources
PubMed1996

Anaphylaxis after treatment with recombinant factor VIII.

BACKGROUND: Treatment of hemophilia patients with recombinant factor VIII concentrates has not previously been associated with anaphylaxis. STUDY DESIGN AND METHODS: A 5-week-old boy with severe hemophilia A developed dyspnea, cyanosis, hypotension, and a diffuse urticarial rash following treatment with a recombinant factor VIII (Recombinate). To identify the cause of anaphylaxis in this patient, the vial lot was examined for the presence of endotoxin, and a checkerboard immunoblotting technique was used to test serum and/or plasma samples from the patient and mother for the presence of antibodies (IgA, IgG, IgE, and IgM) to Recombinate-related antigens (recombinant factor VIII, von Willebrand factor, human serum albumin, Chinese hamster ovary proteins, bovine serum albumin, mouse monoclonal anti-human factor VIII, polyethylene glycol 3350), and to ethylene oxide, the agent used to sterilize the infusion equipment. RESULTS: No immune response directed against the Recombinate-related antigens or ethylene oxide that could be associated with the anaphylactic reaction was identified. Endotoxin was not present upon rabbit pyrogen testing of the therapeutic product. CONCLUSION: These studies failed to show any association between Recombinate and the onset of the allergic reaction. This seems to be the first reported case of anaphylaxis following the infusion of a recombinant form of factor VIII concentrate.

Anaphylaxis↗
PubMed1994

A multicenter study of recombinant factor VIII (recombinate): safety, efficacy, and inhibitor risk in previously untreated patients with hemophilia A. The Recombinate Study Group.

In July 1990, the Recombinate Study Group initiated a prospective, open-labeled investigation of recombinant factor VIII (r-FVIII) to assess its safety and efficacy and to characterize the natural history of inhibitor development in previously untreated patients (PUPs) with hemophilia A. All study subjects have severe FVIII deficiency (baseline FVIII level < or = 2% of normal) and no history of blood product exposure before study entry. Following the first r-FVIII infusion, plasma was screened for inhibitors once every 3 months, and plasma recovery of r-FVIII at 30 minutes and 24 hours postinfusion was assayed at least once every 6 months. As of May 1993, 73 of 79 patients originally enrolled in the trial continue to participate. The median number of r-FVIII exposure-days for the 71 subjects who have received at least one r-FVIII infusion is 11. A total of 1,785 infusions have been administered to treat 810 bleeding events. Ninety-two percent of bleeding events responded as anticipated to one or two infusions. Two, nonrecurring, acute adverse reactions occurred coincident with r-FVIII infusion, one of which was unrelated and the other, possibly related to the infusion. Seventeen (23.9%) subjects have developed inhibitors: five with peak titers more than 10 Bethesda units (BU) and 12 with peak titers < or = 10 BU (range, 0.5 to 10). Survival analysis showed that the probability of remaining inhibitor-free in this group of patients with severe hemophilia A is 88.4% after 8, 73.6% after 10, and 61.6% after 25 r-FVIII exposure-days. Inhibitors disappeared in five (29.4%) subjects on retesting 2 to 16 months after the last positive inhibitor assay. r-FVIII is safe and effective in the treatment of hemophilia A-related bleeding. To date, the inhibitor risk associated with its use is comparable to that in patients treated with plasma-derived concentrates. The majority of inhibitors identified are low in titer and do not preclude continued on-demand therapy with r-FVIII.

Antibodies↗
PubMed1994

Immune and serologic profiles of HIV-infected and noninfected hemophilic children and adolescents. Hemophilia Growth and Development Study Group.

OBJECTIVES: To assess relationships among the effects of HIV on hemophilic children and adolescents' immunologic parameters and vaccine-related serology. METHODS: We analyzed data from extensive baseline immunologic evaluations of 207 HIV antibody-positive (HIV+) and 126 HIV antibody-negative (HIV-) hemophilic children and adolescents. RESULTS: HIV+ and HIV- participants differed significantly in T-lymphocyte subpopulation numbers, immunoglobulin levels, and seroprevalence rates for diphtheria toxoid, measles, and mumps antigens, IgG levels, IgM levels, and serologic titers to vaccine antigens showed little correlation with T-cell parameters. Proportionately more HIV+ participants were nonreactive to each and all of a panel of 7 skin test antigens (71% vs 28% anergic, RR 2.6). The odds of anergy increased 1.6 times for every decline of 200 CD4+ cells/microliters. CONCLUSIONS: HIV had significant, largely independent T- and B-lymphocyte effects on this pediatric cohort.

Adolescent↗
PubMed1994

Delayed somatic growth and pubertal development in human immunodeficiency virus-infected hemophiliac boys: Hemophilia Growth and Development Study.

As part of the Hemophilia Growth and Development Study, we investigated the impact of human immunodeficiency virus (HIV) infection on statural growth, weight gain, and skeletal and sexual maturity in more than 300 boys with moderate to severe hemophilia, of whom 62% were infected with HIV. Age-adjusted height and weight were reduced in the HIV-infected subjects (p < 0.001). However, mean weight for height and triceps skin-fold thickness of the infected-boys closely resembled those of the uninfected group. In HIV-infected boys, height for age was positively related to the CD4+ lymphocyte count when the count was < 200 cells/mm3. Age-adjusted serum testosterone levels did not differ by HIV status, but in the infected participants the mean age-adjusted bone age was significantly reduced (p = 0.038) and the distribution of Tanner stages, adjusted for age, differed significantly (p = 0.003). The probability of advancing one or more Tanner stages in the first study year was significantly slowed in HIV-infected boys more than 14 years of age (p = 0.0003). We conclude that linear growth was significantly impaired in boys with hemophilia and HIV infection, but the wasting of malnutrition was not found. The delays in bone age and pubertal maturation strongly suggest that part of the growth failure seen in acquired immunodeficiency syndrome can be attributed to pubertal delay. We speculate that the lack of demonstrable difference in age-adjusted testosterone concentrations might reflect subtle differences in the pattern of secretion of testosterone or in the concentration of sex-hormone binding globulin.

Adolescent↗
PubMed1994

A clinical evaluation of genetic stability.

Mutation in a genetically engineered cell line has not been shown to have been responsible for adverse clinical reactions in a currently licensed biotechnology product. There exists, however, the theoretical possibility that mutations in the production cell line could ultimately lead to patient exposure to aberrant proteins which could result in unanticipated or deleterious effects. The clinical trials of recombinant antihaemophilic factor, a large complex glycoprotein, which is administered chronically, offered a unique opportunity to explore this theoretical concern. In this retrospective analysis of patient data, evidence for unanticipated or adverse events which could possibly be attributed to mutations in the genetically engineered cell line was sought. Extensive analysis of a variety of patient data such as the efficacy, alterations in pharmacokinetic parameters, and inhibitor formation, gave no support for concern over host cell mutation. While this retrospective analysis cannot absolutely exclude the possibility of mutational events, those clinical data in combination with the product characterization information indicate that for this recombinant product, mutation is a highly improbable event.

Biotechnology↗
PubMed1993

Hemophilia growth and development study. Design, methods, and entry data.

PURPOSE: The study design, research questions, and baseline data are presented from a multicenter longitudinal epidemiologic investigation of the impact of human immunodeficiency virus (HIV) infection on three areas of functioning in children and adolescents with hemophilia: physical growth and sexual maturation, immune function, and neurological and neuropsychological functioning. PATIENTS AND METHODS: Sixty-nine percent (n = 333) of a population of males between the ages of 6 and 19 years with moderate to severe hemophilia participated in a comprehensive baseline examination. Approximately 62% of the study group was HIV seropositive and 38% HIV seronegative. RESULTS: Adjusted for age, HIV-positive participants were three times as likely as HIV-negative participants to exhibit declines in height-for-age attainment (p = 0.05), twice as likely to have delays in sexual maturation (p = 0.414), and more than three times as likely to exhibit antibody levels that were not indicative of prior exposure or vaccination (p < 0.001). In addition, analysis of a comprehensive battery of neuropsychological tests showed that HIV-positive participants were 50% more likely to show scores approximately 1 SD below expected levels in three of nine functional areas (p = NS) compared with HIV-negative participants. CONCLUSIONS: Entry data for this study reveal a greater likelihood for HIV-positive children and adolescents with moderate to severe hemophilia to have abnormal growth, and to exhibit antibody levels not indicative of prior exposure to disease or vaccination, which could be attributed to HIV infection. Lowered neuropsychological test performance in both groups may be attributable to the deleterious effects of chronic illness. Data are being collected from a group of non-HIV infected non-hemophiliac siblings for comparison.

Adolescent↗
PubMed1992

Coagulation factor IX: successful surgical experience with a purified factor IX concentrate.

The use of plasma-derived coagulation factor concentrates has been marked by the transmission of viral agents. Infusions of factor IX complex concentrates have been additionally complicated by inappropriate thrombosis. Use of these concentrates in the neonate, in those with liver disease, and in surgical patients results in increased risk for this complication. Twenty patients have been infused with a purified coagulation factor IX concentrate for fall-off and recovery studies. A two-compartment model indicated an initial phase half-life of 4.06 +/- 2.86 hr and a beta phase half-life of 20.0 +/- 3.8 hr following the administration of AlphaNine, Coagulation Factor IX (Human). In vivo recovery was 62.7% +/- 13.8%, with an average factor IX coagulant level of 73% +/- 16% at 15 min after the infusion of a mean dose of 45 U/kg. Thirteen previously transfused patients with hemophilia B underwent major orthopedic or general or dental surgery using this purified factor IX. Operative outcomes were excellent in all patients. No excessive bleeding was noted. There was no laboratory or clinical evidence for a disseminated intravascular coagulopathy. The excellent surgical outcomes observed in this multitransfused group with biochemical evidence for active liver disease demonstrates the utility and safety of a purified coagulation factor IX concentrate.

Adult↗
PubMed1992

Arterial thrombosis and protein S deficiency.

A previously healthy boy had progressive painful discoloration of the lower extremities and was treated with exchange transfusion and anticoagulation, which were unsuccessful in arresting pedal ischemia; amputation of all of the child's toes was required. Studies of the patient and his parents resulted in a diagnosis of inherited protein S deficiency.

Amputation, Surgical↗
PubMed1992

The impact of clotting factor concentrates on the immune system in individuals with hemophilia.

All reported studies to date, whether comparative or not, have shown a tendency toward a slower decrease in CD4+ numbers in patients receiving very high-purity agents with the rapidity in fall-off being affected by level of CD4+ numbers (low CD4+ numbers decreasing more rapidly), age (older persons showing more rapid CD4+ cell fall-off), and anti-HIV therapy. Clearly, these observations need to be extended in numbers, and the high-purity agents should also be similarly compared with the very high-purity therapies.

Antigens↗
PubMed1991

In vivo recovery and survival of monoclonal-antibody-purified factor VIII concentrates.

In response to reports of discrepant in vitro assays of high-purity concentrates, a double-blind crossover study of in vivo recovery and half-life of two brands of monoclonal-antibody-purified factor VIII concentrates (Monoclate and Hemofil-M) was performed in 23 patients with hemophilia A. In vivo recoveries were close to values predicted from the labelled unitage when plasma samples were assayed by a one-stage method. When a two-stage assay was used, lower recoveries were calculated and the recovery with Hemofil-M was slightly but significantly lower than that with Monoclate. The concentrates were re-assayed in vitro by the two-stage method. Monoclate (which is assayed by the manufacturer using a two-stage method) contained 97% of the labelled potency and Hemofil-M (which is assayed by the manufacturer using a one-stage method) contained 81% of the labelled potency. Differences in in vitro and in vivo assay methods contribute to disparities between expected and observed factor VIII recovery. Clearance of Hemofil-M was significantly faster than that of Monoclate, but volume of distribution at the steady state, mean residence time, and plasma half-disappearance times of the two concentrates were not significantly different.

Adolescent↗
PubMed1990

Bone mineral density and its association with inherited protein S deficiency.

Two unrelated children with thrombotic disease associated with inherited protein S deficiency and osteopenia have been identified. Measurement of protein S yielded markedly reduced levels of free protein S (less than 12.5%) in both propositi, a normal level of total protein S (79%) in propositus #1, and markedly reduced level of total protein S (34%) in propositus #2. Bone densitometry measurements of the two children revealed trabecular vertebral bone mineral content below two standard deviations. This defect is associated with vertebral body compression fractures in propositus #2. Therefore, it is hypothesized that protein S deficiency is associated with abnormalities of bone mineral density.

Adult↗