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Biomedical subjects

H S Kingdon

Publications and source records attributed to H S Kingdon.

At least 19 recordsLinked to original sources
PubMed1992

Treatment of hemophilia A with a highly purified factor VIII concentrate prepared by anti-FVIIIc immunoaffinity chromatography.

To reduce the risk of pathogenic virus transmission associated with the therapeutic administration of plasma-derived anti-hemophilic factor (FVIIIc), a process utilizing anti-FVIIIc immunoaffinity chromatography to isolate FVIIIc has been developed. In addition, the starting cryoprecipitate solution has been treated with an organic solvent/detergent mixture to inactivate lipid-enveloped viruses. A final ion exchange chromatography step is used to further remove contaminants, e.g., anti-FVIIIc antibody, potentially leached with FVIIIc during the immunoaffinity step. The purified FVIII is stabilized for lyophilization and storage by the addition of human albumin. The monoclonal anti-FVIIIc antibody used in the immunoaffinity step of the process is not detectable in the final preparation. Viral reduction studies performed at specific steps of the process demonstrate that 11 logs of human immunodeficiency virus (HIV) and greater than 4-5 logs of other lipid-enveloped viruses are inactivated within the first 30 s of exposure to the solvent/detergent mixture and 4-5 logs of various model viruses, e.g. Endomyocarditis virus (EMC), are physically removed during washing of the immunoaffinity column. The lyophilized product is reconstituted using sterile water in a matter of seconds. The pharmacokinetics of Hemofil M were compared to those obtained using a standard heat-treated concentrate (Hemofil CT) in five severe factor VIII deficient hemophiliacs in a randomized, cross-over study. No statistically significant differences were observed in mean half life (p greater than 0.6) or median recovery (p = 0.4) between the two preparations. No clinically significant adverse effects were observed in patients receiving either FVIII preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗
PubMed1990

A two-phase linear regression model for biologic half-life data.

In estimating the biologic half-life of an infused drug or biologic agent, one very frequently used model is the biexponential, which reflects a two-compartment physiologic model. The difficulty in using this model is that it is nonlinear in the parameters and requires relatively sophisticated analysis. Furthermore, an interval estimate is not usually reported. We propose the use of a two-phase linear regression approach, which is tantamount to breaking down the model into two straight lines based on the selection of the logarithm of concentration as the ordinate and time as the abscissa. We show how to determine the joint or changeover point for the two lines using a simple iterative procedure, how to select between a one-phase and a two-phase model, and how to provide a simple confidence interval estimate for half-life when it exists. An example using data from a study of Factor VIII pharmacokinetics is given.

Factor VIII↗
PubMed1987

Agents causing non-A non-B hepatitis: could one be a prion?

Non-A non-B hepatitis is caused by an unknown infectious agent or agents, and can be transmitted by blood or products derived from blood. Laboratory and clinical data demonstrate that procedures which inactivate the AIDS virus are not sufficient to prevent non-A non-B hepatitis transmission. The possibility is suggested that at least one of the putative non-A non-B hepatitis agents might be a unique infectious agent such as a prion.

Blood Preservation↗
PubMed1987

Safety of an intravenous immunoglobulin preparation: lack of seroconversion for human immunodeficiency virus antibodies.

A retrospective analysis of 18 patients who had received a human intravenous immunoglobulin (IGIV) preparation was undertaken to ascertain the safety of this preparation with respect to transmission of human immunodeficiency virus (HIV), the virus that causes the acquired immune deficiency syndrome (AIDS). Patients were followed up by means of periodic enzyme-linked immunosorbent assay (ELISA) for the presence of circulating antibodies against HIV; a negative ELISA was evidence that HIV had not been transmitted to the recipients of IGIV. Results in 16 patients were negative, and two patients were determined to have had false-positive ELISAs because the Western blot test was negative for seroconversion. It is thus concluded that the IGIV product tested has little or no potential for transmitting HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Early experience with the use of anti-inhibitor coagulant complex to treat bleeding in hemophiliacs with inhibitors to factor VIII.

Early clinical experience with anti-inhibitor coagulant complex in the treatment of bleeding in patients with factor VIII inhibitors is described. Sixty patients with a total of 120 bleeding episodes were studied. Satisfactory responses were obtained in 86.6% of bleeding episodes. Efficacy was slightly better in open bleeding than in closed bleeding. Higher doses were significantly better than lower doses in treating open bleeding. The incidence of adverse reactions was low. The results reported support the safety and efficacy of anti-inhibitor coagulant complex in the treatment of bleeding in patients with factor VIII inhibitors.

Adolescent↗
PubMed1987

Efficacy of a new intravenous immunoglobulin preparation in primary immunodeficient patients.

The safety and efficacy of a new second-generation intravenous immunoglobulin manufactured using ion-exchange chromatographic methods was studied in 17 patients with primary immunodeficiency. In assessing safety, the incidence of adverse reactions during the first 48 hours after each infusion and long-term changes in laboratory values were considered. Efficacy was determined by the number of acute and new chronic infections as well as by the number of prescriptions filled for antibiotics. These results were compared with those reported for similar preparations. Results showed a low (4.4%) incidence of acute adverse reactions, and no serious reactions or significant changes were noted in any of the laboratory test results. The incidences of infection and antibiotic usage were as low as or lower than those reported with other preparations. Thus we conclude that this new intravenous immunoglobulin product is a safe, effective prophylactic treatment for patients who have primary immunodeficiency.

Adolescent↗
PubMed1986

PROPLEX vs. PROPLEX SX: a controlled double blind study of the effectiveness in treating acute hemarthroses in hemophilia A patients with inhibitors to factor VIII.

A blinded randomized multicenter trial of two non-activated prothrombin complex concentrates was carried out to determine the clinical effectivity in the treatment of acute hemarthrosis in hemophiliac patients with inhibitors. The one product was prepared via DEAE Sephadex chromatography, while the second was fractionated via various precipitation procedures including polyethylene glycol. Equivalence of the two products was established with less than 15% difference in efficacy rates.

Blood Coagulation Factors↗
PubMed1979

The covalent differences between bovine alpha- and beta-thrombin. A structural explanation for the changes in catalytic activity.

The partial covalent structure of bovine beta-thrombin has been determined by the use of automated Edman degradation and carboxypeptidase digestion of the component polypeptide chains separated by gel filtration following either reduction and carboxymethylation or performic acid oxidation. beta-Thrombin has been found to contain three peptide chains derived by proteolysis of the parent alpha-thrombin molecule. The A chain of alpha-thrombin has been cleaved at two points yielding a peptide (A1 chain) which contains 17 amino acids, beginning with threonine 14 and ending with lysine 30. The B chain of alpha-thrombin has been cleaved at two positions to yield a B1 chain which begins with the NH2-terminal isoleucine and terminates with lysine 65 and a B2 chain which begins with lysine 74 and continues through COOH-terminal serine 259. The A1 chain and B2 chain are linked by a disulfide bridge. Although there is no evidence for a covalent bond between the B1 chain and the B2-A1 chains, the B1 chain is tightly bound to the remainder of the molecule, for separation is achieved only under denaturing conditions.

Amino Acid Sequence↗
PubMed1979

Correlation of in vivo and in vitro inhibition of thrombin by plasma inhibitors.

Rabbit antithrombin III and thrombin were purified to homogeneity to determine the in vivo relationship of these proteins in an autologous system. These proteins, radiolabeled with Na[125I], were injected into rabbits to determine the circulatory half-life. The mean half-life values were 125I-antithrombin III, 54.75 +/- 3.10 hr; 125I-thrombin, 7.25 +/- 1.49 hr; 125I-thrombin-antithrombin III, 7.25 +/- 1.09 hr; 125I[thrombin-antithrombin III], 11.13 +/- 0.88 hr; and Tos-Lys-CH2Cl-125I-thrombin, 27.75 +/- 3.18 hr. All the mean half-life values were statistically different from that of thrombin alone except for the two forms of thrombin-antithrombin III complex. Following injection of the radiolabeled proteins, plasma samples were obtained and gel-filtered to analyze the molecular weight distribution of the radiolabel. An identical elution position on gel filtration of 125I-antithrombin III with native antithrombin III was observed. The 125I-thrombin distributed into two peaks of radioactivity, with a molecular weight of 100,000 (79%) and a molecular weight greater than 200,000 (21%). The 100,000 dalton peak is consistent with a thrombin--antithrombin III complex, and the greater than 200,000 dalton peak is consistent with a thrombin-alpha 2-macroglobulin complex as confirmed by in vitro immunochemical studies. Thrombin inactivated with Tos-Lys-CH2Cl also showed two peaks of radioactivity on gel filtration, one peak which was excluded from the column and the other peak with an elution volume that was consistent with the position of native thrombin.

Antithrombin III↗