We asked whether the anesthetic requirement (MAC) of fetal lambs is lower than that of pregnant ewes. In five pregnant ewes anesthetized with a subarachnoid block, a fetal foot was withdrawn through a hysterotomy. The ewe then breathed 1.5% halothane and a clamp was applied to the fetal foot at 2-min intervals. We concomitantly obtained arterial blood from previously implanted catheters. When fetal movement in response to clamping the foot ceased, halothane was discontinued and the stimulus and sampling continued until the fetus began to move. Anesthesia was again resumed and continued until movement stopped. Anesthesia was then deepened and MAC was determined in the mother (stimulus--ear clamp). The fetal blood concentrations of halothane at MAC were 48 +/- 28 mg/L; they were 133 +/- 5 mg/L in the mother. This difference was highly significant (P less than 0.001). Calculated end-tidal concentrations were 0.33% and 0.69%, respectively. In two animals delivered by cesarean section, MAC increased progressively over the first 12 h of life. Progesterone levels concomitantly decreased.
Rats were subjected to total cerebral ischemia by occluding outflow from the heart. In control experiments and following different periods of ischemia, potassium concentration was measured in cisternal cerebrospinal fluid (CSF). It rose to 19.4 mEq/liter following 16 minutes of ischemia. Changes in cerebrovascular resistance (CVR) were also assessed by measuring the cerebral perfusion rate (CPR). Following two minutes of ischemia, CVR was decreased to half control value. After 8 and 16 minutes of ischemia, CVR was markedly increased, and "no-flow" state was approached after 16 minutes of ischemia. The CVR increased concomitantly with increase in potassium concentration in cisternal CSF. We suggest that the increase in CVR following cerebral ischemia is due to increase in potassium concentration in brain extracellular fluid and is part of a vicious circle that leads to brain death.
We assessed the ability of the Manitoba Medical Service Foundation (MMSF, a small not-for-profit foundation affiliated with Manitoba Blue Cross) to determine the best candidates for selection to receive research funding support among new researchers applying to the Research Operating Grants Programme (ROGP). Using bibliometric and grants funding analyses, we retrospectively compared indices of academic outputs from five cohorts of MMSF-funded and not MMSF-funded applicants to the annual MMSF ROGP over 2008 to 2012, from 1 to 5 years after having received evaluation decisions from the MMSF enhanced grant review process. Those researchers funded by the MMSF competition (MMSF-funded) had a statistically significant greater number of publications, a higher h-index and greater national Tri-Council (TC) funding, versus those not selected for funding (not MMSF-funded). MMSF-funded applicants and the Manitoba research community have created a strong and rapid (within 1 to 5 years of receiving the MMSF grant) local economic return on investment associated with the MMSF ROGP that supports new investigators, of approximately nine-fold for TC grants by the principal investigator, and of 34-fold for the principal investigator on collaborative (total) TC grants. The use of small amounts of seed money for competitive research grants at early stages of an MMSF-funded applicant’s career correlates with future short-term success of that applicant. The ability to correctly select promising candidates who subsequently demonstrate greater academic performance after the MMSF funding shows the selection process and the ROGP to be of merit. Multiple components may have contributed to this outcome, including a direct presentation and interview process of the candidate with five-person selection subcommittees, plus an assessment by an external reviewer (the enhanced grant review process). The selection methods used here may add value to the research grant selection processes of new researchers.
Resuscitation of the brain following total circulatory arrest may be impeded by difficulty in establishing cerebral tissue perfusion, a postischemic "low-flow"state. We have confirmed this hypothesis in a rat model of total cerebral ischemia and have demonstrated marked imporvement in post-ischemic brain tissue perfusion following epinephrine injection. This is mainly due to the systemic vascular effects of epinephrine, resulting in improved central arotic pressure and cerebral perfusion pressure. Hyperkalemic induced vasoconstriction has also been postulated as a cause of the "low-flow/. We have, therefore, investigated the in vitro effects of increasing potassium ion concentration on cerebrovascular smooth muscle strips. Large arteries constrict, while small arteries dilate in response to hyperkalemia. The net effect on cerebral blood flow remains unsettled. Our research to date suggests that resuscitation of the totally ischemic brain, in animal models at least, is enhanced by epinephrine, mainly via its effects on central aortic pressure.
Thirty patients with epidermoid carcinoma of the anus, ranging in age from 40 to 89 years, were treated with combined chemotherapy (CT) and radiation therapy (RT) in lieu of abdominoperineal resection. Two courses of 5-FU (1000 mg/m2/day X four days) by continuous infusion and mitomycin-C (10-15 mg/m2 IV bolus on day 1 of each course) were given 3 to 4 weeks apart simultaneously, with whole pelvis RT to 4140 to 4500 cGy. Twenty-one of 28 patients had T3-T4 primaries and ten had positive nodes (N1). Two of the 30 patients were treated for local recurrence following surgical excision and one was treated immediately after local excision. Twenty-six of the 30 patients attained biopsy-confirmed complete remission. Four of the 30 patients demonstrated residual disease at completion of therapy but all subsequently achieved complete remission with additional nonsurgical treatment. One patient, initially treated for local recurrence following excision failed locally at four years and was salvaged with chemotherapy followed by abdominoperineal resection. No patient has experienced distant failure. Twenty-seven of 30 patients were alive and disease free after 9 to 76 months of follow-up and three died, disease-free, of unrelated causes. Acute toxicities were mild and did not necessitate interruption of treatment. A brisk perineal reaction and diarrhea were noted in all patients. Late complications were unusual. All patients were treated in a community-based, private practice setting. The authors conclude that combined CT-RT, as employed herein, represents a first-line curative treatment for the majority of patients with epidermoid anal carcinoma. For patients who demonstrate residual disease following this therapy, salvage regimens such as 5-FU infusion and cisplatin, or sequential MTX-5-FU-Leucovorin with additional synchronous RT should be employed before resorting to radical surgery.
Department of Anaesthesia, University of Manitoba, Winnipeg, Manitoba, Canada, and Departments of Anesthesia, Pediatrics, and Cardiovascular Research Institute, University of California, San Francisco, California
