Thirty-nine, older, large-breed dogs with multilobular osteochondrosarcoma (MLO) each presented primarily with a fixed mass involving the flat bones of the skull. Twenty-five dogs were treated with surgical resection alone, nine were treated with adjuvant therapy, and five were not treated. Forty-seven percent of dogs treated had local tumor recurrence, and 56% had metastasis. Median time to recurrence, median time to metastasis, and median survival time were 797, 542, and 797 days, respectively. Histological grade, surgical margins, and tumor location affected outcome. Long-term remission can be obtained with aggressive treatment of MLO, although it is locally invasive and moderately metastatic.

This study was performed to determine the pharmacokinetics and local and systemic effects of cis-diamminedichloroplatinum II (cisplatin) released from an open-cell polylactic acid polymer when the drug delivery device was placed adjacent to a cortical allograft. Bilateral intercalary femoral allografts were implanted in six normal beagles. The polymer containing cisplatin was implanted adjacent to the allograft in one femur, and the polymer without cisplatin was implanted adjacent to the allograft in the contralateral femur. Systemic toxicity was evaluated clinically by hematologic and serum biochemistry tests and urinalysis. Healing of the allograft was monitored radiographically. The femora were evaluated biomechanically, histologically, and histomorphometrically 7.5 months after surgery. Total serum platinum levels were measured by atomic absorption spectrophotometry, and pharmacokinetic parameters were calculated. Healing was impaired slightly by the presence of the polymer with cisplatin, and systemic and local toxicity was mild and transient. After implantation of the polymer with cisplatin, the mean peak total serum platinum concentration was low (1.71 +/- 0.19 micrograms/ml). However, the area under the curve for total serum platinum concentration versus time for the first 21 days was large (27,050 +/- 3,201 micrograms.min/ml). When cisplatin was given as an intravenous bolus at a dose of 70 mg/m2 to six other beagles, the mean peak total platinum concentration was 8.80 +/- 2.1 micrograms/ml and the area under the curve was 940.3 +/- 256.7 micrograms.min/ml. These results indicate that a sustained release of cisplatin can be delivered safely from an open-cell polylactic acid polymer. This device may be useful in the treatment of solid tumors.

The effects of alpha-MSH and testosterone propionate on sebum secretion, sebaceous gland volume, dermal lipogenesis, and preputial gland weight and lipogenesis were examined in hypophysectomized rats. Hypophysectomy reduced sebum secretion, sebaceous and preputial gland size, and dermal and preputial gland lipogenesis. The greatest effects were seen on the biosynthesis of wax esters and squalene. Testosterone propionate (TP) increased sebum secretion, sebaceous gland volume and preputial gland weight and lipogenic activity, but had no significant effect on the pattern of lipid labelling. alpha-MSH had no effect on sebaceous or preputial gland size, but increased sebum secretion and dermal lipogenesis, especially wax ester biosynthesis. When given together TP and alpha-MSH had a synergistic effect on sebum secretion and on dermal and preputial gland lipogenesis, and the pattern of lipid labelling was shifted towards normal. TP and alpha-MSH also showed synergism in increasing preputial gland weight, but together they had no greater effect on sebaceous gland volume than that achieved with TP alone. These results suggest that TP and alpha-MSH have different actions on the sebaceous glands with alpha-MSH acting predominantly on lipogenesis and TP on cellualr proliferation and turnover leading to an increase in gland size. Preputial glands differ from cutaneous sebaceous glands in their response to alpha-MSH and androgen which could be a reflection of their more specilized function.

The purpose of this study was to evaluate the effect of intramedullary polymethylmethacrylate (PMMA) bone cement on the healing of intercalary allografts. Thirteen adult beagles had bilateral intercalary femoral allografts implanted. The medullary canal of one randomly assigned allograft in each dog was filled with PMMA. Healing was followed clinically and femora were evaluated radiographically, biomechanically, histologically, and histomorphometrically 9 months after surgery. There was an increased percent of eroded surface at the endosteal area of the center region of grafts containing PMMA and there was an increased percent osteoblast surface in this area in grafts not containing PMMA. There was an increased percent eroded surface at the periosteal area in the center region in grafts not containing PMMA and there was an increased percent osteoblast surface at the periosteal area in the graft adjacent to the host junction in grafts containing PMMA. There was no significant difference between PMMA-treated and untreated allografts in any other parameters measured. The results from this study suggest that, although the pattern of incorporation is altered, intramedullary PMMA does not appear to effect allograft healing adversely.

—Lipid‐free extracts of rat and human brain have been prepared and shown to contain phospholipase A1 and A2 activities and a lysophospholipase. The phospholipase Aj activity has pH optima of 4·2 and 4·6 in rat and human brain, respectively; it can be partially purified and isolated in high yields by dialysing the extracts at low pH. The purified preparations hydrolyse the ester bond at the 1‐position in lecithin, phosphatidyl‐ethanolamine and phosphatidylserine, but have little or no action on triglyceride or cholesterol ester. An assay system for the enzyme is described. Phospholipase A2 activity is optimal at pH 5·5 in rat brain extracts and at pH 5·0 in extracts of human brain. The phospholipase A2 activity of human cerebral cortex is largely unaffected by heating extracts at 70°C for 5 min, whereas this treatment substantially inactivates phospholipase A1 and completely destroys lysophospholipase. Phospholipase A1 is widely distributed in both grey and white matter of human brain and is also present in peripheral nerve. Phospholipase A2 activity is lower than A1 in all regions of the CNS examined so far, and is absent from peripheral nerve. Neither enzyme appears to require Ca2+ but both are inhibited by di‐isopropylfluorophosphate (DFP, 2 × 10−6 m) and thus differ from phospholipase A of pancreas. These studies confirm that the phospholipase A1 and A2 activities in brain are due to separate enzymes.

Ten dogs were given mitoxantrone at a dose of 5 mg/m2 body surface area intravenously. Recombinant canine granulocyte colony-stimulating factor (rcG-CSF) was administered subcutaneously daily for 20 days after an infusion of mitoxantrone in five of these dogs to determine the effect of the hematopoietic growth factor on the duration and severity of myelosuppression. The median neutrophil counts dropped below normal (less than 3,000/uL) for 2 days in the dogs that received rcG-CSF, and for 5 days in the dogs that received only mitoxantrone. Four of five dogs not treated with rcG-CSF and none of those receiving rcG-CSF developed serious neutropenia (less than 1,500/uL). The neutrophil counts were significantly (P less than 0.05) higher in the rcG-CSF treated dogs at all time points except before the administration of the colony-stimulating factor, and the sixth day after the mitoxantrone was administered. These findings demonstrate that rcG-CSF is capable of reducing the duration and severity of mitoxantrone-induced myelosuppression.

SummaryThe osteoinductive capacity of canine demineralized bone matrix (DBM), implanted in epaxial muscle sites of athymic rats, was evaluated using calcium content and histomorphometry at two, four and six weeks after implantation. Results of this study confirm that DBM, derived from canine sources, does possess significant osteoinductive ability since histological examination revealed the presence of new cartilage, bone, or both, at 21/24 implantation sites. The osteogenesis induced by canine DBM continued as an active, cumulative process throughout the six week investigation period. The mean percentage of total induced osteogenic components including new, live cartilage, woven bone, lamellar bone and bone marrow cellular elements, was significantly greater after six weeks than after two weeks of implantation (p <0.01). Comparison of histomorphometric point counts at two, four and six weeks of implantation supported the conclusion that bone for mation as induced by canine DBM, proceeds primarily via an endochondral ossification pathway. Although the amount of calcium deposited in tissues harvested from DBM implanted sites tended to increase as implantation time lengthened, there was not a statistically significant correlation between calcium content and the level of osteogenic activity seen histologically (r = 0.32, p = 0.13).The osteoinductive capacity of canine demineralized bone matrix (DBM), implanted in ep-axial muscle sites of athymic rats, was evaluated using calcium content and histomorphometry at two, four and six weeks after implantation. Results of this investigation confirm that DBM, derived from canine sources, does possess significant osteo-inductive ability and that bone formation proceeds primarily via a pathway of endochondral ossification.

Epidermal lipid biosynthesis was normal in patients with mild ichthyosis due to Hodgkin's disease, but greatly reduced in one patient with severe ichthyosis. Dermal (sebaceous) lipid synthesis was decreased in all patients with Hodgkin's disease, whether or not they had ichthyosis, and was greatly reduced in the patient with severe ichthyosis. Neither the mechanism nor the possible relationship between the dermal and epidermal changes is understood.