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Biomedical subjects

J F Harrison

Publications and source records attributed to J F Harrison.

At least 37 records · Page 2Linked to original sources
PubMed1994

Pharmacokinetics and pharmacodynamics of recombinant factor VIIa.

OBJECTIVE: To evaluate the pharmacokinetics and pharmacodynamics of recombinant activated factor VII (rFVIIa). METHODS: Single-dose pharmacokinetics of three dose levels (17.5, 35, and 70 micrograms/kg) of rFVIIa were investigated in 15 patients with hemophilia with severe factor VIII or factor IX deficiency (with or without inhibitors) while they were in the nonbleeding state and during bleeding episodes. Factor VII clotting activity (FVII:C) was determined 5 minutes before and at 10, 20, and 50 minutes and 2, 4, 6, 8, 12, and 24 hours after rFVIIa administration. Model-independent pharmacokinetic analysis of FVII:C plasma concentration-time data included determination of plasma clearance, mean residence time, and volume of distribution. rFVIIa recovery was determined from the plasma FVII:C observed 10 minutes after administration. Pharmacodynamic assessments of prothrombin time, activated partial thromboplastic time, and Factor X values obtained concurrently with FVII:C samples were performed. RESULTS: Sufficient data to allow pharmacokinetic parameter calculation were available for 25 nonbleeding episodes in 11 patients (17.5 micrograms/kg, n = 8; 35 micrograms/kg, n = 9; 70 micrograms/kg, n = 8) and for five bleeding episodes in three patients (17.5 micrograms/kg, n = 2; 35 micrograms/kg, n = 2; 35 micrograms/kg, n = 1). Recovery was calculated during 27 nonbleeding and 17 bleeding episodes. rFVIIa distribution volume is two to three times that of plasma. Median clearance was low--31.0 ml/hr.kg in nonbleeding episodes and 32.5 mg/hr.kg in bleeding episodes. In nonbleeding episodes, median mean residence time was 3.44 hours and median half-life was 2.89 hours. In bleeding episodes, the elimination rate appears to be higher, with a median mean residence time of 2.97 hours and a median half-life of 2.30 hours. Recovery was 45.6% during nonbleeding conditions and 43.5% during bleeding episodes (p = 0.0006); it was statistically lower with the highest dose level than with the 17.5 and 35 micrograms/kg doses (p = 0.007). A significant statistical relationship was observed between values of the prothrombin time and activated partial thromboplastin time, and values of FVII:C with use of maximum effect model. CONCLUSIONS: The pharmacokinetics of rFVIIa are linear in the dose range evaluated. The results suggest potential value of prothrombin time determination in the monitoring of rFVIIa therapy.

Adolescent↗
PubMed1993

Safety and initial clinical efficacy of three dose levels of recombinant activated factor VII (rFVIIa): results of a phase I study.

The safety and efficacy of recombinant DNA-produced factor VIIa (rFVIIa) was investigated in 15 haemophilic patients in non-bleeding states and during bleeding episodes (mild to moderate joint bleed). Patients with severe haemophilia A without inhibitors (n = 4), haemophilia A with inhibitors (n = 10), and haemophilia B with inhibitor (n = 1) received one or more doses of rFVIIa during 32 non-bleeding study episodes and 23 bleeding episodes. The study was an open, uncontrolled, dose-escalation (17.5 micrograms/kg, 35 micrograms/kg, 70 micrograms/kg) trial. Physical evaluation, laboratory assessment, and immunology testing were conducted at baseline, monthly for 3 months and every 3 months thereafter. The immediate safety of rFVIIa was assessed by monitoring of D-dimer, fibrinogen, platelet count, antithrombin III, thrombin-antithrombin complex, and alpha 2-antiplasmin 5 min before and at multiple times throughout the following 24 h. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) values were also obtained. Pain, swelling, joint circumference, and range of motion were recorded before administration of the initial dose of rFVIIa in bleeding patients and at 6, 12, and 24 h. Haemostatic response to rFVIIa was observed in patients with severe VIII and IX deficiency with and without inhibitors. Therapy with rFVIIa was judged effective in 19 of the 22 evaluable bleeding episodes at one or more time points. The 35 micrograms/kg and 70 micrograms/kg doses were associated with higher response rates at 6 and 12 h compared to the 17.5 micrograms/kg dose level. A second dose of rFVIIa was administered in 20 of the 22 bleeding episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Viral release from HIV-I-induced syncytia of CD4+ C8166 cells.

Infection of the permissive C8166 CD4+ lymphoid cell line with human immunodeficiency virus (HIV)-I rapidly leads to syncytium formation. Ultrastructural features of medium-sized (40 to 60 microns) syncytia and larger syncytia are presented, with emphasis upon HIV-I release from the syncytial surface and into intrasyncytial vacuoles. Although surface release of HIV-I is shown to diminish with increasing syncytial size, it does not totally stop. Massive HIV-I release and entrapment within intrasyncytial vacuoles is clearly apparent within the "foamy" multivacuolated zones within medium and large syncytia. Numerous multicored aberrant viruses are routinely detected within the intrasyncytial vacuoles, and double-budding events likewise are readily detectable at the vacuolar membranes, but less so at the syncytial surface. It is suggested that this observation may be a reflection of the more restricted availability of vacuolar membrane area for excessive viral budding as compared with that at the syncytial surface.

Cells, Cultured↗
PubMed1989

Hepatitis A antibody in blood donors in North East Thames region: implications to prevention policies.

A total of 1786 blood donors were screened for the presence of anti-hepatitis A antibody (anti HAV). 64.5% of the donors were found to be positive. The prevalence of the antibody was found to be age-related, 55% at 18 years and 75% at 65 years. No relationship was noted between the presence of antibody, foreign travel or a specific destination. Assay of antibody levels in selected seropositive individuals gave a mean level of 5.0 IU/ml. The prevalence of infection in this selected population is important in the context of passive immunization with normal human immunoglobulin and for defining a policy of immunization with hepatitis A vaccines, which are currently undergoing clinical trials.

Adult↗
PubMed1989

Effect of gamma irradiation on the human immunodeficiency virus and human coagulation proteins.

The effect of gamma irradiation on HIV and plasma coagulation factors F VIII:C, F VIII:vWF and FIX was studied. Donor plasma was harvested from single donations, frozen and irradiated in the frozen state at target doses from 0 to 40 kGy (0-4 mRad). HIV was inoculated into human plasma and irradiated in a similar manner. A range of other viruses, not suspended in plasma, were also irradiated to establish viral inactivation. An inactivation rate of 0.164 TCID50 dose/ml/kGy was demonstrated for HIV compared to rates of 0.00173, 0.00526 and 0.00286 log10 units/ml/kGy for F VIII:C,F VIII:vWF and FIX respectively. The use of gamma irradiation to inactivate infectious agents present in human plasma may eliminate the need for any post-production viral inactivation methods and provide a means of assuring the safety of as yet untreated products such as cryoprecipitate and fresh frozen plasma.

Blood Coagulation Factors↗
PubMed1988

Incidence and significance of hepatitis B core antibody in a healthy blood donor population.

To determine the current incidence of hepatitis B core antibody (anti-HBc) in a healthy blood donor population, 1,893 donors were screened for anti-HBc. Forty-one (2.16%) were found to be initially positive and 35 (1.85%) repeatably positive. Sera from the repeatably positive donors were further screened for hepatitis B surface antibody (anti-HBs), and hepatitis B virus DNA (HBV DNA) by dot hybridisation. The repeatably positive donors were subsequently recalled for further investigation, and their peripheral blood lymphocytes were also screened for HBV DNA by dot hybridisation. Eighteen (51.4%) of the anti-HBc-positive donors were also anti-HBs-positive. HBV DNA was not detected in the serum or the lymphocytes of any of the anti-HBc-positive donors.

Blood Donors↗
PubMed1986

Anaphylaxis to precurarising doses of gallamine triethiodide.

Two cases are described in which patients developed acute anaphylactic reactions to precurarising doses of gallamine. Life threatening complications can arise from the use of small doses of drugs as adjuncts to anaesthesia and raises the question whether the benefits of precurarisation outweigh the risks of anaphylaxis.

Adult↗
PubMed1985

Hepatitis B virus DNA and e antigen in serum from blood donors in the United Kingdom positive for hepatitis B surface antigen.

Serum samples from 214 blood donors in the United Kingdom who were carriers of hepatitis B surface antigen (HBsAg) were examined for hepatitis B virus deoxyribonucleic acid (DNA) by DNA:DNA hybridisation and for hepatitis B e antigen (HBeAg) and its antibody. One fifth of the donors carried infectious virus in their circulation. The presence of hepatitis B virus DNA correlated well with that of HBeAg, although hepatitis B virus DNA was found in five serum samples that were negative for HBeAg. It is concluded that analysis of serum samples for hepatitis B virus DNA by hybridisation should be the method of choice for determining whether carriers of HBsAg are infectious.

Antibodies, Viral↗
PubMed1983

Production of human monoclonal antibody to rhesus D antigen.

Peripheral-blood mononuclear cells from an individual known to produce antibody to the rhesus D blood group were enriched for specific antibody-producing cells before transformation with Epstein-Barr virus. An anti-rhesus-D antibody-producing cell line (UCH D4) was obtained and cloned. Culture supernatants contained about 20 micrograms/ml of rhesus-D-specific IgG-class antibody. The antibody reactivity compared well with that of reagents used routinely for rhesus blood-grouping.

Antibodies, Monoclonal↗
PubMed1983

A study of the routine use of the Imugard IG500 Leukocyte Removal Filter illustrating a possible cause of transfusion reactions and a method of prevention.

The results of the use of the Imugard IG500 Leukocyte Removal Filter in the transfusion of 100 patients requiring leucocyte poor blood are presented. The patients were suffering from a variety of disorders. Many of them had previously received leucocyte poor blood prepared by other methods. Five patients developed non-haemolytic transfusion reactions. Subsequent investigations suggested that these were reactions to the plasma proteins present in the leucocyte poor blood prepared by filtration. A simple method of removal of these plasma proteins combined with filtration is described. The resultant product has been transfused, without incident, into the patients who previously reacted.

Anemia, Sideroblastic↗
PubMed1980

Acute leukaemia in siblings.

Unequivocal lymphoblastic leukaemia in a 4-year-old boy was followed 3 years later by equally unequivocal myeloblastic leukaemia in his 20-year-old brother. The boy achieved complete remission and remains well more than 6 years later whereas his brother failed to respond to treatment and died after 5 months. The parents and 3 remaining siblings showed no recognized features suggesting a constitutional predisposition to leukaemia despite thorough investigation.

Acute Disease↗
PubMed1977

Treatment of juvenile chronic myeloid leukemia with sequential subcutaneous cytarabine and oral mercaptopurine.

Three cases of the juvenile type of chronic myeloid leukemia are described, all of which have shown a clinical and hematologic response to repeated cycles of sequential subcutaneous cytarabine and oral mercaptopurine. It appears that this regime, as described, may afford some control of a disease process previously supposed to be unresponsive to chemotherapy. This control, however, is likely to be reflected in an improvement in well-being, rather than overall survival time. Patient 1 survived 26 mo from diagnosis, and patients 2 and 3 are alive and well 12 and 9 mo from diagnosis, respectively.

Administration, Oral↗