Oral glucose tolerance tests have generally been used to differentiate between diabetes mellitus and the various forms of non-diabetic glycosuria (1).On the basis of such oral tests alterations in carbohydrate metabolism have also been reported in numerous disorders other than diabetes mellitus. These include endocrine, intracranial and hepatic diseases (2), arthritis (3), and convulsive disorders of various types (4). Oral METHODSSixty normal adult subjects were studied. All were in the post-absorptive state and remained in a recumbent position throughout the morning. After a fasting venous blood sample had been obtained, 50 ml. of a 50 per cent solution of glucose in distilled water were injected intravenously during a period of two minutes. Samples of venous blood were obtained at intervals during the next two or three hours. In the majority of cases hourly urine samples were collected as well. A modification of Benedict's macro-method (6) was used for blood sugar analyses, protein-free filtrates of whole blood being employed. Protein was removed by the zinc precipitation method of Somogyi (7), which also removes most of the non-fermentable reducing substances. Rothberg and Evans' (8) tubes were used in the final visual colorimetric comparison. Urine samples were analyzed for glucose by the quantitative method of Benedict (9).The same procedure was applied to 271 patients in the New Haven Hospital. Only a few with outright diabetes were included. The majority were selected either because, on clinical grounds, some abnormality of carbohydrate metabolism was suspected or because they had some one of a variety of disorders reputedly attended by derangement of carbohydrate metabolism.RESULTS

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In the United States, the two-stage theory of blood coagulation is widely accepted. This theory recently reviewed by Quick (1) and Eagle (2) suggests that in the first stage prothrombin, calcium ion and thromboplastin interact to form thrombin. Thrombin, in the second stage, converts fibrinogen to fibrin. Plasma thromboplastin has been considered to be of platelet origin. The phenomenon of the initiation of coagulation when blood is shed has been considered by many investigators to be due to the disintegration of platelets with the release of thromboplastin.It has been known for many years that the coagulation time of blood taken in paraffin tubes is much longer than that of blood taken in glass tubes. The explanation usually offered for this phenomenon is that the glass, acting as a foreign surface, destroys the platelets at a more rapid rate than occurs in the presence of paraffin. The increased amount of thromboplastin so liberated is then considered to be responsible for the shorter coagulation time in glass vessels. Nolf (3) has criticized this explanation. He states that his experimental data indicate that cell-and platelet-free plasma already contains all of the factors necessary for blood coagulation. He believes that the initiation of coagulation is the result of the direct modification of one or more of the constituents of cellfree plasma by contact with a foreign surface such as glass.In view of this difference of opinion, it seemed advisable to reinvestigate the role which foreign surfaces play in the blood coagulation reaction.

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Previous investigations in this laboratory have shown that normal human plasma rendered free from cellular elements, by Berkefeld filtration, is capable of reducing the coagulation time of the blood of patients with hemophilia both in vitro and in vivo (1). It has also been demonstrated that this coagulation activity of the plasma was associated with the globulin fraction of the plasma proteins (2, 3). The published data do not however identify the active material as a protein, nor do they differentiate it from fibrinogen and prothrombin, constituents of the globulin fraction which also play a role in blood coagulation. Indeed " globulin substance " as prepared by previous methods was known to contain both prothrombin and fibrinogen (2). The present communication concerns a study of the clot promoting activity of nornal human plasma, after the removal of prothrombin and fibrinogen. PREPARATION OF MATERIALSSeveral authors (4, 5, 6) have described methods for the removal of prothrombin from blood plasma. These methods consist essentially of adsorption of this substance on the hydroxides of aluminum, calcium, or magnesium. Chew (7) has suggested recently that following filtration through Seitz filters (calcium magnesium aluminum iron silicate) a prothrombin free filtrate of plasma can be obtained.By the use of the Quick et al. technique (8) it is possible to obtain a measure of the amount of prothrombin contained in preparations made from plasma.2 Table I 1The expenses of this investigation were defrayed in part by a gift to Harvard University from Smith, Kline, and French Laboratories, Philadelphia; and by a grant given in honor of Francis Weld Peabody by the Ella Sachs Plotz Foundation.2All plasmas studied were derived from normal human 0.25 per cent citrated blood centrifuged 30 minutes at 2000 r.p.m., filtered through 2 thicknesses of Number 2 Whatman paper and then through a Berkefeld V filter.shows the " prothrombin times " of certain of these preparations. It will be observed that while preparations with commercial aluminum hydroxide were quite inefficient the use of aluminum hydroxide C-gamma (9) gave preparations relatively free from prothrombin. The amount of prothrombin remaining depended upon the number of times the adsorption was repeated. More striking results were obtained however by passing Berkefeld filtrates of citrated normal human plasma 5 times through Seitz filters using fresh pads for each filtration. In addition to being prothrombin free these preparations had the advantage of being sterile. On the basis of these observations the Seitz filtration method was used routinely for the removal of prothrombin from plasma. Each batch of plasma treated in this manner was tested for prothrombin by the Quick technique and none was found. The presence of fibrinogen in the Seitz filtrate was demonstrated by the formation of a clot upon the addition of fresh serum as a source of thrombin. In one typical experiment one-tenth ml. of such serum clotted one-tenth ml. of the Seitz filtrate in 29 seconds.Plasma...