Histiocytic sarcoma with central nervous system involvement in dogs: 19 cases (2006-2012).

BACKGROUND: Reports of histiocytic sarcoma (HS) involving the central nervous system (CNS) are sparse and consist mainly of case reports describing 1-3 animals. OBJECTIVE: The objective of this study was to report the signalments, clinical signs, clinicopathologic and diagnostic imaging findings, treatment, and outcome of a series of dogs with HS and CNS involvement. ANIMALS: Nineteen dogs with HS examined at veterinary referral hospitals. METHODS: Retrospective case series. Medical records were reviewed and cases with a histopathological diagnosis of CNS HS were included in the study. Diagnostic imaging studies of the CNS were evaluated and histopathologic samples were reviewed to confirm the diagnosis. RESULTS: Retrievers and Pembroke Welsh Corgis were overrepresented in this cohort of dogs. Tumors involved the brain in 14 dogs and the spinal cord in 5. In 4 dogs, HS was part of a disseminated, multiorgan process whereas it appeared confined to the CNS in 15 dogs. Diagnostic imaging had variable appearances although extraaxial masses predominated in the brain. There was meningeal enhancement in all dogs that was often profound and remote from the primary mass lesion. Pleocytosis was present in all dogs with CSF evaluation. Median survival was 3 days. CONCLUSIONS AND CLINICAL IMPORTANCE: Breed predispositions appear to vary from reports of HS in other organ systems. Some unique imaging and clinicopathologic characteristics, particularly brain herniation, profound meningeal enhancement, and pleocytosis in combination with 1 or more mass lesions, might help to differentiate this neoplasm from others involving the CNS, although this requires further study.

Impact of insulin lispro on HbA1c values in insulin pump users.

AIM: To compare the therapeutic efficacy of the short-acting insulin analogue insulin lispro (Humalog) with that of buffered regular human insulin (Velosulin) in patients on insulin pump therapy. PATIENTS AND METHODS: Sixty-two (45 women and 17 men) young patients with type 1 diabetes using insulin pump therapy were compared while using buffered regular human insulin for a mean +/- s.e.m. of 20.1+/-1.2 months or insulin lispro for a mean +/- s.e.m. of 19.7+/-0.5 months. The initial mean +/- s.e.m. age and duration of diabetes were 29.1+/-0.9 and 17.7+/-0.9 years, respectively. The mean HbA1c values, basal insulin dosages, premeal insulin dosages and number of low blood sugars were recorded during treatment with both insulins. RESULTS: Mean +/- s.e.m. HbA1c values were significantly lower (p < 0.001; paired Wilcoxon t-test) during insulin lispro treatment (7.4+/-0.1%) as compared to treatment with buffered regular human insulin (7.9+/-0.1%). Total units of insulin (mean +/- s.e.m.)/kg/day was significantly (p = 0.03) lower (0.61+/-0.02) during the insulin lispro treatment period as compared to the buffered regular human insulin treated period (0.65+/-0.03). Total mean +/- s.e.m. (U/kg/day) of basal insulin administered per day was higher when patients received insulin lispro treatment (0.44+/-0.02 vs. 0.42+/-0.01 for buffered regular human insulin treated period; p = 0.002). The premeal insulin boluses (mean +/- s.e.m.) for the two treatment groups were significantly different with less insulin required for the insulin lispro treatment period for all three meals (p < 0.001, t-test). The number of mild/moderate and severe hypoglycaemic episodes were similar in the two groups. CONCLUSION: We conclude that use of insulin lispro in pump therapy significantly lowers HbA1c values in comparison to therapy with buffered regular human insulin insulin without increasing hypoglycaemic episodes.

Long-term efficacy of humalog in subjects with Type 1 diabetes mellitus.

AIMS: To evaluate the long-term effectiveness of Humalog insulin in lowering post meal glucose excursions. METHODS: Twenty young subjects with Type 1 diabetes mellitus (DM) who had received insulin-lispro (Humalog) for a least 1 year (mean +/- SD 1.8+/-1.6 years) were studied on two occasions, 3-14 days apart. They consumed a similar breakfast consisting of 450-600 kCal having fasted overnight. The same amount of human soluble Humulin Regular or Humalog insulin was given 10 min before the meal in a randomized, double-blind fashion. RESULTS: Postprandial glucose excursions at 30, 60, and 120 min were significantly lower (P<0.001, ANCOVA) when subjects received Humalog as compared to human soluble insulin. Serum-free insulin levels were significantly higher (P<0.001, ANOVA) at 30 and 60 min when subjects received Humalog as compared with human soluble insulin. Humalog antibody levels after up to 5.4 years of receiving Humalog insulin were not elevated beyond the values at 1 year. CONCLUSIONS: We conclude that Humalog insulin is effective in lowering postprandial glucose excursions even after up to 5.4 years of treatment.

Pre-meal insulin analogue insulin lispro vs Humulin R insulin treatment in young subjects with type 1 diabetes.

The present prospective one-year randomized study was conducted to compare soluble human insulin, with a new rapid-acting human insulin analogue, lispro, with respect to postprandial glucose excursions, frequency of hypoglycaemic episodes, glucose control, and long-term safety in 39 subjects (20 females, 19 males) with Type 1 diabetes. The duration of diabetes, gender distribution, and age were similar in the two groups. The total number of hypoglycaemic episodes was significantly less (p < 0.04, Wilcoxon rank sum test) in subjects receiving insulin lispro compared with regular human insulin over the 12-month period. The 2-h postprandial glucose excursion at 1 year was also significantly less (p < 0.05, ANOVA) in the group treated with insulin lispro. The reductions in the total number of hypoglycaemic episodes and in the postprandial glucose excursion with use of insulin lispro may be beneficial for the long-term management of subjects with Type 1 diabetes. However, the greatest benefit identified by the subjects receiving insulin lispro was the greater convenience of the rapid-acting analogue.

Release of arachidonic acid metabolites by human monocytes or lymphocytes: effect of treatment with interferon on stimulation by phorbol ester or calcium ionophore.

The simultaneous production of prostaglandins, leukotrienes, and hydroxyeicosatetraenoic acids was studied in human peripheral blood monocytes obtained by counter-current centrifugal elutriation. Monocytes prelabeled for 4 hr with [3H]arachidonic acid (AA) released label into the surrounding medium in response to treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) or calcium ionophore (A23187). High-performance liquid chromatography of monocyte supernatants demonstrated that labeled compounds included those which eluted with authentic standards for thromboxane B2, 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT), 6-keto-prostaglandin F alpha, prostaglandin E2, and 15-hydroxyeicosatetraenoic acid (HETE). 5-HETE and leukotriene B4 (LtB4) were detected only in response to ionophore treatment. Highly purified lymphocytes did not convert AA to autocoids, despite the release of free arachidonate in response to either stimulus. Pretreatment of monocytes with recombinant human interferon (IFN)-gamma or IFN-alpha for 18 hr resulted in enhanced release of labeled arachidonic acid and increased conversion to autocoids after TPA or ionophore stimulation. Absolute amounts of prostaglandin E2 produced in response to TPA or ionophore treatment were increased as well. These results demonstrate the autocoid profile released by stimulated human monocytes and illustrate the effects of IFN treatment on the production of lipoxygenase metabolites of arachidonic acid as well as cyclooxygenase products.