Accurate determination of phenotypic information from historic thoroughbred horses by single base extension.

Historic DNA data have the potential to identify phenotypic information otherwise invisible in the historical, archaeological and palaeontological record. In order to determine whether a single nucleotide polymorphism typing protocol based on single based extension (SNaPshot™) could produce reliable phenotypic data from historic samples, we genotyped three coat colour markers for a sample of historic Thoroughbred horses for which both phenotypic and correct genotypic information were known from pedigree information in the General Stud Book. Experimental results were consistent with the pedigrees in all cases. Thus we demonstrate that historic DNA techniques can produce reliable phenotypic information from museum specimens.

MRI of Paget's disease of bone.

Paget's disease is a relatively common condition in the elderly population and is not uncommonly seen as an incidental finding on imaging studies, including magnetic resonance imaging (MRI). It is important, therefore, for the radiologist to be aware of the MRI manifestations of the condition, so as not to mistake it for more sinister pathology. MRI can also be used to investigate the various complications of Paget's disease, particularly sarcomatous degeneration. This review describes the appearances of uncomplicated Paget's disease during its different pathological stages and in the setting of its various complications.

The impact of longer-than-average anesthesia times on the billing of academic anesthesiology departments.

UNLABELLED: Academic anesthesiology departments provide clinical services for surgical procedures that have longer-than-average surgical times and correspondingly increased anesthesia times. We examined the financial impact of these longer times in three ways: 1) the estimated loss in revenue if billing were done on a flat-fee system by using industry-averaged anesthesia times; 2) the estimation of incremental operating room (OR) sites necessitated by longer anesthesia times; and 3) the estimated potential gain in billed units if the hours of productivity of current anesthesia time were applied to surgical cases of average duration. Health Care Financing Administration average times per anesthesia procedure code were used as industry averages. Billing data were collected from four academic anesthesiology departments for 1 yr. Each claim billed with ASA units was included except for obstetric anesthesia care. All clinical sites that do not bill with ASA units were excluded. Base units were determined for each anesthesia procedure code. The mean commercial conversion factor (US$45 per ASA unit) for reimbursement was used to estimate the impact in dollar amounts. In all four groups, anesthesia times exceeded the Health Care Financing Administration average. The loss per group in billed ASA units if a flat-fee billing system were used ranged from 18,194 to 31,079 units per group, representing a 5% to 15% decrease (estimated billing decrease of US$818,719 to US$1,398,536 per group). The number of excess OR sites necessitated by longer surgical and anesthesia times ranged from 1.95 to 4.57 OR sites per group. The potential gain in billed units if the hours of productivity of current anesthesia time were applied to surgical cases of average duration was estimated to be from 13,273 to 21,368 ASA units. Longer-than-average anesthesia and surgical times result in extra hours or additional OR sites to be staffed and loss of potential reimbursement for the four academic anesthesiology departments. A flat-fee system would adversely affect academic anesthesiology departments. IMPLICATIONS: We examined the economic impact of longer-than-average anesthesia times on four academic anesthesiology departments in three ways: the estimated loss in revenue under a flat-fee system, the excess operating room sites staffed, and the potential gain in revenue if the surgeries were of average length. These results should be considered both in productivity measurements and strategies for operating room management.

Sickle cell.

The initiation of newborn screening and its virtually universal implementation will eventually yield a population in which sickle cell disease has been identified and comprehensive care is provided for children. The situation with SCT is different; there will continue to be the identification of parents who have the potential for having a child with a sickle cell disease but because they will not be tested or counseled, there will continue to be a population of children with a sickle cell disease whose parents have not been enabled to make informed decisions that they believe are in their best interest relative to family planning. Also, we will continue to have a population of pregnant women with a fetus with sickle cell disease who will not be given an opportunity to decide whether they wish to continue or terminate the pregnancy. They all will give birth to a child with a lifetime of chronic illness with its associated psychological, social, and financial burdens for the individual and his or her parents. The failure to implement prenatal diagnosis is an abridgment of two fundamental rights: the right to know and the right to decide. In this case it is the right to know about the potential health status of their children if that is possible, and the right to decide about the actual health care status of their children if options are available.

The use of lepirudin for anticoagulation in patients with heparin-induced thrombocytopenia during major vascular surgery.

The method of anticoagulation in patients undergoing major vascular surgery with a history of heparin-induced thrombocytopenia (HIT) is controversial. We present two cases in which a bolus only technique using recombinant hirudin (Lepirudin or Refludan) was used successfully in patients with HIT scheduled for vascular surgery.

Ketamine suppresses endotoxin-induced NF-kappaB expression.

PURPOSE: Ketamine reduces endotoxin-induced production of proinflammatory cytokines, including tumour necrosis factor-alpha (TNF), in several types of inflammatory cells, including monocytes and macrophages. Transcription of the genes that encode production of these proinflammatory cytokines is regulated by nuclear factor-kappa B (NF-kappaB). Cytoplasmic B protein is activated by endotoxin (LPS) as well as by TNF, allowing B protein to migrate into the cell nucleus to activate gene transcription for these inflammatory mediators. Because NF-kappaB is likely involved in brain injury and inflammatory neurodegenerative disease, such as multiple sclerosis, we examined whether ketamine inhibits LPS-induced activation of NF-kappaB in human glioma cells in vitro and intact mouse brain cells in vivo. METHODS: Endotoxin-induced NF-kappaB expression in both the human glioma cells in vitro and the intact mouse brain cells in vivo was determined by electrophoretic mobility shift assays (EMSA) of nuclear extracts and measurement of NF-kappaB expression by densitometry. Endotoxin was injected intracerebroventricularly in vivo and intact brain was harvested. Klenow fragment labeling was used to identify NF-kappaB protein for both the in vivo and vitro experiments. RESULTS: Endotoxin treatment increased NF-kappaB expression (P < 0.05) both in vivo and vitro compared with control (untreated) cells. Ketamine suppressed endotoxin-induced neuronal NF-kappaB activation in a dose-dependent manner (P < 0.05, except for the 10(-5) M concentration in vitro) both in vivo and vitro. CONCLUSION: Ketamine inhibits endotoxin-induced NF-kappaB expression in brain cells in vivo and vitro and it is suggested that this may have implications in the neuroprotective effects of ketamine reported by other investigators.

Ketamine inhibits agonist-induced cAMP accumulation increase in human airway smooth muscle cells.

PURPOSE: Cyclic 3',5' adenosine monophosphate (cAMP) is a second messenger of the beta adrenergic receptor (betaAR). Ketamine causes an increase in the intracellular accumulation of cAMP in several non-human tissue preparations. A "species effect" may explain the differing results of ketamine on betaAR mediated responses, thus reports of a ketamine-induced increase in cAMP in other species may not be applicable to humans. METHODS: The effect of ketamine (10(-3), 10(-4), or 10(-5) M) pretreatment (60 and 120 min) on isoproterenol [ISO, a beta adrenergic receptor (AR) agonist] or forskolin [FSK, an activator of adenylylcyclase (AC)]-induced intracellular accumulation of cAMP in a human airway smooth muscle (tracheal) cell line (HASM) was evaluated. In an in vitro HASM culture, cells with or without pretreatment were labeled with [3H]adenine to produce [3H]ATP, and following stimulation with ISO or FSK to convert the [3H]ATP to [3H]cAMP, the intracellular accumulation of [3H]cAMP was measured by sequential chromatography over Dowex and alumina columns. RESULTS: Pretreatment of the HASM cells with ketamine (10(-3) and 10(-4) M) caused a reduction (P < 0.05, when compared to untreated cells) in ISO-induced cAMP accumulation, but did not effect cAMP accumulation following FSK stimulation. This effect of ketamine was greater at 120 min of pretreatment than at 60 min (10(-3) M ketamine only)(P < 0.05). No effect was found at either time period following pretreatment of the HASM cells with ketamine 10(-5) M. CONCLUSIONS: These results demonstrate that pretreatment of the HASM cells with ketamine reduces ISO-induced cAMP accumulation. Since only ISO-induced cAMP was effected by ketamine, these data suggest that ketamine inhibits production of cAMP proximal to AC in the cAMP production pathway. These results also demonstrate that a mechanism other than that involving the betaAR and intracellular cAMP accumulation is responsible for the ketamine induced bronchodilation in humans.

Vegetarian food guide pyramid: a conceptual framework.

The purpose of this article and the accompanying vegetarian food guide pyramid graphic is to provide the conceptual framework for the development of a new and unique food guide. Food guides for vegetarians have tended to be adaptations of guides developed for the general nonvegetarian population instead of being designed to emphasize the healthy components of vegetarian dietary patterns. A subcommittee of the organizers of the Third International Congress on Vegetarian Nutrition began a process that led to the development of a pyramid-shaped graphic illustration and a supporting document, both of which were introduced at the congress. The 5 major plant-based food groups (whole grains, legumes, vegetables, fruit, nuts, and seeds) form the trapezoid-shaped lower portion of the pyramid. Optional food groups, which may be avoided by some vegetarians (vegetable oils, dairy, eggs, and sweets), form the smaller, separate, triangle-shaped top portion of the pyramid. The supporting document discusses the concepts that affect vegetarian food guidance and the rationale for selecting the food groups. It is hoped that this framework will provide the impetus for further research and discussion and will lead to the development of a guide that is nutritionally adequate, is conducive to good health, and can be adopted by vegetarians of diverse eating practices.

D-Dimer formation during cardiac and noncardiac thoracic surgery.

UNLABELLED: The ability to make therapeutic decisions regarding excessive fibrinolysis in the perioperative period is limited by the lack of availability of a near site monitor of fibrinolysis. We investigated the use of a latex agglutination D-dimer assay to detect perioperative fibrinolysis in patients undergoing thoracic surgery with and without extracorporeal circulation. We studied 27 patients who underwent thoracic surgery requiring cardiopulmonary bypass (CPB; coronary artery bypass grafting, n = 12; valvular surgery, n = 15) and a cohort of 20 patients who underwent noncardiac thoracic surgical procedures not requiring CPB. The purpose of this investigation was to determine the relationship among alterations in the latex agglutination D-dimer assay, use of extracorporeal circulation, type of cardiac surgical procedure, and mediastinal and/or chest tube drainage (cardiac surgery only) in patients undergoing thoracic surgery. Perioperative D-dimer levels, measured by latex agglutination, had significant (P < or = 0.05) intragroup changes among patients undergoing cardiac surgery (requiring CPB) and the cohort of patients who underwent noncardiac thoracic surgery without CPB. Although intraoperative D-dimer levels were not increased in patients undergoing noncardiac thoracic surgery, postoperative levels were significantly (P < 0.05) increased (compared with preinduction). In cardiac surgery patients requiring CPB, intraoperative D-dimer formation was significantly (P < or = 0.05) increased but did not demonstrate any intragroup (coronary artery bypass grafting versus valvular surgery) differences. Finally, D-dimer levels were not associated with postoperative mediastinal and/or chest tube accumulative drainage measured at intervals up to 48 h postoperatively in patients undergoing cardiac surgery requiring CPB. Our study indicates that the latex agglutination D-dimer assay can detect excessive fibrinolysis perioperatively, and that extracorporeal circulation can significantly influence the pattern of D-dimer formation in patients undergoing thoracic surgery. IMPLICATIONS: We assessed the ability of a readily available D-dimer assay to detect excessive fibrinolysis in patients undergoing thoracic surgery with and without extracorporeal circulation. The findings demonstrate that the assay used in this investigation reflected variable amounts of fibrinolysis in patients undergoing both types of thoracic surgery.

Comparison of adenosine and remifentanil infusions as adjuvants to desflurane anesthesia.

BACKGROUND: Because adenosine has been alleged to produce both anesthetic and analgesic sparing effects, a randomized, double-blinded study was designed to compare the perioperative effects of adenosine and remifentanil when administered as intravenous adjuvants during general anesthesia for major gynecologic procedures. METHODS: Thirty-two women were assigned randomly to one of two drug treatment groups. After premedication with 0.04 mg/kg intravenous midazolam, anesthesia was induced with 2 micro/kg intravenous fentanyl, 1.5 mg/kg intravenous propofol, and 0.6 mg/kg intravenous rocuronium, and maintained with desflurane, 2%, and nitrous oxide, 65%, in oxygen. Before skin incision, an infusion of either remifentanil (0.02 microg x kg(-1) x min(-1)) or adenosine (25 microg x kg(-1) x min(-1)) was started and subsequently titrated to maintain systolic blood pressure, heart rate, or both within 10-15% of the preincision values. RESULTS: Adenosine and remifentanil infusions were effective anesthetic adjuvants during lower abdominal surgery. Use of adenosine (mean +/- SEM, 166+/-17 microg x kg(-1) x min(-1)) was associated with a significantly greater decrease in systolic blood pressure and higher heart rate values compared with remifentanil (mean +/- SEM, 0.2+/-0.03 microg kg(-1) x min(-1)). Total postoperative opioid analgesic use was 45% and 27% lower in the adenosine group at 0-2 h and 2-24 h after surgery, respectively. CONCLUSIONS: Adjunctive use of a variable-rate infusion of adenosine during desflurane-nitrous oxide anesthesia was associated with acceptable hemodynamic stability during the intraoperative period. Compared with remifentanil, intraoperative use of adenosine was associated with a decreased requirement for opioid analgesics during the first 24 h after operation.

Pump prime only aprotinin inhibits cardiopulmonary bypass-induced neutrophil CD11b up-regulation.

BACKGROUND: The expression of neutrophil integrin CD11b is up-regulated after cardiopulmonary bypass (CPB) and is the neutrophil adhesive molecule of most importance in neutrophil- endothelial adherence. This neutrophil-endothelial adherence is responsible for post-CPB neutrophil-induced reperfusion injury. Low-dose aprotinin protocols inhibit the CPB-induced neutrophil CD11b up-regulation. This investigation was undertaken to evaluate the effects of pump prime only aprotinin (280 mg) on the CPB-induced up-regulation of this neutrophil integrin. METHODS: Twenty-two patients scheduled for elective myocardial revascularization were randomized into two groups: (1) control (n = 12), or (2) pump prime only aprotinin (280 mg) (n = 10). Neutrophils were isolated at baseline, 50 minutes of CPB, and 30 minutes after CPB and neutrophil CD11b expression was measured. RESULTS: The control group demonstrated a significant (p < 0.05) increase in neutrophil CD11b immunofluorescent staining at 50 minutes of CPB and at 30 minutes after CPB when compared to same group baseline and to the pump prime only aprotinin group at similar time intervals. CONCLUSIONS: These results indicate that pump prime only aprotinin modulates the CPB-induced up-regulation of neutrophil CD11b integrin, an important indicator of the systemic inflammatory response to CPB. In addition to blunting of the CPB-induced up-regulation of this neutrophil integrin expression, this pump prime only dose of aprotinin is also reported to be effective at reducing post-CPB bleeding and transfusion requirements. This salutary effect of pump prime only aprotinin suggests that such low-dose regimens can be both therapeutically effective and cost effective.

Postbaccalaureate program at Wayne State University School of Medicine: a 30-year report.

In 1969, Wayne State University School of Medicine established the first postbaccalaureate program for medical students, with the focus on African American students whose applications to medical school had been rejected. The ten-month program was designed to improve students' scientific knowledge, academic skills, and personal adjustment and thereby ultimately to increase the number of African Americans enrolled in the school. The criteria included the quality of the student's high school, employment workload, parents' ability to assist financially, and several other factors. The school covered expenses, provided a living stipend, and guaranteed admission for students who attained a B average in the program. Consistent with the Bakke court decision, in 1979 the program eligibility was shifted to disadvantaged students irrespective of race or ethnicity; all other criteria remained unchanged. Until 1990 Wayne State University's program was the only one of its type. From 1969 to 1992, 214 African American students who could have graduated by 1997 had been admitted to the program: 192 (90%) of them attained a B average in the program and matriculated in the medical school, and 160 (83%) graduated. From 1978 (when the program was opened to all racial and ethnic groups) to 1992, 58 non-African American students who could have graduated by 1997 were been admitted to the program: 54 (93%) attained a B average and matriculated in the medical school, and 51 (94%) graduated. The program's success suggests that similar programs at more medical schools could have an immediate and substantial impact on the number of underrepresented-minority students who enter medical education and succeed.

Unexplained decrease in measured oxygen saturation by pulse oximetry following injection of Lymphazurin 1% (isosulfan blue) during a lymphatic mapping procedure.

A rare case of alteration in measured pulse oximetry during a lymphatic mapping procedure for cervical carcinoma is reported. Over a 5-min period following injection of perilesional Lymphazurin 1% dye (3 ml total), a profound pulse oximetry desaturation was observed. Concomitant arterial blood gas determinations confirmed patient's well-being. Interaction of this agent's absorptive spectroscopy and wavelengths used to measure oxygen saturation by commercial pulse oximetry devices is suspected.

Near-site monitoring of the antiplatelet drug abciximab using the Hemodyne analyzer and modified thrombelastograph.

OBJECTIVE: This investigation examines the hypothesis that the antiplatelet effect of abciximab and its reversal can be monitored using the Hemodyne (Hemodyne, Inc, Midlothian, VA) analyzer and modified Thrombelastograph (Haemoscope, Skokie, IL). DESIGN: In vitro dose-response and reversal study. SETTING: Anesthesia Research (Dallas, TX) and Special Studies Coagulation Laboratories (Washington, DC). PARTICIPANTS: Nine healthy volunteers. INTERVENTIONS: The addition of increasing concentrations of abciximab, 0 to 10 microg/mL, and purified fibrinogen, 50 to 400 mg/dL. The reversal of abciximab, 4 microg/mL, with the addition of fresh platelet-rich plasma (PRP) sufficient to increase the platelet concentration by approximately 10%. MEASUREMENTS AND MAIN RESULTS: Platelet aggregation and platelet contractile force using the Hemodyne analyzer were used as platelet-specific measurements. The Thrombelastograph maximum amplitude (MA) for platelets (MA(PLT)) was calculated by subtracting the MA from a platelet-poor plasma (PPP) sample (MA(ppp)) determined in one thromboelastography well from that of whole-blood MA (MA(WB)) run simultaneously in the second thromboelastography well. The addition of abciximab, 0 to 10 microg/mL, resulted in significant concentration-dependent reductions in platelet aggregation (p < 0.001), platelet contractile force (p < 0.001), and MA(PLT) (p < 0.001). Platelet contractile force (p < 0.03) and MA(PLT) (p < 0.05) were significantly more responsive than MA(WB) to the effect of abciximab, 4 microg/mL, and its reversal with the addition of fresh PRP. Purified fibrinogen concentration directly correlated with thromboelastography MA (r(s) = 0.97; p < 0.001), yet had no effect on platelet contractile force. The addition of abciximab had no measurable influence on the MA(ppp). CONCLUSION: This in vitro study suggests that the Hemodyne analyzer and modified Thrombelastograph might be clinically useful methods to monitor the platelet inhibitory effects of agents such as abciximab.

Assessment of changes in coagulation in parturients with preeclampsia using thromboelastography.

BACKGROUND: Preeclampsia is associated with a risk of abnormal hemostasis that occurs most commonly secondary to thrombocytopenia. Thromboelastography measures whole blood coagulation and has been used to manage coagulation defects in obstetric patients. The authors conducted this investigation in a large number of preeclamptic women to assess changes in coagulation using thromboelastography. METHODS: Thromboelastography and platelet counts were performed in 52 healthy pregnant women, 140 mild preeclamptic women, and 114 severe preeclamptic women in active labor using disposable plastic cups and pins and native whole blood. In preeclamptic patients with a platelet count <100,000/mm3, conventional coagulation tests were also performed. Epidural analgesia was provided in some women when they requested pain relief. RESULTS: Fifteen percent of all preeclamptic women (38 of 254) and 2% (1 of 52) of healthy pregnant women had a platelet count <100,000/mm3. The incidence of thrombocytopenia <100,000/mm3 was 3% (4 of 140) and 30% (34 of 114) in mild preeclamptic patients and severe preeclamptic patients, respectively. Severe preeclamptic patients with a platelet count <100,000/mm3 were significantly hypocoagulable when compared to the other study groups. Ten severe preeclamptic women with a platelet count <100,000/mm3 had a maximum amplitude <54 mm (the lower limit of maximum amplitude in healthy pregnant women enrolled in this investigation). None of the mild preeclamptic women had a maximum amplitude <54 mm. Five severe preeclamptic women with a platelet count <100,000/mm3 had an abnormal coagulation profile, whereas all four mild preeclamptic women with a platelet count <100,000/mm3 had a normal coagulation profile. CONCLUSION: This study shows that severe preeclamptic women with a platelet count <100,000/mm3 are hypocoagulable when compared to healthy pregnant women and other preeclamptic women.

Effects of pretreatment with cisatracurium, rocuronium, and d-tubocurarine on succinylcholine-induced fasciculations and myalgia: a comparison with placebo.

STUDY OBJECTIVE: To evaluate the efficacy of cisatracurium, rocuronium, and d-tubocurarine in preventing succinylcholine-induced fasciculations and postoperative myalgia in patients undergoing ambulatory surgery. DESIGN: Randomized, prospective, placebo-controlled trial SETTING: Teaching hospital. SUBJECTS: 80 ASA physical status I and II patients scheduled for elective ambulatory surgery with general anesthesia. INTERVENTION: A standardized balanced anesthetic technique was used for all patients. MEASUREMENTS AND MAIN RESULTS: Patients were randomized to receive cisatracurium 0.01 mg/kg, rocuronium 0.06 mg/kg, d-tubocurarine 0.05 mg/kg, or saline, 3 minutes prior to intravenous (i.v.) succinylcholine 1.5 mg/kg. The intensity of fasciculations and intubating conditions were assessed using a four-point rating scale. In addition, the severity of myalgia was assessed using a four-point rating scale in the postanesthesia care unit and at 24 hours postoperatively. No patient complained of any side effects after the administration of the study drug. Fasciculations were observed less frequently (p < 0.05) in the d-tubocurarine and rocuronium groups compared with the placebo and cisatracurium groups. However, there was no difference between the d-tubocurarine group and the rocuronium group (21% vs. 10%, respectively). Although fasciculations occurred less frequently in the cisatracurium group than in the placebo group (59% vs. 85%, respectively), this difference did not reach statistical significance. There was no difference among the four groups in the intubating conditions or the incidence of postoperative myalgia. CONCLUSION: Pretreatment with rocuronium and d-tubocurarine was superior to cisatracurium in preventing succinylcholine-induced fasciculations. However, pretreatment did not have any effect on the incidence of myalgia after ambulatory surgery.

Antiemetic activity of propofol after sevoflurane and desflurane anesthesia for outpatient laparoscopic cholecystectomy.

BACKGROUND: Controversy exists regarding the effectiveness of propofol to prevent postoperative nausea and vomiting. This prospective, randomized, single-blinded study was designed to evaluate the antiemetic effectiveness of 0.5 mg/kg propofol when administered intravenously after sevoflurane- compared with desflurane-based anesthesia. METHODS: Two hundred fifty female outpatients undergoing laparoscopic cholecystectomy were assigned randomly to one of four treatment groups. All patients were induced with intravenous doses of 2 mg midazolam, 2 microg/kg fentanyl, and 2 mg/kg propofol and maintained with either 1-4% sevoflurane (groups 1 and 2) or 2-8% desflurane (groups 3 and 4) in combination with 65% nitrous oxide in oxygen. At skin closure, patients in groups 1 and 3 were administered 5 ml intravenous saline, and patients in groups 2 and 4 were administered 0.5 mg/kg propofol intravenously. Recovery times were recorded from discontinuation of anesthesia to awakening, orientation, and readiness to be released home. Postoperative nausea and vomiting and requests for antiemetic rescue medication were evaluated during the first 24 h after surgery. RESULTS: Propofol, in an intravenous dose of 0.5 mg/kg, administered at the end of a sevoflurane-nitrous oxide or desflurane-nitrous oxide anesthetic prolonged the times to awakening and orientation by 40-80% and 25-30%, respectively. In group 2 (compared with groups 1, 3, and 4), the incidences of emesis (22% compared with 47%, 53%, and 47%) and requests for antiemetic rescue medication (19% compared with 42%, 50%, and 47%) within the first 6 h after surgery were significantly lower, and the time to home-readiness was significantly shorter in duration (216 +/- 50 min vs. 249 +/- 49 min, 260 +/- 88 min, and 254 +/- 72 min, respectively). CONCLUSIONS: A subhypnotic intravenous dose of propofol (0.5 mg/kg) administered at the end of outpatient laparoscopic cholecystectomy procedures was more effective in preventing postoperative nausea and vomiting after a sevoflurane-based (compared with a desflurane-based) anesthetic.