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The forward resuscitative surgery system (FRSS) is the Navy's most forward-deployed echelon II medical unit. Between March and August 2003, six FRSS teams were deployed in support of Operation Iraqi Freedom (OIF). During the combat phase of OIF (March 21 to May 1, 2003), a total of 34 Marine Corps and 62 Iraqi patients underwent treatment at a FRSS. FRSS teams were assigned two distinct missions; "forward" FRSS teams operated with combat service support elements in direct support of regimental combat teams, and "jump" FRSS teams served as a forward element of a surgical company. This article presents the experiences of the FRSS teams in OIF, including a discussion of time to presentation from wounding, time to operation, time to evacuation, and lessons learned from the deployment of the FRSS. [ABSTRACT FROM AUTHOR]

The Consumers' Boston AIDS Information Outreach Project (CBAIOP) was implemented to improve access to health care information for HIV/AIDS consumers in Massachusetts and Southern New Hampshire. The Project, sponsored by the Boston University Medical Center Library and the Boston Public Health Commission AIDS Program, included three primary components: (1) information skills workshops for HIV/AIDS consumers, (2) a Web site with quality-filtered links to HIV/AIDS information resources, and (3) a Web-based information skills tutorial. This article provides an overview of the project and discusses the impact of collaborative programs on improved informationaccess and information-seeking skills for HIV/AIDS and other health care consumers. [ABSTRACT FROM AUTHOR]

Mientras se sigue discutiendo la implementación de la estructura de Recursos, Descripción y Acceso (RDA) en los procesos de descripción bibliográfica, es importante conocer por qué surgieron, en su momento, las Reglas de Catalogación Angloamericanas (RCAA), qué tan funcionales han sido hasta la fecha y cómo el avance tecnológico ha afectado su uso; es decir, ¿se adaptan las RCAA al presente? Por otra parte, es necesario estar al tanto de los cambios que trae consigo RDA, qué aspectos justifican migrar de RCAA a este nuevo formato y qué tan adecuada está RDA a las necesidades actuales. En esta revisión también se abarcan algunas diferencias entre RCAA y RDA, y se muestran razones por las que se ha vuelto una necesidad implementar un nuevo código de catalogación. Al término de la lectura, se concluye que las RCAA han sido un sistema de descripción bibliográfica importante, pero que RDA representa el cambio necesario para mejorar el procesamiento técnico de la información y su recuperación.

Abstract Background It was hypothesized that a pro-atherogenic, high saturated fat and cholesterol diet (HCD) would increase the inflammatory response to E. coli endotoxin (LPS) and increase its concentration in plasma after administration to mice. Methods C57Bl/6 mice were fed a HCD or a control diet (CD) for 4 weeks, and then treated with saline, 0.5, 1 or 2 mg LPS/kg, ip. Liver injury (alanine:2-oxoglutarate aminotransferase and aspartate aminotransferase, collagen staining), circulating cytokines (tumor necrosis factor-α, interleukin-6 and interferon-γ), factors that can bind LPS (serum amyloid A, apolipoprotein A1, LPS binding protein, and CD14), and plasma levels of LPS were measured. The hepatic response was assessed by measuring vascular cell adhesion molecule (VCAM)-1, inducible nitric oxide synthase (iNOS) and signal transducer and activator of transcription-1 proteins, and VCAM-1 and iNOS mRNAs. Hepatic mRNA encoding the LPS receptor, Toll like receptor 4, was also determined. Results Two mg LPS/kg killed 100% of mice fed HCD within 5 d, while no mice fed CD died. All mice treated with 0 to 1 mg LPS/kg survived 24 h. HCD increased plasma alanine:2-oxoglutarate aminotransferase and aspartate aminotransferase, and the enzymes were increased more by LPS in HCD than CD mice. Induction of plasma tumor necrosis factor-α, interleukin-6, and interferon-γ by LPS was greater with HCD than CD. Hepatic VCAM-1 and iNOS protein and mRNA were induced by LPS more in mice fed HCD than CD. Tyrosine phosphorylation of signal transducer and activator of transcription-1 caused by LPS was prolonged in HCD compared with CD mice. Despite the hepatic effects of HCD, diet had no effect on the LPS plasma concentration-time profile. HCD alone did not affect circulating levels of plasma apolipoprotein A1 or LPS binding protein. However, plasma concentrations of serum amyloid A and CD14, and hepatic toll-like receptor-4 mRNA were increased in mice fed HCD. Conclusion HCD increased the sensitivity of mice to LPS without affecting its plasma level. Although increased serum amyloid A and CD14 in the circulation may inhibit LPS actions, their overexpression, along with hepatic toll-like receptor-4 or other factors, may contribute to the heightened sensitivity to LPS.

Purpose: Despite the potential value of point-of-care ultrasonography (POCUS) in resource-limited environments, it is not widely used in low- and middle-income countries compared with high-income countries. We sought to evaluate the current POCUS practice of Ukrainian anesthesiologists who attended POCUS courses to guide future POCUS training in Ukraine., Methods: We conducted a 25-question web-based survey. It was distributed to 255 participants of POCUS courses held in Ukraine in 2023. The survey sections described current POCUS practice, perception of POCUS value, POCUS skills self-assessment, and perceived barriers to implementing POCUS in clinical practice., Results: Two hundred and forty-four out of 255 course participants completed the survey, representing 214 unique respondents. Those who self-rated their skills identified themselves as either novices or beginners in areas of POCUS knowledge (118/157, 75%), image acquisition (110/158, 70%), image interpretation (117/158, 74%), and integration into clinical decision-making (105/155, 68%). Among all survey responders, 55% (118/214) reported using POCUS for vascular access procedures, 45% (97/214) for trauma assessment, and 44% (93/214) for regional anesthesia. Reported barriers to POCUS implementation included lack of ultrasound devices (101/214, 47%) and lack of trained faculty (112/214, 52%)., Conclusion: Among anesthesiologists who participated in POCUS courses in Ukraine, the majority were in early stages of ultrasound practice. Respondents identified POCUS applications not currently practiced and evaluated barriers to POCUS use. Based upon these survey findings, we propose the following measures in Ukraine: 1) developing a standardized national POCUS curriculum; 2) increasing the number of experienced instructors of POCUS; and 3) acquiring ultrasound devices to support clinical applications of POCUS, especially in the Central, Southern, and Eastern regions., (© 2024. Canadian Anesthesiologists' Society.)

Background: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood., Methods: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models., Results: Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma N-Ag compared with placebo (95% confidence interval, 12%-27%; P < .001), and a steeper rate of decline through the first 5 days (P < .001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale., Conclusions: Our study suggests that nmAb has an antiviral effect assessed by plasma N-Ag among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed., Clinical Trials Registration: NCT04501978., Competing Interests: Potential conflicts of interest. A. L. G. reports receiving institutional funding from Novavax, insititutaional partnership with Astra Zeneca, and reports being personally named as inventor on a patent used by Astra Zeneca. D. D. M. reports receiving grant from the Danish National research Foundation. E. M. reports payments to his institution received from SciClone Pharmaceuticals, Regeneron Pharmaceuticals, Pfizer, Chemic Labs/KODA Therapeutics, Cidara, and Leidos Biomedical Research Inc; E. M. also reports being on an advisory board for Basilea. K. W. reports receiving a honorarium for international ARDS conference and travel support from UCSF. M. A. reports a grant from NINDS. M. A. M. reports institutional grants from NHLBI/NIAID, the department of defence, California Institute of Regeneration, Roche-Genentech, and Quantum Health. M. A. M. has also received personal consulting fees from Novartis, Pliant Therapeutics, Johnson and Johnson, Gilead, and Citius Pharmaceuticals. M. K. J. reports institutional grants from Gilead, Laurent, and Regeneron; personal consulting fees from Gilead; and personal honoraria from Cooper Clinic. S. T. is funded by grants from the Australian Medical Foundation and New South Wales Health. The remaining authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Hands-on training and social media sites have heavily emphasized the use of tourniquets to treat limb injuries during the Ukraine war. Tourniquet overuse or misuse can lead to significant tragedy-limb loss, physiologic complications, and even death. Casualty evacuation in Ukraine often exceeds 6 hours, and the liberal use of limb tourniquets may have unintentionally increased morbidity. Tourniquet application was appropriate in 24.6% of the wounded with tourniquets in one recent publication by a Ukrainian vascular surgeon. The longer a limb tourniquet is in place raises the risk of compartment syndrome, vascular thrombosis, rhabdomyolysis, and irreversible myonecrosis resulting in major tissue loss and often necessitating limb amputation. If bleeding is controlled with a tourniquet, attempts to remove the tourniquet as early as possible to avoid the negative consequences are essential. Training in tourniquet use without explaining possible limb loss and other complications resulting from tourniquets left in situ more than 2 hours makes use risky. Tourniquets should be loosened at one hour if the tactical situation allows, and the injury assessed to determine if major bleeding persists or to determine if other methods of hemostasis would be effective. Ukraine must improve the training so that everyone becomes aware of the risks of prolonged or improper tourniquet use. This tourniquet training information must be transmitted to military medical leaders, Ukrainian military medics, civilian volunteers, volunteers in Ukraine, and NATO trainers in allied countries conducting medical training for Ukrainian soldiers. A trauma registry and tracking through echelons of care can enhance performance improvement through timely feedback., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The senior authors traveled to Ukraine to teach specific skills to Ukrainian physicians and other medical professionals, utilizing a 2-day ATLS course, workshops in point-of-care ultrasonography (POCUS), lectures and webinars on damage control resuscitation, damage control surgery, and transfusion of whole blood. The authors have focused on providing skill sets that Ukrainian doctors can utilize within their existing system to improve immediate patient care for casualties resulting from the unanticipated Russian invasion and improve outcomes. Given the resource limitations and differences of the Ukrainian healthcare systems, the authors believe Western-based professionals who come to Ukraine to help for short periods should resist the temptation to offer western solutions that may not work in Ukraine. Major improvements in Ukrainian health care will require long-term efforts in teaching but also need to include increased efforts to improve hospitals, clinics, staffing, education, supplies, and equipment. Those who travel to help in Ukraine can still teach short courses that provide skills that Ukrainian doctors and nurses can use within their existing healthcare system to improve the quality of patient care in the immediate period of crisis and hopefully improve outcomes in the near term. It is not a reasonable expectation to think that the delivery of 2-day courses such as ATLS or POCUS will significantly change the country-wide delivery of healthcare. This sort of practice change requires the engagement of medical and political leaders and a sustained reform effort over years, not days or weeks. Supportive countries and non-governmental organizations need to prepare for a long and extensive investment in improving Ukrainian healthcare., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2023 The Author(s).)

Tidal wetlands are critical but highly threatened ecosystems that provide vital services. Efficient stewardship of tidal wetlands requires robust comparative assessments of different marshes to understand their resilience to stressors, particularly in the face of relative sea level rise. Existing assessment frameworks aim to address tidal marsh resilience, but many are either too localized or too general, and few directly translate resilience evaluations to recommendations for management strategies. In response to the deficiencies in existing frameworks, we identified a set of metrics that influence overall marsh resilience that can be assessed at any spatial scale. We then developed a new comprehensive assessment framework to rank relative marsh resilience using these metrics, which are nested within three categories. We represent resilience as the sum of results across the three metric categories: current condition, adaptive capacity, and vulnerability. Users of this framework can add scores from each category to generate a total resilience score to compare across marshes or take the score from each category and refer to recommended management actions we developed based on expert elicitation for each combination of category results. We then applied the framework across the contiguous United States using publicly available data, and summarized results at multiple spatial scales, from regions to coastal states to National Estuarine Research Reserves to finer scale marsh units, to demonstrate the framework's value across these scales. Our national analysis allowed for comparison of tidal marsh resilience across geographies, which is valuable for determining where to prioritize management actions for desired future marsh conditions. In combination, the assessment framework and recommended management actions function as a broadly applicable decision-support tool that will enable resource managers to evaluate tidal marshes and select appropriate strategies for conservation, restoration, and other stewardship goals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Military medicine has made significant advancements in decreasing mortality by addressing the lethal triad - metabolic acidosis, coagulopathy, and hypothermia. However, casualties are still succumbing to injury. Recent conflict zones have led to the development of remarkable life-saving innovations, including the management of compressible hemorrhage and whole blood transfusions. Nevertheless, hypothermia prevention and treatment techniques remain relatively unchanged. Hypothermia prevention is anticipated to become more critical in future operations due to a predicted increase in evacuation times and reliance on Prolonged Casualty Care (PCC). This is likely secondary to increasingly distanced battlespaces and the mobility challenges of operating in semi-/non-permissive environments. Innovation is essential to combat this threat via active airway rewarming in the vulnerable patient. Thus, we propose the development, fabrication, and efficacy testing of a device in which we estimate being able to control temperature and humidity at physiologic levels in the PCC setting and beyond., (2022.)

Methicillin-resistant Staphylococcus aureus is a considerable pathogen in the setting of skin and soft tissue infections (SSTIs). MRSA PCR swab testing is widely used in the setting of respiratory tract infections, however little data exists relating to the use of MRSA PCR swab testing in SSTIs. Three thousand, nine hundred and ninety-five patients were included in this retrospective study that aimed to validate the clinical correlation of MRSA PCR wound swab testing in SSTIs through sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) analysis. From this review, MRSA PCR wound swabs were found to have a sensitivity of 97.6% (97.5-98.5), a specificity of 94.9% (94.3-95.7), a PPV of 92.3% (91.4-93.2), and a NPV of 98.4% (98.0-98.8). The study results demonstrate that the MRSA SSTI PCR assays have a high NPV and the potential to be a vital tool in de-escalating antimicrobial therapy associated with SSTIs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: The independent and central role of the patient with a complex chronic respiratory disease in targeted, personalized disease management strategies is becoming increasingly important. Patients are the ones living with the disease and are finally responsible for their lives underlining their role as essential members of the interdisciplinary treatment team. Areas covered: The present paper narratively reviews existing research and discusses the special, as well as specialized, role of the patient with a complex chronic respiratory disease in the healthcare system and highlights fundamental elements of the (future) relationship between patient and healthcare professionals. Expert commentary: Since the chronic respiratory disease at hand is part of the patient's entire life, we need holistic, personalized approaches optimizing patients' quality of life by not only treating the disease but considering the patients' whole environment and where healthcare professionals and patients are co-creating value care.

Prolonged ketamine exposure in neonates at anesthetic doses is known to cause long-term impairments of learning and memory. A current theoretical mechanism explains this phenomenon as being neuro-excitotoxicity mediated by compensatory upregulation of N-methyl-d-aspartate receptors (NMDARs), which then initiates widespread neuroapoptosis. Additionally, the excitatory behavior of GABAergic synaptic transmission mediated by GABA A receptors (GABA A Rs), occurring during the early neuronal development period, is proposed as contributing to the susceptibility of neonatal neurons to ketamine-induced injury. This is due to differential developmental expression patterns of Na + -K + -2Cl - co-transporter (NKCC1) and K + -Cl - co-transporter. Studies have shown that bumetanide, an NKCC1 inhibitor, allows neurons to become inhibitory rather than excitatory early in development. We thus hypothesized that bumetanide co-administration during ketamine treatment would reduce over excitation and protect the neurons from excitotoxicity. In this initial study, the Morris Water Maze test was used to assess the effects of co-administration of ketamine and bumetanide to neonatal Sprague-Dawley rats on long-term learning and memory changes seen later in life. It was revealed that bumetanide, when co-treated with ketamine neonatally, significantly impeded behavioral deficits typically seen in animals exposed to ketamine alone. Therefore, these findings suggest a new mechanism by which neonatal ketamine induced learning impairments can be prevented., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Short-stemmed femoral components facilitate reduced exposure surgical techniques while preserving native bone. A clinically successful stem should ideally reduce risk for stress shielding while maintaining adequate primary stability for biological fixation. We asked (1) how stem-length changes cortical strain distribution in the proximal femur in a fit-and-fill geometry and (2) if short-stemmed components exhibit primary stability on par with clinically successful designs., Methods: Cortical strain was assessed via digital image correlation in composite femurs implanted with long, medium, and short metaphyseal fit-and-fill stem designs in a single-leg stance loading model. Strain was compared to a loaded, unimplanted femur. Bone-implant micromotion was then compared with reduced lateral shoulder short stem and short tapered-wedge designs in cyclic axial and torsional testing., Results: Femurs implanted with short-stemmed components exhibited cortical strain response most closely matching that of the intact femur model, theoretically reducing the potential for proximal stress shielding. In micromotion testing, no difference in primary stability was observed as a function of reduced stem length within the same component design., Conclusion: Our findings demonstrate that within this fit-and-fill stem design, reduction in stem length improved proximal cortical strain distribution and maintained axial and torsional stability on par with other stem designs in a composite femur model. Short-stemmed implants may accommodate less invasive surgical techniques while facilitating more physiological femoral loading without sacrificing primary implant stability., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Schistosomiasis is a known risk after exposure to freshwater in tropical parts of the world. In March 2014, 28 off-duty U.S. service members went on a water adventure in the Nile River in Jinja, Uganda. In April 2014, 10 of the 28 service members returned for a second water adventure. Twelve weeks after freshwater exposure, schistosomiasis enzyme-linked immunosorbent assay testing was performed. Twenty-five percent had elevated Schistosomiasis mansoni immunoglobulin G (7 positive of 28 exposed); all had negative pre-exposure serology. The serology-positive service members were treated with oral praziquantel 60 mg/kg in divided doses. Our report is the first schistosomiasis report among U.S. service members deployed to Africa since World War II. The absence of reports among U.S. service members and several reports among deployed foreign military units and tourists in sub-Saharan Africa suggest a lack of postexposure testing. We recommend schistosomiasis testing of prior and future U.S. military units deployed to sub-Saharan Africa with fresh water exposure. Unit commanders and medical personnel should discourage unnecessary fresh water contact in sub-Saharan Africa., (Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.)

A historic perspective of family medicine's development, the work of Gayle Stephens, and prior Keystone conferences constitute an important backdrop for the fourth Keystone Conference. Decisions made in the past constrain what can be done now, but they may also offer opportunities for family medicine. A major challenge for Keystone IV was to discern what is a constraint and what is an opportunity-in particular when it comes to the role of the personal physician. This article provides reflections based on decades of observation and study and confirms that knowing something and doing something are not the same., (© Copyright 2016 by the American Board of Family Medicine.)

Understanding the dynamics of interacting proteins is a crucial step toward describing many biophysical processes. Here we investigate the backbone dynamics for protein GB1 in two different assemblies: crystalline GB1 and the precipitated GB1-antibody complex with a molecular weight of more than 300 kDa. We perform these measurements on samples containing as little as eight nanomoles of GB1. From measurements of site-specific (15) N relaxation rates including relaxation dispersion we obtain snapshots of dynamics spanning nine orders of magnitude in terms of the time scale. A comparison of measurements for GB1 in either environment reveals that while many of the dynamic features of the protein are conserved between them (in particular for the fast picosecond-nanosecond motions), much greater differences occur for slow motions with motions in the >500 ns range being more prevalent in the complex. The data suggest that GB1 can potentially undergo a small-amplitude overall anisotropic motion sampling the interaction interface in the complex., (© 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.)

Charles E. Rosenberg has had a major influence in defining the history of medicine as a field. However, critics who focus on his leadership or "school" in terms of defined scholarly perspectives, including those of social history and the framing of disease, offer inadequate descriptions of the messages, breadth, and scope of his scholarly work as a whole. Shoehorning the history of medicine into prescribed patterns in order to build a more unitary discipline would weaken rather than strengthen the field and is not in the Rosenberg tradition.

Delayed processing of peripheral blood or peripheral blood mononuclear cell isolation and cryopreservation can lead to the detection of somewhat higher levels of CD31 expression on naïve CD4 T cells by flow cytometry. These observations should be considered in the planning of multicenter clinical trials and in the interpretation of the results of functional studies.

An accurate and reproducible CD4 count is a fundamental clinical tool for monitoring and treating human immunodeficiency virus infection and its complications. Two methods exist for calculating absolute CD4 counts: dual-platform technology (DPT) and single-platform technology (SPT). Numerous studies have documented the unacceptably wide range of variation in absolute CD4 counts between laboratories. SPT was introduced in 1996 to reduce the interlaboratory variation in absolute CD4 counts. The aim of this study was to compare DPT with the BD Biosciences Trucount method (an SPT method). Both the percentages of CD4 (r = 0.986; P = 0.0541) and the absolute CD4 counts (r = 0.960; P = 0.0001) had very good correlation between the two methods. However, poor correlation was observed for the CD8(+) RO(-) (r = 0.314; P = 0.0002), CD8(+) DR(+) (r = 0.666; P = 0.0138), CD3(+) CD38(+) (r = 0.8000; P = 0.0004), CD3(+) CD25(+) (r = 0.464; P = 0.0082), and CD4(+) CD38(+) (r = 0.357; P = 0.0127) measurements.

Background: The interleukin-7 (IL-7)/IL-7 receptor alpha (IL-7Ralpha) system is an important regulator of T-cell homeostasis. We evaluated the IL-7/IL-7Ralpha system in a large cohort of HIV-infected patients, including a subset treated with intermittent IL-2., Methods: IL-7 serum levels and CD127 (IL-7Ralpha) expression on T cells were evaluated in a cross-sectional study of 36 healthy volunteers, 151 HIV-infected patients, and 83 HIV-infected patients who had received IL-2 therapy. Multivariate regression models were used to determine predictors of CD127 expression., Results: HIV-infected patients had higher IL-7 levels compared with healthy volunteers (P = 0.022) and IL-2-treated patients (P = 0.012). CD127 expression was significantly lower on CD4 and CD8 T cells of HIV-infected patients compared with healthy volunteers (P = 0.008 and P < 0.001, respectively), and CD127 median fluorescence intensity was lowest on CD4 T cells in IL-2-treated patients (P < 0.001 compared with HIV-infected patients). The proportion of naive and effector memory/effector T cells were significant predictors of CD127 expression on T cells. IL-2 immunotherapy led to the expansion of a CD25/CD127-low subset of CD4 T cells., Conclusions: CD127 expression on T cells remains low in HIV-infected patients despite antiretroviral therapy, reflecting persistent aberration in the subset composition of the T-cell pool.

Decreases in the detection of CD127 expression on T cells of human immunodeficiency virus-infected patients by flow cytometry can occur by delayed processing or by peripheral blood mononuclear cell isolation and cryopreservation. These observations should be considered in the interpretation of functional studies and the planning of multicenter clinical trials.

Post-dural puncture headache (PDPHA) has been a vexing problem for patients undergoing dural puncture for spinal anaesthesia, as a complication of epidural anaesthesia, and after diagnostic lumbar puncture since Bier reported the first case in 1898. This Chapter discusses the pathophysiology of low-pressure headache resulting from leakage of cerebrospinal fluid (CSF) from the subarachnoid to the epidural spaces. Clinical and laboratory research over the last 30 years has shown that use of small-gauge needles, particularly of the pencil-point design, is associated with a lower risk of PDPHA than traditional cutting point needle tips (Quincke-point needles). A careful history can rule out other causes of headache. A positional component of headache is the sine qua non of PDPHA. In high-risk patients (e.g. age < 50 years, post-partum, large-gauge-needle puncture), patients should be offered early (within 24-48 h of dural puncture) epidural blood patch. The optimum volume of blood has been shown to be 12-20 ml for adult patients. Complications of autologous epidural blood patch are rare.

Intrathecal neurolytic blocks for the treatment of chronic pain were first described by Dogliotti in 1931. Since then, many authors have described the intrathecal injection of various neurolytic substances for the treatment of oncologic pain. In recent years, alcohol and phenol have been the substances most commonly used for this purpose. There are no controlled studies, so the literature consists of observations, reports and book chapters reflecting the opinions of experienced clinicians. This chapter describes the indications, contraindications, potential complications, and expected benefits of intrathecal injection of alcohol and phenol in the treatment of cancer pain. Four cases of cancer patients whose intractable pain was treated by the authors using intrathecal neurolysis are presented. Pertinent literature is reviewed. In this account, the emphasis is on proper selection of patients and techniques.

To evaluate the relationship between T cell turnover, immune activation, and CD4 recovery in HIV infection, 32 antiretroviral-naive HIV-1-infected patients were studied before and after initiation of highly active antiretroviral therapy (HAART). Elevated CD4 and CD8 T cell turnover (measured by Ki67) in HIV infection decreased with HAART in blood and lymphoid tissue. Increased peripheral CD4 T cell turnover was strongly associated with immune activation even after viral suppression to less than 50 copies/mL (R = 0.8; p <.001). Increased CD4 T cell turnover correlated strongly with CD4 cell counts both before (R = -0.6; p <.001) and after (R = -0.4; p =.05) HAART. In patients with baseline CD4 cell counts of less than 350/microL, decreases in CD4 T cell turnover with HAART significantly correlated with increases in CD4 cell counts. In addition, persistently elevated levels of CD4 T cell turnover after HAART were associated with incomplete CD4 T cell recovery despite HIV RNA levels of less than 50 copies/mL. These data suggest that immune activation is central to CD4 cell depletion in HIV infection and immune reconstitution with HAART.

Professionalism in medicine is an ambiguous term. Discussions are hampered by understandings of the past that are counterproductive to today s debates. Three decades of criticism of physicians as self-interested and arrogant, and of professional organizations as unfairly monopolistic have shaken the confidence of professional leaders and their constituents in their ability to act as a positive social force, and left the concept of professional autonomy without a useful meaning. Inherited assumptions about conflict between the profession, government and the market have encouraged organizational policies to fight familiar enemies for short-term gains, rather than reinvent professionalism as a social force or seek new strategic alliances. This article stresses the importance of distancing the present from the past in re-inventing professionalism for the future, and lists eight fundamental goals.

In mature male snakes and lizards, a distal portion of the nephron is hypertrophied in relation to its appearance in females and immature males. This sexual segment of the male kidney apparently provides seminal fluid that is mixed with sperm and released into the female cloaca during copulation. In this article, we provide the first study at the ultrastructural level of seasonal variation in the sexual segment of the kidney of a squamate, the natricine snake Seminatrix pygaea. Previous workers have indicated that the sexual segment is secretory only when the testes are spermatogenically active. The sexual segment of the kidney in S. pygaea does not go through an extended period of inactivity but does show a cycle of synthesis and secretion that can be related to the spermatogenic cycle and mating activity. We show that synthesis of secretory product is initiated with the onset of spermatogenic activity in the spring and culminates with completion of spermiation in the fall. Secretion of the product, however, occurs in a premating period in March when the testes are inactive. Secretion during this premating period is probably necessary to provide time for the passage of the products down the ureter in order to mix with sperm during mating later in spring., (Copyright 2002 Wiley-Liss, Inc.)

The effects of HIV infection upon the thymus and peripheral T cell turnover have been implicated in the pathogenesis of AIDS. In this study, we investigated whether decreased thymic output, increased T cell proliferation, or both can occur in HIV infection. We measured peripheral blood levels of TCR rearrangement excision circles (TREC) and parameters of cell proliferation, including Ki67 expression and ex vivo bromodeoxyuridine incorporation in 22 individuals with early untreated HIV disease and in 15 HIV-infected individuals undergoing temporary interruption of therapy. We found an inverse association between increased T cell proliferation with rapid viral recrudescence and a decrease in TREC levels. However, during early HIV infection, we found that CD45RO-CD27high (naive) CD4+ T cell proliferation did not increase, despite a loss of TREC within naive CD4+ T cells. A possible explanation for this is that decreased thymic output occurs in HIV-infected humans. This suggests that the loss of TREC during HIV infection can arise from a combination of increased T cell proliferation and decreased thymic output, and that both mechanisms can contribute to the perturbations in T cell homeostasis that underlie the pathogenesis of AIDS.

To investigate the effects of age and dose on the spread of thoracic epidural anesthesia, we placed thoracic epidural catheters in 50 surgical patients divided into groups by age (Group I [young], 18-51 yr; Group II [old], 56-80 yr) and randomly assigned patients to receive either 5 mL (A) or 9 mL (B) of 2% lidocaine (plain) injected via the epidural catheter. Hemodynamic variables were measured (heart rate, mean arterial blood pressure, noninvasive impedance cardiac index) at baseline and every 5 min for 30 min. Detectable blockade occurred within 8 min after injection of 3 + 2 mL or 3 + 6 mL in 48 of 50 patients. Maximum spread of analgesia to pinprick occurred 15-23 min after completion of local anesthetic injection and was significantly different between age and volume groups by two-way analysis of variance (Group IA [young 5], 10.9 +/- 4.0 dermatomes; Group IIB [young 9], 13.9 +/- 4.5 dermatomes; Group IIA [old 5], 14.1 +/- 5.6 dermatomes; and Group IIB [old 9], 17.4 +/- 5.1 dermatomes). Minor decreases in mean arterial blood pressure (8%-17%) and heart rate (4%-11%) were noted. Two patients in the Old 9 group required IV ephedrine or ephedrine/atropine to treat hypotension and bradycardia. We conclude that given the rapid onset (3-8 min), extensive spread (11-14 dermatomal segments), and consistent hemodynamic stability, thoracic epidural anesthesia should be initiated with lidocaine 100 mg (5 mL 2% lidocaine) to establish proper location of the catheter in the epidural space in both younger and older patients.

Background and Objectives: Prolonged motor and sensory block following epidural anesthesia can be associated with extended postoperative care unit stays and patient dissatisfaction. Previous studies have demonstrated a more rapid motor recovery following the administration of epidural crystalloids in patients who had received plain bupivacaine and lidocaine epidural anesthesia. However, epinephrine is commonly added to local anesthetics to improve the quality and prolong the duration of the epidural block. The objective of this study was to determine the relationship of 0.9% NaCl epidural catheter flush volume (i.e., washout) to the recovery of motor and sensory block in patients undergoing 2% lidocaine with epinephrine epidural anesthesia., Methods: A prospective, randomized, double-blind study design was utilized. Thirty-three subjects scheduled for elective gynecologic or obstetrical surgical procedures underwent epidural anesthesia using 2% lidocaine with epinephrine (1:200,000). A T4 dermatome level of analgesia, determined by toothpick prick, was maintained intraoperatively. Following surgery, subjects were randomized to 1 of 3 treatment groups. Group 1 (control, n = 11) received no epidural 0.9% NaCl (normal saline [NS]) postoperatively. Group 2 (15 mL NS x 1, n = 10) received an epidural bolus of 15 mL NS. Group 3 (15 mL NS x 2, n = 12) received an epidural bolus of 15 mL NS postoperatively and a second 15-mL NS bolus 15 minutes later. Assessment of motor and sensory block was performed at 15-minute intervals until complete motor and sensory recovery., Results: Times to partial and full motor and sensory recovery were significantly faster in the epidural NS groups than in the control group. Full motor recovery was more rapid in subjects receiving two 15-mL NS epidural NS boluses (30 mL total) compared with those receiving a single 15-mL NS bolus (108 +/- 9 min v 136 +/- 13 min) and significantly faster than control group subjects (153 +/- 14 min). Both NS x 1 and NS x 2 epidural bolus groups experienced significantly reduced times to complete sensory recovery when compared with the control group (NS x 1 = 154 +/- 13 min, NS x 2 = 153 +/- 9 min, control 195 +/- 14 min)., Conclusions: A more rapid recovery of motor and sensory block in patients undergoing 2% lidocaine with epinephrine epidural anesthesia can be achieved with the use of 30 mL NS epidural washout. Reg Anesth Pain Med 2001;26:246-251.

The activation of progelatinase A to gelatinase A requires cleavage of an asparaginyl bond to form the N-terminus of the mature enzyme. We have asked whether the activation can be mediated by legumain, the recently discovered lysosomal cysteine proteinase that is specific for hydrolysis of asparaginyl bonds. Addition of purified legumain to the concentrated conditioned medium from HT1080 cell culture that contained both progelatinases A and B caused the conversion of the 72 kDa progelatinase A to the 62 kDa form. The progelatinase B in the medium was unaffected. Incubation of recombinant progelatinase A with legumain resulted in an almost instantaneous activation as judged by the fluorometric assay with a specific gelatinase A substrate, Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2. Legumain also activated progelatinase A when it was in complex with TIMP-2. Zymographic analysis and N-terminal sequencing revealed that legumain cleaved the 72 kDa progelatinase A at the bonds between Asn109-Tyr110 or Asn111-Phe112 to produce the 62 kDa mature enzyme, and that further cleavage at Asn430 also occurred to generate a 36 kDa active form. More 62 kDa gelatinase A was detected in cultures of C13 cells that over-expressed legumain than in those of the control HEK293 cells. We conclude that legumain is clearly capable of processing progelatinase A to the active enzyme in vitro and in cultured cells.

Family practice became the 20th medical specialty in 1969, identified by its leaders as a harbinger of health care reform, as well as practice excellence, and with expectations of continuing government support of its purpose and role. Since that time, the cultural and political environments have changed significantly in some ways, and not changed in others as initially expected, thus challenging the new specialty with pressures for reinvention with respect to its identity, function, and prestige. The most important impediment to a clear-cut role for family practice has been the lack of a formal administrative structure for primary care practice on a nationwide basis in the United States. Differentiation of the field from all other parts of medicine was also difficult because of the identification of family practice with the professional accoutrements of a specialty, parallel to other specialist fields. Family practice moved from an outsider role in medicine to a position of entrenchment in the medical establishment, including hospitals and academic medical centers. And, family practice became one of several overlapping and competing primary care fields. The role of family practice in US culture is now less clear than the potential role envisioned for it in 1969. Its multiple and not always well-defined roles in medicine may make it difficult to establish a clear identity for the specialty in the future. If it is to be successful, family practice must develop allies and work aggressively to establish its role in primary care. It must also work to institute primary care in the US medical system and act politically (as in the 1960s), taking advantage of current cultural trends, notably the information revolution and the growth of biomedical research.

The future role of national medical organizations as a moral voice in health policymaking in the United States deserves attention from both scholarly and strategic perspectives. Arguments for strengthening the public roles of organized professionalism include its long (if neglected) history of public service. Scholarship of the past 40 years has emphasized the decline of a profession imbued with self-interest, together with associated theories of organizational conflict. Through new concepts and language, a different version of organized medicine from that of the past might be invented for the future--one that draws on multiple medical organizations, encourages more effective cooperation with other health care groups, and builds on traditional professional agendas through adaptation and extension.

To evaluate the effects of HIV infection on T cell turnover, we examined levels of DNA synthesis in lymph node and peripheral blood mononuclear cell subsets by using ex vivo labeling with BrdUrd. Compared with healthy controls (n = 67), HIV-infected patients (n = 57) had significant increases in the number and fraction of dividing CD4(+) and CD8(+) T cells. Higher percentages of dividing CD4(+) and CD8(+) T cells were noted in patients with the higher viral burdens. No direct correlation was noted between rates of T cell turnover and CD4(+) T cell counts. Marked reductions in CD4(+) and CD8(+) T cell proliferation were seen in 11/11 patients 1-12 weeks after initiation of highly active antiretroviral therapy (HAART). These reductions persisted for the length of the study (16-72 weeks). Decreases in naive T cell proliferation correlated with increases in the levels of T cell receptor rearrangement excision circles. Division of CD4(+) and CD8(+) T cells increased dramatically in association with rapid increases in HIV-1 viral loads in 9/9 patients 5 weeks after termination of HAART and declined to pre-HAART-termination levels 8 weeks after reinitiation of therapy. These data are consistent with the hypothesis that HIV-1 infection induces a viral burden-related, global activation of the immune system, leading to increases in lymphocyte proliferation.

Unlabelled: Because succinylcholine has obvious advantages for facilitating endotracheal intubation in the ambulatory setting (e.g., low cost, fast onset, and no need for reversal of neuromuscular block), it is important to determine whether this muscle relaxant is indeed associated with an increased incidence of postoperative myalgias, compared with alternative but more expensive nondepolarizing muscle relaxants. We studied 119 outpatients undergoing endoscopic nasal sinus surgery or septoplasty. The anesthetic technique consisted of propofol/lidocaine for induction, followed by isoflurane/nitrous oxide/oxygen for maintenance. Oral tracheal intubation was performed by using a fiberscope. Patients were randomly assigned to one of two muscle relaxant groups. Group 1 patients received d-tubocurarine 3 mg followed by succinylcholine 1.5 mg/kg. Group 2 patients received mivacurium 0.2 mg/kg. After recovery from anesthesia, patients were asked whether they had any muscle pain and/or stiffness. Pain was categorized by location and quantified by using a verbal scale (from 0 to 10). Analgesic usage and myalgias limiting ambulation were recorded. After discharge from the ambulatory surgery unit, patients were contacted by telephone on Postoperative Day 1. If patients complained of myalgias, they were contacted by telephone on Days 2 and 3. Only one patient (in the mivacurium-treated group) reported myalgia as a limiting factor in ambulation or resumption of normal activity. There were no differences between groups with respect to the incidence (21% in the succinylcholine-treated group and 18% in the mivacurium-treated group), location, or severity of myalgia. In conclusion, succinylcholine (preceded by pretreatment with d-tubocurarine and lidocaine) is not associated with an increased incidence of myalgias, compared with mivacurium, when used to facilitate tracheal intubation in patients undergoing ambulatory nasal surgery., Implications: The results of this study show that the frequency of muscle pains after surgery in outpatients is approximately 20%, regardless of whether succinylcholine (after precurarization) or mivacurium is used to assist in insertion of the breathing tube.

Background: The availability of various routes of administration of opioid analgesics can be confusing when determining an appropriate, efficacious, and cost-effective regimen to manage cancer pain., Methods: The indications, contraindications, and pharmacokinetic properties of oral, intravenous, subcutaneous, transdermal, transmucosal, rectal, and perispinal routes of opioid administration are reviewed., Results: To determine the most efficacious, cost-effective, and user-friendly option to manage cancer pain, several factors must be considered: the ability of the patient to use a specific type of delivery system, the efficacy of that system to deliver acceptable analgesia, the ease of use for the patient and family, the potential or actual complications associated with that system, and the cost., Conclusions: Administering opioids to manage cancer pain requires knowledge of potency relative to morphine and bioavailability of the route chosen. Changes in the route, dosage, or opioid used should be accompanied with close patient follow-up.