Toward the ideal state mental hospital: the human equation

This paper gives the historical sketch necessary for an understanding of the current state of American psychiatry. It reviews some of the reasons why the rendering of good hospital care must be reconsidered, and describes some of the main features of the future public institution.     

Dysfibrinogenemia associated with hepatoma. Increased carbohydrate content of the fibrinogen molecule.

Abnormal coagulation studies indicative of a dysfibrinogen were found in the plasma of four of seven patients with malignant hepatoma. The abnormal fibrinogen was characterized by prolonged prothrombin, thrombin and reptilase times and inhibition of the coagulation of normal plasma. Purified fibrinogen revealed abnormalities similar to those in plasma. The functional defect was one of delayed polymerization of the fibrin monomer. The carbohydrate content of the abnormal fibrinogen was increased, and this change was related to the abnormal fibrinogen function. Enzymatic cleavage of sialic acid from the abnormal fibrinogen restored fibrinogen function to normal. This hepatoma-associated dysfibrinogen (acquired dysfibrinogenemia) is similar in many respects to fetal fibrinogen and may represent the presence of a fetal form of fibrinogen in hepatoma.     

Studies of the Procoagulant and Fibrinolytic Activity of Promyelocytes in Acute Promyelocytic Leukaemia

Malignant cells from four patients with acute promyelocytic leukaemia (APL) were analysed for coagulant and fibrinolytic activity. For comparison polymorphonuclear leucocytes from normal donors and myeloblasts from patients with acute myelogenous leukaemia (AML) were also tested. The APL cells compared to the other cells consistently shortened the recalcification time and partial thromboplastin time of normal, factor VIII deficient and factor IX deficient plasma, but had no effect on factor X deficient or factor VII-X deficient plasma. APL cells demonstrated increased (250–1500%) tissue factor activity when tested in a two-stage assay in which tissue factor is the rate limiting component. The increased tissue factor activity was primarily found in the granular fraction of APL cells. Fibrinolytic and proteolytic activity of the APL cells was variable. Cells from three of the APL patients demonstrated a slight increase (150–400%), while the cells from one APL patient had markedly diminished proteolytic activity. The increased fibrinolytic activity was associated primarily with the granular fraction. Although the fibrinolytic activity is increased, it does not parallel the increase in tissue factor activity. This imbalance of coagulation and fibrinolysis in the cellular composition of promyelocytes could explain the high incidence of clinical thrombo-haemorrhagic disorders related to intravascular coagulation in APL.     

Proposals for the Classification of the Acute Leukaemias French-American-British (FAB) Co-operative Group

A uniform system of classification and nomenclature of the acute leukaemias, at present lacking, should permit more accurate recording of the distribution of cases entered into clinical trials, and could provide a reference standard when newly developed cell-surface markers believed to characterize specific cell types are applied to cases of acute leukaemia. Proposals based on conventional morphological and cytochemical methods are offered following the study of peripheral blood and bone-marrow films from some 200 cases of acute leukaemia by a group of seven French, American and British haematologists. The slides were examined first independently, and then by the group working together. Two groups of acute leukaemia, 'lymphoblastic' and myeloid are further subdivided into three and six groups. Dysmyelopoietic syndromes that may be confused with acute myeloid leukaemia are also considered. Photomicrographs of each of the named conditions are presented.     

Role of carbohydrate in multimeric structure of factor VIII/von Willebrand factor protein.

The carbohydrate moiety of the factor VIII/von Willebrand (vW) factor protein is important in the expression of vW factor activity and the intravascular survival of the protein. Studies of normal human factor VIII/vW factor protein indicate that there is a requirement of a full complement of penultimate galactose for the maintenance of a normal multimeric structure. Release of penultimate galactose by beta-galactosidase or modification by galactose oxidase results in loss of the largest molecular weight multimers and increased numbers of intermediate and smaller multimers. In contrast, terminal galactose on the factor VIII/vW factor protein does not appear to play a significant role in the maintenance of the multimer organization. The abnormalities in multimeric structure and molecular size were demonstrated by NaDodSO4/polyacrylamide/agarose gel electrophoresis, NaDodSO4/glyoxyl-agarose electrophoresis, and sucrose density ultracentrifugation. These studies indicate that the penultimate galactose plays a role in the maintenance of the largest multimers of the factor VIII/vW factor protein. This may explain why, in some patients with variant forms of vW disease, a carbohydrate abnormality also may affect the multimeric structure of the plasma factor VIII/vW factor protein.     

The effect of suramin on laboratory tests of coagulation.

The antitrypanosomal drug suramin, which has recently been under investigation as a cancer chemotherapeutic agent, has previously been found to induce heparin-like anticoagulants in treated patients. In the currently reported work suramin is shown to have an additional anticoagulant activity that is due to direct effects of the drug on procoagulant proteins. The studies were conducted with pooled normal plasma treated in vitro with suramin and with plasma samples obtained from patients who had received the drug intravenously for 2 weeks. It is demonstrated that in plasma suramin inhibits factors V, VIII, IX, X, XI, and XII, while thrombin, prothrombin, and factor VII are unaffected. The inhibition of factor V is virtually irreversible, although the effect of suramin on the other factors is readily reversed by dilution.