Tamoxifen was administered in the diet (420 p.p.m.) to female F344 (Fischer), Wistar (LAC-P) and LEW (Lewis) rats to determine for each strain the early morphological and biochemical changes ...associated with the subsequent development of liver cancer. Hepatic DNA damage, as determined by 32P-postlabelling, showed a cumulative increase with time from 500 adducts/10(8) nucleotides at 30 days to almost 3000 adducts/10(8) nucleotides after 180 days, with little difference between strains at this time point. A significant strain difference was found in the number of adducts present in the Fischer rats at 90 days, compared to the Wistar and Lewis strains. There was a marked strain differences in the time to development of liver tumours. After 6 months treatment, both Wistar and Lewis rats had tumours while none were seen in the Fischer animals. After 11 months, all of the Wistar and Lewis rats had developed liver carcinoma, while the Fischer rats developed liver carcinoma by 20 months. Depression in cell proliferation, relative to age-matched controls, was seen in the livers of Fischer rats after six months of exposure to tamoxifen, in contrast to an increase in the Wistar and Lewis rats. This observation is consistent with the promotion of foci to tumours and the subsequent progression of tumours to carcinomas in the latter two strains. These data may assist in establishing the possible risk factors, such as extent of DNA damage and increased liver cell proliferation, to women with long-term prophylactic exposure to tamoxifen.
The purified cytochrome b-c1 complex of Rhodopseudomonas sphaeroides has two b cytochromes distinguishable by optical, thermodynamic and electron paramagnetic resonance criteria (gz values are ...approximately equal to 3.75 and approximately equal to 3.4). EPR features typical of a Rieske iron sulfur cluster (g values of 2.03 1.90 and 1.81) and a c1 type cytochrome (g approximately equal to 3.4) were also observed. The b and c1 cytochromes were individually purified from the complex. The cytochrome c1 retained its native EPR spectrum. The b cytochrome lost over 90% of the intensity from the 'b566 type' heme site (g approximately equal to 3.75), while the 'b561 type' heme site (g approximately equal to 3.4) retained its native EPR spectrum.
To characterize causes of death in the operating room (OR) following major trauma, a retrospective review of admissions to eight academic trauma centers was conducted to define the etiology of death ...and challenges for improvement in outcome. Five hundred thirty seven OR deaths of 72,151 admissions were reviewed for mechanism of injury, physiologic findings, resuscitation, patterns of injury, surgical procedures, cause of death, and preventability. Blunt injuries accounted for 61% of all injuries, gunshot wounds (GSW) accounted for 74% of penetrating injuries. Sixty two percent of all patients arrived in shock. Average blood pressure (BP) was 52 mm Hg at the scene and 60 mm Hg on admission, with the period of shock > 10 minutes in 74%. Only 56% were resuscitated to a BP > 90 mm Hg before surgery. Average time to the OR was 30.1 minutes and mean best postresuscitation pH was 7.18. Mean best OR temperature was 32.2 degrees C. Recurrent injury patterns judged as the primary cause of patient death included head/neck injury (16.4%), chest injury (27.4%), and abdominal injury (53.4%). Actual cause of death was bleeding (82%), cerebral herniation (14.5%), and air emboli (2.2%). A different strategy for improved outcome was identified in 54 patients with the following conclusions: (1) delayed transfer to the OR remains a problem with significant BP deterioration during delay, particularly following interfacility transfer; (2) staged injury isolation and repair to allow better resuscitation and warming may lead to improved results; (3) combined thoraco-abdominal injuries, particularly with thoracic aortic disruption, often require a different sequence of management; (4) aggressive evaluation of retroperitoneal hematomas is essential; (5) OR management of severe liver injuries remains a technical challenge with better endpoints for packing needed; and (6) resuscitative thoracotomy applied to OR patients in extremis from exsanguination offers little.
