American Board of Anesthesiology Mock Standardized Oral Examination Faculty Development Workshop.

Introduction: Preparation for oral board examination is an important part of residency training. Anesthesiology programs provide mock oral exams for their trainees, but often, faculty have little guidance on the conduct of these exams. We describe a faculty development workshop for anesthesiology faculty to enhance their familiarity with the American Board of Anesthesiology Standardized Oral Examination (SOE). Methods: We created a faculty development workshop to administer to a live audience. The session consisted of didactic and practical components. A one-page tip sheet was also included to distribute to all faculty administering mock SOEs, for review and reference prior to administering an exam. Faculty and residents were surveyed before and after the session. Results: Eleven faculty participated in the live session. Eighty-two percent of faculty (nine of 11) committed to making a change in the way they delivered mock SOE as a result of attending the session. Fifty-eight percent of faculty (32 of 55) who responded to the postintervention survey reported that they used the tip sheet prior to administering a subsequent mock SOE. Residents described improvement in the clarity and organization of feedback following the intervention. Discussion: Faculty members play a vital role in preparing residents for board certification. It is therefore important that faculty are appropriately oriented to the goals and conduct of the mock SOE. After taking this workshop, faculty members will be more likely to adapt their examiner style to focus on the ABA-defined examinee attributes and to provide feedback after the mock SOE.

Intraoperative hyperglycemia is independently associated with infectious complications after non-cardiac surgery.

BACKGROUND: Perioperative hyperglycemia and its associated increase in morbidity and mortality have been well studied in the critical care and cardiac surgery literature. However, there is little data regarding the impact of intraoperative hyperglycemia on post-operative infectious complications in non-cardiac surgery. METHODS: All National Surgery Quality Improvement Program patients undergoing general, vascular, and urological surgery at our tertiary care center were reviewed. After integrating intraoperative glucose measurements from our intraoperative electronic health record, we categorized patients as experiencing mild (8.3-11.0 mmol/L), moderate (11.1-16.6 mmol/L), and severe (≥ 16.7 mmol/L) intraoperative hyperglycemia. Using multiple logistic regression to adjust for patient comorbidities and surgical factors, we evaluated the association of hyperglycemia with the primary outcome of postoperative surgical site infection, pneumonia, urinary tract infection, or sepsis within 30 days. RESULTS: Of 13,954 patients reviewed, 3150 patients met inclusion criteria and had an intraoperative glucose measurement. 49% (n = 1531) of patients experienced hyperglycemia and 15% (n = 482) patients experienced an infectious complication. Patients with mild (adjusted odds ratio 1.30, 95% confidence interval [1.01 to 1.68], p-value = 0.04) and moderate hyperglycemia (adjusted odds ratio 1.57, 95% confidence interval [1.08-2.28], p-value = 0.02) had a statistically significant risk-adjusted increase in infectious complications. The model c-statistic was 0.72 [95% confidence interval 0.69-0.74]. CONCLUSIONS: This is one of the first studies to demonstrate an independent relationship between intraoperative hyperglycemia and postoperative infectious complications. Future studies are needed to evaluate a causal relationship and impact of treatment.

Intraoperative bispectral index monitoring and time to extubation after cardiac surgery: secondary analysis of a randomized controlled trial.

BACKGROUND: Fast track recovery is a care process goal after cardiac surgery. Intraoperative anesthetic depth may impact recovery, but the impact of brain monitoring on time to extubation and intensive care unit (ICU) length of stay after cardiac surgery has not been extensively studied. Our goal was to determine if BIS-guided anesthesia improves time to extubation compared to MAC-guided anesthesia in a cardiac surgery population. METHODS: In this secondary outcome analysis of a randomized controlled study, we analyzed 294 patients undergoing elective coronary bypass grafting, valve replacements, and bypass plus valve replacements at a single tertiary referral center between February 1, 2009 and April 30, 2010. We analyzed cardiac surgery patients that had been randomized to BIS-guided anesthesia alerts (n = 131) or MAC-guided anesthesia alerts (n = 163). The primary outcome measure was time to extubation in the BIS-guided and anesthetic concentration-guided groups. Secondary outcomes were length of stay in the ICU and total postoperative hospital length of stay. RESULTS: Valid extubation time data were available for 247 of 294 patients. The median [IQR] time to extubation was 307 [215 to 771] minutes in the BIS group and 323 [196 to 730] minutes in the anesthetic concentration group (p = 0.61). The median [IQR] ICU length of stay was 54 [29 to 97] hours versus 70 [44 to 99] hours (p = 0.11). In terms of postoperative hospital length of stay, there was no difference between the groups with median [IQR] times of 6 [5-8] days (p = 0.69) in each group. CONCLUSIONS: The use of intraoperative BIS monitoring during cardiac surgery did not change time to extubation, ICU length of stay or hospital length of stay. Data regarding BIS monitoring and recovery in an exclusively cardiac surgery population are consistent with recent effectiveness studies in the general surgical population. TRIAL REGISTRATION: ClinicalTrials.gov number NCT00689091.

Differential regulation of aortic growth in male and female rodents is associated with AAA development.

BACKGROUND: The objective was to examine effects of gonadal hormone manipulation on aortic diameter and macrophage infiltration in rodents during abdominal aortic aneurysm (AAA) formation. METHODS: Experiment 1: 17-beta estradiol and testosterone pellets were implanted in male (ME) and female (FT) rats. No pellet was implanted in shams (MES, FTS). Experiment 2: Testes and ovaries were removed from males (MO) and females (FO), respectively. No organs were removed from shams (MOS, FOS). Experiment 3: Male and female rats were orchiectomized and oophorectomized, respectively. Four weeks post-castration, testosterone (MOT) and 17-beta estradiol (FOE) pellets were implanted. Shams underwent castration, but no pellet was implanted (MOTS, FOES). All rats underwent infrarenal aortic infusion with elastase postimplantation/postcastration. Diameters were measured on postoperative d 14. Tissue was stained for macrophages by immunohistochemistry. RESULTS: Diameter (P = 0.046) and macrophage counts (P = 0.014) decreased in ME compared with shams, but not in females treated with testosterone (FT). Diameter (P = 0.019) and macrophage infiltration (P = 0.024) decreased in MO compared with shams, but not in FO. Diameter increased in MOT compared with MOTS (P = 0.033), but decreased in FOE compared with FOES (P = 0.002). Macrophages decreased in FOE compared with FOES (P = 0.002). CONCLUSION: This study documents a decrease in AAA diameter in males treated with estrogen or undergoing orchiectomy, but no changes in females treated with testosterone or undergoing oophorectomy; and an increase in diameter in MOT and a decrease in FOE. These data suggest that gonadal hormones differentially regulate AAA growth in association with changes in macrophages.

Differential effect of 17-beta-estradiol on smooth muscle cell and aortic explant MMP2.

OBJECTIVE: The present investigation tested the hypothesis that intrinsic gender-related differences exist in rat aortic smooth muscle cell matrix metalloproteinase 2 (MMP2). METHODS: This investigation comprised 3 sets of experiments. Experiment I: Adult male and female rat aortic smooth muscle cells (RASMCs) at passages 4-8 were stimulated in serum-free media for 48 h with interleukin(IL)1beta at doses encountered in human abdominal aortic aneurysms (2 ng/mL). Messenger RNA was extracted from the RASMCs, and gene expression of MMP2 and tissue inhibitor of metalloproteinase 2 (TIMP2), a major MMP2 inhibitor, was measured by real-time polymerase chain reaction. MMP2 protein levels in conditioned media were measured by Western blotting, and MMP2 and TIMP2 activity quantified by standard and reverse gelatin zymography. Experiment II: Male and female RASMCs were incubated for 48 h in Dulbecco's modified Eagler's medium containing IL-1beta and 17-beta-estradiol at doses from 1x10(-10) to 1x10(-6) molar. MMP2 activity in the conditioned media was then determined. Experiment III: Male rats underwent sustained 17-beta-estradiol exposure for 21 d using extended-release, subcutaneously implanted pellets prior to sacrifice and aortic explantation. Aortas from males, females, and estradiol-treated males were stimulated with IL-1beta for 48-h, and MMP2 activity in the conditioned media was determined. RESULTS: Experiment I: MMP2 gene expression was 3-fold higher in male compared with female IL-1beta stimulated RASMCs (P<0.0001). MMP2:TIMP2 gene expression ratio was 7.5-fold greater in male versus female RASMCs. MMP2 protein levels were 3-fold higher (2.68 versus 0.96 o.d./mg total protein, P=0.003) in male versus female RASMCs. Gelatinolytic activity was more than 6-fold higher (15,010 versus 2,472 o.d./mg total protein, P=0.002) in male versus female RASMCs. Experiment II: MMP2 activity in male and female RASMCs was not altered by a wide range of 17-beta-estradiol concentrations. Experiment III: When pretreated with 17-beta-estradiol, MMP2 activity in the media of male rat whole-aortic explants decreased 2-fold (P=0.002). This post-17-beta-estradiol treatment male level was not different than baseline female aortic explant MMP2 levels. CONCLUSIONS: MMP2 is higher in male RASMCs compared to female RASMCs. Exogenous 17-beta-estradiol did not alter MMP2 activity in vitro, but in vivo 17-beta-estradiol exposure greatly decreased male aortic MMP2 production to levels seen in the female aorta. Gender differences in MMP2 are speculated to be associated with phenotypic differences in human abdominal aortic aneurysm formation.

LapMentor metrics possess limited construct validity.

BACKGROUND: Many surgical training programs are introducing virtual-reality laparoscopic simulators into their curriculum. If a surgical simulator will be used to determine when a trainee has reached an "expert" level of performance, its evaluation metrics must accurately reflect varying levels of skill. The ability of a metric to differentiate novice from expert performance is referred to as construct validity. The present study was undertaken to determine whether the LapMentor's metrics demonstrate construct validity. METHODS: Medical students, residents and faculty laparoscopic surgeons (n = 5-14 per group) performed 5 consecutive repetitions of 6 laparoscopic skills tasks: 30 degrees Camera Manipulation, Eye-Hand Coordination, Clipping/Grasping, Cutting, Electrocautery, and Translocation of Objects. The LapMentor measured performance in 4 to 12 parameters per task. Mean performance for each parameter was compared between subject groups for the first and fifth repetitions. Pairwise comparisons among the 3 groups were made by post hoc t-tests with Bonferroni technique. Significance was set at P < 0.05. RESULTS: Of the 6 tasks evaluated, only the Eye-Hand Coordination task (3/12 parameters) and the Clipping and Grasping (1/7 parameters) had expert-level discrimination when performance was compared after completion of 1 repetition. Comparison of the fifth repetition performance (representing the plateau of the learning curves), demonstrated that the parameters Time and Score had expert level discrimination on the Eye-Hand Coordination task, and Time on the Cutting task. The remaining LapMentor tasks evaluated did not exhibit the ability to differentiate level of expertise based on the built-in metrics on either repetition 1 or 5. CONCLUSIONS: The majority of the LapMentor tasks' metrics were unable to differentiate between laparoscopic experts and less skilled subjects. Therefore, performance on those tasks may not accurately reflect a subject's true level of ability. Feedback to the manufacturer about these findings may encourage the development of evaluation parameters with greater sensitivity.

Proximate versus nonproximate risk factor associated primary deep venous thrombosis: clinical spectrum and outcomes.

OBJECTIVE: Although the treatment for acute deep vein thrombosis (DVT) is uniform, the circumstances under which it develops vary widely and may impact outcomes. This study compared clinical features and outcomes in patients who developed a primary DVT associated with a defined risk to those without any proximate risk factor. METHODS: Consecutive patients with a primary DVT and no past venous thromboembolism history from 2000 to 2002 were abstracted for demographics, risk factors, DVT anatomical characteristics, treatment, and outcomes of death and new pulmonary embolism. Comparison between patients with a proximate risk event within 30 days of DVT (Inpt) and those presenting with DVT with no defined proximate event (Outpt) was done by univariable and multivariable statistics. A validated survey was mailed to all living patients to assess long-term sequela. RESULTS: A total of 293 patients with a mean age of 55 years and 49% men had confirmed DVT by objective means (92% duplex) with a mean follow-up of 25 +/- 21 months. Inpts were more likely to have recent surgery or blunt trauma, bilateral DVT, less use of low molecular weight heparin (LMWH), and new pulmonary emboli (all P <.05). Outpts with DVT were more likely to have a history of malignancy, tibial-popliteal DVT compared with iliofemoral DVT, higher use of LMWH, and coumadin. However, there was no difference in mortality. From the patient survey (21% response), Outpts were more likely than Inpts to develop later varicosities and have daily frustration related to their legs (P < .05), but no difference in edema or ulceration. Considering the entire group, independent factors associated with freedom from PE included ambulation (odds ratio [OR] = 2.3; 95% confidence interval [CI] = 1.1-5.0; P = .04) while bilateral DVT (OR = .26; 95% CI = .09-.76; P = .013) or subcutaneous heparin (OR = 22; 95% CI = .05-.98; P = .047) were associated with greater risk. Independent factors associated with survival included ambulation (OR = 3.0; 95% CI = 1.3-7.2; P = .02), Coumadin use (OR = 2.7; 95% CI = 1.2-6.1; P = .015), and tibiopopliteal DVT (OR = 2.4; 95% = 1.1-5.5; P = .03), while malignancy (OR = 0.1; 95% CI = .05-.24; P < .01) and myocardial infarction (OR = 0.12; 95% CI = .01-.92; P = .04) were associated with lower survival. CONCLUSION: Patients who develop DVT related to a defined proximate risk event (Inpt) generally have more extensive DVT, an increased risk of PE, but less long-term functional morbidity and no difference in long-term mortality compared to those with no proximate risk.

Laparoscopic skills are improved with LapMentor training: results of a randomized, double-blinded study.

OBJECTIVE: To determine if prior training on the LapMentor laparoscopic simulator leads to improved performance of basic laparoscopic skills in the animate operating room environment. SUMMARY BACKGROUND DATA: Numerous influences have led to the development of computer-aided laparoscopic simulators: a need for greater efficiency in training, the unique and complex nature of laparoscopic surgery, and the increasing demand that surgeons demonstrate competence before proceeding to the operating room. The LapMentor simulator is expensive, however, and its use must be validated and justified prior to implementation into surgical training programs. METHODS: Nineteen surgical interns were randomized to training on the LapMentor laparoscopic simulator (n = 10) or to a control group (no simulator training, n = 9). Subjects randomized to the LapMentor trained to expert criterion levels 2 consecutive times on 6 designated basic skills modules. All subjects then completed a series of laparoscopic exercises in a live porcine model, and performance was assessed independently by 2 blinded reviewers. Time, accuracy rates, and global assessments of performance were recorded with an interrater reliability between reviewers of 0.99. RESULTS: LapMentor trained interns completed the 30 degrees camera navigation exercise in significantly less time than control interns (166 +/- 52 vs. 220 +/- 39 seconds, P < 0.05); they also achieved higher accuracy rates in identifying the required objects with the laparoscope (96% +/- 8% vs. 82% +/- 15%, P < 0.05). Similarly, on the two-handed object transfer exercise, task completion time for LapMentor trained versus control interns was 130 +/- 23 versus 184 +/- 43 seconds (P < 0.01) with an accuracy rate of 98% +/- 5% versus 80% +/- 13% (P < 0.001). Additionally, LapMentor trained interns outperformed control subjects with regard to camera navigation skills, efficiency of motion, optimal instrument handling, perceptual ability, and performance of safe electrocautery. CONCLUSIONS: This study demonstrates that prior training on the LapMentor laparoscopic simulator leads to improved resident performance of basic skills in the animate operating room environment. This work marks the first prospective, randomized evaluation of the LapMentor simulator, and provides evidence that LapMentor training may lead to improved operating room performance.

Construct validity of the LapSim laparoscopic surgical simulator.

BACKGROUND: Computer-aided simulators may increase the safety and efficiency of training in laparoscopic surgery. Before implementation of the Immersion LapSim (Gaithersburg, MD) simulator in our training curriculum, we wished to determine its construct validity (ie, whether the simulator could differentiate laparoscopic novices from trainees with greater experience). METHODS: Subjects were medical students (MS), residents (RES), and laparoscopic faculty (FAC). Subjects performed 10 repetitions of 6 LapSim tasks. The LapSim measured performance in 6 to 10 parameters per task, and performance was compared between groups. Post hoc t tests were used to make pair-wise comparisons among the 3 groups using the Bonferroni technique. Statistical significance was set at P < .05. RESULTS: The degree of prior laparoscopic experience was reflected in performance on at least 1 parameter for each task. Several patterns of performance between MS, RES, and FAC were observed. CONCLUSIONS: The LapSim has performance parameters that reliably differentiate between subjects with varying laparoscopic experience. However, some performance parameters do not differentiate between groups. To accurately measure a trainee's skill level, only parameters that sensitively measure the true level of performance should be used.

The nitric oxide donor DETA-NONOate decreases matrix metalloproteinase-9 expression and activity in rat aortic smooth muscle and abdominal aortic explants.

Our objective was to examine the role of an exogenous nitric oxide (NO) donor, DETA-NONOate (DETA), on matrix metalloproteinase (MMP)-9, MMP-2, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 expression and activity in interleukin (IL)-1beta-induced rat aortic smooth muscle cells (RA-SMCs) and rat aortic explants (RAEs). RA-SMCs were incubated with IL-1beta (2 ng/ml), an inflammatory cytokine known to induce MMP-9 expression, and increasing concentrations of DETA (0, 1.0, 10, 100 microM; n = 3/group) for 48 hr. RAEs were incubated with IL-1beta (2 ng/mL) and increasing concentrations of DETA (0, 5.0, 50, 100, and 500 microM; n = 3/group) for 48 hr. Media were collected and assayed for NO(x) by the Griess reaction and MMP-9 activity by zymography. Messenger RNA (mRNA) was extracted from cells and analyzed for MMP-9, MMP-2, and TIMP-1 expression levels by quantitative real-time reverse-transcriptase polymerase chain reaction. All statistical analyses were performed by analysis of variance. In RA-SMCs and RAEs, DETA administration resulted in a dose-dependent increase in media NOx concentration (RA-SCM p < 0.01, RAE p < 0.01) and a concurrent decrease in both MMP-9 expression (RASMC p = 0.01, RAE p = 0.01) and activity (RASMC p = 0.04, RAE p = 0.006). There were no significant differences seen in MMP-2 and TIMP-1 expression or activity in response to DETA exposure. DETA decreased IL-1beta-induced MMP-9 expression and activity in both RA-SMCs and RAEs in a dose-dependent fashion. In addition, DETA administration had no effect on MMP-2 or TIMP-1 expression or activity in vitro. These data suggest that NO donors may be beneficial in decreasing MMP-9 levels and might serve to inhibit MMP-9-dependent vessel wall remodeling seen during abdominal aortic aneurysm formation.

Revisiting lithium-associated hyperparathyroidism in the era of intraoperative parathyroid hormone monitoring.

BACKGROUND: Chronic lithium therapy may cause hyperparathyroidism (HPT). The utility of intraoperative parathyroid hormone monitoring (IOPTH) in these patients is unknown. The authors' hypothesis was that multiglandular disease is more common in these patients, and the ability of IOPTH to predict cure may be limited. METHODS: Twelve patients had HPT during chronic lithium therapy and underwent parathyroidectomy with IOPTH. Criteria for curative resection were a decrease > or =50% from baseline and into the normal range. Calcium and PTH levels were measured during follow-up. RESULTS: Preoperatively, mean calcium was 11.0 +/- 0.1 mg/dL, and PTH was 116 +/- 14 pg/mL. Fifty percent of patients had multiglandular disease confirmed by IOPTH levels. Mean IOPTH decrease from baseline was 74 +/- 4%. Although 10 of 12 patients met criteria for curative resection, only 8 remain normocalcemic. The 2 patients who did not meet criteria remain normocalcemic. Mean postoperative calcium for all patients was 9.5 +/- 0.2 mg/dL. Of the 10 normocalcemic patients, 4 also have hyperparathormonemia (mean PTH, 119 +/- 19 pg/mL). CONCLUSIONS: The incidence of multiglandular disease in HPT after chronic lithium exposure is higher than standard HPT. The ability of IOPTH to predict durable normocalcemia is limited. Bilateral neck exploration should be considered for these patients regardless of whether IOPTH monitoring is used.

Gender differences in rat aortic smooth muscle cell matrix metalloproteinase-9.

BACKGROUND: A predilection exists for men to develop abdominal aortic aneurysms (AAAs), but the reasons for this gender predisposition are not known. Matrix metalloproteinase-9 (MMP-9) has been implicated in both human and experimental AAAs. This investigation tested the hypothesis that male and female gender differences exist in the production of MMP-9 by rat aortic smooth muscle cells (RASMCs). STUDY DESIGN: In the first set of experiments, cultured male and female RASMCs were stimulated with interleukin-1 beta (IL-1beta) at 2 ng/mL. Messenger RNA was extracted from the RASMCs and gene expression of MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1), an MMP-9 inhibitor, was measured by quantitative real-time polymerase chain reaction. Cell culture media were collected for measurement of MMP-9 protein levels and MMP-9 activity by Western blotting and gelatin zymography, respectively. In the second set of experiments, male RASMCs were treated with 17-beta-estradiol (10(-10) to 10(-6) mol/L) and MMP-9 activity was measured. In the third set of experiments, male rats were pretreated with estradiol, and MMP-9 activity was measured in the media from explanted aortas. RESULTS: MMP-9 gene expression was 10-fold higher in male versus female RASMCs (p=0.003). MMP-9 protein levels (p=0.005) and gelatinolytic activities (p=0.01) were also greater in male than female RASMCs. TIMP-1 expression was fourfold higher in male versus female RASMCs (p<0.001). Estradiol-treated male RASMCs did not exhibit a decrease in MMP-9 activity. But aortic explants from male rats pretreated with 17-beta-estradiol had 60% less MMP-9 activity than explants from male controls (p=0.03). CONCLUSIONS: MMP-9 and TIMP-1 are greater in male than in female RASMCs. These findings support the tenet that gender-related differences in MMP-9 may contribute to AAA formation.

L-selectin-mediated neutrophil recruitment in experimental rodent aneurysm formation.

BACKGROUND: This investigation tested the hypothesis that L-selectin is important in experimental abdominal aortic aneurysm (AAA) formation in rodents. METHODS AND RESULTS: Rat abdominal aortas were perfused with saline (control) or porcine pancreatic elastase and studied on postperfusion days 1, 2, 4, 7, and 14 (n=5 per treatment group per day). Neutrophil (polymorphonucleur leukocyte, PMN) and macrophage counts per high-powered field (HPF) were performed on fixed sections. L-selectin expression and protein levels in aortic tissue were determined by polymerase chain reaction and Western blot, respectively. Elastase-perfused aortic diameters were significantly increased compared with control aortas at all time points except day 1 (P<0.05). PMN counts significantly increased in elastase-perfused aortas compared with control aortas at days 1, 2, and 4, reaching maximum levels at day 7 (40.8 versus 0.3 PMNs/HPF, P=0.001). L-selectin mRNA expression in elastase-perfused aortas was 18 (P=0.018), 17 (P<0.001), and 8 times (P=0.02) times greater than control aortas at days 1, 2, and 4, respectively. Western blot demonstrated a significant 69% increase in L-selectin protein at day 7 in elastase- as compared with saline-perfused aortas (P=0.005). Subsequent experiments involved similar studies on postperfusion days 4, 7, and 14 of aortas from C57BL/6 wild-type (WT) mice (n=21) and L-selectin-knockout (LKO) mice (n=19). LKO mice had significantly smaller aortic diameters at day 14 as compared with WT mice (88% versus 123%, P=0.02). PMN counts were significantly greater in elastase-perfused WT mouse aortas as compared with LKO mouse aortas at day 4 after perfusion (12.8 versus 4.8 PMNs/HPF, P=0.02). Macrophage counts were significantly greater at all time points after perfusion in elastase-perfused WT mouse aortas compared with elastase-perfused LKO mouse aortas, with a maximum difference at day 7 after perfusion (13.3 versus 0.5 macrophages/HPF, P<0.001). CONCLUSIONS: L-selectin-mediated neutrophil recruitment may be a critical early step in AAA formation.

Neutrophil depletion inhibits experimental abdominal aortic aneurysm formation.

BACKGROUND: Neutrophils may be an important source of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two matrix-degrading enzymes thought to be critical in the formation of an abdominal aortic aneurysm (AAA). The purpose of this investigation was to test the hypothesis that neutrophil depletion would limit experimental AAA formation by altering one or both of these enzymes. METHODS AND RESULTS: Control, rabbit serum-treated (RS; n=27) or anti-neutrophil-antibody-treated (anti-PMN; n=25) C57BL/6 mice underwent aortic elastase perfusion to induce experimental aneurysms. Anti-PMN-treated mice became neutropenic (mean, 349 cells/microL), experiencing an 84% decrease in the circulating absolute neutrophil count (P<0.001) before elastase perfusion. Fourteen days after elastase perfusion, control mice exhibited a mean aortic diameter (AD) increase of 104+/-14% (P<0.0001), and 67% developed AAAs, whereas anti-PMN-treated mice exhibited a mean AD increase of 42+/-33%, with 8% developing AAAs. The control group also had increased tissue neutrophils (20.3 versus 8.6 cells per 5 high-powered fields [HPFs]; P=0.02) and macrophages (6.1 versus 2.1 cells per 5 HPFs, P=0.005) as compared with anti-PMN-treated mice. There were no differences in monocyte chemotactic protein-1 or macrophage inflammatory protein-1alpha chemokine levels between groups by enzyme-linked immunosorbent assay. Neutrophil collagenase (MMP-8) expression was detected only in the 14-day control mice, with increased MMP-8 protein levels by Western blotting (P=0.017), and MMP-8-positive neutrophils were seen almost exclusively in this group. Conversely, there were no statistical differences in MMP-2 or MMP-9 mRNA expression, protein levels, enzyme activity, or immunostaining patterns between groups. When C57BL/6 wild-type (n=15) and MMP-8-deficient mice (n=17) were subjected to elastase perfusion, however, ADs at 14 days were no different in size (134+/-7.9% versus 154+/-9.9%; P=0.603), which suggests that MMP-8 serves only as a marker for the presence of neutrophils and is not critical for AAA formation. CONCLUSIONS: Circulating neutrophils are an important initial component of experimental AAA formation. Neutrophil depletion inhibits AAA development through a non-MMP-2/9-mediated mechanism associated with attenuated inflammatory cell recruitment.

Tamoxifen up-regulates catalase production, inhibits vessel wall neutrophil infiltration, and attenuates development of experimental abdominal aortic aneurysms.

BACKGROUND: Selective estrogen receptor modulators (SERMs), similar to estrogens, possess vasoprotective effects by reducing release of reactive oxygen species. Little is known about the potential effects of SERMs on the pathogenesis of abdominal aortic aneurysms (AAAs). This study's objective was to investigate the growth of experimental AAAs in the setting of the SERM tamoxifen. METHODS: In the first set of experiments, adult male rats underwent subcutaneous tamoxifen pellet (delivering 10 mg/kg/day) implantation (n = 14) or sham operation (n = 16). Seven days later, all animals underwent pancreatic elastase perfusion of the abdominal aorta. Aortic diameters were determined at that time, and aortas were harvested 7 and 14 days after elastase perfusion for immunohistochemistry, real-time polymerase chain reaction, Western blot analysis, and zymography. In the second set of experiments, a direct irreversible catalase inhibitor, 3-amino-1,2,4-triazole (AT), was administered intraperitoneally (1 mg/kg) daily to tamoxifen-treated (n = 6) and control rats (n = 6), starting on day 7 after elastase perfusion. Aortic diameters were measured on day 14. In a third set of experiments, rats were perfused with catalase (150 mg/kg) after the elastase (n = 5), followed by daily intravenous injections of catalase (150 mg/kg/day) administered for 10 days. A control group of rats (n = 7) received 0.9% NaCl instead of catalase. RESULTS: Mean AAA diameters were approximately 50% smaller in tamoxifen-treated rats compared with sham rats 14 days after elastase perfusion (P = .002). The tamoxifen-treated group's aortas had a five-fold increase in catalase mRNA expression (P = .02) on day 7 and an eight-fold increase in catalase protein on day 14 (P = .04). Matrix metalloprotroteinase-9 activity was 2.4-fold higher (P = .01) on day 7 in the aortas of the controls compared to the tamoxifen-treated group's aortas. Tamoxifen-treated rats had approximately 40% fewer aortic polymorphonuclear neutrophils compared to controls on day 7 (P = .05). Administration of the direct catalase inhibitor AT to tamoxifen-treated rats partially reversed the aneurysm inhibitory effect of tamoxifen by nearly 30% (P = .02). In contrast, catalase administration inhibited AAA formation by 44% (P = .002). CONCLUSIONS: The selective estrogen receptor modulator tamoxifen inhibits the development of AAAs in male rats in association with an up-regulation of catalase and inhibition of aortic wall neutrophil infiltration.

Role of 131I in the treatment of well differentiated thyroid cancer.

(131)I is an integral component in postsurgical management of well-differentiated thyroid cancer (WDTC), which includes papillary and follicular types. (131)I is used postsurgically to either destroy remaining thyroid tissue (thyroid ablation) or to treat recurrence and metastases (radioiodine therapy). (131)I is no longer a routine diagnostic modality, but it is widely used for remnant ablation after thyroidectomy for WDTC > 1 cm, under conditions of thyroxine withdrawal. It is generally-though not unanimously-accepted that postsurgical radioiodine is the most powerful method by which to lengthen disease-free survival. (131)I cannot be used if the residual thyroid remnant is large; many surgeons therefore perform near-total or total thyroidectomy for all WDTC > 1 cm. Since 1997, radioiodine treatment has been performed in outpatient settings, where side effects are common, but mild and transient. Secondary screening is by physical exam, thyroglobulin measurements, and (131)I diagnostic whole-body scans. This is performed under conditions of thyrotropin stimulation, which is accomplished either by thyroxine withdrawal or administration of recombinant human thyrotropin. While most cancers are well treated with radioiodine, some advanced cancers may no longer take up radioiodine, rendering them resistant to treatment. For these cancers, redifferentiation therapy and molecular target-specific medicines hold future promise for improved treatment.

The influence of sample site on intraoperative PTH monitoring during parathyroidectomy.

BACKGROUND: Intraoperative parathyroid hormone (IOPTH) monitoring is common during parathyroidectomy. We hypothesized that sample site (peripheral vs central vein) may impact IOPTH interpretation. METHODS: Two hundred and one patients underwent curative parathyroidectomy for single-gland disease. IOPTH was drawn peripherally (PV) in 114 patients and centrally (CV, jugular vein) in 87 patients. Decrease from baseline IOPTH and the presence of a normal value at 10 and 15 minutes were determined. The slope of IOPTH decay was calculated. These data were compared between sample sites. RESULTS: Median baseline IOPTH was 268 pg/mL (CV) and 191 pg/mL (PV, P = .003). The mean IOPTH decay slopes were -0.75 (PV) and -0.76 (CV, P = NS), and the mean percent IOPTH decrease at 10 minutes was 79% PV and 80% CV (P = NS). At 10 minutes, a > or =50% drop from baseline was seen in 94% (CV) versus 97% (PV) of patients ( P = NS), resulting in a median IOPTH of 40 pg/mL (CV) versus 34 pg/mL (PV, P = .09). By 15 minutes, the central IOPTH had decreased by > or =50% of baseline in 98% of patients ( P = NS when compared to the 10-minute PV site). CONCLUSIONS: IOPTH kinetics are largely the same for PV and CV sample sites, but baseline values are higher with central sampling. Consequently, CV IOPTH levels are generally higher at 10 minutes, but this discrepancy resolves by 15 minutes. The surgeon utilizing CV samples may need to extend the sampling period.