Streamlining quantitative joint-wide medial femoro-tibial histopathological scoring of mouse post-traumatic knee osteoarthritis models.

OBJECTIVES: Histological scoring remains the gold-standard for quantifying post-traumatic osteoarthritis (ptOA) in animal models, allowing concurrent evaluation of numerous joint tissues. Available systems require scoring multiple sections/joint making analysis laborious and expensive. We investigated if a single section allowed equivalent quantitation of pathology in different joint tissues and disease stages, in three ptOA models. METHOD: Male 10-12-week-old C57BL/6 mice underwent surgical medial-meniscal-destabilization, anterior-cruciate-ligament (ACL) transection, non-invasive-ACL-rupture, or served as sham-surgical, non-invasive-ACL-strain, or naïve/non-operated controls. Mice (n = 12/group) were harvested 1-, 4-, 8-, and 16-week post-intervention. Serial sagittal toluidine-blue/fast-green stained sections of the medial-femoro-tibial joint (n = 7/joint, 84 µm apart) underwent blinded scoring of 40 histology-outcomes. We evaluated agreement between single-slide versus entire slide-set maximum or median scores (weighted-kappa), and sensitivity/specificity of single-slide versus median/maximum to detect OA pathology. RESULTS: A single optimal mid-sagittal section showed excellent agreement with median (weighted-kappa 0.960) and maximum (weighted-kappa 0.926) scores. Agreement for individual histology-outcomes was high with only 19/240 median and 15/240 maximum scores having a weighted-kappa ≤0.4, the majority of these (16/19 and 11/15) in control groups. Statistically-significant histology-outcome differences between ptOA models and their controls detected with the entire slide-set were reliably reproduced using a single slide (sensitivity >93.15%, specificity >93.10%). The majority of false-negatives with single-slide scoring were meniscal and subchondral bone histology-outcomes (89%) and occurred in weeks 1-4 post-injury (84%). CONCLUSION: A single mid-sagittal slide reduced the time needed to score diverse histopathological changes by 87% without compromising the sensitivity or specificity of the analysis, across a variety of ptOA models and time-points.

Cultural Competence Is Everyone's Business: Embedding Cultural Competence in Curriculum Frameworks to Advance Veterinary Education.

Cultural competence in professional and research practice is important to effectively deliver animal and One Health services and programs. Veterinarians work with culturally and linguistically diverse teams, clients, and communities. Cultural perspectives on the significance and perceptions of animals and differences in consultation and engagement protocols and strategies can influence client-practitioner and researcher-community relationships, impacting animal health, welfare, and/or research outcomes. Curricula have been proposed to build cultural capacity in graduates, but these have not been reported in veterinary programs, and early attempts to integrate cultural competency into the University of Sydney veterinary curriculum lacked a formal structure and were ad hoc with respect to implementation. To address this, the authors introduced a broad curriculum framework into the University of Sydney veterinary program, which defines cultural competence, perceptions of animals, effective communication, and community engagement in a range of contexts. Cultural competency learning outcomes were described for units of study. These were contextually relevant and aligned to course learning outcomes and University of Sydney graduate qualities. Constructive alignment was achieved by linking learning outcomes to teaching and learning activities and assessment. The continuum of cultural competency underpinned mapping of cultural competency across the curriculum with staged, vertical integration of key principles. Additionally, action to engage staff, students, and stakeholders in a cultural competence agenda assisted in sustaining curriculum change. The result was integration of cultural competency across the curriculum aligning with recommendations from accrediting bodies and with best practice models in medicine, nursing, and allied health programs.

Animal models of osteoarthritis : the benefits and costs of reducing variability.

Cite this article: Bone Joint Res 2022;11(8):514-517.

Employability as a Guiding Outcome in Veterinary Education: Findings of the VetSet2Go Project.

This paper presents a mini-review of employability as a guiding outcome in veterinary education-its conceptualisation, utility, core elements and dimensions, and pedagogical approaches-through a summary of the findings of a major international project with the same aims (the VetSet2Go project). Guided by a conception of the successful veterinary professional as one capable of navigating and sustainably balancing the (sometimes competing) needs and expectations of multiple stakeholders, the project integrated multiple sources of evidence to derive an employability framework representing the dimensions and capabilities most important to veterinary professional success. This framework provides a useful complement to those based in narrower views of competency and professionalism. One notable difference is its added emphasis on broad success outcomes of satisfaction and sustainability as well as task-oriented efficacy, thus inserting "the self" as a major stakeholder and bringing attention to resilience and sustainable well-being. The framework contains 18 key capabilities consistently identified as important to employability in the veterinary context, aligned to five broad, overlapping domains: veterinary capabilities (task-oriented work performance), effective relationships (approaches to others), professional commitment (approaches to work and the broader professional "mission"), psychological resources (approaches to self), plus a central process of reflective self-awareness and identity formation. A summary of evidence supporting these is presented, as well as recommendations for situating, developing, and accessing these as learning outcomes within veterinary curricula. Though developed within the specific context of veterinarian transition-to-practise, this framework would be readily adaptable to other professions, particularly in other health disciplines.

Resilience of veterinarians at different career stages: The role of self-efficacy, coping strategies and personal resources for resilience in veterinary practice.

BACKGROUND: The aim of this study was to determine the effect of demographic and psychological factors on resilience in new graduate-, mid- and late-career veterinarians working in Australia. METHOD: An online cross-sectional survey of 800 veterinarians collected demographic and descriptive data in two stages from late 2015 to 2017, such as gender, average hours worked per week, type and region of practice and intention to leave veterinary medicine. Psychological factors were measured utilising the Brief Resilience Scale, the Veterinary Resilience Scale-Personal Resources, the Brief COPE and General Self-Efficacy measures. RESULTS: Using a full-factorial univariate General Linear Model, no significant difference in general resilience was evident between the three career-stage groups (p > 0.05). However, higher self-efficacy, higher personal resources for resilience in veterinary practice, and lower problem-focused, higher emotion-focused and lower dysfunctional coping strategies were related to higher resilience. In the model for mid- and late-career veterinarians, a weak positive relationship existed between higher average hours worked per week and higher resilience, while intention to leave veterinary practice was also related to lower resilience in mid- and late-career veterinarians. CONCLUSION: This study supports the value of personal resources, rather than career stage, gender or region of work, as influential in developing veterinarian resilience.

Long-term Effect of a Single Subcritical Knee Injury: Increasing the Risk of Anterior Cruciate Ligament Rupture and Osteoarthritis.

BACKGROUND: Rupture of the anterior cruciate ligament (ACL) is a well-known risk factor for the development of posttraumatic osteoarthritis (PTOA), but patients with the "same injury" can have vastly different trajectories for the onset and progression of disease. Minor subcritical injuries preceding the critical injury event may drive this disparity through preexisting tissue pathologies and sensory changes. PURPOSE: To investigate the role of subcritical injury on ACL rupture risk and PTOA through the evaluation of pain behaviors, joint mechanics, and tissue structural change in a mouse model of knee injury. STUDY DESIGN: Controlled laboratory study. METHODS: Ten-week-old male C57BL/6J mice were allocated to naïve control and subcritical knee injury groups. Injury was induced by a single mechanical compression to the right hindlimb, and mice were evaluated using joint histopathology, anteroposterior joint biomechanics, pain behaviors (mechanical allodynia and hindlimb weightbearing), and isolated ACL tensile testing to failure at 1, 2, 4, or 8 weeks after injury. RESULTS: Subcritical knee injury produced focal osteochondral lesions in the patellofemoral and lateral tibiofemoral compartments with no resolution for the duration of the study (8 weeks). These lesions were characterized by focal loss of proteoglycan staining, cartilage structural change, chondrocyte pathology, microcracks, and osteocyte cell loss. Injury also resulted in the rapid onset of allodynia (at 1 week), which persisted over time and reduced ACL failure load (P = .006; mean ± SD, 7.91 ± 2.01 N vs 9.37 ± 1.01 N in naïve controls at 8 weeks after injury), accompanied by evidence of ACL remodeling at the femoral enthesis. CONCLUSION: The present study in mice establishes a direct effect of a single subcritical knee injury on the development of specific joint tissue pathologies (osteochondral lesions and progressive weakening of the ACL) and allodynic sensitization. These findings demonstrate a predisposition for secondary critical injuries (eg, ACL rupture) and an increased risk of PTOA onset and progression (structurally and symptomatically). CLINICAL RELEVANCE: Subcritical knee injuries are a common occurrence and, based on this study, can cause persistent sensory and structural change. These findings have important implications for the understanding of risk factors of ACL injury and subsequent PTOA, particularly with regard to prevention and management strategies following an often underreported event.

Exploring translational gaps between basic scientists, clinical researchers, clinicians, and consumers: Proceedings and recommendations arising from the 2020 mine the gap online workshop.

Objective: To provide a summary of the translational gaps in musculoskeletal research as identified in the Mine the Gap workshop and propose possible solutions. Methods: The Mine the Gap online workshop was hosted on October 14th and 15th, 2020. Five international panels, each comprised of a clinician, clinical researcher and basic scientist, presented gaps and proposed solutions for the themes of biomechanics, pain, biological measurements, phenotypes and imaging. This was followed by an interactive panel discussion with consumer insights. Results: A number of translational gaps and proposed solutions across each of the five themes were identified. A consumer panel provided constructive feedback highlighting the need for improved resources, communication and shared decision making, and treatment individualisation. Conclusion: This brief report provides a greater understanding of the diverse work and gaps relevant to fundamental/discovery scientists, clinical researchers and clinicians working across the musculoskeletal field. The numerous translational gaps highlight the need to improve communication and collaboration across the musculoskeletal field.

Corrigendum to "Exploring translational gaps between basic scientists, clinical researchers, clinicians, and consumers: Proceedings and recommendations arising from the 2020 mine the gap online workshop" [Osteoarthritis Cartilage Open 29 (2021) 100163].

[This corrects the article DOI: 10.1016/j.ocarto.2021.100163.].

Development and validation of a contextualised measure of resilience in veterinary practice: the Veterinary Resilience Scale-Personal Resources (VRS-PR).

BACKGROUND: This article reports on the development and validation of a contextualised measure of personal resources for resilience in veterinary practice. METHODS: Exploratory factor analysis and structural equation modelling were used to evaluate data from two surveys of veterinary practitioners. RESULTS: Exploratory factor analysis of the first survey (n=300) revealed six items comprising the Veterinary Resilience Scale-Personal Resources (VRS-PR). These items focused on flexibility, adaptability, optimism, building strengths, enjoying challenges, and maintaining motivation and enthusiasm at work. Structural equation modelling using the second survey (n=744) confirmed the factor structure of the VRS-PR and established convergent validity with an established measure of general resilience, the Brief Resilience Scale. Examination of the mean and standard deviation of the combined survey data enabled scores on the VRS-PR to be provisionally classified into 'low', 'moderate' and 'high' (reported by approximately 13%, 72% and 15% of respondents, respectively). Respondents also reported results spanning 'low', 'moderate' and 'high' classifications for the Brief Resilience Scale (approximately 34%, 57% and 9%, respectively). CONCLUSION: The VRS-PR may be used to evaluate the extent to which respondents draw upon the personal resources captured in the scale and identify areas for improvement.

The relationship between synovial inflammation, structural pathology, and pain in post-traumatic osteoarthritis: differential effect of stem cell and hyaluronan treatment.

BACKGROUND: Synovitis is implicated in the severity and progression of pain and structural pathology of osteoarthritis (OA). Increases in inflammatory or immune cell subpopulations including macrophages and lymphocytes have been reported in OA synovium, but how the particular subpopulations influence symptomatic or structural OA disease progression is unclear. Two therapies, hyaluronan (HA) and mesenchymal stem cells (MSCs), have demonstrated efficacy in some clinical settings: HA acting as device to improve joint function and provide pain relief, while MSCs may have immunomodulatory and disease-modifying effects. We used these agents to investigate whether changes in pain sensitization or structural damage were linked to modulation of the synovial inflammatory response in post-traumatic OA. METHODS: Skeletally mature C57BL6 male mice underwent medial-meniscal destabilisation (DMM) surgery followed by intra-articular injection of saline, a hyaluronan hexadecylamide derivative (Hymovis), bone marrow-derived stem cells (MSCs), or MSC + Hymovis. We quantified the progression of OA-related cartilage, subchondral bone and synovial histopathology, and associated pain sensitization (tactile allodynia). Synovial lymphocytes, monocyte/macrophages and their subpopulations were quantified by fluorescent-activated cell sorting (FACS), and the expression of key inflammatory mediators and catabolic enzyme genes quantified by real-time polymerase chain reaction (PCR). RESULTS: MSC but not Hymovis significantly reduced late-stage (12-week post-DMM) cartilage proteoglycan loss and structural damage. Allodynia was initially reduced by both treatments but significantly better at 8 and 12 weeks by Hymovis. Chondroprotection by MSCs was not associated with specific changes in synovial inflammatory cell populations but rather regulation of post-injury synovial Adamts4, Adamts5, Mmp3, and Mmp9 expression. Reduced acute post-injury allodynia with all treatments coincided with decreased synovial macrophage and T cell numbers, while longer-term effect on pain sensitization with Hymovis was associated with increased M2c macrophages. CONCLUSIONS: This therapeutic study in mice demonstrated a poor correlation between cartilage, bone or synovium (histo)pathology, and pain sensitization. Changes in the specific synovial inflammatory cell subpopulations may be associated with chronic OA pain sensitization, and a novel target for symptomatic treatment.

Challenging identity: development of a measure of veterinary career motivations.

BACKGROUND: While little is known about the motivations underpinning veterinary work, previous literature has suggested that the main influences on veterinary career choice are early/formative exposure to animals or veterinary role models. The aim of this study was to develop and provisionally validate a veterinary career motivations questionnaire to assess the strength of various types of career motivations in graduating and experienced veterinarians. METHODS: A cross-sectional sample of experienced veterinarians (n=305) and a smaller cohort of newly graduated veterinarians (n=53) were surveyed online using a long-form questionnaire. Exploratory factor analysis (EFA) was used to iteratively derive a final, short-form questionnaire for survey of a second cross-sectional sample of experienced veterinarians (n=751). RESULTS: EFA derived a final questionnaire with 22 items loading onto six factors (social purpose, animal orientation, vocational identity, challenge and learning, career affordances, and people orientation). While motivations based on animal orientation were predictably strong, those based on vocational identity were not universal and were weaker in younger and graduate veterinarians; both of these motivations were rated lower by male veterinarians. Motivations based on challenge and learning emerged as some of the strongest, most universal and most influential; people orientation and social purpose were also important, particularly for older veterinarians. CONCLUSION: The major motivations for pursuing a veterinary career may best be represented as an intrinsic passion for animal care and for learning through solving varied challenges. These motivations are largely intrinsically oriented and autonomously regulated, thus likely to be supportive of work satisfaction and wellbeing.

An Exploration of the Career Motivations Stated by Early-Career Veterinarians in Australia.

Despite the critical influence of motivation on education and work outcomes, little is known about the motivations driving people to become and remain veterinarians. This qualitative study explored the career motivations stated by Australian veterinary graduates (n = 43) using a free-response Ten Statements Test (TST) at graduation, with follow-up interviews 6-8 months later (n = 10). TST responses were coded using an alternate inductive-deductive approach that tested their fit against existing theories of motivation. Results showed that the stated motivations were predominantly oriented to perceived value, rather than self-beliefs such as expectancy of success. About a quarter of the statements were animal-related, principally themed around intrinsic animal orientation (e.g., I like animals) or extrinsic animal-related purpose (e.g., I want to help animals). However, many non-animal themes also emerged, including both intrinsic (e.g., love of learning, challenge/problem solving, variety, social relatedness) and extrinsic (e.g., helping people, social contribution, career opportunity) motivations. Interview data revealed a motivational narrative of early formative influences, with some interviewees describing a later transition toward more people- or goal-oriented motivations. This exploratory study, outlining a broad taxonomy of veterinary career motivations and their alignment to self-determination theory in particular, may provide a useful framework for exploring career motivations in veterinary education.

One health in our backyard: Design and evaluation of an experiential learning experience for veterinary medical students.

BACKGROUND: New educational approaches are needed to improve student understanding of the wider sociological and ecological determinants of health as well as professional responsibilities in related areas. Field trips allow students to observe interaction between plant, animal and human communities, making them an ideal tool for teaching One Health concepts. METHODS: Veterinary medical students participated in a field trip to a local parklands area, frequented by humans, dogs, horses, and wildlife. Students rotated through 5 learning activities ('stations') that focused on: (1) response to exotic animal disease incursion (equine influenza); (2) impact of cultures and belief systems on professional practice; (3) management of dangerous dogs; (4) land use change, biodiversity and emerging infectious disease; and (5) management of environmentally-acquired zoonoses (botulism). Intended learning outcomes were for students to: evaluate the various roles and responsibilities of veterinarians in society; compare the benefits and risks associated with human-animal and animal-animal interactions; and evaluate the contributions made by various professionals in safeguarding the health and welfare of animals, humans and the environment. Following the field trip, students participated in a debrief exercise and completed an online survey on their experiences. RESULTS: Feedback from students collected in 2016/2017 (n = 211) was overwhelmingly positive. The learning experience at each station was rated as 4 ('Good') or 5 ('Very Good') out of 5 by 82-96% of students. Responses to closed- and open-ended questions - as well as outputs generated in the debrief session - indicated that students achieved the learning outcomes. Overall, 94% of students agreed or strongly agreed that they had a better understanding of One Health because of the field trip. CONCLUSIONS: Field trips to local parklands are effective in promoting learning about One Health and can be incorporated into the core curriculum to maximize student exposure at relatively low cost.

Resilience in Veterinary Students and the Predictive Role of Mindfulness and Self-Compassion.

Resilience is a dynamic and multifaceted process in which individuals draw on personal and contextual resources. In difficult situations, resilient people use specific strategies to learn from the situation without being overcome by it. As stressors are inherent to veterinary work, including long work hours, ethical dilemmas, and challenging interactions with clients, resilience is an important component of professional quality of life. However, while resilience in other health professionals has received attention, it has received little in the veterinary field. In this cross-sectional study, veterinary students from six veterinary schools in Australia completed an online survey, with 193 responses (23%). Very few veterinary students (6%) reached the threshold to be considered highly resilient using the Brief Resilience Scale, and approximately one third classified as having low levels of resilience. In the final linear multiple regression model, predictors of resilience included nonjudgmental and nonreactive mindfulness (Five Facet Mindfulness Questionnaire) and self-compassion (Neff Self-Compassion Scale). Students with higher nonjudgmental and nonreactive mindfulness and self-compassion had higher resilience scores. These findings indicate that fostering these qualities of mindfulness and self-compassion may be aligned with strengthening veterinary student resilience. Importantly, if the factors that help veterinary students develop a capacity for resilience can be identified, intervention programs can be targeted to educate future veterinary professionals with a high quality of life, both professional and personal.

An evaluation of fresh gas flow rates for spontaneously breathing cats and small dogs on the Humphrey ADE semi-closed breathing system.

OBJECTIVE: To evaluate the fresh gas flow (FGF) rate requirements for the Humphrey ADE semi-closed breathing system in the Mapleson A mode; to determine the FGF at which rebreathing occurs, and compare the efficiency of this system to the Bain (Mapleson D) system in spontaneously breathing cats and small dogs. STUDY DESIGN: Prospective clinical study. ANIMALS: Twenty-five healthy (ASA score I or II) client-owned cats and dogs (mean ± SD age 4.7 ± 5.0 years, and body weight 5.64 ± 3.26 kg) undergoing elective surgery or minor procedures. METHODS: Anaesthesia was maintained with isoflurane delivered via the Humphrey ADE system in the A mode using an oxygen FGF of 100 mL kg(-1) minute(-1). The FGF was then reduced incrementally by 5-10 mL kg(-1) minute(-1) at approximately five-minute intervals, until rebreathing (inspired CO(2) >5 mmHg (0.7 kPa)) was observed, after which flow rates were increased. In six animals, once the minimum FGF at which rebreathing occurred was found, the breathing system was changed to the Bain, and the effects of this FGF delivery examined, before FGF was increased. RESULTS: Rebreathing did not occur at the FGF recommended by the manufacturer for the ADE. The mean ± SD FGF that resulted in rebreathing was 60 ± 20 mL kg(-1) minute(-1). The mean minimum FGF at which rebreathing did not occur with the ADE was 87 ± 39 mL kg(-1) minute(-1). This FGF resulted in significant rebreathing (inspired CO(2) 8.8 ± 2.6 mmHg (1.2 ± 0.3 kPa)) on the Bain system. CONCLUSIONS: The FGF rates recommended for the Humphrey ADE are adequate to prevent rebreathing in spontaneously breathing cats and dogs <15 kg. CLINICAL RELEVANCE: The Humphrey ADE system used in the A mode is a more efficient alternative to the Bain system, for maintenance of gaseous anaesthesia in spontaneously breathing cats and small dogs.

Depletion of protease-activated receptor 2 but not protease-activated receptor 1 may confer protection against osteoarthritis in mice through extracartilaginous mechanisms.

OBJECTIVE: To explore the involvement of protease-activated receptor 1 (PAR-1) and PAR-2 in the pathologic processes of osteoarthritis (OA) and to identify the cells/tissues primarily affected by ablation of PAR-1 or PAR-2 in mice. METHODS: OA was induced in the joints of wild-type (WT), PAR-1(+/+) , PAR-1(-/-) , and PAR-2(-/-) mice by destabilization of the medial meniscus (DMM), and scores of histologic features (cartilage aggrecan loss and erosion, subchondral bone sclerosis, osteophytes, and synovitis) were compared at 1, 4, and 8 weeks post-DMM. The effects of PAR ablation on cartilage degradation and chondrocyte metalloproteinase expression/activity were studied in cultures of mouse femoral head tissue with or without interleukin-1α (IL-1α). At 1 week post-DMM, synovial expression of cytokines and metalloproteinase genes was measured by reverse transcription-polymerase chain reaction, and populations of inflammatory cells were quantified by flow cytometry. RESULTS: Deletion of PAR-2, but not that of PAR-1, in mice significantly delayed the progression of cartilage damage and inhibited subchondral bone sclerosis following DMM. There was no inhibitory effect of PAR-1 or PAR-2 ablation on IL-1α-induced cartilage degradation or chondrocyte metalloproteinase expression/activation. A low but significant level of synovitis persisted in mice subjected to DMM compared to that in control mice subjected to sham surgery, but no differences between the genotypes were seen 4 or 8 weeks post-DMM. One week after DMM, increased synovial expression of proinflammatory cytokines and metalloproteinase genes, along with increased levels of CD4+ T cells, inflammatory monocytes, and activated macrophages, were seen in all genotypes. However, there was a significant reduction in the percentage of activated macrophages in PAR-2(-/-) mice compared to PAR-1(-/-) and WT mice. CONCLUSION: Deletion of PAR-2, but not that of PAR-1, results in a significant decrease in DMM-induced cartilage damage. The chondroprotection in PAR-2(-/-) mice appears to occur indirectly through modulation of extracartilaginous events such as subchondral bone remodeling and synovial macrophage activation, rather than through alteration of chondrocyte catabolic responses.

Bradyarrhythmia in an anaesthetised, elderly, hypertensive cat.

A 14-year-old neutered male domestic shorthaired cat was presented to the University Veterinary Centre Sydney for evaluation and treatment of dental disease. This cat developed an unusual bradyarrhythmia under anaesthesia. The possible causes and treatment of the dysrythmia are discussed.

Pleural fluid IL-8 as an inflammatory mediator for discriminating transudates and exudates.

The differential diagnosis of pleural effusion is a frequent clinical problem. The possible role of pleural fluid cytokines in discriminating transudates from exudates has not been studied adequately. The aim of this study was to evaluate serum and pleural fluid levels of interleukin-8 (IL-8) and compare it with common biochemical parameters such as total protein lactate dehydrogenase (LDH). Forty patients with pleural effusion were studied. IL-8 was measured simultaneously in serum and pleural fluid using a commercially available ELISA kit. Standard laboratory methods were employed for biochemical parameters. Serum IL-8 levels were higher in the exudative group (8.1 +/- 0.2), but without statistical difference, when compared with transudate patients (6.8 +/- 0.1) (p > 0.05). Pleural IL-8 levels were significantly increased in exudate effusion when compared with transudate (26.6 +/- 3.7, 7.1 +/- 0.04 respectively, p < 0.001). In addition, a significant difference was found between pleural IL-8 in the malignant group (28.2 +/- 4.4) in comparison with the tuberculous group (21.1 +/- 2.9) (p < 0.01). Using ROC analysis, a pleural IL-8 cut off level of 19.7 pg/ml was found the best discriminating ratio in distinguishing exudates from transudates, with sensitivity of 100%, low specificity (from 50 to 66.7%) and good PPV (from 94.4 to 94.7%). Regarding pleural protein, the best discriminating value was 3 g/dl, while that for LDH was 200 IU/L. It is concluded that IL-8 could be considered as a sensitive, but not specific marker in differentiating pleural effusion into exudate and transudate, specially when used together with other criteria such as protein and LDH levels.

Role of CCL3 protein (monocyte inflammatory protein-1 alpha) in lymphoid malignancy.

Monocyte inflammatory protein-1 alpha (MIP-1alpha) has been shown to be active as an inhibitor of primitive hematopoietic cell proliferation in vitro and in vivo. A dysfunction in this inhibitory process has been postulated to contribute to leukemogenesis. The aim of this study was to clarify the role of monocyte inflammatory protein-1 alpha (MIP-1alpha) in the pathogenesis of lymphoid malignancy. The study comprised 54 patients and 15 healthy controls. Patients were divided into 3 groups (25 with lymphoma, 12 with multiple myeloma and 17 with chronic lymphocytic leukemia). Serum MIP-1alpha level was estimated by Enzyme-Linked Immunosorbent Assay (ELISA). Sixteen patients were followed up to examine the relationship between serum MIP-1alpha level and response to treatment and survival of patients. The serum level (pg/ml) of MIP-1alpha was significantly higher in patients with lymphoid malignancy compared to controls (97.9 +/- 171.1 versus 2.5 +/- 2.2, p < 0.05). Comparing with controls, the correlation was statistically significant in patients with multiple myeloma and chronic lymphocytic leukemia (192.3 +/- 156.6, P < 0.001; 78.7 +/- 115.9, p < 0.05 respectively) but not in lymphoma patients (65.9 +/- 196.5, p > 0.05). There was a significant correlation between MIP-1alpha serum level and the overall survival of patients. Patients with higher MIP-1alpha level showed an increased percentage of death and relapse than patients with normal MIP-1alpha (72.72% versus 21.87%, p < 0.05). In conclusion, MIP-1alpha serum level could be a valuable prognostic parameter and may provide insight into creating a new therapeutic modality.