Models describing the evolution of the partial pressure of atmospheric oxygen over Phanerozoic time are constrained by the mass balances required between the inputs and outputs of carbon and sulfur to the oceans. This constraint has limited the applicability of proposed negative feedback mechanisms for maintaining levels of atmospheric O(2) at biologically permissable levels. Here we describe a modeling approach that incorporates O(2)-dependent carbon and sulfur isotope fractionation using data obtained from laboratory experiments on carbon-13 discrimination by vascular land plants and marine plankton. The model allows us to calculate a Phanerozoic O(2) history that agrees with independent models and with biological and physical constraints and supports the hypothesis of a high atmospheric O(2) content during the Carboniferous (300 million years ago), a time when insect gigantism was widespread.

Factor VIII was purified from cryoprecipitate by ion exchange chromatography on solid phase polyelectrolyte E-5 (PE-E5). The product was highly purified (3.5 u VIII:C/mg protein) compared to conventional concentrate (0.3 u VIII:C/mg protein) with low fibrinogen, low isoagglutinin titre, and a ratio of factor VIII coagulant activity (VIII:C) to factor VII related antigen (VIIIR:Ag) of 16:1. Trial infusions of this material (PE VIII) were given to three patients with severe haemophilia A and one patient with homozygous von Willebrand's disease. These patients also each received separate infusions of intermediate purity concentrate (IPC) for comparison. There were no adverse effects. The mean half life of VIII:C after PE VIII infusion in the haemophiliacs was 10.9 h and after IPC was 12.1 h, a statistically insignificant difference. The survival of factor VIII coagulant antigen (VIII:CAg) was similar to that of VIII:C. In contrast, the half life of VIII:C and of VIII:CAg was very short after infusion of PE VIII in the patient wih von Willebrand's disease (2.4 h). IPC when infused in this patient produced a typical secondary rise of VIII:C. Two bleeding episodes in severe haemophiliacs were satisfactorily treated with PE VIII. PE-E5 deserves further study as a means of preparing clinical concentrates of factor VIII.

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SummaryFactor XI deficiency is an uncommon bleeding disorder usually manifested by excessive bleeding after surgery or trauma. Until recently the only effective therapy has been fresh-frozen plasma (FFP) infusion. We describe the efficacy and safety of a new factor XI concentrate produced from human donor plasma by a modification of the method used for antithrombin III concentrate. The mean recovery of factor XI in the circulation measured on 62 occasions was approximately 91% of the injected dose, and the mean half-disappearance-time was 52 h. The concentrate was used for 31 invasive procedures in 30 patients, including 16 patients who had a definite bleeding tendency on previous occasions, with normal haemostasis being achieved in all but 1. Only 1 patient (previously experiencing allergy to FFP) experienced adverse effects during infusion. Monitoring of liver function tests and viral antibody status in suitable patients has shown no evidence of transmission of hepatitis viruses, HIV-1 or parvovirus B19.We conclude that this concentrate provides effective treatment for patients with factor XI deficiency. Preliminary results suggest safety from virus transmission, but this needs to be established in further studies of previously untreated patients.

Systemic arterial pressure, superior mesenteric arterial and venous pressures, blood flow, arteriovenous oxygen difference, lymph flow, and intestinal volume were monitored continuously from an autoperfused loop of cat ileum to determine the effects of locally infused adenosine on intestinal hemodynamics, oxygen consumption, and capillary fluid exchange. The results indicate that adenosine, inosine, and hypoxanthine are vasodilators in the intestinal circulation. Local infusion of adenosine significantly reduces vascular resistance, but lymph flow, lymph oncotic pressure, and lymphatic protein flux remained unchanged from control, and the intestinal volume rapidly became constant after an initial blood volume shift. Intestinal oxygen consumption decreased significantly in both autoperfused and constant flow preparations. Pretreatment with aminophylline prevented the reduction in oxygen consumption and greatly attenuated the vasodilatory effect of adenosine. The reactive hyperemic response to 60-s arterial occlusions was virtually unchanged following aminophylline treatment. Adenosine depressed oxygen utilization of mucosal and muscularis strips in vitro and caused a significant redistribution of blood flow from the mucosal-submucosal layer to the muscularis in autoperfused preparations. The results of this study indicate that adenosine significantly reduces vascular resistance and oxygen consumption, yet does not alter fluid exchange in the small intestine.