Altered radioprotective properties of interleukin I alpha (IL-1) in non-hematologic tumor-bearing animals

The radioprotective properties of IL-1 were investigated in the respective murine hosts for the Lewis lung (LLca) and EMT-6 tumors. For these studies, doses of total body irradiation were selected for the C57B1/6 (9.5 Gy) and Balb/c (7.5 Gy) mice that resulted in a 60% mortality over a 30-day interval. When a "priming" dose of 2.5 x 10(5) U IL-1 was administered 24 hr prior to the radiation exposure, animal mortality was markedly reduced (60% vs 5-10%). Under identical experimental conditions, however, the presence of either the LLca or the EMT-6 tumors in their respective host strains was found to compromise the level of radioprotection conferred by this priming dose of IL-1. In Balb/c mice bearing the EMT-6 tumor, a priming dose of IL-1 resulted in only a modest level of radioprotection when compared to non-tumor-bearing control animals (median animal survival increased by 11.5 days). In C57B1/6 mice bearing the LLca tumor, IL-1 failed to demonstrate any evidence of radioprotection. Following a sublethal dose of total body irradiation, the appearance of an accelerated repopulation of the stem cell (8d CFUs and CFU-GEMM) and the myeloid progenitor (CFU-M) compartment in the marrow of the IL-1 primed EMT-6, but not the LLca, tumor-bearing animals was consistent with the hypothesis that the mechanism leading to radioprotection in IL-1 primed rodents involves an accelerated recovery of hematopoietic activity. It was also noted that the presence of the EMT-6 tumor was associated with an increase in the "radiosensitivity" of the Balb/c mouse. Collectively, these data suggest that the use of biological modifiers should be examined under altered physiological conditions prior to attempting to translate them into the clinic.     

Combination antibody therapy with epratuzumab and rituximab in relapsed or refractory non-Hodgkin's lymphoma.

PURPOSE: To explore the safety and therapeutic activity of combination anti-B-cell monoclonal antibody therapy in non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Twenty-three patients with recurrent B-cell lymphoma received anti-CD22 epratuzumab 360 mg/m(2) and anti-CD20 rituximab 375 mg/m(2) monoclonal antibodies weekly for four doses each. Sixteen patients had indolent histologies (15 with follicular lymphoma) and seven had aggressive NHL (all diffuse large B-cell lymphoma [DLBCL]). Indolent patients had received a median of one (range, one to six) prior treatment, with 31% refractory to their last therapy and 81% with high-risk Follicular Lymphoma International Prognostic Index scores. Patients with DLBCL had a median of three (range, one to eight) prior regimens (14% resistant to last treatment) and 71% had high intermediate-risk or high-risk International Prognostic Index scores. All patients were rituximab na?ve. RESULTS: Treatment was well tolerated, with toxicities principally infusion-related and predominantly grade 1 or 2. Ten (67%) patients with follicular NHL achieved an objective response (OR), including nine of 15 (60%) with complete responses (CRs and unconfirmed CRs). Four of six assessable patients (67%) with DLBCL achieved an OR, including three (50%) CRs. Median time to progression for all indolent NHL patients was 17.8 months. CONCLUSION: The full-dose combination of epratuzumab with rituximab was well tolerated and had significant clinical activity in NHL, suggesting that this combination should be tested in comparison with single-agent treatment.     

Influence of food on the oral bioavailability of deramciclane from film-coated tablet in healthy male volunteers.

The effect of a high-fat meal on the oral bioavailability of deramciclane 30 mg tablet was evaluated in 18 healthy male volunteers in a randomised, single dose, two-way crossover study. The drug was administered following an overnight fast or a standardised high-fat breakfast. The plasma concentrations of deramciclane and N-desmethylderamciclane were determined by using a validated HPLC-MS -MS/MS method. An effect of food on the bioavailability was indicated if the 90% confidence interval (CI) for the ratio of geometric means of fed and fasted treatments was not contained in the equivalence limit of 0.8-1.25 for AUC and C(max). The ratios of the mean C(max) and AUC(0-infinity) values of deramciclane were 1.24 (90% CI 1.12-1.38) and 1.31 (90% CI 1.21-1.41) in fed versus fasted subjects, which overlapped but exceeded the equivalence limit. In contrast to the parent compound, the 90% CI of the mean ratios for AUC(0-infinity) and C(max) of N-desmethylderamciclane were within the predefined range. The 24 and 31% increase in C(max) and AUC(0-infinity) of deramciclane, respectively, under fed condition is modest and probably has no clinical significance since it is relatively small compared to the inter-individual variability of these parameters.     

Time Pressure Management as a Compensatory Strategy Training after Closed Head Injury

Following severe closed head injury, deficits in speed of information processing are common. As a result, many head-injured patients experience a feeling of “information overload” in daily tasks that once were relatively easy. Many remedial programmes have been designed that treat different aspects of attention (often including mental speed requirements) by repetitive exercises. In the present study, a different approach to slow information processing has been taken, namely Time Pressure Management (TPM). TPM consists of a set of alternative cognitive strategies that allow head-injured patients in real-life tasks to compensate for their mental slowness. In a randomised pre-training vs. post-training vs. follow-up group study, the effectiveness of TPM training was compared with concentration training in which verbal instruction was the key element. The results indicate that specific TPM strategies are learned by the experimental subjects but that both treatments improve task performance significantly for an information intake task. TPM, however, produces greater gains than concentration training and also appears to generalise to other measures of speed and memory function.     

A case of cutaneous angiolipoleiomyoma (angiomyolipoma) in a budgerigar (Melopsittacus undulatus)

We report a case of cutaneous angiolipoleiomyoma (angiomyolipoma) found on the anterior wall of the ventral part of the abdomen of a three-year-old female budgerigar (Melopsittacus undulatus). Histologic examination of the well-circumscribed, surgically removed tumour (1.5 cm in diameter) showed a benign admixed proliferation of blood vessels of different size, smooth muscle bundles, and mature adipose tissue, without evidence of malignancy. Endothelial cells of the haemangioma component were positive for claudin-5 endothelium-specific immunohistochemical marker, and the leiomyoma component was positive for α-smooth muscle actin. The differentiated lipocytes showed S-100 protein positivity. The Ki-67 labelling index was 2 to 3%. The mesenchymal tumour was negative for HMB45 melanocytic immunhistochemical marker. To the best of our knowledge, this is the first report describing a cutaneous angiolipoleiomyoma in a budgerigar with histological and immunohistochemical analyses.