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Background: Spontaneous perioperative otorrhagia is an extremely rare entity with only 4 cases reported in the literature to date, all of which were recognized after the termination of the procedure., Case: We describe the first reported case of otorrhagia recognized intraoperatively causing abortion of the procedure in a 60-year-old woman undergoing laparoscopic sacrocolpopexy. Otoscopy by the otolaryngology service revealed multiple intracutaneous hematomas and bleeding in bilateral external auditory canals. Computed tomography scan of the head revealed no intracranial hemorrhage. She underwent postoperative drainage by the otolaryngology service with no permanent ear-related sequelae., Conclusions: We present the fifth reported case of spontaneous perioperative otorrhagia, the first of which to be noticed intraoperatively and cause premature termination of the procedure. The etiology is postulated to be increased arterial and venous pressures causing rupture of subcutaneous capillaries. In our case, several factors may have contributed to this event, including steep Trendelenburg patient positioning, intraperitoneal carbon dioxide insufflation from laparoscopy, and an intraoperative hypertensive episode.

Sirolimus (rapamycin) is an immunosuppressant used in preventing allograft rejection and in drug-eluting stents to prevent restenosis after angioplasty. Zotarolimus, an analogue of sirolimus, was designed to have a shorter in vivo half-life. Zotarolimus was found to be mechanistically similar to sirolimus in having high-affinity binding to the immunophilin FKBP12 and comparable potency for inhibiting in vitro proliferation of both human and rat T cells. Rat pharmacokinetic studies with intravenous dosing demonstrated terminal elimination half-lives of 9.4 hours and 14.0 hours for zotarolimus and sirolimus, respectively. Given orally, T1/2 values were 7.9 hours and 33.4 hours, respectively. Consistent with its shorter duration, zotarolimus showed a corresponding and statistically significant 4-fold reduction in potency for systemic immunosuppression in 3 rat disease models. Pharmacokinetic studies in cynomolgus monkey underpredicted the half-life difference between zotarolimus and sirolimus apparent from recent clinical data. In vitro inhibition of human coronary artery smooth muscle cell proliferation by zotarolimus was comparable to sirolimus. Drug-eluting stents for local delivery of zotarolimus to the vessel wall of coronary arteries are in clinical development. The pharmacological profile of zotarolimus suggests it may be advantageous for preventing restenosis with a reduced potential for causing systemic immunosuppression or other side effects.

Metabotropic glutamate receptors (mGluRs) have previously been shown to play a role in pain transmission during inflammatory or neuropathic pain states. However, the role of mGluR5 in post-operative pain remains to be fully investigated. The present study was conducted to characterize analgesic activity of 2-methyl-6-(phenylethynyl)-pyridine (MPEP) in the skin-incision-induced post-operative pain model in rats. MPEP is a potent and selective mGluR5 antagonist with high affinity (K(i)=6.3+/-0.9 nM) in rat cortex using [(3)H]-MPEP as a radioligand, while not competing with the mGluR1-selective radioligand [(3)H]-R214127 (K(i)>10,000 nM) in rat cerebellum. Post-operative pain was examined 2 h following surgery using weight-bearing (WB) difference between injured and uninjured paws as a measure of non-evoked pain. In this model, MPEP, as morphine, showed dose-dependent effects and full efficacy after systemic administration (ED(50)=15 mg/kg, i.p. for MPEP, ED(50)=1.3 mg/kg, s.c. for morphine). In addition, intrathecal (i.t.) and intracerebroventricular (i.c.v.) MPEP reduced WB difference (ED(50)=65 microg/rat i.t. and ED(50)=200 microg/rat i.c.v.). Interestingly, intraplantar (i.pl.) injection of MPEP either before or after surgery induced a similar reduction in WB difference (ED(50)=90 microg/rat, i.pl.) while contralateral i.pl. MPEP injection did not produce any effect. These results demonstrate that both peripheral and central mGluR5 receptors play a role in nociceptive transmission observed during post-operative pain. In addition, the data suggest that mGluR5 antagonists could offer a new therapeutic approach to the treatment of post-operative pain.

Objective: To examine the influence of race and other potentially confounding variables on the outcome of carotid endarterectomy (CEA)., Summary: Previous studies have demonstrated that CEA is performed less frequently in black patients, although little attention has been focused on the influence of race on the outcome of surgery., Methods: The Maryland Health Services Cost Review Commission database was reviewed to identify all elective CEA procedures performed in all nonfederal acute care hospitals in the state from 1990 through 1995 to examine the influence of race and other factors on the rates of in-hospital complications, in-hospital stroke, length of stay, and total hospital charges., Results: Carotid endarterectomy was performed in 9,219 (94%) white and 623 (6%) black patients during this period. The in-hospital stroke rate was 1.7%-3. 1% among black patients and 1.6% among white patients. Black patients had a longer length of stay and higher mean hospital charges than white patients. Multivariate logistic regression analysis identified black race as an independent risk factor for in-hospital stroke. Performance of CEA by a high-volume surgeon was protective for the combined occurrence of in-hospital stroke or death, and whites were more than twice as likely to undergo surgery performed by high-volume surgeons. Conversely, undergoing surgery in a low-volume hospital was associated with in-hospital stroke, and blacks were four times as likely to use low-volume hospitals., Conclusions: Black patients who underwent elective CEA in Maryland from 1990 to 1995 had an increased incidence of in-hospital stroke, a longer hospital stay, and higher hospital charges than whites. Black race was identified as an independent risk factor for in-hospital stroke, although the reasons for this influence of race on outcome are undefined. The authors' observations also suggest the possibility of limited access to optimal surgical care among blacks, and this issue warrants further study.

Rapamycin, a macrolide antibiotic known to prevent allograft rejection, is a potent inhibitor of cell proliferation. Therefore we studied the effects of orally administered rapamycin in a pig model of balloon injury in an attempt to reduce the cellular proliferation and neointimal formation thought to play a role in restenosis. Twenty Yucatan minipigs, divided into groups of 10 animals each, were subjected to balloon inflation of the carotid arteries. One group received the methylcellulose vehicle for rapamycin, whereas the second group was treated for a total of 31 days with 2.0 mg/kg of rapamycin administered daily by oral gavage. This dose and treatment regimen produced significant (p < 0.05) reductions in neointimal area (59%) and in the maximal thickness of the neointima (59%) when comparisons were made with vehicle-treated animals. These effects were accompanied by a significant increase in the lumen area in animals that received rapamycin (33%). Medial area was decreased by 18% in these animals. Blood samples from rapamycin-treated pigs indicated peak concentrations of 1.87 +/- 0.45 and 1.70 +/- 0.24 ng/ml at 2 and 4 weeks after balloon angioplasty, respectively. Significant increases in blood pressure of 21 mm Hg and decreases in heart rate of 25 beats/min also were observed in rapamycin-treated animals relative to those that received vehicle. These results indicate that the antiproliferative effect of rapamycin can be demonstrated after oral dosing in a pig vascular injury model, suggesting a possible therapeutic utility for rapamycin or its analogs in patients undergoing balloon angioplasty.