Two mechanisms may account for brain edema in fulminant hepatic failure: the osmotic effects of brain glutamine, a product of ammonia detoxification, and a change of cerebral blood flow (CBF). We have shown brain edema, a marked increase in brain glutamine, and a selective rise in CBF in rats after portacaval anastomosis receiving an ammonia infusion. In this study, we inhibited the activity of glutamine synthetase with methionine-sulfoximine (MSO) and examined ammonia levels, brain water and CBF. A major complication of fulminant hepatic failure (FHF) is the development of brain edema and intracranial hypertension, a leading cause of death in this syndrome. 1 The pathogenesis of the increase in brain water in the setting of a failing liver remains controversial. Over a decade of research in this area, 2 main theories have emerged. In the first, the accumulation of glutamine in glial cells would account for the development of brain edema. 2 Glutamine is the product of detoxification of ammonia, a reaction localized to astrocytes in view of the selective localization of glutamine synthetase to this cell. 3 Glial swelling is a prominent neuropathological feature of experimental 4 and human FHF. 5 Inhibition of glutamine synthesis with methionine-sulfoximine (MSO) prevents the development of ammonia-induced brain edema in normal rats, 6 decreases astrocyte swelling, 7 and ameliorates brain edema in rats after portacaval anastomosis receiving an ammonia infusion. 8 A second view emphasizes a pathogenic role for disturbances in the cerebral circulation. 9 A high cerebral blood flow (CBF) is noted in patients with FHF who develop brain edema. 10,11 In addition, failure of cerebrovascular autoregulation to changes in arterial pressure is also prominent in these subjects. 12 The possibility that this increase in CBF may be linked to brain edema is further supported by reports of selective abnormalities of the blood-brain barrier, a controversial observation in experimental models of FHF. 13,14 The rat after portacaval anastomosis receiving a continuous intravenous ammonia infusion is a well-standardized, controlled paradigm of brain edema, in which cerebral swelling occurs in the absence of acute liver failure. In this preparation, we have recently reported the simultaneous presence of a marked increase in brain glutamine and a selective 3-fold increase in cerebral perfusion at the time of an increase in brain water and intracranial pressure. 15 Furthermore, mild hypothermia (35°C, 33°C) prevented the development of brain edema in spite of a similar increase in brain glutamine as the normothermic animals. The main effect of hypothermia was to prevent the rise in CBF seen in the edematous, normothermic rats.If MSO ameliorates brain edema in this model by inhibiting glutamine synthesis and hypothermia also prevents brain swelling by normalizing CBF, it is of interest to determine the effects of MSO on cerebral perfusion. Normalization of CBF with MSO would suggest that the 2 postulated mechanisms of brain edema may in fac...

Four cases of pancreatic pseudocyst in African children are described. There is some evidence that they followed pancreatitis of unknown aetiology. None had a history of trauma. Three were treated by cystogastrostomy, and the fourth by excision of the cyst.

The rapid single intravenous injection of the cholecystokinin preparation Cecekin (Vitrum) was found to inhibit the responses of Heidenhain pouch dogs to stimulation by gastrin extract or synthetic gastrin-like penta-peptide at both submaximal and supramaximal dose rates, to histamine, to the stable cholinergic drug Amechol, and to feeding a meat meal. The pattern of inhibition suggested that the inhibitor effect was exerted in the region of the acid secreting cell. Pure cholecystokinin was capable of inhibiting the acid response of the Heidenhain pouch dogs to histamine. Although both pure secretin and pure cholecystokinin have now been demonstrated to be possible inhibitor agents arising from duodenal mucosa, it is likely that endogenous duodenal acidification releases a further as yet unidentified humoral inhibitor agent, or that secretin and/or cholecystokinin may act in collaboration with each other or a further inhibitor agent. In dogs with both a Heidenhain pouch and a simple fistula into the normally vagally innervated gastric remnant and in which antrectomy had been performed, a single rapid intravenous injection of the Cecekin had no effect on the Heidenhain pouch responses to the continuous intravenous infusion of histamine. The acid output from the main gastric remnant, however, was increased by the Cecekin injection. Several hypotheses to account for the difference in behaviour in the two preparations are discussed. The possibility is raised that Cecekin contains some gastrin-like activity.

1965). This procedure entails simple digital fracture of the occluding membrane which is approached through the right atrium. However, from the experience of the cases described here it is apparent that this is not always feasible. Moreover, if the membrane is not excised, there is always the possibility of re-stenosis. In Case I complete obstruction of the inferior vena cava recurred 4 years after the membrane had been split and dilated.The ideal procedure would therefore seem to be excision of the membrane under direct vision, with the aid of cardiopulmonary by-pass. The inferior vena cava should be drained by a catheter introduced into the femoral vein and advanced to the site of the obstruction. The superior vena cava should be drained by a catheter introduced via the right atrium and arterial perfusion effected by cannulating the femoral artery. The occluding membrane may then be visualized by opening the right atrium. Palpation of the drainage catheter in the inferior vena cava will give accurate assessment of the thickness of the obstructing membrane. It should then be possible to cut down on the drainage catheter and to excise the membrane with little risk of perforation of the inferior vena cava. SUMMARYFour cases of membranous obstruction of the hepatic segment of the inferior vena cava are described.The clinical presentation and problems of surgical management are discussed.Addendum.-Since submitting this paper for publication we have encountered a 35-year-old Bantu female with recurrent varicose ulceration of the legs. Several unsuccessful operations had been performed in an attempt to cure the varicosities. Angiography revealed membranous obstruction of the hepatic segment of the inferior vena cava. The membrane was successfully resected under cardiopulmonary bypass as described in the text.

No abstract