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Summary. The results are reported of a pilot study and two separate double blind controlled trials of the effectiveness of epsilon‐aminocaproic acid (EACA) in dental extractions in patients with haemophilia and Christmas disease. In the major trial 31 patients were studied; 23 at Oxford and eight at Cardiff. All patients received either EACA (6 g four times daily for 10 days at Oxford or for 7 days at Cardiff) or a placebo, in conjunction with a single preoperative dose of therapeutic materials expected to raise the plasma factor‐VIII or factor‐IX level to 50%. Post‐operative therapeutic materials were withheld unless intraoral bleeding occurred. Despite the fact that plasma factor‐VIII or factor‐IX levels were, on average, lower, the number of teeth extracted larger, the amount of therapeutic concentrates less and the postinfusion plasma factor‐VIII or factor‐IX levels lower in the EACA group at Oxford, the incidence of postoperative intraoral bleeding was lower and the requirements for postoperative therapeutic materials less in the group treated with EACA. Side‐effects were not a major problem. The number of patients studied at Cardiff was too few for statistical analysis but the results were similar to those at Oxford. The total conservation of therapeutic materials at Oxford in comparison to the amount utilized before EACA was used is estimated on the basis of these results to be approximately 12 000 factor‐VIII or factor‐IX units/patient, or approximately 190 units/kg/patient, equivalent, for each patient, to the amount derived from approximately 120 blood donations. These results show that EACA in conjunction with preoperative therapeutic concentrates sufficient to raise the plasma factor‐VIII or factor‐IX level to 50% can be useful for all patients with haemophilia and Christmas disease undergoing tooth extraction. In some patients EACA therapy is contraindicated and for these patients adequate cover with therapeutic materials must be provided during the postoperative period.

The outer membrane protein F (porin) from the PAO1 strain of Pseudomonas aeruginosa was purified by two different methods. One procedure involved separation by column chromatography of proteins extracted from isolated outer membranes, whereas the other involved extraction from gels after slab polyacrylamide gel electrophoresis of proteins extracted from cell envelopes. Both procedures yielded protein F preparations which successfully immunized mice from subsequent challenge with the PAO1 strain. The protein F preparations contained small quantities of lipopolysaccharide (LPS). This level of LPS contamination protected immunized mice from challenge with the homologous LPS serotype strain. However, immunization of mice with protein F preparations from the PAO1 strain also afforded protection against challenge with two different LPS serotype strains. This protective ability was lost when the protein F preparation was treated with papain before use as a vaccine. These observations support the conclusion that protein F has protective ability, which is not due to LPS contamination, when given as a vaccine. After immunization with the protein F preparation, mice showed an increase in antibody titer to the purified protein F preparation by enzyme-linked immunosorbent assay. Mice were protected passively by administration of rabbit antisera raised to the protein F preparation. These results indicate that the protein F preparation elicits a specific humoral antibody response in immunized animals. Our results suggest that purified protein F has potential as an effective vaccine for P. aeruginosa.

THE treatment of haemorrhage in patients severely affected with von Willebrand's disease has presented difficulty. Not only do these patients have a capillary defect evidenced by a greatly prolonged bleeding-time test but also a low level of Factor VIII in the blood. It has usually been assumed that adequate control requires that both defects be corrected. From the observations of Weiss (1962), Cornu, Larrieu, Caen andBernard (1963) and from our own records the duration of the bleeding recorded by the bleeding-time test is shortened erratically and for short periods of time following suitable treatment. The preparations with the best ability to shorten the bleeding time are those derived from fresh plasma collected into siliconecoated or plastic containers: such fractions are not readily available. When patients with von Willebrand's disease are treated with preparations containing Factor VIII the elevation of the Factor-VIII level in the blood continues for longer than in haemophilic patients. Also the administration of haemophilic plasma causes a rise in the blood level of Factor VIII (Nilsson, Blomback and Blombick, 1960; Cornu et al., 1963). It seems that these patients have some ability to form Factor VIII but lack an essential stimulating factor which is present in normal and haemophihc plasma. It is therefore much easier to raise the blood level of Factor VIII than effectively to reduce the bleeding time.

Knochenusur durch em hamophiles subperiostales H#{228}matom. Mitteilungen aiis den Grenzgebieten der Medizin und Chirurgie, 31, 381.TRUETA,

Summary1. Earlier it had been found that during fat mobilization there was an increased blood flow in the adipose tissue and the tissue contained a vasodilator substance. 2. Extract of an activated fat pad contained 3 to 25 times as much activity as the contralateral resting fat pad. 3. The following findings suggest that the vasodilator substance is prostaglandin E2: (a) It caused contractions of the guinea-pig ileum which were not reduced by mepyramine, but were reduced by atropine.(b) It caused a prolonged vasodilator response when injected closearterially to the epigastric fat pad. (c) It was eluted from a silicic acid column by a solvent system which is known to elute prostaglandins of the E series but not those of the F series.(d) Its indices of discrimination were similar to those of prostaglandin E's when assayed on three different pharmacological preparations.(e) On thin-layer chromatography it behaved more like prostaglandin E2 than E1.4. Neither prostaglandin E1 nor prostaglandin E2 inhibited the release of free fatty acids from the rabbit epigastric fat pad by ACTH1-24. 5. It seems likely that prostaglandin E2 is responsible for the vasodilatation accompanying fat mobilization from adipose tissue.

Summary. 24 haemophiliacs with factor VIII antibodies were treated with factor VIII replacement therapy for haemorrhagic episodes. In seven patients with low level of antibody the antibody disappeared over 1–5 years. In six patients with high levels of antibody the titre of antibody has fallen to low levels. In the remaining 11 patients, some of whom were frequently and others infrequently treated, the level of antibody has changed very little except in one patient who showed a dramatic fall in antibody titre while receiving 1500 units of factor VIII weekly over an 8 month period.

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