Evaluation of a single subcutaneous infusion of carboplatin as adjuvant chemotherapy for dogs with osteosarcoma: 17 cases (2006-2010)

Objective-To evaluate adverse effects and survival times in dogs with osteosarcoma that received a single SC infusion of carboplatin as adjunctive chemotherapeutic treatment following limb amputation or limb-sparing surgery. Design-Retrospective case series. Animals-17 client-owned dogs with spontaneously occurring osteosarcoma. Procedures-Medical records of dogs that underwent limb amputation or limb-sparing surgery followed by a single continuous SC infusion of carboplatin (total dose, 300 mg/m(2) infused over 3, 5, or 7 days) were evaluated. Signalment, tumor location, type of surgery (amputation or limb-sparing), duration of carboplatin infusion, results of hematologic and serum biochemical analyses, and adverse effects were recorded. Kaplan-Meier survival analysis was performed. Results-Median survival time for all dogs was 365 days. Nine dogs had adverse bone marrow-related (hematologic) effects, 1 had adverse gastrointestinal effects, and 7 had infections at the surgical site. No significant differences were detected in survival times of dogs grouped according to tumor location, type of surgery, duration of carboplatin infusion, or development of postoperative infection. Conclusions and Clinical Relevance-Median survival time and adverse effects in dogs with osteosarcoma that received a single SC infusion of carboplatin over a 3-, 5-, or 7-day period as adjunctive treatment following limb amputation or limb-sparing surgery were comparable to those of previously reported chemotherapy protocols requiring IV drug administration over several weeks. Further investigation is needed to evaluate the efficacy of this protocol as adjunctive treatment for osteosarcoma and other tumors in dogs.     

Fertilizer ammonium : nitrate ratios determine phosphorus uptake by young maize plants

We investigated the interacting effects of inorganic nitrogen and the main inorganic phosphorus form in dairy manure (dicalcium phosphate, CaHPO₄) on growth, nutrient uptake, and rhizosphere pH of young maize plants. In a pot experiment, three levels of CaHPO₄ (0, 167, and 500 mg P pot^?1) were combined with nitrogen (637 mg N pot^?1) applied at five NH₄‐N : NO₃‐N ratios (0 : 100, 25 : 75, 50 : 50, 75 : 25, and 100 : 0) and a nitrification inhibitor in a concentrated layer of a typical acid sandy soil from Denmark. ¹⁵N‐labeled NH₄‐N was applied to differentiate the role of nitrification and to partition nitrogen uptake derived from NH₄‐N. Among treatments including nitrogen, shoot biomass, rooting and phosphorus uptake were significantly higher at the five‐leaf stage when CaHPO₄ was applied with NH₄‐N : NO₃‐N ratios of 50 : 50 and 75 : 25. In these treatments, rhizosphere pH dropped significantly in direct proportion with NH₄‐N uptake. The fertilizers in the concentrated layer had a root‐inhibiting effect in treatments without phosphorus supply and in treatments with pure NO₃‐N or NH₄‐N supply. Increased nitrogen uptake as NH₄‐N instead of NO₃‐N reduced rhizosphere pH and enhanced acquisition of applied CaHPO₄ by young maize plants, which may have positive implications for the enhanced utilization of manure phosphorus.     

Metastatic immune infiltrates correlate with those of the primary tumour in canine osteosarcoma

Our lack of understanding of the immune microenvironment in canine osteosarcoma (cOSA) has limited the identification of potential immunotherapeutic targets. In particular, our ability to utilize readily available tissue from a dog's primary tumour to predict the type and extent of immune response in their pulmonary metastatic lesions is unknown. We, therefore, collected 21 matched pairs of primary tumours and pulmonary metastatic lesions from dogs with OSA and performed immunohistochemistry to quantify T‐lymphocyte (CD3), FOXP3+ cell, B‐lymphocyte (Pax‐5), and CD204+ macrophage infiltration. We found that T‐lymphocytes and FOXP3+ infiltrates in primary tumours positively correlated with that of metastatic lesions (ρ = 0.512, P = 0.038 and ρ = 0.698, P = 0.007, respectively), while a strong trend existed for CD204+ infiltrates (ρ = 0.404, P = 0.087). We also observed T‐ and B‐lymphocytes, and CD204+ macrophages to be significantly higher in a dog's pulmonary metastasis compared to their primary tumour (P = 0.018, P = 0.018, P = 0.016, respectively), while FOXP3+ cells were only significantly higher in metastases when all primary tumour and metastasis lesions were compared without pairing (P = 0.036). Together, these findings suggest that the metastatic immune microenvironment may be influenced by that of the primary cOSA, and that primary tumour immune biomarkers could potentially be applied to predict immunotherapeutic responses in gross metastatic disease. We, therefore, provide a rationale for the treatment of cOSA pulmonary metastases with immunotherapeutics that enhance the anti‐tumour activity of these immune cells, particularly in dogs with moderate to high immune cell infiltration in their primary tumours.     

Association of macrophage and lymphocyte infiltration with outcome in canine osteosarcoma

Immunotherapeutic strategies have shown promise for the treatment of canine osteosarcoma (cOSA). Very little is known about the immune microenvironment within cOSA, however, limiting our ability to identify potential immune targets and biomarkers of therapeutic response. We therefore prospectively assessed the disease‐free interval (DFI) and overall survival time (ST) of 30 dogs with cOSA treated with amputation and six doses of adjuvant carboplatin. We then quantified lymphocytic (CD3+, FOXP3+) and macrophage (CD204+) infiltrates within the primary tumours of this cohort using immunohistochemistry, and evaluated their association with outcome. Overall, the median DFI and ST were 392 and 455 days, respectively. The median number of CD3+ and FOXP3+ infiltrates were 45.8 cells/mm² (4.6‐607.6 cells/mm²) and 8.5 mm² (0‐163.1 cells/mm²), respectively. The median area of CD204+ macrophages was 4.7% (1.3%‐23.3%), and dogs with tumours containing greater than 4.7% CD204+ macrophages experienced a significantly longer DFI (P = 0.016). Interestingly, a significantly lower percentage of CD204+ macrophages was detected in cOSA arising from the proximal humerus compared to other appendicular bone locations (P = 0.016). Lymphocytic infiltrates did not appear to correlate with outcome in cOSA. Overall, our findings suggest that macrophages may play a role in inhibiting cOSA progression, as has been suggested in human osteosarcoma.     

Behaviour and Impact of Cow Slurry Beneath a Storage Lagoon: 1. Groundwater Contamination 1975–1982

The chemical and biological composition of groundwater sampled from a 76 m deep borehole situated 80 m from an unlined, earth-banked lagoon excavated in Upper Chalk and continuously used to store liquid cow manure was regularly monitored from August 1975 to January 1982 for signs of pollution. The lagoon became self-sealing 3 months after the start of filling in 1975, but was further enlarged and re-filled in autumn 1976, and emptied by dragline in September 1978 and 1980. No significant changes in groundwater composition were detected in the period August 1975 to December 1978. In January 1979, significant numbers of Escherichia coli and a large, rapid increase in concentrations of ammonium-nitrogen (NH₄-N), phosphorus (P), potassium (K), sodium (Na), chloride (Cl) and sulphate (SO4) were detected in the groundwater. Nutrient concentrations fluctuated at elevated levels throughout 1979 but decreased during 1980. Additional bacterial and chemical (NH₄-N, P and K) contamination was recorded in January 1981 and subsequent months. The contamination was considered to have occurred as a result of fissure flow through the unsaturated zone of the Upper Chalk following repeated disruption of the self-sealing layer during emptying of the lagoon by dragline in September 1978 and 1980. The results indicate that unlined, earth-banked slurry storage lagoons need to be carefully managed to avoid biological and chemical pollution of Chalk aquifers.     

Soil phosphorus management and water quality: a UK perspective

Abstract. An increasing proportion of P reaching surface waters appears to be derived from agricultural land; apportioning the relative contribution to particular farming systems is not straightforward. The majority of farms in the UK operate on the basis of an annual agricultural P surplus, the size of which varies across different farm types. Particularly high values (>20kg ha^-1) are commonly associated with intensive-livestock production and the lower values (<10kg P ha^-1) with arable farms. The geographical divide between the predominance of arable cropping in the east and livestock enterprises in the west of the UK should result in an uneven pattern to the distribution of annual P surplus. The expected cumulative effects of this surplus should be a noticeable increase in total and extractable soil P concentrations, but this is not readily apparent. While evidence from experimental plots suggests a relationship between the concentration of available soil P and that present in drainage waters, extrapolating this information so that it can be useful at the scale of a whole catchment is difficult. The loss of P from agricultural land is controlled by factors which are independent of the size of the annual P surplus. The pattern of P cycling, together with the dominant loss pathways, differ greatly between livestock and arable farming systems. Proportioning the contributions that either increased soil erosion arising from changing agricultural practices or the cumulative effect of a P surplus have had upon P loss is a necessary prerequisite to effective management.     

Mitigation options for diffuse phosphorus loss to water

Abstract. Agriculture contributes significant loads of P to surface waters. The reductions in these diffuse P inputs necessary to help prevent eutrophication problems and/or assist in the restoration of water quality will require controls over both nutrient inputs and their subsequent transport in land runoff. Specific mitigation options include nutrient budgeting, input management, soil conservation, land use management and the establishment of riparian, and other buffer zones. The variable nature of diffuse P loss suggests that the best approach to control is through integrated management at a range of scales. Critical control concepts at the farm level include targeting source areas adequately, maintaining P input loading rates within recommended limits and avoiding high-risk management actions. Since eutrophication is a natural phenomenon and with potential conflicts with the need to meet production targets and/or minimize loss of other nutrients (N), some assessment of acceptable levels of P loss, of cost effectiveness of options and some prioritization of goals are necessary to find optimal solutions. As the requirements of individual waterbodies differ, these solutions need to be site specific and their successful adoption requires an appreciation by farmers of the importance of minimizing agricultural P loss both as individuals and collectively within a catchment.     

A review of climate change and the implementation of marine biodiversity legislation in the United Kingdom

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