The effects of pharmacologic intervention on the fates of severely traumatized small veins and arteries have been studied in a rabbit model. Controls were given bolus doses of saline and a group treated with a combination of dextran 40 and acetylsalicylic acid starting prior to traumatization and continuing until postoperative day 5. Relative to controls, bleeding times in the treated group were significantly lengthened in arteries but not in veins, and venous patency significantly improved throughout the interval ending 2 weeks postoperatively. Arterial patency was at first highly improved but by 2 weeks, occlusion was virtually 100 percent. Since some of the occlusions took place more than a week after traumatization, the effects of antithrombotic agents on patency may need to be evaluated over considerably longer time periods than has previously been the rule.

Administration of indomethacin may aid treatment of intracranial hypertension, and the present study was conducted to determine the optimal dose, In healthy volunteers, cerebral blood flow (CBF) has been shown to decrease considerably after a bolus dose of indomethacin, 0.4 mg/kg, followed by continuous infusion, 0.4 mg/kg/h. This decrease was sustained for 6 h without any evidence of adaptation. In a randomized study in healthy volunteers, indomethacin, 0.1, 0.2, and 0.3 mg/kg, was given as bolus, followed by continuous infusion of 0.1, 0.2, and 0.3 mg/kg/h. CBF decreased from normal levels (52-74 ml/100 mg/min) to 38-51 ml/100 g/min. There were no differences among the three groups in CBF reduction, and the reduction was sustained during the 6-h infusion period. Rectal application of 100 mg indomethacin was found to reduce CBF from normal levels (54-74 ml/100 mg/min) to 33-48 ml/100 mg/min. These low levels were only sustained for 2 h, and values returned to normal over the next 6 h. We observed no rebound phenomenon 2 h after stopping the infusion and no rebound after 100 mg of rectally applied indomethacin. Since a dose as low as 0.1 mg/kg/h is effective, it is possible to treat most patients in a 24-h schedule without going over maximum recommended doses.

Arteriotomy/intimectomy and venotomy/intimectomy were performed in the rabbit ear. Low molecular-weight dextran (dextran 40) was infused 2 h before reperfusion and on postoperative days 1, 3 and 5 using a standard clinical protocol. Bleeding-times at reperfusion were recorded and patencies determined at intervals up to 2 weeks. Rabbits given single preoperative bolus doses of saline were used as controls. Dextran significantly prolonged bleeding-times in arteries and significantly improved early patency in both types of vessel, but the enhancements disappear by one week. Dextran 40 infusion thus has little effect on long-term patency.

A case of severe polyuria elicited by intravenous administration of a normal pharmacological dose of dexamethasone is reported. The polyuria did not respond to treatment with vasopressin. A 15-year-old girl with a brain tumour was referred for surgery. After induction of anaesthesia she received dexamethasone 4 mg i.v., and developed a massive polyuria with hourly diuresis of up to 1250 ml. There was no response to treatment with vasopressin in doses well above those normally used. The patient did not fulfil any known cause of diabetes insipidus, and to our best knowledge, this case is the first with glucocorticoid-induced and vasopressin-resistant polyuria ever reported in man.

Arteriotomy/intimectomy and venotomy/intimectomy were performed in the ears of 43 rabbits. Twenty were treated with iloprost given as intravenous doses of 10 micrograms/kg body weight (bw) administered shortly before reperfusion followed by hourly infusions (3 micrograms/kg b w) until 12 hrs after reperfusion. At reperfusion venous and arterial bleeding times were noted. Patency was determined at 15-min intervals until 2 hrs after reperfusion and at 1 and 2 weeks postoperatively. As controls, 23 rabbits were given a single infusion of saline. Compared to controls, iloprost significantly prolonged arterial and venous bleeding times and significantly improved patency 2 hrs after reperfusion. One and two weeks later, however, virtually all vessels were occluded. Administered in this fashion, iloprost does not improve long-term patency in highly traumatized small veins and arteries.

The peroxidase-catalyzed aerobic oxidation of a linear aldehyde, leading to the next lower homologue in the triplet state, is accompanied by Norrish type II product ethylene when the substrate is pentanal. This system appears to provide an example of "photobiochemistry without light" because ethylene is a plant hormone and is formed in lipid peroxidation when the recurrent oxidation of linear aldehydes occurs.

In the presence of the surfactant hexadecyltrimethyl ammonium bromide (CTAB) a cascade of electronically excited states accompanies the successive steps in the peroxidative metabolization of the strong estrogenic and tumourogenic diethylstilbestrol. Reversing the order by necessity, we report in this first paper results with the metabolites.Exposure of 4-hydroxypropiophenone, Z,Z-dienestrol or E,E-dienestrol to horseradish peroxidase and H2O2 promotes oxygen uptake and spectral alterations. Light emission is observed provided that the surfactant CTAB is present. With the three substrates, 4-hydroxybenzoic acid and a new metabolite, p-benzoquinone, have been identified. With both dienestrol isomers, 1-(4'-hydroxyphenyl)-propan-1-on-2-ol has been identified.In all cases the emission spectrum indicates the presence of several emitters. Possible chemiexcitation routes are pointed out. From the dramatic increase of the emission by enhancers, values as high as 1 x 10(-5) are inferred for the product of the quantum yields of chemiexcitation and energy transfer.