An alternate origin for the placental isoenzyme of alkaline phosphatase.

By means of an electrofocusing technique, the serum specimens of pregnant women routinely revealed three bands of alkaline phosphatase (ALP) that were released by placental syncytiotrophoblast, germ cell (ovary), and fetal intestine at pl of 4.73, 4.65, and 4.55, respectively. When defining reference ranges for ostensibly healthy persons of all decades of age and investigating patients with elevated total ALP activity, we found the isoenzyme at pl 4.73 to be above the established reference range in some nonpregnant women and in men. Evidence suggests that T lymphocytes from whole blood or in vivo tissue were the origin of this pl 4.73 ALP band; the isoenzyme being released during cell lysis, in cellular turmoil from any cause, or when active cell division occurs. A designation of lymphocyte ALP is proposed for this ALP band that is observed in a broad group of diseases associated with abnormal lymphocyte function.     

External fixation of complex open humeral fractures

Seven cases of complex open humeral fractures treated by external fixation are reported. The external fixation allowed the associated injuries to nerves, arteries and soft tissues to be adequately treated. Four cases developed non-union and of these, three cases treated by bone-grafting and plating united, but the one case treated by intramedullary nail without bone-graft did not unite. Frame construction and pin placement are discussed. The recommended plan for treatment of these fractures is initial external fixation until adequate soft tissue healing is achieved and sepsis controlled. Then early bone-grafting and plating is advocated if there is no progressive fracture healing. The problems and advantages encountered in the use of external fixation are also described.     

Traumatic rupture of extracardiac valved conduit: unusual late complication producing outflow tract obstruction

A 22-year-old woman died suddenly 15 years after successful repair of truncus arteriosus with a valved Dacron conduit. At autopsy there was complete obstruction of the right ventricular outflow tract by a large organizing thrombus between the outer aspect of the conduit and the adherent pericardial tissue. This rare late complication may have resulted from an unrecognized deceleration injury occurring at the time of a serious automobile accident 5 months before death.     

1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 1. Synthesis and biological properties of alkyl alcohol and statine derivatives

A series of 1,2,4-triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity, which incorporate (1S,2S)-2-amino-1,3-dicyclohexyl-1-hydroxypropane, statine (Sta), and (3S,4S)-4-amino-5-cyclohexyl-3-hydroxy-pentanoic acid (ACHPA) transition-state mimetics, have been prepared. Structure-activity relationships for renin inhibitory activity in the series are consistent with the 2-[8-isobutyl-6-phenyl-1,2,4-triazolo[4,3-a]pyrazin-3-yl]-3-(3 pyridyl)propionic acid moiety 10b acting as a non-peptidic replacement for the P4-P2 (Pro-Phe-His) residues of the natural substrate angiotensinogen. Compounds 12m, 12o and 12q were potent inhibitors of partially purified human renin (IC50 values 1.7, 6.8, and 3.7 nM, respectively), and also effectively lowered blood pressure in anesthetized, sodium depleted marmosets following intravenous administration. On oral administration however, no blood pressure lowering activity could be detected, and absorption studies in bile duct cannulated rats indicate that this may be due primarily to poor oral absorption, rather than rapid biliary excretion. The reason for the observed poor oral activity is not clear, but it seems unlikely that poor aqueous solubility or metabolic instability to gut enzymes are rate-determining, and other factors such as high molecular weight may also be very important.     

Strain-specific alterations in consumption of a palatable diet following repeated stressor exposure.

Exposure to acute inescapable shock caused reductions in the consumption of a highly palatable diet. The magnitude and duration of the reduction varied across strains of mice. With repeated exposure to footshock, consumption of the diet returned to baseline levels, although alterations of weight appeared to be more persistent. The course of the adaptation varied across strains of mice; however, the rate of adaptation was unrelated to the extent of the alterations of consumption induced by the acute stressor. When mice were exposed to a series of different stressors, the adaptation progressed less readily, and reductions of diet consumption were apparent in strains that had not shown such an effect following acute stressor application or when repeatedly exposed to a single type of stressor. Data were discussed with respect to the mechanisms that might be operative in subserving stressor-induced anhedonia.