Search PubMed⌕ Search

Biomedical subjects

E Gomperts

Publications and source records attributed to E Gomperts.

36 records · Page 2Linked to original sources
PubMed1992

The manufacturing process of recombinant factor VIII, recombinate.

In summary, this brief report documents the cell culture and rAHF purification systems used to produce rFVIII and has focused on the unique characteristics of the cell line, the production process, and purification system used. This review emphasizes the general philosophy used throughout the research and development of this innovative and complex therapeutic agent, in order to provide a safe and efficacious rAHF in the management of individuals with hemophilia A. This review provides a brief description of the in-process system and controls that have been incorporated to meet the high standards and safety objective.

Animals↗
PubMed1989

Lymphocyte phenotype does not predict immune function in pediatric patients infected with human immunodeficiency virus type 1.

To determine whether assays of lymphocyte phenotype were predictive of antigen-specific immunologic function in children infected with human immunodeficiency virus type 1 (HIV-1), we compared the antigen-specific cellular and humoral functions (tetanus toxoid-induced T lymphocyte blastogenesis and anti-tetanus toxoid antibody) with the patients' T lymphocyte phenotype, determined at the same time. Although both HIV-1-infected patient populations studied (pediatric hemophilia patients and other pediatric patients) had decreases in the values determined by their functional and phenotypic assays, no association between the functional and phenotypic assays was demonstrated. Thus some HIV-1-infected patients with a normal phenotype had no antigen-specific function, whereas other patients with a markedly abnormal T lymphocyte phenotype had normal antigen specific T lymphocyte function. These results indicate that the assessment of HIV-1-infected patients should include assays of antigen-specific immune function in addition to assays of T lymphocyte phenotype.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Biochemical pharmacology of zidovudine in human T-lymphoblastoid cells (CEM).

HIV is the causative agent of AIDS. The purpose of this study was to examine the biochemical pharmacology of the anti-viral agent zidovudine (AZT) in the T-cell origin line (CEM). We have shown that zidovudine is activated by thymidine kinase (TK) in CEM cells to the triphosphate anabolite, which is incorporated into DNA. One microM zidovudine is sufficient for saturation of activation by TK and also of zidovudine monophosphate, by thymidylate kinase, to the diphosphate. Zidovudine triphosphate peaked 4 h after initiation of drug administration in CEM cells and then declined biexponentially. Nucleoside triphosphate (NTP) cellular concentrations declined rapidly in the cells after exposure to zidovudine. Concomitantly phosphorylation of zidovudine to zidovudine monophosphate and zidovudine monophosphate to zidovudine diphosphate declined in a similar manner in the CEM cells. The amount of zidovudine anabolite incorporated into purified DNA peaked 1 h after zidovudine treatment and declined thereafter with first order elimination kinetics. These studies elucidate the cellular activation of zidovudine in a T-cell line, CEM, and enhance our understanding of this important anti-HIV drug.

Cell Division↗
PubMed1989

HIV and hemophilic children's growth.

The acquired immune deficiency syndrome (AIDS) often has profound effects on growth; however, the effects of human immunodeficiency virus (HIV) on asymptomatic children's growth are unknown. Before heat inactivation/HIV donor screening of factor concentrates, many hemophilic children became infected with HIV. We evaluated four hemophilic groups without AIDS, using age-standardized growth parameters: group 1, 41 HIV-seropositive children (median age of 13 years); group 2, 11 HIV-seronegative children (median age of 4 years); group 3, 20 children frequently receiving concentrates, evaluated before 1979 (median age of 9 years); and group 4, 11 children rarely receiving concentrates, evaluated before 1979 (median age of 6 years). Median height for age (HA), weight for age (WA), and weight for height (WH) of groups 1 and 2 exceeded the 50th percentile of referent norms. HA, WA, WH, and weight/height did not vary significantly by group, nor did these decline over periods of 11 to 70 months. However, for those less than 11 years of age in group 1, HA declined by 25 percentile points over at least a 3 year period. Also, group 1's T helper-to-suppressor cell ratios at 12 +/- 3 months following the latest growth evaluation were positively associated with both HA and WA at the last evaluation. Eight children were evaluated before 1979 and again after they seroconverted to HIV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Continuous infusion of low-dose urokinase in the treatment of central venous catheter thrombosis in infants and children.

Thrombotic occlusion is a frequent complication associated with the use of central venous catheters. The purpose of this study was to evaluate the efficacy of a continuous infusion of low-dose urokinase (200 U/kg/h) in clearing catheters that had not cleared after two bolus doses of urokinase in a pediatric oncology population. Fifty-eight incidents of catheter-related occlusions (49 Hickman-type catheters/nine implantable ports) as documented by radiographic dye study occurred in 227 pediatric oncology patients with 254 central venous catheters during a 1-year period. Fourteen of 58 catheters failed to clear after two bolus instillations of urokinase (5,000 U and 10,000 U). Thirteen catheters were treated for 24 hours with urokinase, 200 U/kg/h, and one catheter with urokinase, 100 U/kg/h for 24 hours. Twelve catheters were used for study. Coagulation studies were monitored preinfusion, 12 hours into the infusion, and postinfusion. Patency was reestablished in 11/12 catheters (92%) with a mean infusion time of 28.7 hours. No coagulation abnormalities or clinical bleeding associated with the urokinase infusion occurred. Only one patient exhibited a prolonged partial thromboplastin time (greater than 150 seconds); this was associated with a heparin effect. These data indicate that low-dose urokinase may be a safe and effective means to clear occluded central venous catheters in children.

Blood Coagulation↗
PubMed1988

Comparative evaluation of the bone marrow by the volumetric method, particle smears, and biopsies in pediatric disorders.

Bone marrow cellularity estimated by biopsy was compared to the cellularity of the aspirate particle smear and the volumetric method in two groups of children. In the first group, 101 consecutive bone marrow biopsies and aspirates were evaluated from patients with various diagnoses. In the second group, 20 patients with acute nonlymphoblastic leukemia were studied with 80 biopsies and aspirates at diagnosis and following chemotherapy. A wide discrepancy was noted between bone marrow cellularity confirmed by biopsy vs. the particle smear or the volumetric method in both groups. Neither the volumetric nor the particle method provides a good correlation of bone marrow cellularity. We also compared the volumetric method with that of the biopsy to evaluate the efficacy of the former method in detecting bone marrow infiltration by solid tumors. The volumetric method is an accurate modality of identifying solid tumor infiltration in the bone marrow.

Biopsy↗
PubMed1987

Type IIA von Willebrand disease with apparent recessive inheritance.

Type IIA von Willebrand's Disease (vWD) is the most common type II variant, and all reported cases (56 individuals in 26 families) have had autosomal dominant inheritance. An eight-year-old female with an increased bleeding tendency since infancy was found to have laboratory values typical of type IIA vWD, but her parents and siblings were asymptomatic. With the exception of uniformly decreased levels of ristocetin cofactor in relation to von Willebrand factor antigen, the results of family studies were normal including the presence of large multimeric forms of von Willebrand factor antigen. These findings are consistent with the propositus having the homozygous state of an autosomal recessive trait. Desmopressin infusion in the propositus was followed by a significant increase of factor VIII coagulant and von Willebrand factor antigen but a limited change in ristocetin cofactor with no development of large multimers.

Antigens↗
PubMed1986

Kasabach-Merritt syndrome treated by therapeutic embolization with polyvinyl alcohol.

The authors describe a 6 1/2-month-old boy with a large hemangioma involving the left buttock associated with a severe consumptive coagulopathy. Cosmetic improvement and resolution of the coagulation defect followed occlusion of the nutrient vessels to the hemangioma with polyvinyl alcohol. This is the first report of successful treatment of this condition with therapeutic embolization.

Blood Coagulation Disorders↗
PubMed1986

Selection of replacement therapy for patients with severe factor VII deficiency.

The risk of significant bleeding in patients with severe Factor VII (FVII) deficiency is well documented. However, controversy regarding management exists not only for the choice of FVII replacement product, but also for the desired hemostatic level of FVII. Two case reports are presented where fresh frozen plasma (FFP) and several Factor IX (FIX) complex concentrates were used to achieve hemostasis. Significantly higher FVII levels were achieved with Proplex (FIX Complex, Hyland Therapeutics) than with other products. Although this and other reports indicate that minor bleeding can be controlled with levels of FVII under 15%, life-threatening hemorrhages require higher FVII levels that can be attained only by using a product with a significant FVII content. It is important to know the FVII content of FIX concentrates in order to plan appropriate therapy for patients with FVII deficiency.

Blood Coagulation Factors↗
PubMed1980

Inhibitory effects of interferon on mouse megakaryocytic progenitor cells in culture.

Mouse bone marrow cells were grown in plasma clots, megakaryocyte formation was stimulated with human urinary erythropoietin (Ep). The expression of megakaryocyte colony forming units (CFUM) and of single megakaryocyte forming units (M) was evaluated after seven days in culture. Usually ten times more M than CFUM were found. Megakaryocytic colony formation showed a linear dependence on cell dose from 0.5 to 2 X 10(5) cells/clot. The colony size frequency distribution exhibited a single peak in the two-cell size class, followed by a continuous decrease, suggesting that cell division may occur asynchronously in cells making up a colony. Mouse L cell interferon (IF) in doses from 10 to 1000 U/ml was included in clots together with Ep. This resulted in a biphasic, dose dependent reduction of colony formation and of single megakaryocyte formation. At all doses tested CFUM were more sensitive to IF than M. These observations are best explained by a differential inhibitory effect of IF on replication of two or more classes of megakaryocytic progenitor cells.

Animals↗
PubMedDate not supplied

Use of fibrin sealant in thermal injury.

Fibrin glue is hemostatic in skin grafting and other therapeutic situations. This prospective, open-labeled comparative study involved thermally injured patients: 34 patients received fibrin sealant (FS) and 61 did not, at Loyola University Medical Center, Maywood, Illinois, and Shriners Burn Institute, Cincinnati, Ohio. FS-treated patients were 23.6 +/- 16.8 years old, versus 20.8 +/- 16.8 years for controls. The percentage of total body surface areas burn was 10.0% +/- 4.5% in the study patients versus 10.9% +/- 7.9% in the controls. The FS group did not receive packed red blood cell transfusions, albumin infusion, or topical bovine thrombin (TBT). The control group received 1.56 +/- 2.1 units of packed red blood cells, 186 +/- 194 ml 5% albumin, and TBT (20,000 units) 2.6 +/- 0.8 kits during excision and grafting procedures. The estimated blood loss/graft ration was 0.50 +/- 0.30 ml/cm2 (median = 0.46) for the study group versus 0.98 +/- 2.4 ml/cm2 (median = 0.56) for the control group (p = 0.14); for patients more than 16 years of age, this difference was significant (p = 0.03). FS may be a viable alternative to standard hemostatic techniques, because it reduced the need for blood transfusion, alloantigen exposure, and blood-borne viral infection risk. FS also eliminated the need for TBT and epinephrine, did not have an adverse impact on the surgical outcome, and tended to improve the cost differential.

Adolescent↗
PubMedDate not supplied

Investigational use of tissue plasminogen activator (t-PA) for occluded central venous catheters.

Urokinase and streptokinase are commonly used thrombolytic agents for fibrin obstructed central venous catheters. Although proven to be efficacious, these two agents have the potential to induce systemic fibrin breakdown and hemorrhage. We report our initial experience with tissue plasminogen activator (t-PA) for the treatment of occluded central venous catheters which failed urokinase. Of 25 incidents of catheter occlusion in 142 right atrial catheters, six failed to clear after an initial bolus dwell of urokinase. Five of these six catheters cleared following treatment with 2 mg/2 cc of t-PA with a mean of 1.5 bolus installations. The one catheter failure was due to catheter tip position and age of clot. No coagulation abnormalities or bleeding was observed. These data suggest that t-PA may be a safe, effective thrombolytic agent in the treatment of occluded central venous catheters.

Adolescent↗