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Context: In 1999, the US Congress directed the Centers for Disease Control and Prevention to conduct a pivotal safety and efficacy study of anthrax vaccine adsorbed (AVA).Objective: To determine the effects on serological responses and injection site adverse events (AEs) resulting from changing the route of administration of AVA from subcutaneous (s.q.) to intramuscular (i.m.) and omitting the week 2 dose from the licensed schedule.Design, Setting, and Participants: Assessment of the first 1005 enrollees in a multisite, randomized, double-blind, noninferiority, phase 4 human clinical trial (ongoing from May 2002).Intervention: Healthy adults received AVA by the s.q. (reference group) or i.m. route at 0, 2, and 4 weeks and 6 months (4-SQ or 4-IM; n = 165-170 per group) or at a reduced 3-dose schedule (3-IM; n = 501). A control group (n = 169) received saline injections at the same time intervals.Main Outcome Measures: Noninferiority at week 8 and month 7 of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer (GMT), and proportion of responders with a 4-fold rise in titer (%4 x R). Reactogenicity outcomes were proportions of injection site and systemic AEs.Results: At week 8, the 4-IM group (GMC, 90.8 microg/mL; GMT, 1114.8; %4 x R, 97.7) was noninferior to the 4-SQ group (GMC, 105.1 microg/mL; GMT, 1315.4; %4 x R, 98.8) for all 3 primary end points. The 3-IM group was noninferior for only the %4 x R (GMC, 52.2 microg/mL; GMT, 650.6; %4 x R, 94.4). At month 7, all groups were noninferior to the licensed regimen for all end points. Solicited injection site AEs assessed during examinations occurred at lower proportions in the 4-IM group compared with 4-SQ. The odds ratio for ordinal end point pain reported immediately after injection was reduced by 50% for the 4-IM vs 4-SQ groups (P < .001). Route of administration did not significantly influence the occurrence of systemic AEs.Conclusions: The 4-IM and 3-IM regimens of AVA provided noninferior immunological priming by month 7 when compared with the 4-SQ licensed regimen. Intramuscular administration significantly reduced the occurrence of injection site AEs. Trial Registration clinicaltrials.gov Identifier: NCT00119067. [ABSTRACT FROM AUTHOR]

The safety of outpatient direct laryngoscopy has recently been challenged in the literature. We reviewed the first 589 direct laryngoscopies performed at a new outpatient surgery center. There were nine unplanned admissions to the hospital, including five airway emergencies that developed within the first 30 min after extubation. Three patients required reintubation before leaving the operating room. On postoperative telephone follow-up, 9% complained of mild to moderate sore throat. There were no major complications after discharge. We conclude that the risk of airway emergencies after direct laryngoscopy is less than 1% in carefully selected patients. The procedure can be safely performed as an outpatient procedure as long as transportation to a hospital is readily available for the few patients in whom complications arise. [ABSTRACT FROM AUTHOR]

Black and Latino sexual minority men (SMM) continue to be disproportionately impacted by HIV. We utilized eight components of the Meaningful Involvement of People Living with HIV/AIDS (MIPA) framework to assess the engagement of Black and Latino SMM. Thirty-six (36) studies were included in the literature review. Forty-two percent of studies were Black SMM-specific, followed by Latino SMM-specific (31%) studies. Twenty-eight percent of studies were conducted among both groups. Most studies (72%) were intervention-related and focused on HIV prevention. The top five most common methods of community engagement were focus groups (39%), followed by interviews (36%), community-based participatory research (14%), the utilization of community advisory boards or peer mentorship (11%), and the establishment of multi-stakeholder coalitions, observations, or surveys (8%). We documented at least 7 MIPA components in 47% of the included studies. Community-based participatory research was more commonly utilized to engage Latino SMM. Researchers were more likely to initiate the engagement across all included studies. Few studies documented how Black and Latino SMM perceived the engagement. Engagement responsiveness was a well-documented MIPA component. In terms of engagement power dynamics, there were several examples of power imbalances, especially among Black SMM-specific studies. The inclusion of Black and Latino SMM had robust impacts on HIV research and interventions. There were limited examples of engagement capacity and maintenance. This is one of the first studies focused on utilizing MIPA to document the engagement of SMM of color. MIPA served as a useful framework for understanding the engagement of SMM of color in the US HIV response. The engagement of SMM of color is critical to reducing health inequities., (© 2022. W. Montague Cobb-NMA Health Institute.)

Background and Hypothesis: The sexual and reproductive health (SRH) of young people with psychosis has been largely overlooked. We hypothesised that there are key deficiencies in the existing literature on the SRH of adolescents and young adults with psychotic disorders., Study Design: We conducted a systematic scoping review using Pubmed, Web of Science, Embase, PsycINFO, and CINAHL. We included empirical studies and case reports focused on SRH issues in young people (aged 14-24 years) with psychotic disorders. A qualitative synthesis was completed. Joanna Briggs Institute Critical Appraisal Tools were utilized to assess study quality., Study Results: Seventeen empirical studies and 52 case reports met inclusion criteria. Most focused on sexual dysfunction which was identified as common among this cohort and associated with both psychotic disorders and antipsychotics. The study population was more likely to engage in sexual risk-taking behavior and was at higher risk of sexually transmissible infections than those without psychosis. SRH topics of clinical relevance in older patients with psychosis such as pregnancy, abortion, sexual violence, coercion, sexual identity, and gender were poorly addressed in this younger group. We found empirical studies generally lacked identification and controlling of confounders whilst case reports provided limited description of mental health and SRH outcomes following clinical intervention., Conclusion: Research and clinical practice addressing sexual and reproductive health is needed for young people living with psychosis. To address research gaps future studies should focus on women's health, sexual violence, gender, and sexuality in young people with psychosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Support from social networks buffers against negative effects of stress but is disrupted by incarceration. Few studies examine incarceration, social support networks, and health among Black sexual minority men (BSMM) and Black transgender women (BTW). We conducted a secondary analysis using HIV Prevention Trials Network 061 (HPTN 061), a sample of BSMM/BTW recruited from six US cities. We measured associations between recent incarceration reported at six months follow-up and social support networks at twelve months follow-up, and cross-sectional associations between support networks and twelve-month health outcomes (e.g., sexual partnerships, substance use, healthcare access and depressive symptoms). Among the analytic sample (N = 1169), recent incarceration was associated with small medical support networks (adjusted risk ratio [aRR] 1.16, 95% CI 1.01, 1.34) and small financial support networks (aRR 1.18, 95% CI 1.04, 1.35). Support networks were associated with multiple partnerships (adjusted prevalence ratio [aPR] 0.77, 95% CI 0.65, 0.90), unhealthy alcohol use (aPR 1.20, 95% CI 0.96, 1.51), and depressive symptoms (aPR 1.16, 95% CI 0.99, 1.36). Incarceration adversely impacts social support networks of BSMM/BTW, and support networks were associated with a range of important health outcomes., Competing Interests: The authors declare no conflict of interest.

Objective: To present a practical, easy-to-implement clinical framework designed to support evidence-based quality prescribing for people with early psychosis., Method: Identification and explanation of key principles relating to evidence-based pharmacotherapy for people with early psychosis. These were derived from the literature, practice guidelines and clinical experience., Results: Key principles include (1) medication choice informed by adverse effects; (2) metabolic monitoring at baseline and at regular intervals; (3) comprehensive and regular medication risk-benefit assessment and psychoeducation; (4) early consideration of long-acting injectable formulations (preferably driven by informed patient choice); (5) identification and treatment of comorbid mood disorders and (6) early consideration of clozapine when treatment refractory criteria are met., Conclusions: Current prescribing practices do not align with the well-established evidence for quality pharmacotherapy in early psychosis. Adopting evidence-based prescribing practices for people with early psychosis will improve outcomes.

Background: Despite young African American adults (ages 18-24) being among the highest risk groups for HIV infection, little is known about their awareness of HIV pre-exposure prophylaxis (PrEP) - a once daily pill shown to be > 90% effective in preventing HIV. To explore awareness and acceptability of PrEP among college students in this demographic, we conducted a survey of attendees at two large historically Black universities (HBCU) in North Carolina., Methods: We administered a 14-item questionnaire to students at two HBCUs in North Carolina between February and April 2018. Questions were formatted in a yes/no or multiple choice format. Questionnaire items specifically addressed PrEP awareness and acceptability. Surveys were administered to students at a campus health fair and while transiting the campus student union via iPad. Response to all questions was optional. We fit a logistic regression model to determine association of key demographic determinants with PrEP acceptability and awareness. Statistical analyses were conducted using SAS 9.4 (SAS, Cary, NC)., Results: Overall, 210 students participated in the survey, of which 60 completed all survey items as presented. The survey cohort was 75% female, 89% heterosexual and 39% freshmen. The mean age of respondents was 19.8 years (SD: 1.8). Fifty-two percent of survey respondents reported that they were aware of PrEP prior to the time of survey administration. Only 3% of respondents reported that they were on PrEP. The most common sources of information on PrEP were campus health services (24%) and non-social media advertising (15%). Of respondents who were aware of PrEP, 61% reported that they had heard about in the 6 months prior to survey administration, while only 19% say they were aware of it for more than a year. Regarding acceptability of PrEP, 58% of respondents reported that they would take a once a day pill for HIV if they were at risk. Our logistic regression analysis found no statistically significant associations between key demographic factors and PrEP awareness. However, persons who perceived themselves to be at risk for HIV acquisition were more likely to find once daily oral PrEP (relative risk 2.66 (95% CI 1.31-5.42)) as an acceptable prevention strategy than the rest of the survey cohort., Conclusions: African American HBCU students are becoming aware of PrEP, and generally perceive the intervention as acceptable and worth consideration.

Management of large herbivores depends on providing habitats for forage supply and refuge from risks of temperature, predation and disease. Moose ( Alces alces ) accumulate body energy and nutrient stores during summer, while reducing the impact of warm temperatures through physiological and behavioural thermoregulation. Building on the animal indicator concept, we used rumen temperature sensors and GPS collars on captive moose ( n  = 6) kept in large natural enclosures to evaluate how behaviour and habitat selection influence the rate of change in rumen temperature during the growing season on the Kenai Peninsula, Alaska, USA. We compared movement and habitat selection of individual females during tolerance days (daily amplitude in rumen temperature was ≥1.2°C in 24 h) with those of control days (daily amplitude in rumen temperature was < 1.2°C) before and after the tolerance day. Moose moved more during tolerance days (172 m • h -1 ; 95% confidence intervals (CI)  = 149-191 m • h -1 ) than on control days (151 m • h -1 ; 95% CI = 128-173 m • h -1 ). The rate of change in rumen temperature (°C • h -1 ) declined with low to moderate movement rates that were probably associated with foraging in all habitats. Movement only increased the rate of change in rumen temperature at high activity (~ > 500 m • h -1 ). Additionally, the relationship between rate of change in rumen temperature and movement rate was different during tolerance and control days in open meadow and wetland habitats. In all habitats except wetlands, the rate of change in rumen temperature increased while resting, which probably is a result of diet-induced thermogenesis. Our study demonstrates that the behavioural choices of moose on the landscape are associated with the rate of change in rumen temperature and their ability to thermoregulate. Wildlife managers must consider high-value habitats where wildlife can employ both behavioural and physiological mechanisms to tolerate warm ambient conditions in a landscape of forage, predators and pests., (© The Author(s) 2021. Published by Oxford University Press and the Society for Experimental Biology.)

Protective antigen (PA)-specific antibody and cell-mediated immune (CMI) responses to annual and alternate booster schedules of anthrax vaccine adsorbed (AVA; BioThrax) were characterized in humans over 43 months. Study participants received 1 of 6 vaccination schedules: a 3-dose intramuscular (IM) priming series (0, 1, and 6 months) with a single booster at 42 months (4-IM); 3-dose IM priming with boosters at 18 and 42 months (5-IM); 3-dose IM priming with boosters at 12, 18, 30, and 42 months (7-IM); the 1970 licensed priming series of 6 doses (0, 0.5, 1, 6, 12, and 18 months) and two annual boosters (30 and 42 months) administered either subcutaneously (SQ) (8-SQ) or IM (8-IM); or saline placebo control at all eight time points. Antibody response profiles included serum anti-PA IgG levels, subclass distributions, avidity, and lethal toxin neutralization activity (TNA). CMI profiles included frequencies of gamma interferon (IFN-γ)- and interleukin 4 (IL-4)-secreting cells and memory B cells (MBCs), lymphocyte stimulation indices (SI), and induction of IFN-γ, IL-2, IL-4, IL-6, IL-1β, and tumor necrosis factor alpha (TNF-α) mRNA. All active schedules elicited high-avidity PA-specific IgG, TNA, MBCs, and T cell responses with a mixed Th1-Th2 profile and Th2 dominance. Anti-PA IgG and TNA were highly correlated (e.g., month 7,r(2)= 0.86,P< 0.0001, log10 transformed) and declined in the absence of boosters. Boosters administered IM generated the highest antibody responses. Increasing time intervals between boosters generated antibody responses that were faster than and superior to those obtained with the final month 42 vaccination. CMI responses to the 3-dose IM priming remained elevated up to 43 months. (This study has been registered at ClinicalTrials.gov under registration no. NCT00119067.)., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Background: A substantial fraction of all American healthcare expenditures are potentially wasted, and practices that are not evidence-based could contribute to such waste. We sought to characterize whether Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) tests of preoperative patients are used in a way unsupported by evidence and potentially wasteful., Methods and Findings: We evaluated prospectively-collected patient data from 19 major teaching hospitals and 8 hospital-affiliated surgical centers in 7 states (Delaware, Florida, Maryland, Massachusetts, New Jersey, New York, Pennsylvania) and the District of Columbia. A total of 1,053,472 consecutive patients represented every patient admitted for elective surgery from 2009 to 2012 at all 27 settings. A subset of 682,049 patients (64.7%) had one or both tests done and history and physical (H&P) records available for analysis. Unnecessary tests for bleeding risk were defined as: PT tests done on patients with no history of abnormal bleeding, warfarin therapy, vitamin K-dependent clotting factor deficiency, or liver disease; or aPTT tests done on patients with no history of heparin treatment, hemophilia, lupus anticoagulant antibodies, or von Willebrand disease. We assessed the proportion of patients who received PT or aPTT tests who lacked evidence-based reasons for testing., Conclusions: This study sought to bring the availability of big data together with applied comparative effectiveness research. Among preoperative patients, 26.2% received PT tests, and 94.3% of tests were unnecessary, given the absence of findings on H&P. Similarly, 23.3% of preoperative patients received aPTT tests, of which 99.9% were unnecessary. Among patients with no H&P findings suggestive of bleeding risk, 6.6% of PT tests and 7.1% of aPTT tests were either a false positive or a true positive (i.e. indicative of a previously-undiagnosed potential bleeding risk). Both PT and aPTT, designed as diagnostic tests, are apparently used as screening tests. Use of unnecessary screening tests raises concerns for the costs of such testing and the consequences of false positive results.

Objectives: We tested the efficacy of an adapted evidence-based HIV-sexually transmitted infection (STI) behavioral intervention (Providing Opportunities for Women's Empowerment, Risk-Reduction, and Relationships, or POWER) among incarcerated women., Methods: We conducted a randomized trial with 521 women aged 18 to 60 years in 2 correctional facilities in North Carolina in 2010 and 2011. Intervention participants attended 8 POWER sessions; control participants received a single standard-of-care STI prevention session. We followed up at 3 and 6 months after release. We examined intervention efficacy with mixed-effects models., Results: POWER participants reported fewer male sexual partners than did control participants at 3 months, although this finding did not reach statistical significance; at 6 months they reported significantly less vaginal intercourse without a condom outside of a monogamous relationship and more condom use with a main male partner. POWER participants also reported significantly fewer condom barriers, and greater HIV knowledge, health-protective communication, and tangible social support. The intervention had no significant effects on incident STIs., Conclusions: POWER is a behavioral intervention with potential to reduce risk of acquiring or transmitting HIV and STIs among incarcerated women returning to their communities.

Background: Although prison provides the opportunity for HIV diagnosis and access to in-prison care, following release, many HIV-infected inmates experience clinical setbacks, including nonadherence to antiretrovirals, elevations in viral load, and HIV disease progression. HIV-infected former inmates face numerous barriers to successful community reentry and to accessing healthcare. However, little is known about the outcome expectations of HIV-infected inmates for release, how their post-release lives align with pre-release expectations, and how these processes influence engagement in HIV care following release from prison., Methods: We conducted semi-structured interviews (24 pre- and 13 post-release) with HIV-infected inmates enrolled in a randomized controlled trial of a case management intervention to enhance post-release linkage to care. Two researchers independently coded data using a common codebook. Intercoder reliability was strong (kappa = 0.86). We analyzed data using Grounded Theory methodology and Applied Thematic Analysis. We collected and compared baseline sociodemographic and behavioral characteristics of all cohort participants who did and did not participate in the qualitative interviews using Fisher's Exact Tests for categorical measures and Wilcoxon rank-sum tests for continuous measures., Results: Most participants were heterosexual, middle-aged, single, African American men and women with histories of substance use. Substudy participants were more likely to anticipate living with family/friends and needing income assistance post-release. Most were taking antiretrovirals prior to release and anticipated needing help securing health benefits and medications post-release. Before release, most participants felt confident they would be able to manage their HIV. However, upon release, many experienced intermittent or prolonged periods of antiretroviral nonadherence, largely due to substance use relapse or delays in care initiation. Substance use was precipitated by stressful life experiences, including stigma, and contact with drug-using social networks. As informed by the Social Cognitive Theory and HIV Stigma Framework, findings illustrate the reciprocal relationships among substance use, experiences of stigma, pre- and post-release environments, and skills needed to engage in HIV care., Conclusion: These findings underscore the need for comprehensive evidence-based interventions to prepare inmates to transition from incarceration to freedom, particularly those that strengthen linkage to HIV care and focus on realities of reentry, including stigma, meeting basic needs, preventing substance abuse, and identifying community resources.

Objective: This paper qualitatively evaluates a one-year trial of Balint clinical reflection groups for medical students in psychiatry at a large Australian tertiary referral hospital. The trial considered whether clinical reflection groups following the Balint process would be perceived as useful and relevant to the learning needs of the student participants., Method: A grounded theory approach was undertaken. This included survey data, thematic analysis of written feedback, and facilitator reflection on the process. Facilitators adapted the group process in response to participants' needs. These modifications included: increased education regarding the Balint process; the introduction of co-presenters; and the inclusion of a didactic summary following each session., Results: The evaluation suggested that fidelity of the Balint group experience was achieved and that student attitudes were neutral to mildly positive regarding the educational experience., Conclusions: Balint groups are potentially useful to medical students in the Australian context. We suggest that Balint groups may be more useful when applied in less alienating learning environments, such as during general practice rotations. Emphasis is placed on the need to maintain a dynamic approach by adapting the group and the educational processes as the work unfolds.

Objective: We evaluated an alternative administration route, reduced schedule priming series, and increased intervals between booster doses for anthrax vaccine adsorbed (AVA). AVA's originally licensed schedule was 6 subcutaneous (SQ) priming injections administered at months (m) 0, 0.5, 1, 6, 12 and 18 with annual boosters; a simpler schedule is desired., Methods: Through a multicenter randomized, double blind, non-inferiority Phase IV human clinical trial, the originally licensed schedule was compared to four alternative and two placebo schedules. 8-SQ group participants received 6 SQ injections with m30 and m42 "annual" boosters; participants in the 8-IM group received intramuscular (IM) injections according to the same schedule. Reduced schedule groups (7-IM, 5-IM, 4-IM) received IM injections at m0, m1, m6; at least one of the m0.5, m12, m18, m30 vaccine doses were replaced with saline. All reduced schedule groups received a m42 booster. Post-injection blood draws were taken two to four weeks following injection. Non-inferiority of the alternative schedules was compared to the 8-SQ group at m2, m7, and m43. Reactogenicity outcomes were proportions of injection site and systemic adverse events (AEs)., Results: The 8-IM group's m2 response was non-inferior to the 8-SQ group for the three primary endpoints of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer, and proportion of responders with a 4-fold rise in titer. At m7 anti-PA IgG GMCs for the three reduced dosage groups were non-inferior to the 8-SQ group GMCs. At m43, 8-IM, 5-IM, and 4-IM group GMCs were superior to the 8-SQ group. Solicited injection site AEs occurred at lower proportions in the IM group compared to SQ. Route of administration did not influence the occurrence of systemic AEs. A 3 dose IM priming schedule with doses administered at m0, m1, and m6 elicited long term immunological responses and robust immunological memory that was efficiently stimulated by a single booster vaccination at 42 months., Conclusions: A priming series of 3 intramuscular doses administered at m0, m1, and m6 with a triennial booster was non-inferior to more complex schedules for achieving antibody response., (Published by Elsevier Ltd.)

Background: Women who have been in prison carry a greater lifetime risk of HIV for reasons that are not well understood. This effect is amplified in the Southeastern United States, where HIV incidence and prevalence is especially high among African-American (AA) women. The role of consensual sexual partnerships in the context of HIV risk, especially same-sex partnerships, merits further exploration., Methods: We conducted digitally recorded qualitative interviews with 29 AA women (15 HIV positive, 14 HIV negative) within 3 months after entry into the state prison system. We explored potential pre-incarceration HIV risk factors, including personal sexual practices. Two researchers thematically coded interview transcripts and a consensus committee reviewed coding., Results: Women reported complex sexual risk profiles during the 6 months before incarceration, including sex with women as well as prior sexual partnerships with both men and women. Condom use with primary male partners was low and a history of transactional sex work was prevalent. These behaviors were linked with substance use, particularly among HIV-positive women., Conclusions: Although women may not formally identify as bisexual or lesbian, sex with women was an important component of this cohort's sexuality. Addressing condom use, heterogeneity of sexual practices, and partner concurrency among at-risk women should be considered for reducing HIV acquisition and preventing forward transmission in women with a history of incarceration., (Copyright © 2013 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.)

Background: DNA vaccines have been very poorly immunogenic in humans but have been an effective priming modality in prime-boost regimens. Methods to increase the immunogenicity of DNA vaccines are needed., Methods: HIV Vaccine Trials Network (HVTN) studies 070 and 080 were multicenter, randomized, clinical trials. The human immunodeficiency virus type 1 (HIV-1) PENNVAX®-B DNA vaccine (PV) is a mixture of 3 expression plasmids encoding HIV-1 Clade B Env, Gag, and Pol. The interleukin 12 (IL-12) DNA plasmid expresses human IL-12 proteins p35 and p40. Study subjects were healthy HIV-1-uninfected adults 18-50 years old. Four intramuscular vaccinations were given in HVTN 070, and 3 intramuscular vaccinations were followed by electroporation in HVTN 080. Cellular immune responses were measured by intracellular cytokine staining after stimulation with HIV-1 peptide pools., Results: Vaccination was safe and well tolerated. Administration of PV plus IL-12 with electroporation had a significant dose-sparing effect and provided immunogenicity superior to that observed in the trial without electroporation, despite fewer vaccinations. A total of 71.4% of individuals vaccinated with PV plus IL-12 plasmid with electroporation developed either a CD4(+) or CD8(+) T-cell response after the second vaccination, and 88.9% developed a CD4(+) or CD8(+) T-cell response after the third vaccination., Conclusions: Use of electroporation after PV administration provided superior immunogenicity than delivery without electroporation. This study illustrates the power of combined DNA approaches to generate impressive immune responses in humans.

Introduction: Full-length tyrosine kinase B (TrkB.FL) and truncated TrkB (TrkB.t1) receptors are colocalized with acetylcholine receptors (AChRs) at the neuromuscular junction. We have recently shown that reduced TrkB expression leads to age-related alterations in AChR structure, neurotransmission failure, and muscle weakness., Methods: We investigated whether TrkB expression is reduced in the soleus muscle during aging., Results: TrkB protein expression was decreased in senescent (24-month-old) compared with 3-12-month-old mice. Loss of TrkB expression was concurrent with age-related changes in AChR morphology. Changes in mRNA levels did not correlate with protein expression, because TrkB.FL copy number was increased in the senescent soleus. No change was seen in TrkB.t1 levels., Conclusions: The results suggest that reduced TrkB expression during aging may result from reduced TrkB.FL mRNA translation or increased TrkB protein turnover. Thus, maintaining adequate TrkB signaling is a potential therapeutic tool to improve muscle function during senescence., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: After the Department of Defense implemented a mandatory anthrax vaccination program in 1998 concerns were raised about potential long-term safety effects of the current anthrax vaccine. The CDC multicenter, randomized, double-blind, placebo-controlled Anthrax Vaccine Adsorbed (AVA) Human Clinical Trial to evaluate route change and dose reduction collected data on participants' quality of life. Our objective is to assess the association between receipt of AVA and changes in health-related quality of life, as measured by the SF-36 health survey (Medical Outcomes Trust, Boston, MA), over 42 months after vaccination., Methods: 1562 trial participants completed SF-36v2 health surveys at 0, 12, 18, 30 and 42 months. Physical and mental summary scores were obtained from the survey results. We used Generalized Estimating Equations (GEE) analyses to assess the association between physical and mental score difference from baseline and seven study groups receiving either AVA at each dose, saline placebo at each dose, or a reduced AVA schedule substituting saline placebo for some doses., Results: Overall, mean physical and mental scores tended to decrease after baseline. However, we found no evidence that the score difference from baseline changed significantly differently between the seven study groups., Conclusions: These results do not favor an association between receipt of AVA and an altered health-related quality of life over a 42-month period., (Published by Elsevier Ltd.)

Several lines of evidence have supported a host genetic contribution to vaccine response, but genome-wide assessments for specific determinants have been sparse. Here we describe a genome-wide association study (GWAS) of protective antigen-specific antibody (AbPA) responses among 726 European-Americans who received Anthrax Vaccine Adsorbed (AVA) as part of a clinical trial. After quality control, 736,996 SNPs were tested for association with the AbPA response to 3 or 4 AVA vaccinations given over a 6-month period. No SNP achieved the threshold of genome-wide significance (p=5 × 10(-8)), but suggestive associations (p<1 × 10(-5)) were observed for SNPs in or near the class II region of the major histocompatibility complex (MHC), in the promoter region of SPSB1, and adjacent to MEX3C. Multivariable regression modeling suggested that much of the association signal within the MHC corresponded to previously identified HLA DR-DQ haplotypes involving component HLA-DRB1 alleles of *15:01, *01:01, or *01:02. We estimated the proportion of additive genetic variance explained by common SNP variation for the AbPA response after the 6 month vaccination. This analysis indicated a significant, albeit imprecisely estimated, contribution of variation tagged by common polymorphisms (p=0.032). Future studies will be required to replicate these findings in European Americans and to further elucidate the host genetic factors underlying variable immune response to AVA., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Host genetic variation, particularly within the human leukocyte antigen (HLA) loci, reportedly mediates heterogeneity in immune response to certain vaccines; however, no large study of genetic determinants of anthrax vaccine response has been described. We searched for associations between the immunoglobulin G antibody to protective antigen (AbPA) response to Anthrax Vaccine Adsorbed (AVA) in humans, and polymorphisms at HLA class I (HLA-A, -B, and -C) and class II (HLA-DRB1, -DQA1, -DQB1, -DPB1) loci. The study included 794 European-Americans and 200 African-Americans participating in a 43-month, double-blind and placebo-controlled clinical trial of AVA (clinicaltrials.gov identifier NCT00119067). Among European-Americans, genes from tightly linked HLA-DRB1, -DQA1, -DQB1 haplotypes displayed significant overall associations with longitudinal variation in AbPA levels at 4, 8, 26 and 30 weeks from baseline in response to vaccination with three or four doses of AVA (global P=6.53 × 10(-4)). In particular, carriage of the DRB1-DQA1-DQB1 haplotypes (*)1501-(*)0102-(*)0602 (P=1.17 × 10(-5)), (*)0101-(*)0101-(*)0501 (P=0.009) and (*)0102-(*)0101-(*)0501 (P=0.006) was associated with significantly lower AbPA levels. In carriers of two copies of these haplotypes, lower AbPA levels persisted following subsequent vaccinations. No significant associations were observed amongst African-Americans or for any HLA class I allele/haplotype. Further studies will be required to replicate these findings and to explore the role of host genetic variation outside of the HLA region.

Acute blockade of signaling through the tyrosine kinase receptor B (TrkB) attenuates neuromuscular transmission and fragments postsynaptic acetylcholine receptors (AChRs) in adult mice, suggesting that TrkB signaling is a key regulator of neuromuscular function. Using immunohistochemical, histological, and in vitro muscle contractile techniques, we tested the hypothesis that constitutively reduced TrkB expression would disrupt neuromuscular pre- and postsynaptic structure, neurotransmission, muscle fiber size, and muscle function in the soleus muscle of 6- to 8-mo-old TrkB⁺/⁻ mice compared with age-matched littermates. Age-like expansion of postsynaptic AChR area, AChR fragmentation, and denervation was observed in TrkB⁺/⁻ mice similar to that found in 24-mo-old wild-type mice. Neurotransmission failure was increased in TrkB⁺/⁻ mice, suggesting that these morphologic changes were sufficient to alter synaptic function. Reduced TrkB expression resulted in decreased muscle strength and fiber cross-sectional area. Immunohistochemical and muscle retrograde labeling experiments show that motor neuron number and size are unaffected in TrkB⁺/⁻ mice. These results suggest that TrkB- signaling at the neuromuscular junction plays a role in synaptic stabilization, neurotransmission, and muscle function and may impact the aging process of sarcopenia.

There is an urgent need for a vaccine capable of preventing HIV infection or the development of HIV-related disease. A number of approaches designed to stimulate HIV-specific CD8+ cytotoxic T cell responses together with helper responses are presently under evaluation. In this phase 1, multi-center, placebo-controlled trial, we tested the ability of a novel multiepitope peptide vaccine to elicit HIV-specific immunity. To enhance the immunogenicity of the peptide vaccine, half of the vaccine recipients received recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) protein as a coadjuvant. The vaccine was safe; tolerability was moderate, with a number of adverse events related to local injection site reactogenicity. Anti-GM-CSF antibody responses developed in the majority of GM-CSF recipients but were not associated with adverse hematologic events. The vaccine was only minimally immunogenic. Six of 80 volunteers who received vaccine developed HIV-specific responses as measured by interferon-gamma ELISPOT assay, and measurable responses were transient. This study failed to demonstrate that GM-CSF can substantially improve the overall weak immunogenicity of a multiepitope peptide-based HIV vaccine.

Mammalian neuromuscular synapses undergo an activity-dependent competitive transition from multiple to single innervation during postnatal life. The presence of temporally correlated motor neuron activity, which, in part, is controlled by gap junctional coupling within the spinal cord, appears to modulate synapse elimination. Postnatal injection of dizocilpine maleate (MK801), a specific NMDA antagonist, has been shown to maintain gap junctional coupling among motor neurons. Thus, we tested the hypothesis that MK801 would maintain correlated motor neuron activity and delay postnatal synapse elimination. Temporally correlated motor neuron activity, which is normally lost during the second postnatal week, was maintained and synaptic competition was delayed by several days in 2-week-old mice injected daily with MK801. MK801 appears to modulate motor neuron activity patterns through enhancing mRNA expression of multiple connexins within the spinal cord and delaying motor neuron growth. Our results suggest that MK801 injection preserves correlated neural activity via both synaptic mechanisms and maintenance of gap junctional coupling among neurons within the spinal cord, ultimately delaying synapse elimination.

We have constructed a replication competent, gamma(1)34.5-deleted herpes simplex virus type-1 (HSV-1) vector (J200) that expresses the gag gene from human immunodeficiency virus type-1, primary isolate 89.6 (HIV-1(89.6)), as a candidate vaccine for HIV-1. J200 replicates in vitro, resulting in abundant Gag protein production and accumulation in the extracellular media. Immunization of Balb/c mice with a single intraperitoneal injection of J200 elicited strong Gag-specific CD8 responses, as measured by intracellular IFN-gamma staining and flow cytometry analysis. Responses were highest between 6 weeks and 4 months, but persisted at 9 months post-immunization, the last time-point evaluated. These data highlight the potential utility of neuroattenuated, replication competent HSV-1 vectors for delivery of HIV-1 immunogens.

Unlabelled: In this systematic review we focused on postoperative recovery and complications using four different anesthetic techniques. The database MEDLINE was searched via PubMed (1966 to June 2002) using the search words "anesthesia" and with ambulatory surgical procedures limited to randomized controlled trials in adults (>19 yr), in the English language, and in humans. A second search strategy was used combining two of the words "propofol," "isoflurane," "sevoflurane," or "desflurane". Screening and data extraction produced 58 articles that were included in the final meta-analysis. No differences were found between propofol and isoflurane in early recovery. However, early recovery was faster with desflurane compared with propofol and isoflurane and with sevoflurane compared with isoflurane. A minor difference was found in home readiness between sevoflurane and isoflurane (5 min) but not among the other anesthetics. Nausea, vomiting, headache, and postdischarge nausea and vomiting incidence were in favor of propofol compared with isoflurane (P < 0.05). A larger number of patients in the inhaled anesthesia groups required antiemetics compared with the propofol group. We conclude that the differences in early recovery times among the different anesthetics were small and in favor of the inhaled anesthetics. The incidence of side effects, specifically postoperative nausea and vomiting, was less frequent with propofol., Implications: A systematic analysis of the literature comparing postoperative recovery after propofol, isoflurane, desflurane, and sevoflurane-based anesthesia in adults demonstrated that early recovery was faster in the desflurane and sevoflurane groups. The incidence of nausea and vomiting were less frequent with propofol.

For all retroviruses, the completion of the viral budding process correlates with the activation of the viral protease by an unknown mechanism, and, as the structural (Gag) polyproteins are cleaved by the viral protease, maturation of the immature virus-like particle into an infectious virion. Unlike most retroviruses, the Mason-Pfizer monkey virus Gag polyproteins assemble into immature capsids within the cytoplasm of the cell before the viral budding event. The results reported here describe a unique experimental system in which Mason-Pfizer monkey virus immature capsids are removed from the cell, and the protease is activated in vitro by the addition of a reducing agent. The cleavage of the protease from the precursor form is a primary event, which proceeds with a half time of 14 min, and is followed by authentic processing of the Gag polyproteins. Activity of the viral protease in vitro depends on pH, with an increase in catalytic rates at acidic and neutral pH. The initiation of protease activity within immature capsids in vitro demonstrates that viral protease activity is sensitive to oxidation-reduction conditions, and that the viral protease can be activated in the absence of viral budding.

Mason-Pfizer monkey virus immature capsids selected from the cytoplasm of baculovirus-infected cells were imaged by scanning transmission electron microscopy. The masses of individual selected Gag particles were measured, and the average mass corresponded to 1,900 to 2,100 Gag polyproteins per particle. A large variation in Gag particle mass was observed within each population measured.

Study Objective: To determine if remifentanil would offer a superior hemodynamic and recovery profile compared to the current standard of care, which implements a fentanyl-based technique., Design: Randomized, single-blind study., Setting: Outpatient center associated with tertiary care center., Patients: 75 outpatients undergoing microsuspension laryngoscopy., Interventions: Patients were randomized to either a remifentanil induction (0.5 microg/kg/min) and maintenance (0.25 microg/kg/min) versus fentanyl (maximum of 250 microg) as the only opioid. All patients received propofol as part of the induction and maintenance with or without the use of nitrous oxide., Measurements: Assessment of hemodynamics [heart rate (HR) and blood pressure(BP)], presence of perioperative myocardial ischemia on ambulatory electrocardiographic monitoring, and time to discharge., Main Results: Significantly fewer patients in the remifentanil group demonstrated episodes of tachycardia (HR > 100 beats per min) compared to the fentanyl group (14% vs. 40%, p<0.05), with significantly fewer episodes of tachycardia and hypertension per patient. Recovery profiles between the two groups did not show clinically significant differences., Conclusions: Remifentanil, a new short-acting opioid, offers excellent hemodynamic control for brief, intense outpatient procedures performed in high-risk patients; however, its use was not associated with any improvement in recovery profiles.

Analysis of the photoactive yellow protein (pyp) gene region of Rhodobacter sphaeroides has revealed the presence of an additional open reading frame, orfD, that had not previously been identified. Here we report the location of this new gene and the predicted amino acid sequence of the encoded protein. The translation product resembles a group of small cytochrome b-like proteins, including Escherichia coli cytochrome b(561), R. sphaeroides cytochrome b(562), and two new cytochrome b(561)-like proteins identified using the E. coli genome sequence, for which functions have not yet been established. To determine OrfD function in R. sphaeroides, an orfD mutant was constructed. The OrfD mutant exhibited growth rates and yields very similar to those of the wild-type strain when grown under a variety of growth conditions. Respiration rates, reduced-minus-oxidised spectra and levels of photosynthetic complexes were also very similar in the two strains. Although the role of OrfD was therefore not determined here, we demonstrate that the orfD gene is expressed in R. sphaeroides under aerobic, semi-aerobic and photosynthetic growth conditions.

Retrovirus assembly involves a complex series of events in which a large number of proteins must be targeted to a point on the plasma membrane where immature viruses bud from the cell. Gag polyproteins of most retroviruses assemble an immature capsid on the cytoplasmic side of the plasma membrane during the budding process (C-type assembly), but a few assemble immature capsids deep in the cytoplasm and are then transported to the plasma membrane (B- or D-type assembly), where they are enveloped. With both assembly phenotypes, Gag polyproteins must be transported to the site of viral budding in either a relatively unassembled form (C type) or a completely assembled form (B and D types). The molecular nature of this transport process and the host cell factors that are involved have remained obscure. During the development of a recombinant baculovirus/insect cell system for the expression of both C-type and D-type Gag polyproteins, we discovered an insect cell line (High Five) with two distinct defects that resulted in the reduced release of virus-like particles. The first of these was a pronounced defect in the transport of D-type but not C-type Gag polyproteins to the plasma membrane. High Five cells expressing wild-type Mason-Pfizer monkey virus (M-PMV) Gag precursors accumulate assembled immature capsids in large cytoplasmic aggregates similar to a transport-defective mutant (MA-A18V). In contrast, a larger fraction of the Gag molecules encoded by the M-PMV C-type morphogenesis mutant (MA-R55W) and those of human immunodeficiency virus were transported to the plasma membrane for assembly and budding of virions. When pulse-labeled Gag precursors from High Five cells were fractionated on velocity gradients, they sedimented more rapidly, indicating that they are sequestered in a higher-molecular-mass complex. Compared to Sf9 insect cells, the High Five cells also demonstrate a defect in the release of C-type virus particles. These findings support the hypothesis that host cell factors are important in the process of Gag transport and in the release of enveloped viral particles.

Study Objective: To determine if providing an Anesthesiology Consultant Report (ACR) to patients would result in enhanced patients' perceptions of their knowledge about their care and improve their perception of the quality of their care., Design: Randomized, unblinded study., Setting: Outpatient center associated with tertiary care center., Patients: 371 outpatients without adverse anesthetic events., Interventions: Patients were randomized to receive either routine discharge instructions or routine instructions and an anesthesia discharge summary (ACR)., Measurements and Main Results: Short questionnaire with discharge packet regarding knowledge of anesthetic and questions regarding satisfaction and perceptions of quality of care was distributed. The patients in the group that received an ACR were more satisfied with the management of their pain and other symptoms (p < 0.05, by Wilcoxon rank sums) and were more satisfied overall with the quality of the anesthesia care (p < 0.01, by Wilcoxon rank sums). Taken another way, significantly more patients deemed the quality of their anesthetic care as excellent in the ACR group compared to control (83% vs. 67%, p < 0.01)., Conclusions: Providing patients, with uneventful anesthetic courses, with information regarding their anesthetic care, in the form of the ACR, results in improved perceptions of the quality of care.

Background: There is increasing pressure to perform traditional inpatient surgical procedures in an outpatient setting. The aim of the current trial was to determine the safety and cost savings of performing laparoscopic cholecystectomy in an outpatient setting using a "mock" outpatient setting., Methods: Patients who were scheduled for laparoscopic cholecystectomy by four attending surgeons and for whom operating time was available in the outpatient center were studied. All patients received a standardized anesthetic, including ondansetron, and were discharged from the outpatient postanesthesia care unit if appropriate. At discharge, all patients were admitted to a clinical research center where they were observed in a "mock home" setting and monitored for complications that would have necessitated readmission. A decision analysis was created assuming all patients underwent outpatient surgery with either direct admission or discharge to home and readmission if complications developed., Results: Of 99 patients who were enrolled in this study, 96 patients would have met the discharge criteria for home. No major complications were observed in these 96 patients. Eleven patients experienced postoperative nausea and vomiting, 3 of whom required an additional 24 h of hospital observation. In the decision model, the optimal strategy would be to perform the procedure on an outpatient basis and readmit patients only for complications, with an average baseline cost savings of $742/patient., Conclusions: The results show that outpatient laparoscopic cholecystectomy is safe and cost-effective in selected patients, and that the mock home setting provides a means of studying the safety of transition of care.

Laparoscopic cholecystectomy has received nearly universal acceptance and is currently considered the "gold standard" for the treatment of cholelithiasis. Many centers have employed "short-stay" units or "23-hour admissions" for postoperative observation following laparoscopic cholecystectomy. The practice of early discharge as "true" outpatients following this procedure has not been well defined. A retrospective analysis of 130 consecutive patients undergoing laparoscopic cholecystectomy in an outpatient surgery unit was performed. A follow-up telephone survey was carried out of patients who successfully completed the procedure as outpatients. One hundred thirty patients underwent outpatient laparoscopic cholecystectomy. The patient population consisted of 78% women, with an age range of 17 to 76 years (mean age 47.1 years). Symptomatic gallstone disease was the indication for laparoscopic cholecystectomy in 92% of the patients. All patients underwent successful completion of laparoscopic cholecystectomy with no conversions to an open procedure. The mean length of operation was 75 +/- 23 minutes (range 25 to 147 minutes). The mean length of stay in the postanesthesia care unit (PACU) ranged from 95 to 460 minutes with a mean length of stay of 200 +/- 79 minutes. A total of eight patients (6.2%) were admitted to the hospital directly from the PACU in the immediate postoperative period. Six of these eight patients were discharged on the first postoperative day. Following discharge from the PACU, an additional six patients (4.6%) required hospital admission. Three of these six patients were discharged after a single day of hospitalization. Ninety-eight of 116 eligible patients were available for follow-up telephone evaluation. The outpatient experience was rated as good by 75.5% of the patients, fair by 22.5%, and poor by 2%. In retrospect, 20.4% of the patients stated that they would have preferred an inpatient to an outpatient procedure. Laparoscopic cholecystectomy can be performed as a true outpatient procedure with patients discharged to home within hours of completion of the procedure. Less than 10% of patients will fail this protocol and another 5% of the patients may require hospitalization after returning to their homes.

Background: Although ischemic injury to the spinal cord is a well-known complication of aortic surgery, no metabolic markers have been identified as predictors of an adverse outcome. This study evaluated the effect of cerebrospinal fluid (CSF) drainage, with and without distal femoral perfusion or moderate hypothermia on blood and CSF lactate concentrations and CSF pressure during thoracoabdominal aortic aneurysm surgery., Methods: Three nonconcurrent groups of patients were studied prospectively: patients with normal body temperature (35 degrees C) but without distal femoral bypass (n = 6), patients with normal body temperature with bypass (n = 7), and patients with hypothermia (30 degrees C) and bypass (n = 8). In all patients, CSF pressure was recorded before, during, and after aortic cross-clamping. During the surgical repair, CSF drainage was performed using a 4-Fr intrathecal silicone catheter. Blood and CSF lactate concentrations were measured throughout the operation., Results: Significant increases in blood (490%) and CSF (173%) lactate concentrations were observed during and after thoracic aortic occlusion in patients with normothermia and no bypass (P < 0.02 and 0.05, respectively). Distal perfusion attenuated the increase in both blood and CSF lactate (P < 0.01), and a further reduction was achieved with hypothermia of 30 degrees C (P < 0.001). Patients who became paraplegic showed a greater increase in CSF lactate concentrations after aortic clamp release compared with those who suffered no neurological damage (275% vs. 123% of baseline; P < 0.05). Increased CSF pressure of 42-60% (P < 0.005) was noted soon after thoracic aortic occlusion, both with and without distal femoral bypass., Conclusions: Incremental reductions in CSF lactate concentrations were achieved using distal femoral bypass and hypothermia. The reduction in CSF lactate correlated with the methods used to protect the spinal cord during thoracoabdominal aortic aneurysm surgery and was associated with better outcome. Decompression by distal bypass of the hemodynamic overload caused by aortic occlusion was insufficient to eliminate the acute increase in CSF pressure. Cerebrospinal fluid lactate measurements during high aortic surgery may accurately represent the spinal cord metabolic balance.

Purpose: To evaluate and compare in vitro microleakage of etched and non-etched Class I amalgam restorations lined with various dentin bonding system primers to amalgam restorations with or without a Copalite liner., Materials and Methods: Class I amalgam preparations were made in 140 extracted molars and divided into 14 groups of 10 teeth each. Permite C dispersed phase alloy restorations were placed after the following treatments: Group 1: No liner; Group 2: Lined with two coats of Copalite; Group 3(A): Lined with Amalgambond AA and 3(B): Etched with 35% Ultra-etch and lined with Amalgambond AA; Group 4(A): Lined with Scotchbond Multi-Purpose Primer and 4(B): Etched and lined with the primer; Group 5(A): Lined with ProBond and 5(B): Etched and lined with the primer; Group 6(A): Lined with All-Bond 2 Primer A & B and 6(B): Etched and lined with the primer; Group 7(A): Lined with OptiBond and 7(B): Etched and lined with the primer; Group 8(A): Lined with Permagen Primer and 8(B): Etched and lined with the primer. All primers were applied per manufacturers' specifications. After storage in water for 24 hours, all restorations were polished and then aged in water at 37 degrees C for 90 days. The specimens were then thermocycled for 300 cycles at 5 degrees C and 55 degrees C in basic fuchsin dye with a 30-second dwell time, mounted in epoxy rings, sectioned longitudinally, mesiodistally and buccolingually into four sections, then evaluated at x100 and the extent of dye penetration at the tooth/amalgam interface scored (two scores for each section, eight for each specimen)., Results: The unlined and Copalite-lined groups and all non-etched groups showed considerable marginal leakage. All the etched restorations were significantly more effective in reducing microleakage than the non-etched, no liner and Copalite-lined groups. Etching prior to application of the primers is significantly more effective than nonetching, however the effectiveness of the primer alone to seal the dentin needs to be evaluated. Overall, Amalgam-bond AA had the least microleakage of all the groups.

The assembly of retroviral particles is mediated by the product of the gag gene; no other retroviral gene products are necessary for this process. While most retroviruses assemble their capsids at the plasma membrane, viruses of the type D class preassemble immature capsids within the cytoplasm of infected cells. This has allowed us to determine whether immature capsids of the prototypical type D retrovirus, Mason-Pfizer monkey virus (M-PMV), can assemble in a cell-free protein synthesis system. We report here that assembly of M-PMV Gag precursor proteins can occur in this in vitro system. Synthesized particles sediment in isopycnic gradients to the appropriate density and in thin-section electron micrographs have a size and appearance consistent with those of immature retrovirus capsids. The in vitro system described in this report appears to faithfully mimic the process of assembly which occurs in the host cell cytoplasm, since M-PMV gag mutants defective in in vivo assembly also fail to assemble in vitro. Likewise, the Gag precursor proteins of retroviruses that undergo type C morphogenesis, Rous sarcoma virus and human immunodeficiency virus, which do not preassemble capsids in vivo, fail to assemble particles in this system. Additionally, we demonstrate, with the use of anti-Gag antibodies, that this cell-free system can be utilized for analysis in vitro of potential inhibitors of retrovirus assembly.

Objective: To determine whether catecholamine and cortisol secretory responses to surgery contribute to postoperative complications., Design: Prospective, randomized, case series., Setting: A university hospital operating suite and surgical intensive care unit., Patients: Sixty patients undergoing lower extremity vascular surgery., Interventions: Patients were randomized to receive either epidural anesthesia/epidural opiate analgesia (regional anesthesia) or general anesthesia/intravenous patient-controlled analgesia (general anesthesia)., Measurements and Main Results: Anesthesia was managed according to a prospectively designed protocol. Hemodynamic parameters and plasma catecholamine concentrations were determined at specific intraoperative and postoperative time points. Intraoperative and postoperative urine samples were collected and analyzed for free cortisol concentrations. Outcomes evaluated were cardiac (nonfatal myocardial infarction and cardiac death) and surgical (graft occlusion). Mean arterial pressure during emergence from anesthesia and in the early postoperative period correlated positively with plasma norepinephrine concentration (p < .01). In addition, plasma catecholamine concentrations were higher in patients with postoperative hypertension. Plasma norepinephrine concentrations at the time of emergence from anesthesia and postoperatively were also higher in patients requiring repeat surgery for graft revision, thrombectomy, or amputation (p < .05). Multivariate analysis indicated that the norepinephrine concentration at the time of emergence, but not type of anesthesia, correlated with reoperation for graft occlusion, suggesting that the previously reported beneficial effect of regional anesthesia may be due to modulation of the stress response. Myocardial infarction or cardiac death occurred in three patients. These patients had markedly increased catecholamine concentrations., Conclusions: The catecholamine response to lower extremity vascular surgery contributes to the development of postoperative hypertension and may also be important in the development of thrombotic complications.

Purpose: Ischemic injury to the spinal cord, kidneys, and viscera occurs in a significant number of patients undergoing surgical repair of thoracoabdominal aortic aneurysms. Partial bypass has been used to perfuse the arterial system distal to the cross-clamp, but the primary determinant of ischemic morbidity remains the duration of aortic cross-clamping. Hypothermia may favorably affect outcome during these procedures, but moderate or deep hypothermia has traditionally required full cardiopulmonary bypass with cardiac arrest., Methods: In a series of patients undergoing thoracoabdominal (n = 14) or thoracic (n = 4) aneurysm repair, we used moderate hypothermia (30 degrees C) and partial bypass (aortofemoral or atriofemoral) while maintaining an intrinsic cardiac rhythm. Body temperature was controlled with a heat exchanger in the bypass circuit, which allowed for rapid cooling and rewarming. In addition to hypothermia and bypass, a segmental sequential surgical repair was used to minimize the duration of ischemia to any given vascular bed., Results: All patients survived the surgical procedure, and 16 patients survived until discharge from the hospital. None of the 18 patients had paraplegia or significant renal dysfunction. The only complication related to hypothermia was atrial fibrillation, which occurred in three patients and was amenable to therapeutic measures., Conclusions: We conclude that moderate hypothermia, partial bypass, and segmental sequential repair may reduce ischemic injury. This combination of adjuncts was not associated with significant complications in this series of patients.

Background: Surgical trauma elicits diffuse changes in hormonal secretion and autonomic nervous system activity. Despite studies demonstrating modulation of the stress response by different anesthetic/analgesic regimens, little is known regarding the determinants of catecholamine and cortisol responses to surgery., Methods: Plasma catecholamines and cortisol secretion data were obtained from 60 patients undergoing lower extremity revascularization. Patients were randomized to receive either general anesthesia combined with patient-controlled intravenous morphine (GA) or epidural anesthesia combined with epidural fentanyl analgesia (RA). All aspects of intra- and postoperative clinical care were defined by written protocol. Plasma catecholamines were measured before induction, intraoperatively, and for the first 18 h postoperatively (by HPLC). Urine cortisol was measured intra- and postoperatively using RIA. Data were evaluated using univariate and multivariate analyses to evaluate demographic and perioperative variables as determinants of stress hormone secretion., Results: Plasma catecholamines increased during skin closure in the GA group, and remained higher relative to the RA group in the postoperative period. Multivariate analysis indicated that age and anesthetic regimen predicted increases in catecholamines during skin closure (P < 0.005), although duration of surgery, blood loss, and body temperature were not correlated. Early postoperative norepinephrine concentrations were correlated with pain score and duration of surgery (P < 0.004), but not with anesthetic management, blood loss, or body temperature. All postoperative norepinephrine levels were highly correlated (r = 0.7) with norepinephrine levels during skin closure. Cortisol excretion was higher postoperatively than intraoperatively. No patient or perioperative variable predicted cortisol excretion, and cortisol excretion was not correlated with catecholamine levels at any time., Conclusions: These data indicate that patient factors, such as age and inherent sympathetic responsivity, are important determinants of the catecholamine response to surgery. Modulation of the norepinephrine response by regional anesthesia/analgesia appears to be related, in part, to superior analgesia. The lack of correlation between catecholamine and cortisol secretion indicates that the stress response may consist of discrete systems responding to different stimuli.

Background: The purpose of this clinical trial was to compare the effects of different anesthetic and analgesic regimens on hemostatic function and postoperative arterial thrombotic complications., Methods: Ninety-five patients scheduled for elective lower extremity vascular reconstruction were randomized to receive either epidural anesthesia followed by epidural fentanyl (RA) or general anesthesia followed by intravenous morphine (GA). Intraoperative and postoperative care were controlled by protocol using predetermined limits for heart rate, blood pressure, and other monitoring criteria. Data collection included serial physical examinations, electrocardiograms, and cardiac isoenzymes to detect arterial thrombosis (defined as unstable angina, myocardial infarction, or vascular graft occlusion requiring reoperation). Fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and D-dimer levels were measured preoperatively and at 24 and 72 h postoperatively., Results: Preoperative fibrinogen levels were similar in both groups, remained unchanged after 24 h, and increased equally (45%) in the first 72 h postoperatively. PAI-1 levels in the GA group increased from 13.6 +/- 2.1 activity units (AU)/ml to 20.2 +/- 2.6 AU/ml at 24 h and returned to baseline at 72 h. In contrast, PAI-1 levels in the RA group remained unchanged over time. Twenty-two of 95 patients (23%) had postoperative arterial thrombosis, 17 of whom had received GA and 5 of whom, RA. Preoperative PAI-1 levels were higher in patients who developed postoperative arterial thrombosis (20.5 +/- 3.6 AU/ml vs. 11.2 +/- 1.4 AU/ml). Multiple logistic regression analysis indicated that GA and preoperative PAI-1 levels were predictive of postoperative arterial thrombotic complications., Conclusions: Impaired fibrinolysis may be related causally to postoperative arterial thrombosis. Because RA combined with epidural fentanyl analgesia appears to prevent postoperative inhibition of fibrinolysis, this form of perioperative management may decrease the risk of arterial thrombotic complications in patients undergoing lower extremity revascularization.

Background: Perioperative morbidity may be modifiable in high risk patients by the anesthesiologist's choice of either regional or general anesthesia. This clinical trial compared outcomes between epidural (EA) and general (GA) anesthesia/analgesia regimens in a group of patients at high risk for cardiac and other morbidity who were undergoing similarly stressful surgical procedures., Methods: One hundred patients scheduled for elective vascular reconstruction of the lower extremities were randomized to receive either EA for surgery followed by epidural analgesia, or GA for surgery followed by intravenous patient-controlled analgesia. Hemodynamic monitoring, blood pressure, and heart rate limits were determined prior to randomization. Management of anesthesia in the immediate postoperative period was standardized. The data collected included continuous electrocardiographic monitoring from the day before surgery through the third postoperative day, serial electrocardiograms, and cardiac enzymes. Cardiac ischemia, myocardial infarction, unstable angina, and cardiac death were identified by a cardiologist blinded to the type of anesthesia received. Other major morbidity was determined at the time of hospital discharge and at 1 and 6 months after surgery., Results: Eleven patients who received GA required regrafting or an embolectomy during their hospital stay, compared with two patients who received EA. This association of GA with reoperation remained significant after adjustment for baseline differences. Cardiac outcomes were similar in the two groups with respect to perioperative death (1 EA and 1 GA), death within 6 months (4 EA and 3 GA), nonfatal myocardial infarction within 7 days (2 EA and 2 GA), unstable angina (0 EA and 2 GA), and myocardial ischemia following randomization (17 EA and 23 GA). Rates of major infections in the two groups (1 EA and 2 GA), renal failure (3 EA and 3 GA), and pulmonary complications (3 EA and 7 GA) also were similar., Conclusions: Carefully conducted epidural and general anesthesia appear to be associated with comparable rates of cardiac and most other morbidity in patients undergoing lower extremity vascular surgery. However, compared with general anesthesia, epidural anesthesia is associated with a lower incidence of reoperation for inadequate tissue perfusion and, therefore, may be advantageous for this surgical population.

Although monitoring of somatosensory evoked potentials elicited from stimulation of lower extremity peripheral nerves has been suggested as a method for assessing neural function during thoracoabdominal aortic aneurysm surgery, this technique has been reported to yield a large number of false positives. It was believed that direct stimulation of the spinal cord would eliminate some of the problems associated with peripheral evoked potentials. The present study compared in 18 patients the use of scalp recorded evoked potential following stimulation of either the posterior tibial nerve via percutaneous needles or the spinal cord via an epidural electrode previously placed fluoroscopically. In 10 patients in whom distal bypass or shunt was not used, peripheral evoked potentials totally disappeared within 5-30 min of aortic clamping. Spinal cord stimulation evoked potentials disappeared permanently in 2 patients shortly after aortic cross-clamping; 1 died shortly after the procedure, and the other awoke densely paraplegic and died the next day. When distal perfusion was maintained by shunt or bypass, the disappearance of both peripheral and spinal evoked potentials accurately predicted the neurologic outcome of 1 paralyzed patient. Loss of spinal cord stimulation evoked potentials was found to be correlated with adverse neurologic outcome. Over the period of aortic clamping a gradual decrease in mean amplitude (50% at 45 min [P less than 0.05]) and a 20% increase in mean latency time were observed. Maintenance of adequate distal perfusion may permit the use of peripheral evoked potentials in the assessment of spinal cord ischemia during aortic cross-clamping.(ABSTRACT TRUNCATED AT 250 WORDS)