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Background: Travelers can experience health problems while abroad. This descriptive study aimed to quantify the disease burden leading to hospital-based care, repatriation or death in Dutch travelers during a stay in a foreign country, including Europe., Methods: Retrospective study of demographic and clinical data from three medical assistance centers (MACs) and the Dutch Ministry of Foreign Affairs on Dutch travelers receiving hospital-based care or who died abroad in the years 2010-2014. Diagnoses were coded according to the International Classification of Diseases (ICD) and classified using the Global Burden of Disease tool., Results: Data was available for 77,741 travelers' incidents: 75,385 medical consultations and 2,356 deaths. Four in five travelers received inpatient care, of which 36% concerned older travelers (65+) who had significantly longer hospital stays. Overall the top three diagnoses were: injuries (29%), infectious diseases (17%), and cardiovascular diseases (17%). Mental illness was reported in nearly 1.5% of the travelers. Incidence proportions were highest in South-Eastern Asia, with enteric infections as most common diagnosis. Injuries and communicable diseases occurred most often in South-Eastern Asia, while non-communicable diseases were mostly reported in South America. One in five travelers who consulted a physician was repatriated back home, mostly on a scheduled flight with or without medical escort. Cardiovascular diseases and injuries were the leading causes of death., Conclusions: Not only communicable diseases, but also injuries and chronic diseases (in particular cardiovascular diseases) frequently affected travelers' health while staying abroad and frequently necessitated hospital-based care. This should be addressed during the pre-travel counseling., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Airway remodeling (AR) increases disease severity, and morbidity of asthmatic patients by contributing to irreversible airflow obstruction and progressive declines in lung function. Arginase isoenzymes and the downstream enzymes ornithine decarboxylase (ODC) and ornithine aminotransferase (OAT) have been implicated in the hyperplastic and fibrotic changes of AR, respectively. Omega-3 polyunsaturated fatty acids ( ω -3 PUFAs) and resolvin metabolites have anti-AR effects, but whether they are mediated through the arginase pathway is unclear. Our study intended to determine the effects of the ω -3 PUFAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), resolvin D1 (RvD1), T H 1 cytokines, acetylsalicylic acid (ASA), cAMP, and dexamethasone (DEX) on the expression of arginase isoenzymes arginase 1 (ARG1) and arginase 2 (ARG2), ODC, and OAT in human lung fibroblasts (HLF) from normal (NHLF) and diseased (DHLF) asthmatic donors using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Our data showed that EPA and EPA+DHA downregulated ARG2 mRNA 2-fold in both types of HLF. DHA, RvD1, and DEX did not alter mRNA levels for any of the genes studied. EPA lowered the ARG2 protein levels in DHLF, but did not affect those levels in NHLF. ASA upregulated ARG2 mRNA 5-fold and 7-fold in NHLF and DHLF, respectively, T H 1 cytokines downregulated ARG2, ODC, and OAT mRNA in DHLF 10-fold, 2-fold, and 2.5-fold, respectively, and cAMP downregulated ARG2 mRNA 2-fold in DHLF. These results are the first to show a direct effect of ω -3 PUFAs on ARG2 mRNA levels and provide further evidence for a role of ω -3 PUFAs in AR., Competing Interests: The authors have no conflict of interest or financial interest in any of the research presented in this manuscript., (Copyright © 2022 Vamsee K. Duggirala et al.)

Background: Yellow fever (YF) vaccination is the single most important preventative measure against YF infection, however the live attenuated vaccine has associated serious adverse events. All YF vaccinations in England, Wales and Northern Ireland (EWNI) are administered in YF Vaccination Centres and comply with National Travel Health Network and Centre (NaTHNaC) Conditions of Designation and Code of Practice, including reporting of vaccine incidents to NaTHNaC. In this study we evaluated the number and type of YF vaccine incidents in EWNI to identify areas for improvement., Methods: NaTHNaC's telephone advice line database was retrospectively searched from 1st January 2016 to 31st December 2018 for YF vaccine incidents. Calls were categorised and analysed according to incident type., Results: Seventy-eight YF vaccine incidents were reported from a total of 17250 calls. The commonest incident was incorrect timing of measles, mumps and rubella vaccine in relation to YF vaccine, where the recommended 28-day interval was not observed (n = 21). Other incidents included accidental partial vaccination (n = 11), inappropriate vaccination (n = 5) and invalid vaccination due to expiry or cold chain breach (n = 4). Inadvertent vaccination in contraindicated individuals occurred in two travellers with thymectomies (resulting in one death), and five immunocompromised travellers., Conclusions: YF vaccine incidents represent a small proportion of total calls. Similar incidents likely occur with other vaccines, but YF vaccine incidents are of particular concern; whilst most incidents were not harmful, vaccination in contraindicated individuals resulted in one death. These findings helped to inform new guidance and update training for staff in YF vaccination centres., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Screening for malaria in the returning traveler has often required repeat testing; however, audit data suggest that patients have not been reattending. We sought to ascertain if this was safe by examining the diagnostic efficacy of a single screen consisting of a rapid diagnostic test (RDT) and a thin film., Methods: We conducted a retrospective cohort study of patients with suspected malaria who attended in the past 5 years from two large teaching hospitals. We assessed the diagnostic accuracy of a single screen, reporting measures of sensitivity and specificity. To establish a reference standard, we cross-linked data with the national malaria registry held at Public Health England and regional centers., Results: The cohort consisted of 1365 patients, of whom 33 opted out of the research and one did not have a complete initial screen. Of those 1331 screens there were 74 cases of Plasmodium falciparum (prevalence of 5.6%) and 104 of any malaria species (prevalence of 7.8%). Sensitivity for the detection of P. falciparum was 100.00% (95% confidence interval [CI] = 95.1 to 100), with a specificity of 99.4% (95% CI = 98.9 to 99.8). For the detection of any species of malaria the sensitivity was slightly lower due to the presence of one false negative; sensitivity was 99.0% (95% CI = 94.8 to 100) and specificity was 99.5% (95% CI = 98.9 to 99.8)., Conclusions: A single thin film and RDT is likely to be sufficient as a first screen for falciparum malaria in the returning traveler with important caveats. For those sent home from emergency departments, appropriate safety netting must be provided. Further prospective study is required to investigate this approach., (© 2021 The Authors. Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Smoking is one of the most impactful lifestyle-related risk factors in many cancer types including esophageal squamous cell carcinoma (ESCC). As the major component of tobacco and e-cigarettes, nicotine is not only responsible for addiction to smoking but also a carcinogen. Here we report that nicotine enhances ESCC cancer malignancy and tumor-initiating capacity by interacting with cholinergic receptor nicotinic alpha 7 subunit (CHRNA7) and subsequently activating the JAK2/STAT3 signaling pathway. We found that aberrant CHRNA7 expression can serve as an independent prognostic factor for ESCC patients. In multiple ESCC mouse models, dextromethorphan and metformin synergistically repressed nicotine-enhanced cancer-initiating cells (CIC) properties and inhibited ESCC progression. Mechanistically, dextromethorphan non-competitively inhibited nicotine binding to CHRNA7 while metformin downregulated CHRNA7 expression by antagonizing nicotine-induced promoter DNA hypomethylation of CHRNA7. Since dextromethorphan and metformin are two safe FDA-approved drugs with minimal undesirable side-effects, the combination of these drugs has a high potential as either a preventive and/or a therapeutic strategy against nicotine-promoted ESCC and perhaps other nicotine-sensitive cancer types as well.

Prostate cancer is one of the most common cancers diagnosed in men in the United States and the second leading cause of cancer-related deaths worldwide. Since over 60% of prostate cancer cases occur in men over 65 years of age, and this population will increase steadily in the coming years, prostate cancer will be a major cancer-related burden in the foreseeable future. Accumulating data from more recent research suggest that the tumor microenvironment (TME) plays a previously unrecognized role in every stage of cancer development, including initiation, proliferation, and metastasis. Prostate cancer is not only diagnosed in the late stages of life, but also progresses relatively slowly. This makes prostate cancer an ideal model system for exploring the potential of natural products as cancer prevention and/or treatment reagents because they usually act relatively slowly compared to most synthetic drugs. Resveratrol (RSV) is a naturally occurring stilbenoid and possesses strong anti-cancer properties with few adverse effects. Accumulating data from both in vitro and in vivo experiments indicate that RSV can interfere with prostate cancer initiation and progression by targeting the TME. Therefore, this review is aimed to summarize the recent advancement in RSV-inhibited prostate cancer initiation, proliferation, and metastasis as well as the underlying molecular mechanisms, with particular emphasis on the effect of RSV on TME. This will not only better our understanding of prostate cancer TMEs, but also pave the way for the development of RSV as a potential reagent for prostate cancer prevention and/or therapy.

Over 100,000 cases of COVID-19 patients infected with the novel coronavirus SARS-COV-2 have been reported worldwide in approximately 2 months, resulting in over 3000 deaths. Potential therapeutic strategies, including remdesivir, chloroquine phosphate, abidol, lopinavir/ritonavir, plasma, antibody, vaccine and stem cells are discussed in this review. With the number of patients increasing daily, there is an urgent need for effective therapeutic intervention., Competing Interests: Conflict of interests: The authors don’t have any conflict of interest to declare., (Copyright: © 2020, Zhu et al. and Applied Systems.)

Recent advances in high throughput technologies have led to the generation of vast amounts of clinical data and the development of personalized medicine approaches in acute myeloid leukemia (AML). The ability to treat cancer patients based upon their individual molecular characteristics or drug sensitivity profiles is expected to significantly advance cancer treatment and improve the long-term survival of patients with refractory AML, for whom current treatment options are restricted to palliative approaches. The clinical development of omics-based and phenotypic screens, however, is limited by a number of bottlenecks including the generation of cost-effective high-throughput data, data interpretation and integration of multiple approaches, sample availability, clinically relevant timelines, and the development and education of multidisciplinary teams. Recently, a number of small clinical trials have shown survival benefits in patients treated based on personalized medicine approaches. While these preliminary studies are encouraging, larger trials are needed to evaluate the utility of these technologies in routine clinical settings., Competing Interests: CONFLICTS OF INTEREST The authors have no conflict of interest to declare.

Immunoglobulin (Ig) G4 (IgG4)-related disease is a recently described clinical entity that can involve multiple organs. It is an autoimmune disorder characterized by a dense lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. A key distinguishing factor is its dramatic response to steroid therapy. Although best described in cases of autoimmune pancreatitis, IgG4-related disease has also been implicated in patients with cholangitis and is now commonly referred to as IgG4-related cholangiopathy. It is characterized by elevated serum IgG4 levels, an IgG4-positive plasma cell infiltration with storiform fibrosis/obliterative phlebitis of the bile duct wall, and a response to steroids. It is crucial to differentiate IgG4-related cholangiopathy from its mimickers, such as primary biliary cholangitis, secondary biliary cholangitis, primary sclerosing cholangitis, secondary sclerosing cholangitis, and cholangiocarcinoma, because treatment modalities and outcomes of IgG4-related cholangiopathy differ significantly from these disorders. Here, we present an interesting case of IgG4-related cholangiopathy, discuss clinical and pathological features crucial to its early diagnosis, and compare and contrast this condition with its potentially confounding mimickers.

Although the newly developed second-generation anti-androgen drug enzalutamide can repress prostate cancer progression significantly, it only extends the survival of prostate cancer patients by 4-6 months mainly due to the occurrence of enzalutamide resistance. Most of the previous studies on AR antagonist resistance have been focused on AR signaling. Therefore, the non-AR pathways on enzalutamide resistance remain largely unknown. By using C4-2, CWR22Rv1 and LNCaP cell lines, as well as mice bearing CWR22Rv1 xenografts treated with either enzalutamide or metformin alone or in combination, we demonstrated that metformin is capable of reversing enzalutamide resistance and restores sensitivity of CWR22Rv1 xenografts to enzalutamide. We showed that metformin alleviated resistance to enzalutamide by inhibiting EMT. Furthermore, based on the effect of metformin on the activation of STAT3 and expression of TGF-β1, we propose that metformin exerts its effects by targeting the TGF-β1/STAT3 axis. These findings suggest that combination of metformin with enzalutamide could be a more efficacious therapeutic strategy for the treatment of castration-resistant prostate cancer.

The significant optical and size benefits of using a curved focal surface for imaging systems have been well studied yet never brought to market for lack of a high-quality, mass-producible, curved image sensor. In this work we demonstrate that commercial silicon CMOS image sensors can be thinned and formed into accurate, highly curved optical surfaces with undiminished functionality. Our key development is a pneumatic forming process that avoids rigid mechanical constraints and suppresses wrinkling instabilities. A combination of forming-mold design, pressure membrane elastic properties, and controlled friction forces enables us to gradually contact the die at the corners and smoothly press the sensor into a spherical shape. Allowing the die to slide into the concave target shape enables a threefold increase in the spherical curvature over prior approaches having mechanical constraints that resist deformation, and create a high-stress, stretch-dominated state. Our process creates a bridge between the high precision and low-cost but planar CMOS process, and ideal non-planar component shapes such as spherical imagers for improved optical systems. We demonstrate these curved sensors in prototype cameras with custom lenses, measuring exceptional resolution of 3220 line-widths per picture height at an aperture of f/1.2 and nearly 100% relative illumination across the field. Though we use a 1/2.3" format image sensor in this report, we also show this process is generally compatible with many state of the art imaging sensor formats. By example, we report photogrammetry test data for an APS-C sized silicon die formed to a 30° subtended spherical angle. These gains in sharpness and relative illumination enable a new generation of ultra-high performance, manufacturable, digital imaging systems for scientific, industrial, and artistic use.

Although androgen deprivation therapy (ADT) serves as the primary treatment option for localized or metastatic prostate cancer, most cases eventually develop into castration-resistant prostate cancer (CRPC). However, androgen receptor (AR) continues to be functional in CRPC through various mechanisms, including the development of AR splicing variants, especially ARV7. Since it lacks the ligand binding domain but retains the intact DNA binding domain, ARV7 is constitutively active, which makes ARV7-positive prostate cancer responsive to neither abiraterone nor enzalutamide. In this study, we explored the effect of resveratrol on ARV7 transcriptional activity and the potential for development of resveratrol as a treatment for ARV7-positive prostate cancer. First, we ectopically expressed ARV7 in PC3 cells, an AR-negative prostate cancer cell line, and demonstrated that resveratrol is capable of inhibiting ARV7 transcriptional activity by downregulating ARV7 protein levels. Of note, resveratrol does not affect the mRNA levels of ARV7 nor its nuclear translocation. Next, we demonstrated that resveratrol is capable of downregulating the levels of the endogenously expressed ARV7 as well as AR target gene mRNAs in 22RV1 prostate cancer cells. Mechanistically, resveratrol downregulates ARV7 by enhancing ARV7 polyubiquitination and subsequent proteasome-mediated degradation. These findings suggest that resveratrol could be a potential treatment for ARV7-positive CPRC., Competing Interests: CONFLICTS OF INTEREST We disclose no potential conflicts of interest.

The threat of serious, cross-border communicable disease outbreaks in Europe poses a significant challenge to public health and emergency preparedness because the relative likelihood of these threats and the pathogens involved are constantly shifting in response to a range of changing disease drivers. To inform strategic planning by enabling effective resource allocation to manage the consequences of communicable disease outbreaks, it is useful to be able to rank and prioritise pathogens. This paper reports on a literature review which identifies and evaluates the range of methods used for risk ranking. Searches were performed across biomedical and grey literature databases, supplemented by reference harvesting and citation tracking. Studies were selected using transparent inclusion criteria and underwent quality appraisal using a bespoke checklist based on the AGREE II criteria. Seventeen studies were included in the review, covering five methodologies. A narrative analysis of the selected studies suggests that no single methodology was superior. However, many of the methods shared common components, around which a 'best-practice' framework was formulated. This approach is intended to help inform decision makers' choice of an appropriate risk-ranking study design.

Objective: To investigate the effectiveness of a neck strengthening program on the isometric neck strength profile of male rugby union players., Design: Controlled laboratory study., Setting: Professional rugby union club., Participants: Fifteen professional and 10 semiprofessional rugby union players., Interventions: The 15 professional players undertook a 5-week neck strengthening intervention, which was performed twice per week, whereas the 10 semiprofessional players acted as the control group., Main Outcome Measures: Isometric strength of the neck musculature was tested using a hand-held dynamometer, for flexion (F), extension (E), left-side flexion (LSF), and right-side flexion (RSF). Preintervention and postintervention evaluations were undertaken., Results: No significant between-group differences in isometric neck strength were noted preintervention. A significant main effect for time was observed (P < 0.05), whereby the intervention group increased isometric neck strength in all planes after the 5-week intervention (F preintervention = 334.45 ± 39.31 N vs F postintervention 396.05 ± 75.55 N; E preintervention = 606.19 ± 97.34 vs E postintervention = 733.88 ± 127.16 N; LSF preintervention = 555.56 ± 88.34 N vs LSF postintervention = 657.14 ± 122.99 N; RSF preintervention = 570.00 ± 106.53 N vs RSF postintervention = 668.00 ± 142.18 N). No significant improvement in neck strength was observed for control group participants., Conclusions: The results of the present study indicate that a 5-week neck strengthening program improves isometric neck strength in rugby union players, which may have implications for injury prevention, screening, and rehabilitation., Clinical Relevance: The strengthening program described in the present study may facilitate rehabilitation specialists in the development of neck injury prevention, screening, and rehabilitation protocols.

Our translational research group focuses on addressing the problem of exercise defects in diabetes with basic research efforts in cell and rodent models and clinical research efforts in subjects with diabetes mellitus. CREB (cAMP-response-element-binding protein) regulates cellular differentiation of neurons, β-cells, adipocytes and smooth muscle cells; it is also a potent survival factor and an upstream regulator of mitochondrial biogenesis. In diabetes and cardiovascular disease, CREB protein content is decreased in the vascular media, and its regulation in aberrant in β-cells, neurons and cardiomyocytes. Loss of CREB content and function leads to decreased vascular target tissue resilience when exposed to stressors such as metabolic, oxidative or sheer stress. This basic research programme set the stage for our central hypothesis that diabetes-mediated CREB dysfunction predisposes the diabetes disease progression and cardiovascular complications. Our clinical research programme revealed that diabetes mellitus leads to defects in functional exercise capacity. Our group has determined that the defects in exercise correlate with insulin resistance, endothelial dysfunction, decreased cardiac perfusion and diastolic dysfunction, slowed muscle perfusion kinetics, decreased muscle perfusion and slowed oxidative phosphorylation. Combined basic and clinical research has defined the relationship between exercise and vascular function with particular emphasis on how the signalling to CREB and eNOS [endothelial NOS (nitric oxide synthase)] regulates tissue perfusion, mitochondrial dynamics, vascular function and exercise capacity. The present review summarizes our current working hypothesis that restoration of eNOS/NOS dysfunction will restore cellular homoeostasis and permit an optimal tissue response to an exercise training intervention.

Objective: The purpose of this study was to investigate the isometric neck strength profiles of rugby union players and to assess the intrarater reliability of isometric neck strength measurement using a handheld dynamometer., Methods: Twenty-five male, academy-level, rugby union players (forwards [n = 16], backs [n = 9]) were tested on 2 occasions during a training week 2 days apart. Isometric strength of the neck musculature was tested using a handheld dynamometer, for flexion (F), extension (E), left side flexion (LSF), and right side flexion (RSF). The average of 3 trials for each test position was used for statistical analysis. The following isometric neck strength values were obtained: F, E, F:E, LSF, RSF, LSF:RSF, and total isometric strength., Results: Intrarater reliability intraclass correlation coefficients ranged from 0.80 to 0.92 (intraclass correlation coefficient values: F, 0.85; E, 0.85; F:E, 0.85; LSF, 0.80; RSF, 0.85; LSF:RSF, 0.91; total isometric strength, 0.92), thus indicating excellent reliability in all instances. Forwards recorded significantly greater E scores compared with backs (637.10 ± 75.15 N vs 537.87 ± 82.25 N). Forwards also recoded significantly greater total isometric neck strength scores (2151.96 ± 231.11 N vs 1814.21 ± 211.26 N)., Conclusion: The results of this study provide isometric neck strength values for the forward and back units in the rugby union and indicate that a handheld dynamometer may be a reliable tool for assessing isometric neck strength in this population., (Copyright © 2013 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.)

Treatment of chlorotriaryl derivatives 3a and 3d or fluorotriaryl derivatives 3b and 3e with potassium diisopropylamide afforded alkyl-shifted phenazine derivatives 5a/5b, rather than the expected 9-membered triazaorthocyclophane 2a. The phenazine derivatives were isolated in 78-98% yield depending on the halogen and alkyl group present. In the absence of the halogen (chloro or fluoro), the apparent alkyl shift proceeds more slowly and cannot proceed via the intermediacy of the aryne intermediate. Mechanistic possibilities include intramolecular nucleophilic attack on an aryne intermediate leading to a zwitterionic intermediate and alkyl transfer via a 5-endo-tet process, or via a Smiles rearrangement.

Werner syndrome (WS) is an autosomal recessive disorder, the hallmarks of which are premature aging and early onset of neoplastic diseases (Orren, 2006; Bohr, 2008). The gene, whose mutation underlies the WS phenotype, is called WRN. The protein encoded by the WRN gene, WRNp, has DNA helicase activity (Gray et al., 1997; Orren, 2006; Bohr, 2008; Opresko, 2008). Extensive evidence suggests that WRNp plays a role in DNA replication and DNA repair (Chen et al., 2003; Hickson, 2003; Orren, 2006; Turaga et al., 2007; Bohr, 2008). However, WRNp function is not yet fully understood. In this study, we show that WRNp is involved in de novo DNA methylation of the promoter of the Oct4 gene, which encodes a crucial stem cell transcription factor. We demonstrate that WRNp localizes to the Oct4 promoter during retinoic acid-induced differentiation of human pluripotent cells and associates with the de novo methyltransferase Dnmt3b in the chromatin of differentiating pluripotent cells. Depletion of WRNp does not affect demethylation of lysine 4 of the histone H3 at the Oct4 promoter, nor methylation of lysine 9 of H3, but it blocks the recruitment of Dnmt3b to the promoter and results in the reduced methylation of CpG sites within the Oct4 promoter. The lack of DNA methylation was associated with continued, albeit greatly reduced, Oct4 expression in WRN-deficient, retinoic acid-treated cells, which resulted in attenuated differentiation. The presented results reveal a novel function of WRNp and demonstrate that WRNp controls a key step in pluripotent stem cell differentiation.

HIV-1-based lentiviral vectors are a promising tool for gene therapy. However, integration of a lentiviral vector into host cell genes may lead to the development of cancer. Therefore, control of integration site selection is critical to the successful outcome of gene therapy approaches that use these vectors. The discovery that integration site selection by HIV-1 and HIV-1-based vectors is controlled by the LEDGF/p75 protein has presented new opportunities to control integration site selection. In this study, we tested the hypothesis that a fusion protein containing the C-terminal HIV integrase-binding portion of LEDGF/p75, and the N-terminal chromodomain of heterochromatin protein-1alpha (HP1alpha), can target HIV-1 vector DNA outside of genes. We show that this fusion protein, termed TIHPLE, associates with the heterochromatin hallmark trimethylated Lys-9 of histone H3 (H3K9me3). Transient overexpression of TIHPLE alters integration site selection by an HIV-1-based vector and decreases the number of integration events that occur in genes. This change in integration site selection was achieved without a reduction in overall integration efficiency. Furthermore, we show that TIHPLE increases integration in the vicinity of H3K9me3 and in repetitive DNA sequences. These data provide a novel approach to address the problem of the tendency of retroviral vectors to integrate at undesirable sites of the human genome.

Transmission measurements of 14 fabrics are presented in the millimeter-wave and submillimeter-wave electromagnetic regions from 130 GHz to 1.2 THz. Three independent sources and experimental set-ups were used to obtain accurate results over a wide spectral range. Reflectivity, a useful parameter for imaging applications, was also measured for a subset of samples in the submillimeter-wave regime along with polarization sensitivity of the transmitted beam and transmission through doubled layers. All of the measurements were performed in free space. Details of these experimental set-ups along with their respective challenges are presented.

The PU.1 transcription factor is a key regulator of hematopoietic development, but its role at each hematopoietic stage remains unclear. In particular, the expression of PU.1 in hematopoietic stem cells (HSCs) could simply represent "priming" of genes related to downstream myelolymphoid lineages. By using a conditional PU.1 knock-out model, we here show that HSCs express PU.1, and its constitutive expression is necessary for maintenance of the HSC pool in the bone marrow. Bone marrow HSCs disrupted with PU.1 in situ could not maintain hematopoiesis and were outcompeted by normal HSCs. PU.1-deficient HSCs also failed to generate the earliest myeloid and lymphoid progenitors. PU.1 disruption in granulocyte/monocyte-committed progenitors blocked their maturation but not proliferation, resulting in myeloblast colony formation. PU.1 disruption in common lymphoid progenitors, however, did not prevent their B-cell maturation. In vivo disruption of PU.1 in mature B cells by the CD19-Cre locus did not affect B-cell maturation, and PU.1-deficient mature B cells displayed normal proliferation in response to mitogenic signals including the cross-linking of surface immunoglobulin M (IgM). Thus, PU.1 plays indispensable and distinct roles in hematopoietic development through supporting HSC self-renewal as well as commitment and maturation of myeloid and lymphoid lineages.

Editor's comment: This is the second Commentary of those that will appear from time to time describing treatments that may not have been validated by appropriate clinical trials but seem to be effective in diabetic patients based on small studies and/or extensive clinical experience. This one describes effective opioid treatment for those diabetic patients failing nonopioid therapies for painful neuropathy.

To develop murine models of leukemogenesis, a series of transgenic mice expressing BCR-ABL in different hematopoietic cell subsets was generated. Here we describe targeted expression of P210 BCR-ABL in stem and progenitor cells of murine bone marrow using the tet-off system. The transactivator protein tTA was placed under the control of the murine stem cell leukemia (SCL) gene 3' enhancer. Induction of BCR-ABL resulted in neutrophilia and leukocytosis, and the mice became moribund within 29 to 122 days. Autopsy of sick mice demonstrated splenomegaly, myeloid bone marrow hyperplasia, and extramedullary myeloid cell infiltration of multiple organs. BCR-ABL mRNA and protein were detectable in the affected organs. Fluorescence-activated cell sorter (FACS) analysis demonstrated a significant increase in mature and immature myeloid cells in bone marrow and spleen, together with increased bilineal B220+/Mac-1+ cells in the bone marrow. tTA mRNA was expressed in FACS-sorted hematopoietic stem cells expanded 26-fold after BCR-ABL induction. Thirty-one percent of the animals demonstrated a biphasic phenotype, consisting of neutrophilia and subsequent B-cell lymphoblastic disease, reminiscent of blast crisis. In summary, this mouse model recapitulates many characteristics of human chronic myeloid leukemia (CML) and may help elucidate basic leukemogenic mechanisms in CML stem cells during disease initiation and progression.

Objective: To develop evidence-based clinical guidelines on smoking cessation, for use throughout the British military., Method: A ten-member, multiprofessional smoking cessation working group met five times between October 2000 and July 2001 to develop targeted smoking cessation guidelines for use by military health professionals in the clinical setting. The guidelines were based on the best available scientific evidence at that time, mainly systematic review of controlled trials, and individual randomised trials., Results: The agreed military guidelines on smoking cessation were promulgated in July 2001. Three tiers of support were defined. Military health professionals have a key role as nonsmoking models and advocates, and should be trained to use 'brief intervention' at every clinical encounter with a military smoker. 'Intermediate support' (defined as a specialist service delivered by military health professionals who have undergone specific training and continuation training) is to be available at local level. The most heavily addicted military smokers will require referral to civilian smoking cessation clinics. Effective technologies for use at any one of the three levels of care are: nicotine skin patches, nicotine gum, nicotine lozenges and bupropion., Conclusions: These are the first ever clinical guidelines for military use which meet accepted modern quality criteria. Informal monitoring of the uptake of these guidelines between July 2001 to December 2001 suggests that they have been well received by military health professionals. An audit of their impact on smoking patterns within the UK Armed Forces will commence in 2002. The guidelines will be updated 5-yearly, or sooner.

An increase in infectious complications has been noted with the introduction of percutaneous femoral artery closure devices. We report five cases of infected groins and/or femoral arteries following angiographic procedures that were completed using the Perclose Suture Mediated Closure Device (Perclose). Each patient required drainage of the abscess and removal of the Perclose suture. Most patients required more extensive vascular reconstructive procedures. When these complications arise, we recommend expeditious drainage of the abscess, removal of the suture, and adequate exposure of the femoral artery to facilitate repair of the vessel.

There is anecdotal and some scientific evidence that females in military service experience an excess of work-related injuries, compared with males. To investigate this more fully, we analysed data collected routinely by the Defence Analytical Services Agency on medical discharges in male and female personnel in the British armed forces. We found that for all disease and injury categories of medical discharge there is a statistically significant excess in females; this disparity is particularly marked for discharges on account of injury [relative risk (RR) = 1.65, 95% confidence interval (95% CI) = 1.30-2.10] and musculoskeletal disease (RR = 3.34, 95% CI = 2.75-4.06). Royal Navy females are eight times more likely (RR = 7.92, 95% CI = 3.03-20.66) and Army females seven times more likely (RR = 6.53, 95% CI = 2.60-16.42) than Royal Air Force females to be medically discharged on account of injury. Over the period 1993-1996, there was a statistically significant increase in the rate of medical discharge for both musculoskeletal disease and injury in female personnel in the British armed forces. During the period 1996-2000, a marked gender differential was maintained, but the rate of increase in females reached a plateau. We concur with previous investigators that mixed-sex training imposes particular ergonomic stresses on females and that it is a major risk factor for overuse injury. We discuss other possible explanations for the marked gender differential in medical discharge rates in the military. Some changes to training programmes are now being introduced to correct this health inequality, but further interventions are needed. Modifications to training programmes must be audited systematically and candidate interventions tested through randomized controlled trials.

This study evaluated the relative effectiveness of two forms of publicly funded substance abuse treatment provided in Washington State: The full continuum (FC), in which clients receive approximately three weeks of inpatient treatment prior to outpatient care, and the partial continuum (PC), in which clients are admitted directly to outpatient treatment. Data on treatment process/proximal outcomes, such as psychological distress and readiness to change, were assessed at 8 weeks post intake, and data on treatment services received were obtained at 2, 4, 8, and 12 weeks. Multidimensional outcomes, including alcohol and drug use as well as a number of psychosocial functioning outcomes, were assessed at 3 and 9 months post intake. Results indicated that clients in the FC had greater alcohol, drug, and legal problem severity at intake than those in the PC, whereas medical and employment problem severity was greater in the PC. Clients in the FC received more treatment services in the first 2 weeks than those in the PC, but there were no differences at subsequent points. Outcome analyses at 3 and 9 months indicated that clients in the FC had greater improvements in alcohol, drug, and psychiatric severity than those in the PC. Matching analyses indicated that clients with greater substance-use severity at baseline improved to a greater degree in the FC as compared to the PC. Matching effects were not obtained with medical or psychiatric severity, or readiness to change.

In interferometry and optical testing, system wave-front measurements that are analyzed on a restricted subdomain of the full pupil can include predictable systematic errors. In nearly all cases, the measured rms wave-front error and the magnitudes of the individual aberration polynomial coefficients underestimate the wave-front error magnitudes present in the full-pupil domain. We present an analytic method to determine the relationships between the coefficients of aberration polynomials defined on the full-pupil domain and those defined on a restricted concentric subdomain. In this way, systematic wave-front measurement errors introduced by subregion selection are investigated. Using vector and matrix representations for the wave-front aberration coefficients, we generalize the method to the study of arbitrary input wave fronts and subdomain sizes. While wave-front measurements on a restricted subdomain are insufficient for predicting the wave front of the full-pupil domain, studying the relationship between known full-pupil wave fronts and subdomain wave fronts allows us to set subdomain size limits for arbitrary measurement fidelity.

The British experience of the past two decades indicates that fixed-schedule chemoprophylaxis is difficult because of the variety of epidemiological situations and increasing incidence of drug resistance. Of the 110 cases of malaria contracted in Kenya between 1982 and 1996, 74% were due to Plasmodium falciparum. Of the 45 malaria infections contracted in Belize, 84% were due to Plasmodium vivax. In 1985 the fixed drug combination of chloroquine base 300 mg weekly plus proguanil 200 mg daily was adopted as standard chemoprophylaxis for use in all parts of the world where chemoresistant Plasmodium falciparum had been observed. Mefloquine was recommended as first-line prophylaxis in Papua New Guinea in 1986 and in East Africa in 1993. Doxycycline hyclate was prescribed in September 1999 when a Gurkha company was deployed on peacekeeping duties to East Timor, but its effectiveness has not yet been evaluated. Chemoprophylaxis must be combined with non-drug antimalaria technologies, especially insecticide-treated bed nets.

Objective: The use of point-of-care technology has increased faster than efforts to validate its effectiveness compared to standard laboratory testing modalities. To address this issue with a current point-of-care coagulation system (HEMOCHRON Jr, International Technidyne Corporation (ITC), Edison, NJ), we designed a study to test the hypothesis that data obtained from point-of-care coagulation equipment correlates with data obtained from standard laboratory coagulation equipment. One of the potential advantages gained using point-of-care testing is the ability to obtain more rapid results. To address this issue, turnaround time, defined as the elapsed time (in minutes) from when the sample was acquired from the patient until the investigators knew the results, was also determined., Methods: Following Human Investigation Committee approval and informed consent, a prospective study was conducted to compare results obtained from point-of-care coagulation equipment with those results obtained from standard laboratory coagulation equipment. The study was performed in three groups of patients undergoing cardiovascular surgery, each requiring different levels of anticoagulation., Results: Of the 83 patients who met the inclusion criteria, the correlation (combining data from groups 1-3) between results obtained from point-of-care and standard laboratory prothrombin time was r = 0.867, p < 0.001. The correlation (group 3) between point-of-care and standard laboratory international normalized ratio was r = 0.943, p < 0.001. The correlation (combining data from groups 1 & 2) between point-of-care and standard laboratory activated partial thromboplastin time was r = 0.825, p < 0.001. Median turnaround time for the standard laboratory was 90 minutes, with a mean turnaround time of 74 to 78 minutes, depending upon the group. In contrast, the median turnaround time for point-of-care testing was two minutes and 14 seconds., Conclusions: The results from this study population reveal that data obtained from point-of-care prothrombin time, international normalized ratio and activated partial thromboplastin time results correlate with results obtained from standard laboratory coagulation testing. The value of obtaining reliable results in a timely fashion offers a potential advantage for point-of-care testing in dinical situations, such as in the operating room, where saving time may translate into financial savings.

Objective: To compare the abilities of the heparin management test (HMT) and the activated coagulation time (ACT) to provide a measurement of heparin effect in patients undergoing cardiac or peripheral vascular surgery. These measurements of heparin effect were also compared with measurements of heparin concentrations tested by anti-Xa activity. A secondary objective was to compare the performance of the noncitrated HMT with that of the citrated HMT., Design: A prospective study., Setting: A single-center study conducted in a university hospital., Participants: After human investigation committee approval and informed consent were obtained, adult patients undergoing cardiac or peripheral vascular surgery were included in this study., Interventions: In both surgical groups, blood was sampled for ACT, HMT, and anti-Xa activity. Each HMT was performed on both noncitrated and citrated samples., Measurements and Main Results: As an indicator of heparin effect, the HMT had a strong correlation with the ACT (r = 0.899; p < 0.01). In addition, the HMT had a significantly stronger correlation with anti-Xa activity than the ACT (p < 0.01). The correlation obtained from the noncitrated samples was identical with that obtained from the citrated samples (r = 0.819; p < 0.001 for both groups)., Conclusion: The ability of the HMT and the ACT to measure heparin effect was similar. The HMT performed better than the ACT when using anti-Xa activity as a measure of heparin concentration. Noncitrated HMT results were similar to citrated HMT results, thus supporting the use of fresh whole blood for testing purposes.

Purpose: Presumed differences in the thrombolytic activity and fibrinolytic specificity of the three commonly used thrombolytic agents, streptokinase, urokinase, and recombinant tissue plasminogen activator (rt-PA), are based on clinical study results, where variability renders meaningful comparisons difficult. An in vitro model of catheter-directed venous thrombolysis was used to compare the three agents., Methods: Retracted iodine 125-radiolabeled clots that simulate those observed in the venous system were infused with thrombolytic agents at doses analogous to those used clinically. Perfusion with heparinized, whole human blood was undertaken for 60 minutes, measuring the efficacy of thrombolysis through serial quantification of radio tracer released into the circuit. Fibrinolytic specificity was determined by following decrements in perfusate fibrinogen concentration., Results: Streptokinase was the agent associated with the slowest rate of clot lysis (p = 0.01 vs urokinase and rt-PA). Urokinase was associated with an intermediate rate of lysis but appeared to be the agent with the greatest degree of fibrinolytic specificity (p = 0.02 vs streptokinase, p = 0.05 vs rt-PA). Although rt-PA was associated with improved efficacy early in the perfusions, the differences between rt-PA and urokinase dissipated after 30 minutes., Conclusions: These laboratory observations suggest that urokinase may be the most appropriate agent for catheter-directed venous thrombolysis, offering an advantageous compromise between fibrinolytic specificity and thrombolytic speed.

To determine whether angiotensin II (ANG II) modulates renal growth and renin and angiotensin type 1 (AT1) gene expression via AT1 during development, weanling rats were given ANG II antagonist losartan (DuP 753) for 3 wk. Body weight (g), kidney weight (g), and kidney weight-to-body weight ratio were lower in losartan-treated rats (162 +/- 7, 1.6 +/- 0.06, and 9.5 +/- 0.1 x 10(-3)) than in control rats (184 +/- 5, 1.8 +/- 0.07, and 10.1 +/- 0.1 x 10(-3); P < 0.05). Renal DNA content (mg/kidney) was lower in losartan-treated (2.4 +/- 0.17) than in control rats (3.3 +/- 0.31; P < 0.05), whereas protein-to-DNA and RNA-to-DNA ratios were similar in losartan-treated and control rats. Renin mRNA levels were sevenfold higher in losartan-treated than in control rats, as determined by quantitative standardized dot blot analysis. In addition, blockade of AT1 with losartan induced recruitment of renin-synthesizing and renin-containing cells in the renal vasculature, as determined by immunocytochemistry and in situ hybridization. To establish whether AT1 blockade has a direct effect on renin gene expression, freshly isolated renin-producing cells were exposed in vitro to losartan (10(-6) M) or culture media (control). Losartan induced a twofold increase in steady-state renin mRNA levels above control (P < 0.05). Intrarenal AT1 mRNA levels were not altered by losartan given either in vivo or in vitro to freshly dispersed cells. To define whether immature renin-secreting cells are responsive to ANG II, renin release was determined by reverse hemolytic plaque assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Unilateral ureteral obstruction (UUO) in the neonate increases ipsilateral renal renin gene expression, an effect which is mediated by renal nerves. To determine whether neonatal UUO alters the number of renal cortical cells secreting renin and whether this change is modulated by renal nerve activity, newborn Sprague-Dawley rats were subjected to left UUO, right uninephrectomy, or sham operation and studied four weeks thereafter. To evaluate the importance of renal nerves in this response, an additional group of animals underwent chemical sympathectomy with guanethidine. Ureteral obstruction was associated with marked reduction in renal mass in the obstructed kidney and contralateral compensatory hypertrophy, changes which were not altered by sympathectomy. Renin messenger RNA and renal renin content were elevated in the obstructed kidney. The number of cells secreting renin, measured by the reverse hemolytic plaque assay, was markedly increased in the obstructed kidney (45 +/- 18 plaques/slide vs. 11 +/- 1 plaques/slide in sham animals), but not in the opposite kidney or following uninephrectomy. This effect was not significantly altered by sympathectomy. There was no change in the amount of renin secreted per cell or in the secretory response to Ca++. These results show that UUO results in recruitment of cells not previously secreting renin by a mechanism independent of renal nerve activity. This recruitment occurs without alteration of the quantity of renin secreted per cell or in the normal regulatory effect of Ca++ on renin secretion. An increase in the number of renin-secreting cells may contribute to the activation of the renin-angiotensin system, and thus to the vasoconstriction observed following ureteral obstruction.

A total of 1572 carotid endarterectomies were performed at one institution between 1975 and 1987. One hundred five patients had early (< 3 weeks) neurologic events following carotid endarterectomy. Sixty-five patients had cerebral vascular accidents (CVAs) (4.1%), 14 patients had reversible ischemic neurologic deficits (0.9%), and 26 patients had transient ischemic attacks (1.7%). Eight patients died from CVAs (0.5%). The mean follow-up was 31 months (range 1 to 137 months) with a 5-year cumulative survival of 77%. The median time of occurrence of neurologic events was 4 hours. Ages, cerebral protection, patches, carotid occlusion time (mean 29 minutes), gender, and status of the contralateral carotid arteries were not predictors of outcome. Death from neurologic events increased significantly in patients who had preoperative CVAs compared with patients with preoperative transient neurologic deficits (p < 0.05). The time of occurrence of CVA after carotid endarterectomy affected outcome, and an early CVA (< 4 hours) was associated with a higher mortality at 30 days and at 4 months as a consequence of the initial CVA (p = 0.11). Patients who had a neurologic event more than 4 hours after surgery had a significantly better resolution of their symptoms (66%) compared with patients who had an early neurologic event (35%, p < 0.05). The long-term follow-up of the surviving patients demonstrated an improvement in neurologic function in 75% of the CVA group (36/48) and 92% (76/83) of all patients who had neurologic events in long-term follow-up.

Angiotensin-converting enzyme inhibition with enalapril increases the number of glomeruli with juxtaglomerular cells and the number of cells in the afferent arteriole that express the renin gene and contain renin. However, renin release from these newly recruited renin-containing cells has not been demonstrated. Sodium depletion also has been shown to increase renal renin messenger RNA levels. The aim of these studies was to determine whether increases in renin secretion are a result of altered numbers of cells synthesizing/releasing renin or a change in the amount of renin release per cell, or both. Adult Wistar-Kyoto rats were treated with enalapril or sodium depleted and single cell renin secretion of enzymatically dispersed renal cortical cells was examined by reverse hemolytic plaque assay. Enalapril treatment increased the number of renin secreting cells by approximately 10-fold (P < 0.05). The newly recruited renin-secreting cells were not responsive to changes in extracellular calcium concentration or the presence of isoproterenol. At physiological (2.5 mM) extracellular calcium concentration, the amount of renin secreted per cell was approximately 2-fold greater (P < 0.05) when cells from enalapril-treated rats were compared to controls and sodium depletion increased both the number of renin-secreting cells and the amount of renin secreted by approximately 35% (P < 0.05). Angiotensin II (AII) inhibited the number of cells secreting renin in cortical cells prepared from enalapril-treated and control rats. In conclusion, angiotensin converting enzyme inhibition increased renin secretion predominantly by recruitment of additional renin-secreting cells and, to a lesser extent, by augmentation of the amount of renin released per cell. In contrast, sodium depletion increased renin secretion equally by both mechanisms. Newly recruited renin-secreting cells were not regulated by the extracellular calcium concentration or beta-adrenergic stimulation. Angiotensin II inhibited renin secretion directly by decreasing the number of individual cells releasing renin through a process which was independent of the extracellular calcium concentration.

Angiotensin is generated within the kidney, but the precise loci for the formation of angiotensin I (ANG I) and angiotensin II (ANG II) have not been demonstrated. We performed electron microscopy immunocytochemistry in kidney sections of 10-day-old (newborn) and adult Wistar-Kyoto (WKY) rats using specific antibodies to renin, ANG I, ANG II, and angiotensinogen (AO). Renin, ANG I, ANG II, and AO were present in juxtaglomerular (JG) cells. Renin was largely confined to cytoplasmic granules; ANG I and ANG II were colocalized to these granules but also were present in the cytoplasm; AO was distributed throughout the cytoplasm. AO also was present in a renal cortical distribution in proximal tubular cells. Northern blot analysis demonstrated AO mRNA in total kidney and liver but not in renal microvessels. Using the reverse hemolytic plaque assay, we demonstrated release of ANG I and renin from individual renocortical cells of adult WKY rats. Under control conditions, the number of releasing cells was 11 +/- 1 for ANG I and 10 +/- 1 for renin. Addition of rat renin inhibitor (RI) (1 x 10(-5) M), which inhibited renin activity in the medium from 37 to 9 pg ANG I.ml-1.h-1, did not alter ANG I plaque number. Addition of rat AO increased ANG I plaque number to 17 +/- 2 (P less than 0.05). Incubation with both RI and AO prevented the increase in ANG I plaque number obtained with AO alone. Enalapril treatment (7 days; n = 5) increased the number of plaque-forming cells to 22 +/- 2 for ANG I (P less than 0.0005) and to 39 +/- 7 for renin (P less than 0.001). The results suggest an intracellular location for AO and angiotensin and release of renin and ANG I by renal cortical cells and suggest that released angiotensin is produced intracellularly and that secretion of ANG I is augmented by converting enzyme inhibition.

Patients with functioning vein grafts may present with wound problems resulting in exposure of the graft. We reviewed the courses of 16 patients presenting with this problem to determine the causative factors and the most appropriate management of this therapeutic dilemma. Diabetes mellitus (11 of 16, 68.7%) and wound infection (12 of 16, 75%) were frequent pre-existing conditions associated with exposed venous grafts. All patients with exposed vein grafts were initially treated conservatively with regular application of moist sterile dressings, followed by split-thickness skin graft coverage of the wounds when clean. The wounds healed in 7 patients, whereas 9 patients developed complications of hemorrhage (7 patients) and graft thrombosis (2 patients). The outcome of therapy was highly dependent on the type of organism originally cultured from the wounds. The incidence of vein graft disruption was lowest when the wounds were sterile (25%) or when gram-positive bacteria grew (25%). Gram-negative infection uniformly resulted in disruption of the exposed venous graft. When a new graft was placed, the secondary graft became reinfected in all patients with gram-negative primary graft infection. There were no instances of secondary graft reinfection when gram-negative bacteria were not present. These data suggest that the outcome of patients presenting with exposed vein grafts is highly dependent on the bacterial flora of the process. Vein graft disruption is frequent in patients with gram-negative infection, suggesting that these patients should be treated with distant graft ligation and extra-anatomic bypass. By contrast, patients without gram-negative infection may be successfully managed with local wound care.

The 10-year experience of a single community was reviewed and a multivariate analysis was performed to determine the relative importance of clinical and environmental factors in mortality after ruptured abdominal aortic aneurysm resection. Ruptured aneurysms were repaired in 243 patients in six area hospitals (one university, five community) by 25 surgeons (16 vascular, 9 general). Overall, 30-day mortality was 55% (133/243). Although the mortality by hospital ranged from 44% to 68%, these differences were not statistically significant. However, significant variations occurred in the mortality rates of individual surgeons, ranging from 44% to 73%. The mortality rate for the vascular surgeons was less than that of the general surgeons, 51% versus 69% (p less than 0.05). Clinical factors were evaluated, and the most significant parameters were systolic blood pressure, presence of chronic obstructive lung disease, and history of chronic renal insufficiency. These results support the implication that the degree of specialization of the surgeon and the preexisting health of the patient are the most important determinants of survival after ruptured abdominal aortic aneurysm. The size and sophistication of the hospital appear to be less influential factors.

Successful application of the reverse hemolytic plaque assay was developed to identify individual renocortical cells that secrete renin directly. The plaque assay was validated by a number of established criteria. Using this technique, we demonstrate an increase in renin secretion with beta-adrenergic stimulation and an inhibition of renin secretion with extracellular calcium in groups of renin-secreting cells. Transmission electron microscopy of the cell in the center of a hemolytic plaque demonstrated a modified vascular smooth muscle cell with densely packed secretory granules. Electron microscopy immunocytochemistry demonstrated the presence of renin in the secretory granules, confirming the identity of the cell as a renal juxtaglomerular cell. The technology developed here has allowed the precise identification and study of the individual renin-secreting juxtaglomerular cell.

A canine model was developed to study the differential response of a gram-negative and a gram-positive bacterial infection on autogenous and prosthetic grafts. After replacing segments of the femoral arteries of 15 dogs with autogenous vein in one groin and polytetrafluoroethylene in the contralateral groin, 10(8) colony-forming units of nonmucin-producing Staphylococcus epidermidis (five dogs), Pseudomonas aeruginosa (five dogs), or sterile saline solution (five dogs) were directly inoculated onto the grafts. The grafts were examined 7 to 10 days after implantation. None of the control dogs exhibited inflammatory signs, and no grafts or anastomoses disrupted. S. epidermidis was unrecoverable from either graft material in any of the animals, although histologic evaluation confirmed neutrophils and bacteria in four of five animals in the vein and polytetrafluoroethylene groups. No dog inoculated with S. epidermidis had graft or anastomotic disruption. By contrast, P. aeruginosa was recovered from both types of grafts in all inoculated animals. Neutrophils, bacteria, and microabscesses were observed in all of these animals. In addition, three of five polytetrafluoroethylene grafts and all five vein grafts disrupted either at the anastomoses or in the body of the vein graft. Therefore S. epidermidis is a less virulent organism that may persist in graft walls despite negative cultures, whereas P. aeruginosa is a highly virulent organism that can disrupt native artery, vein grafts, and anastomoses. The graft material appears to be less important than the bacteria in determining the outcome of infection.