Parvovirus associated antigen in the synovial membrane of patients with rheumatoid arthritis.

Homogenates of synovium from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were centrifuged on caesium chloride density gradients to obtain isolates of a density similar to that of parvoviruses. Six of 11 RA isolates and none of six OA isolates reacted with an antiserum raised against a rheumatoid associated, parvovirus-like agent (RA-1 virus). An anti-B19 parvovirus antiserum did not react with any of the isolates tested. Electron microscopy of negatively stained preparations of the isolates showed that small particles of diameter 10 nm were abundant in most of the RA isolates (11/13) but absent from all OA isolates. Such particles, whose identification is unknown, were also present in RA-1 positive lysates prepared from cultured RA synovial cells. These results suggest that the RA-1 virus can be directly identified in RA synovial tissue and that the virus appears to be unrelated to the human B19 parvovirus.

Anticoagulant antibodies in the synovial membranes of patients suffering from haemophilia, rheumatoid arthritis and other rheumatic disorders.

This study has identified IgG and IgM anticoagulant antibodies in the synovial membranes of patients suffering from haemophilia and rheumatoid arthritis (RA) but not in synovial tissues from normal subjects or in patients with other arthritides. In the majority of cases the antibody appeared to have the specificity of the lupus-like anticoagulant (LLA) seen in patients with systemic lupus erythematosus (SLE). The importance of these findings with regard to the treatment of certain cases of haemophilia and RA and the possible relation between the presence of these antibodies and viral infections is discussed.

Patterns of bleeding in adolescents with severe haemophilia A.

Eighty-two boys with severe haemophilia A who spent some time at Lord Mayor Treloar College during 1973-7 were studied. All episodes of bleeding that occurred during term time were recorded, along with the number of transfusions. The bleeding frequency among these boys, most of them aged 10-17 years, increased steadily from 8,31 episodes/100 days in 1973 to 12,63 episodes/100 days in 1977. At the same time there was a steady fall in bleeding frequency with age. Altogether 24% of bleeding episodes were into the elbow joint, 22% into the knee, and 15% into the ankle. As the boys grew older the proportion of bleeding episodes in the legs declined and that in the arms increased. The overall results reflect the fact that special schools now see only the severest cases of haemophilia. The pattern of bleeding during adolescence suggests that concepts of management of arm bleeding need modifying.

A comparison of coagulation factor replacement with and without prednisolone in the treatment of haematuria in haemophilia and Christmas disease.

A double-blind controlled study was carried out to investigate the effectiveness of treatment with factor VIII or factor IX concentrate and a reducing dose of prednisolone in contolling haematuria in patients with haemophilia and Christmas disease. 41 episodes of haematuria were studied in 30 different patients. No appreciable benefit was observed in the treated, as compared with the control group and this is at variance with the results of the few studies reported elsewhere.

Twice weekly prophylactic therapy in haemophilia A.

Factor VIII-containing materials were administered to four severely affected haemophiliacs twice weekly in doses calculated to raise the factor VIII level to either 15% or 30% of average normal. The pooled results from those patients with statistically similar baseline bleeding frequencies showed a significant reduction in bleeding frequency on both doses in the first 48 hours. The 30% dose produced a more significant reduction than the 15% dose in the first 24 hours, but there was no significant difference between the two doses in the second 24 hours. It appears that to reduce the bleeding frequency of severely affected haemophiliacs by 60% would require a two-and-a-half-fold increase in therapeutic materials. A 90% reduction would need nine times the amount of material currently in use.

Prophylaxis in haemophilia: a double-blind controlled trial.

A double-blind controlled trial of prophylactic factor VIII therapy has been carried out on nine severe haemophiliacs at the Lord Mayor Treloar College. Infusions were given once weekly and calculated to give a post-infusion plasma concentration of at least 0.25 I.U./ml of factor VIII. This regime reduced the overall bleeding frequency by 15%. The bleeding frequency in the first 3 days post-infusion was reduced by 66%. A moderate overall reduction in morbidity was also achieved. It is calculated that to reduce the incidence of bleeding in severe haemophiliacs by 15% would require a 73% increased usage of therapeutic materials. More than twice this amount of material is likely to be needed to reduce the bleeding frequency of the same group by 66%.

Clinical observations and their relationship to laboratory findings in the haemophilias.

Continuous observations in shcool terms have been made on the frequency of spontaneous bleeding episodes in a group of adolescent boys suffereing from haemophilia (39 cases), Christmas disease (9 cases), and von Willebrand's disease (2 cases). The observations suggest that in haemophilia other factors, besides the deficient factor VIII, affect the bleeding frequency. In the two boys with von Willebrand's disease, the lower level of factor VIII was associated with the milder symptoms; whereas in boys with Christmas disease clinical severity and laboratory results seemed to be correlated.