Investigation into clinicopathological and pathological findings, prognosis, and aetiology of lorikeet paralysis syndrome in rainbow lorikeets (Trichoglossus haematodus).

OBJECTIVE: To report the temporal and spatial distribution of rainbow lorikeets presenting with lorikeet paralysis syndrome (LPS) and their clinicopathologic and pathologic findings, exposure to toxins, and response to treatment. METHODS: Records of lorikeets admitted in 2017 and 2018 to facilities in south-east Queensland (QLD) were reviewed and LPS and non-LPS cases were mapped and their distribution compared. Plasma biochemistries and complete blood counts were done on 20 representative lorikeets from south-east QLD and Grafton, New South Wales (NSW). Tissues from 28 lorikeets were examined histologically. Samples were tested for pesticides (n = 19), toxic elements (n = 23), botulism (n = 15) and alcohol (n = 5). RESULTS: LPS occurred in warmer months. Affected lorikeets were found across south-east QLD. Hotspots were identified in Brisbane and the Sunshine Coast. Lorikeets had a heterophilic leucocytosis, elevated muscle enzymes, uric acid and sodium and chloride. Specific lesions were not found. Exposure to cadmium was common in LPS and non-LPS lorikeets. Treated lorikeets had a 60-93% See Table 2 depending on severity of signs. CLINICAL SIGNIFICANCE: The primary differential diagnosis for lorikeets presenting with lower motor neuron signs during spring, summer and autumn in northern NSW and south-east Queensland should be LPS. With supportive care, prognosis is fair to good.

Immune regulation by platelet-activating factor: II. Mediation of suppression by cytokine-stimulated endothelial cells in vitro.

Human umbilical vein endothelial cells (EC) can respond to endotoxin or to the inflammatory cytokines tumor necrosis factor (TNF) and interleukin 1 (IL-1) by producing platelet-activating factor (PAF). When EC were preexposed to TNF-alpha (25 U/ml) for 1 h, and then washed, their subsequent coculture with peripheral blood mononuclear cells (PBMC) resulted in suppressed proliferative response of the latter to the mitogen Con A (P less than 0.05). This effect was completely reversed by the concomitant use of the PAF receptor antagonist BN 52021 (0.1 mM). Preexposure of EC to IL-1 beta (0.5 U/ml) induced similar effects, but IL-1 and TNF were not additive. Removal of monocytes from the PBMC population abolished the effects. On the other hand, coculture of monocytes with cytokine-preexposed EC resulted in significant induction of suppressor activity on lymphocyte proliferation. Our data indicate that EC, preexposed to inflammatory cytokines, can modulate lymphocyte functions via the production of PAF and its action on monocytes.

Platelet-activating factor stimulates interleukin-6 production by human endothelial cells and synergizes with tumor necrosis factor for enhanced production of granulocyte-macrophage colony stimulating factor.

The interaction between human endothelial cells (EC) and leukocytes during inflammation is in part mediated through the release of soluble factors. Since platelet-activating factor (PAF) is a potent mediator of inflammatory responses, we investigated the potential of PAF to modulate IL-6 and GM-CSF production by EC. Exposure of these cells to PAF resulted in a concentration-dependent increase in IL-6 production, with a maximum at 10(-10) M PAF. Sequential incubation of EC with PAF and TNF alpha resulted in a synergistic increase of IL-6 production. This effect was specific for PAF since it was prevented by preincubation with the PAF receptor antagonist, WEB 2086. Northern blot analysis revealed enhanced IL-6 mRNA expression in PAF-treated EC. However, the synergy observed in protein synthesis between PAF and TNF alpha was not reflected in IL-6 mRNA accumulation, suggesting a post-translational modulation. Pretreatment of EC with the protein synthesis inhibitor cycloheximide before their exposure to PAF resulted, after washout of the cycloheximide, in a markedly augmented production of IL-6, suggesting a synergy between augmented IL-6 mRNA accumulation by PAF and IL-6 mRNA superinduction by cycloheximide. GM-CSF production by EC was also stimulated by the combined effects of PAF and TNF alpha, but PAF alone did not affect GM-CSF production. Taken together, our data suggest that PAF can stimulate EC to synthesize cytokines, including IL-6 and GM-CSF, which may contribute to local and, possibly, systemic responses during inflammation.

Patient education for fatigue.

Although fatigue is a frequent complaint of patients undergoing cancer treatment, specific self-care activities are seldom addressed in patient education materials. To fill this void, a patient education tool was developed, with a special emphasis on the management of fatigue. Testing is under way with a large population of patients with cancer.

Cancer-related fatigue: clinical practice issues.

The purpose of this paper is to review current nursing literature and practice in cancer-related fatigue and to provide a suggested plan of treatment. Cancer-related fatigue is one of the most common and challenging symptom-management problems. The successful treatment of fatigue depends on the clinician's understanding of the symptom's continuum within the cancer experience, its etiologies, assessment strategies, and research-based interventions. Clinical outcomes are measured by the patient's ability to balance energy expenditure and restoration. By applying this knowledge to clinical practice, oncology nurses can have a profound impact on the patient's quality of life.

Patent Angiostrongylus mackerrasae infection in a black flying fox (Pteropus alecto).

BACKGROUND: A wild adult male black flying fox (Pteropus alecto) was presented unable to fly or hang strongly. RESULTS: Necropsy and histological examination revealed a severe pneumonia, with numerous Angiostrongylus mackerrasae in the pulmonary artery. The pulmonary parenchyma contained numerous eggs and rare larvae. CONCLUSION: This is the first report of patent Angiostrongylus infection in an accidental (i.e. non-Rattus) host species. It is also the first report of A. mackerrasae infection in an accidental host (including flying foxes). Worms recovered from cases of suspected angiostrongyliasis should be examined in morphological detail to ensure correct identification.

Interleukin-1 beta suppresses apoptosis in CD34 positive bone marrow cells through activation of the type I IL-1 receptor.

Interleukin-1 is a pleiotropic cytokine that has been shown previously to suppress active cell death in T cells. Two cell surface receptors for interleukin-1 have been identified and their genes cloned, type I (IL-RI) and type II (IL-RII) receptors. In the present study, we provide evidence for a role of interleukin-1 beta in the short-term suppression of cell death both in purified CD34+/Lin- bone marrow precursors and in the GM-CSF dependent cell line TF-1. Several lines of evidence suggest that the biologic effects of IL-1 beta are mediated by activation of type I IL-1 receptors (IL-1RI) and induction of GM-CSF production. First, neutralizing antibodies to IL-1RI but not IL-1RII drastically abrogated cell survival induced by IL-1 beta in CD34+/Lin- cells and TF-1 cells. Second, neutralizing antibodies against GM-CSF abrogate cell survival supported by IL-1 both in CD34+/Lin- bone marrow cells and in the cell line TF-1. Furthermore, exposure of TF-1 cells to IL-1 beta results in a transient accumulation of GM-CSF mRNA, with a peak at 3 h, which was dramatically decreased by neutralizing anti-IL-1R1 antibodies. In contrast, neutralizing anti-IL-1RII did not change the IL-1 induced cell survival of bone marrow cells and was followed by a paradoxical increase in viable cell numbers, in c-myc and c-myb mRNA accumulation in IL-1 treated TF-1 cells. Together our results indicate that the increase in cell survival induced IL-1 beta occurs through binding to IL-1RI and the subsequent production of endogenous GM-CSF. IL-1RII does not appear to be involved in signal transduction in primary CD34+/Lin- cells but could negatively regulate the response to IL-1 beta in TF-1 cells.

Adhesion-independent synergy of monocytes and endothelial cells in cytokine production: regulation of IL-6 and GM-CSF production by PAF.

Co-Cultures of monocytes (MO) and endothelial cells (EC) were studied for their capacity to synergize in the production of interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), two cytokines potentially important in vascular physiopathology. Resting monocytes produced detectable amounts of IL-6 but no GM-CSF, whereas confluent EC produced significant quantities of GM-CSF, but minimal IL-6. In co-cultures without stimuli, additive synthesis of both cytokines was observed. When EC were pretreated, however, with either PAF, TNF or both stimuli, before addition of MO, synergistic production of IL-6 was observed. In contrast, GM-CSF production was not enhanced by coculture of monocytes with activated EC. When either cell population was fixed with paraformaldehyde or killed by freeze-thawing before addition to the co-culture, cytokine levels reverted to those produced by the unaffected population alone. On the other hand, separating the two cell populations by a cell-impermeable membrane in transwell cultures did not affect the synergistic production of the cytokines. Taken together, our data suggest that EC and MO can synergize in response to stimuli by producing IL-6 and that this synergy is dependent on the integrity of both cell populations, but independent of cell-cell contact.

Differential regulation of cytokine and cytokine receptor genes by PAF, LTB4 and PGE2.

Immune and inflammatory responses involve a whole array of cells and cell products which interact and mutually regulate each other. Many of these interactions are mediated by cytokines acting through specific receptors. Furthermore, lipid mediators such as PAF and the arachidonic acid metabolites LTB4 and PGE2 are known to affect several of the mechanisms involved in the regulation of the immune and inflammatory responses. In this paper, we review recent data from our laboratory illustrating the differential regulation of IL-6 and TNF alpha production and IL-2 receptor alpha and beta expression by these lipid mediators. We show that the regulation of these genes is both transcriptional and post-transcriptional, and that LT and PG can also be involved as second messengers in these regulatory processes.