Exploring work-related stressors experienced by mental health nurses: A qualitative descriptive study.

INTRODUCTION: The challenging work environments mental health nurses (MHNs) encounter can negatively impact their mental health, psychological well-being and physical health. While these impacts have been investigated in quantitative research, little is known about work-related stress from the perspective of MHNs. AIM: To explore the stresses faced by nurses working in mental health settings and to gain an understanding of the underlying workplace context. METHOD: A descriptive qualitative study with data collected via semi-structured individual telephone interviews conducted with n = 21 Western Australian MHNs. Data were analysed using reflexive thematic analysis. RESULTS: A total of 85 codes were generated that led to the identification of 13 subthemes and 4 main themes: (1) mental health nursing context, (2) work environment stressors, (3) factors that alleviate stress and (4) the impact of workplace stress. DISCUSSION: Many of the stressors MHNs were exposed to are modifiable, such as understaffing and poor skill mix. Modifiable stressors increased risk for MHNs, impeded patient care and exacerbated inherent stressors such as patient acuity and complexity. IMPLICATIONS FOR PRACTICE: This study collected data that provide rich descriptions of the experiences of MHNs and identify modifiable work-related stressors that could be alleviated through effective leadership and management.

A method for determining optimal mean airway pressure in high-frequency oscillatory ventilation.

BACKGROUND: "Optimal" mean airway pressure (MAP) during high-frequency oscillatory ventilation (HFOV) can be defined as the pressure that allows for maximal alveolar recruitment while minimizing alveolar overdistension. Choosing a MAP near or just below the point of maximal curvature (PMC) of the volume-pressure characteristics of the lung can serve as a guide to avoid overdistention during HFOV, while simultaneously preventing derecruitment. The purpose of this study was to assess whether optimal MAP at the PMC can be determined by using measures of PaO(2) in patients with acute respiratory distress syndrome (ARDS) undergoing HFOV. METHODS: We prospectively studied seven patients with ARDS who underwent HFOV after failed conventional ventilation. In addition, 11 healthy subjects were studied to validate measurements of changes in end-expiratory lung volume (∆EELV) using magnetometers. Using this validated method, plots of ∆EELV and MAP were constructed during decremental changes in MAP following a recruitment maneuver in seven ventilated patients with ARDS. The PMC was defined as the point where the slope of the ∆EELV versus MAP curve acutely changed. The MAP at the PMC was compared to that determined from plots of PaO(2) versus MAP. RESULTS: In the healthy cohort, measurements of ∆EELV obtained by magnetometry approximated the line of identity when compared to those obtained by spirometry. The MAP determined using either the ∆EELV or PaO(2) techniques were identical in all seven HFOV ventilated patients. Additionally, there was a significant correlation between the MAP associated changes in PaO2 and the MAP associated changes in ∆EELV (p < 0.001). CONCLUSIONS: The finding that MAP at the PMC is the same whether determined by measures of ∆EELV or PaO(2) suggest that bedside measures PaO(2) may provide an acceptable surrogate for measures of EELV when determining "optimal" MAP during HFOV.

1H NMR spectroscopy of serum reveals unique metabolic fingerprints associated with subtypes of surgically induced osteoarthritis in sheep.

Osteoarthritis (OA) is a highly prevalent joint disease. Its slow progressive nature and the correlation between pathological changes and clinical symptoms mean that OA is often well advanced by the time of diagnosis. In the absence of any specific pharmacological treatments, there is a pressing need to develop robust biomarkers for OA. We have adopted a nuclear magnetic resonance (NMR)-based metabolomic strategy to identify molecular responses to surgically induced OA in an animal model. Sheep underwent one of three types of surgical procedure (sham (control), meniscal destabilization, MD or anterior cruciate ligament transaction, ACLT), and for every animal a serum sample was collected both pre- and postoperatively, thus, affording two types of "control" data for comparison. 1D 1H NMR spectra were acquired from each sample at 800 MHz and the digitized spectral data were analyzed using principal components analysis and partial least-squares regression discriminant analysis. Our approach, combined with the study design, allowed us to separate the metabolic responses to surgical intervention from those associated with OA. We were able to identify dimethyl sulfone (DMSO2) as being increased in MD after 4 weeks, while ACLT-induced OA exhibited increased 3-methylhistidine and decreased branched chain amino acids (BCAAs). The findings are discussed in the context of interpretation of metabolomic results in studies of human disease, and the selection of appropriate "control" data sets.

Perceived effects of attending physician workload in academic medical intensive care units: a national survey of training program directors.

BACKGROUND: Increases in the size and number of American intensive care units have not been accompanied by a comparable increase in the critical care physician workforce, raising concerns that intensivists are becoming overburdened by workload. This is especially concerning in academic intensive care units where attending physicians must couple teaching duties with patient care. METHODS: We performed an in-person and electronic survey of the membership of the Association of Pulmonary and Critical Care Medicine Program Directors, soliciting information about patient workload, other hospital and medical education duties, and perceptions of the workplace and teaching environment of their intensive care units. RESULTS: Eighty-four out of a total 121 possible responses were received from program directors or their delegates, resulting in a response rate of 69%. The average daily (SD) census (as perceived by the respondents) was 18.8 ± 8.9 patients, and average (SD) maximum service size recalled was 24.1 ± 9.9 patients. Twenty-seven percent reported no policy setting an upper limit for the daily census. Twenty-eight percent of respondents felt the average census was "too many" and 71% felt the maximum size was "too many." The median (interquartile range) patient-to-attending physician ratio was 13 (10-16). When categorized according to this median, respondents from intensive care units with high patient/physician ratios (n = 31) perceived significantly more time constraints, more stress, and difficulties with teaching trainees than respondents with low patient/physician ratios (n = 40). The total number of non-nursing healthcare workers per patient was similar in both groups, suggesting that having more nonattending physician staff does not alleviate perceptions of overwork and stress in the attending physician. CONCLUSIONS: Academic intensive care unit physicians that direct fellowship programs frequently perceived being overburdened in the intensive care unit. Understaffing intensive care units with attending physicians may have a negative impact on teaching, patient care, and workforce stability.

Vascular foramina of the metacarpophalangeal sesamoid bones of Greyhounds and their relationship to sesamoid disease.

OBJECTIVE: To apply a novel technique and use the number and size (diameter and mean area) of vascular foramina to estimate potential blood supply in the metacarpophalangeal bones of dogs. ANIMALS: 28 Greyhounds. PROCEDURES: The forelimb sesamoid bones of 23 dogs were obtained after dogs were euthanized. Bones were isolated and examined by scanning electron microscopy. The number, diameter, and area of vascular foramina were determined by image analysis. Arterial distribution was assessed by use of resin injection in the sesamoid bones of 5 additional dogs. RESULTS: Sesamoids 2 and 7 had significantly fewer foramina (mean +/- SE, 38.9+/-2.5) and lower total foramen area (0.55+/-0.04 mm(2)), compared with values for other sesamoids (70.4+/-3.3 foramina and 1.43+/-0.06 mm(2), respectively). Mean area and diameter of foramina of sesamoids 2 and 7 were also smaller in some regions. Comparison of the foramen distribution in dogs with sesamoid disease and clinically normal dogs revealed that for sesamoids 2 and 7, intact sesamoids from dogs with sesamoid disease had a significantly lower total foramen area (20 sesamoids from 9 dogs, 0.45+/-0.04 mm(2)), compared with sesamoids in clinically normal dogs (59 sesamoids from 14 dogs, 0.58+/-0.03 mm(2)). However, for sesamoids other than 2 and 7, dogs with sesamoid disease had a significantly greater foramen area. CONCLUSIONS AND CLINICAL RELEVANCE: The restriction of vascular foramina in sesamoids 2 and 7 appeared to mirror the disease distribution and disease risk for specific dogs.

Comparative Effectiveness of Ranolazine Versus Traditional Therapies in Chronic Stable Angina Pectoris and Concomitant Diabetes Mellitus and Impact on Health Care Resource Utilization and Cardiac Interventions.

Comparative studies evaluating traditional versus newer antianginal (AA) medications in chronic stable angina pectoris (CSA) on cardiovascular (CV) outcomes and utilization are limited, particularly in patients with diabetes mellitus (DM). Claims data (2008 to 2012) were analyzed using a commercial database. Patients with CSA receiving a ß blocker (BB), calcium channel blocker (CCB), long-acting nitrate (LAN), or ranolazine were identified and followed for 12 months after a change in AA therapy. Patients on traditional AA medications were required to have concurrent sublingual nitroglycerin. Therapy change was defined as adding or switching to another traditional AA medication or ranolazine to identify patients whose angina was inadequately controlled with previous therapy. Four groups were identified (BB, CCB, LAN, or ranolazine users) and matched on relevant characteristics. A DM subset was identified. Logistic regression compared revascularization at 30, 60, 90, 180, and 360 days. Negative binomial regression compared all-cause, CV-, and DM-related (in the DM cohort) health care utilization. A total of 8,008 patients were identified with 2,002 patients in each matched group. Majority were men (mean age 66 years). A subset of 3,724 patients with DM (BB, n = 933; CCB, n = 940; LAN, n = 937; and ranolazine, n = 914) resulted from this cohort. Compared to ranolazine in the overall cohort, traditional AA medication exhibited greater odds for revascularization and higher rates in all-cause outpatient, emergency room visits, inpatient length of stay, and CV-related emergency room visits. In the DM cohort, ranolazine demonstrated similar benefits over traditional AA medication. In conclusion, ranolazine use in patients with inadequately controlled chronic angina is associated with less revascularization and all-cause and CV-related health care utilization compared to traditional AA medication.

Hidden costs associated with venous thromboembolism: impact of lost productivity on employers and employees.

OBJECTIVE: To determine productivity loss and indirect costs with deep vein thrombosis (DVT) and pulmonary embolism (PE). METHODS: Medical and pharmacy claims with short-term disability (STD) and long-term disability (LTD) claims from 2007 to 2010 were analyzed from the Integrated Benefits Institute's Health and Productivity Benchmarking (IBI-HPB) database (STD and LTD claims) and IMS LifeLink™ data (medical and pharmacy claims), which were indirectly linked using a weighting approach matching from IBI-HPB patients' demographic distribution. RESULTS: A total of 5442 DVT and 6199 PE claims were identified. Employees with DVT lost 57 STD and 440 LTD days per disability incident. The average per claim productivity loss from STD and LTD was $7414 and $58181, respectively. Employees with PE lost 56 STD and 364 LTD days per disability incident. The average per claim productivity loss from STD and LTD was $7605 and $48,751, respectively. CONCLUSIONS: Deep vein thrombosis and PE impose substantial economic burdens.

The economic burden of acute coronary syndromes for employees and their dependents: medical and productivity costs.

OBJECTIVE: To determine the total burden of illness, including direct and indirect costs for employees and their dependents with acute coronary syndrome (ACS). METHODS: Medical and pharmacy claims along with short-term disability (STD) and long-term disability (LTD) claims from 2007 to 2010 were analyzed using two data sets: Integrated Benefits Institute's Health and Productivity Benchmarking Database (STD and LTD claims) and IMS LifeLink™ Health Plan Data (medical and pharmacy claims). RESULTS: Employees with ACS lost 60.2 ± 0.29 STD and 397.9 ± 8.09 LTD days per disability incident. For employers, the estimated average per claim productivity loss from STD and LTD was $7943 ± 39.7 and $52,473 ± 1114, respectively. Total annual ACS health care costs per employee were $8170 ± 106, with $7545 ± 104 for annual medical costs. Hospitalizations accounted for 75% of total annual ACS health care costs. CONCLUSIONS: ACS imposes a substantial economic burden on employees, employers, and society.

Hemodynamic monitoring in sepsis.

Arterial waveform analysis that does not require continuous calibration, impedance cardiography, electrical cardiometry, velocity-encoded phase contrast magnetic resonance imaging (MRI), pulsed dye densitometry, noninvasive pulse pressure analysis using tonometry, suprasternal Doppler, partial CO2 rebreathing techniques, and transcutaneous Doppler are just some of the other emerging technologies not described in this review that may be used routinely in the management of sepsis and septic shock in the very near future. These innovative approaches may further increase our ability to optimize patients' fluid status and hemodynamics. We also have ability to monitor the microcirculation. This increasingly sophisticated approach to the management of sepsis and septic shock will hopefully translate into better patient outcomes. However, optimal use of any hemodynamic monitoring requires an understanding of its physiologic underpinnings. Accurate interpretation of the hemodynamic information coupled with a protocolized management algorithm is the cornerstone of an effective resuscitation effort. Many forms of hemodynamic monitoring have emerged over the past 20 to 30 years with no convincing evidence for the superiority of any single techniques (Table 2). The goal of hemodynamic monitoring and optimization is to combat the systemic imbalance between tissue oxygen supply and demand ranging from global tissue hypoxia to overt shock and multiorgan failure. It remains unproven that hemodynamic monitoring of disease progression can effectively change patient outcome. However, despite our increased understanding of sepsis pathophysiology, mortality and morbidity from the disease remains high. Therefore, the search for the optimal parameters in resuscitation and the best way they can be monitored will continue.

Multimarker panels in sepsis.

Biomarkers differentiate between 2 or more biologic states. The complexity of diseases like sepsis makes it unlikely that any single marker will allow for precise disease specification. Combining several biomarkers into a single classification rule should help to improve their accuracy and, therefore, their usefulness. This article reviews several studies using multimarker panels, and highlights the potential of more sophisticated diagnostic and prognostic techniques in future multimarker panels. More complex algorithms should accelerate the adoption of multimarker panels into the routine management of patients with sepsis, provided that clinicians understand the multimarker approach.

Hemodynamic monitoring in sepsis.

Tissue hypoperfusion is an important factor in the development of multiple organ failure. Therefore, recognition of sepsis-induced tissue hypoperfusion and timely clinical intervention to prevent and correct this are fundamental aspects of managing patients with sepsis and septic shock. Hemodynamic monitoring plays a key role in the management of the critically ill and is used to identify hemodynamic instability and its cause and to monitor response to therapy. However, the utility of many forms of hemodynamic monitoring that are used in management of sepsis and septic shock remain controversial and unproven. This article examines emerging technologies as well as more established techniques used to monitor hemodynamics in sepsis and assesses their potential roles in optimization of sepsis-induced tissue hypoperfusion.

Changes in gait after bilateral meniscectomy in sheep: effect of two hyaluronan preparations.

BACKGROUND: This study examined the effect of bilateral meniscectomy on ground reaction forces (GRFs) in sheep, and the therapeutic effect of two hyaluronan (HA) preparations. METHODS: Eighteen sheep were subjected to bilateral lateral meniscectomy and were treated from 16 to 20 weeks postoperatively with intraarticular Hyalgan (Fidia Farmaceutici), HYADD4-G (a novel amide derivative; Fidia Farmaceutici), or saline placebo (n = 6 per group). GRFs were assessed at baseline and 6, 12, 16, 22, and 26 weeks postoperatively. Rheological parameters and HA content of synovial fluid samples were assessed using micro-Fourier rheometry. RESULTS: Meniscectomy significantly reduced GRF and abolished the normal two-peak vector. GRF deficits were partially ameliorated by both HA preparations: Hyalgan increased peak vertical forces at 6 weeks post-treatment (week 22), while HYADD4-G increased vertical impulse post-treatment. Both HA treatments, but not saline placebo, restored a twopeak composite force vector at 6 weeks post-treatment. Neither HA preparation significantly modulated osteoarthritis (OA) severity, or synovial fluid parameters. CONCLUSIONS: This study showed that GRF responses to bilateral meniscectomy in sheep mimic available data for human meniscectomy and OA patients. However, this time course suggests that gait deficits are temporally unrelated to observed cartilage or synovial fluid changes. The bilateral ovine meniscectomy model demonstrates modest but quantifiable changes in GRF that mimic human OA and are amenable to modification by known OA therapies such as HA.

Biodistribution and clearance of intra-articular liposomes in a large animal model using a radiographic marker.

The intra-articular (IA) route of administration in treating arthritis has potential for targeting drug delivery to affected tissues, thereby minimising the attendant side-effects of systemically administered drugs. The ultra-structure of the synovium however facilitates rapid drug efflux from the joint; effectively the IA route is equivalent to other non-IV parenteral routes with regards absorption and redistribution into the systemic circulation. The aim of this study was to extend the drug residence time within the knee joint by using a liposome formulation. DPPC-based liposomes were prepared with the radio contrast agent iohexol as a drug marker. 8 sheep had their right knees injected IA with iohexol liposomes and the contralateral joints with either free iohexol or empty liposomes. Joints were radiographed at multiple time points up to 16 days post-injection. Iohexol-mediated radiopacity was quantified by densitometer. Sheep were sacrificed at the end of the study for microscopy of synovial tissues. Good visualization of iohexol-mediated radiopacity with fine anatomical definition was possible throughout the experiment. Also evident on the films was extra-articular radiopacity with liposomes tracking along muscle facial planes. Cellular and tissue localization with light microscopy was possible through use of frozen sections and because of the large liposome size. Residence of encapsulated iohexol within the knee joint was greatly prolonged. Liposomal iohexol declined bi-exponentially with a terminal elimination half-life of 134 hours. In contrast, free iohexol was undetectable at 3 hours post-injection.

Proteoglycan 4 downregulation in a sheep meniscectomy model of early osteoarthritis.

Osteoarthritis is a disease of multifactorial aetiology characterised by progressive breakdown of articular cartilage. In the early stages of the disease, changes become apparent in the superficial zone of articular cartilage, including fibrillation and fissuring. Normally, a monolayer of lubricating molecules is adsorbed on the surface of cartilage and contributes to the minimal friction and wear properties of synovial joints. Proteoglycan 4 is the lubricating glycoprotein believed to be primarily responsible for this boundary lubrication. Here we have used an established ovine meniscectomy model of osteoarthritis, in which typical degenerative changes are observed in the operated knee joints at three months after surgery, to evaluate alterations in proteoglycan 4 expression and localisation in the early phases of the disease. In normal control joints, proteoglycan 4 was immunolocalised in the superficial zone of cartilage, particularly in those regions of the knee joint covered by a meniscus. After the onset of early osteoarthritis, we demonstrated a loss of cellular proteoglycan 4 immunostaining in degenerative articular cartilage, accompanied by a significant (p < 0.01) decrease in corresponding mRNA levels. Early loss of proteoglycan 4 from the cartilage surface in association with a decrease in its expression by superficial-zone chondrocytes might have a role in the pathogenesis of osteoarthritis.

Comparative spatial and temporal localisation of perlecan, aggrecan and type I, II and IV collagen in the ovine meniscus: an ageing study.

This is the first study to immunolocalise perlecan in meniscal tissues and to demonstrate how its localisation varied with ageing relative to aggrecan and type I, II and IV collagen. Perlecan was present in the middle and inner meniscal zones where it was expressed by cells of an oval or rounded morphology. Unlike the other components visualised in this study, perlecan was strongly cell associated and its levels fell significantly with age onset and cell number decline. The peripheral outer meniscal zones displayed very little perlecan staining other than in small blood vessels. Picrosirius red staining viewed under polarised light strongly delineated complex arrangements of slender discrete randomly oriented collagen fibre bundles as well as transverse, thick, strongly oriented, collagen tie bundles in the middle and outer meniscal zones. The collagen fibres demarcated areas of the meniscus which were rich in anionic toluidine blue positive proteoglycans; immunolocalisations confirmed the presence of aggrecan and perlecan. When meniscal sections were examined macroscopically, type II collagen localisation in the inner meniscal zone was readily evident in the 2- to 7-day-old specimens; this became more disperse in the older meniscal specimens. Type I collagen had a widespread distribution in all meniscal zones at all time points. Type IV collagen was strongly associated with blood vessels in the 2- to 7-day-old meniscal specimens but was virtually undetectable at the later time points (>7 month).

Perlecan displays variable spatial and temporal immunolocalisation patterns in the articular and growth plate cartilages of the ovine stifle joint.

Perlecan is a modular heparan sulphate and/or chondroitin sulphate substituted proteoglycan of basement membrane, vascular tissues and cartilage. Perlecan acts as a low affinity co-receptor for fibroblast growth factors 1, 2, 7, 9, binds connective tissue growth factor and co-ordinates chondrogenesis, endochondral ossification and vascular remodelling during skeletal development; however, relatively little is known of its distribution in these tissues during ageing and development. The aim of the present study was to immunolocalise perlecan in the articular and epiphyseal growth plate cartilages of stifle joints in 2-day to 8-year-old pedigree merino sheep. Perlecan was prominent pericellularly in the stifle joint cartilages at all age points and also present in the inter-territorial matrix of the newborn to 19-month-old cartilage specimens. Aggrecan was part pericellular, but predominantly an extracellular proteoglycan. Perlecan was a prominent component of the long bone growth plates and displayed a pericellular as well as a strong ECM distribution pattern; this may indicate a so far unrecognised role for perlecan in the mineralisation of hypertrophic cartilage. A significant age dependant decline in cell number and perlecan levels was evident in the hyaline and growth plate cartilages. The prominent pericellular distribution of perlecan observed indicates potential roles in cell-matrix communication in cartilage, consistent with growth factor signalling, cellular proliferation and tissue development.

Regional assessment of articular cartilage gene expression and small proteoglycan metabolism in an animal model of osteoarthritis.

Osteoarthritis (OA), the commonest form of arthritis and a major cause of morbidity, is characterized by progressive degeneration of the articular cartilage. Along with increased production and activation of degradative enzymes, altered synthesis of cartilage matrix molecules and growth factors by resident chondrocytes is believed to play a central role in this pathological process. We used an ovine meniscectomy model of OA to evaluate changes in chondrocyte expression of types I, II and III collagen; aggrecan; the small leucine-rich proteoglycans (SLRPs) biglycan, decorin, lumican and fibromodulin; transforming growth factor-beta; and connective tissue growth factor. Changes were evaluated separately in the medial and lateral tibial plateaux, and were confirmed for selected molecules using immunohistochemistry and Western blotting. Significant changes in mRNA levels were confined to the lateral compartment, where active cartilage degeneration was observed. In this region there was significant upregulation in expession of types I, II and III collagen, aggrecan, biglycan and lumican, concomitant with downregulation of decorin and connective tissue growth factor. The increases in type I and III collagen mRNA were accompanied by increased immunostaining for these proteins in cartilage. The upregulated lumican expression in degenerative cartilage was associated with increased lumican core protein deficient in keratan sulphate side-chains. Furthermore, there was evidence of significant fragmentation of SLRPs in both normal and arthritic tissue, with specific catabolites of biglycan and fibromodulin identified only in the cartilage from meniscectomized joints. This study highlights the focal nature of the degenerative changes that occur in OA cartilage and suggests that altered synthesis and proteolysis of SLRPs may play an important role in cartilage destruction in arthritis.

The nitric oxide donor glyceryl trinitrate increases subchondral bone sclerosis and cartilage degeneration following ovine meniscectomy.

AIM: To examine the effect of glyceryl trinitrate (GTN), a nitric oxide (NO) donor compound, on the concurrent progression of cartilage and subchondral bone changes in an ovine meniscectomy model of osteoarthritis (OA). METHODS: Bilateral lateral meniscectomy (MX) was performed on 12 ewes to induce OA. Six were treated with topical GTN (0.7mg/kg twice weekly) (MX+GTN). Six other sheep formed non-operated controls (NOC). After sacrifice at six months, the subchondral bone density (BMD) of the lateral and medial femoral condyles (LFC, MFC) and tibial plateau (LTP, MTP) was assessed by DEXA. Dynamic biomechanical testing was performed across the MTP and LTP. Histological sections from each region were scored qualitatively and the thickness of the subchondral bone plate (SCB) was determined by image analysis. RESULTS: MX+GTN displayed significantly greater SCB thickness relative to MX in the LFC (mean increase +88% and +42%, respectively) and the MFC. SCB BMD was 10-12% greater in MX+GTN relative to MX in the LFC, LTP and MTP. MX+GTN sheep also showed greater increases in some histopathology variables, greater central erosion of the LTP, and changes in dynamic stiffness (decreased) and phase lag (increased) in the outer zone of the LTP. CONCLUSIONS: Treatment with GTN significantly increased subchondral bone thickness and density during subchondral remodelling following meniscectomy. In addition, it slightly but significantly worsened degeneration of cartilage structure and function. These results suggest that clinical use of GTN may accelerate both cartilage degeneration and subchondral bone sclerosis if used in the presence of OA, and demonstrate that NO has the potential be an important mediator of the subchondral bone changes seen in OA.

Intact purine biosynthesis pathways are required for wild-type virulence of Brucella abortus 2308 in the BALB/c mouse model.

Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALB/c mouse model, while isogenic mutants with mini-Tn5 insertions in pheA, trpB, and dagA display little or no attenuation in cultured murine macrophages or mice. These experimental findings confirm the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages. In contrast to previous reports, however, these results indicate that exogenous tryptophan and phenylalanine are available for use by the brucellae in the phagosomal compartment.