Blastic natural killer (NK)-cell lymphoma: report of an unusual CD4 negative case and review of the CD4 negative neoplasms with blastic features in the literature

Blastic Natural Killer (NK)-cell lymphoma is a relatively new entity which has been recently included in the WHO classification. CD4 expression is observed in most cases of blastic NK-cell lymphomas and has been related with skin tropism. We report an unusual CD4 negative blastic NK-cell lymphoma with primary presentation in the skin, subsequent infiltration of the bone marrow and aggressive behavior. It is emphasized that extensive immunophenotyping and EBER RNA in situ hybridization are required in order to establish the diagnosis of blastic NK-cell lymphoma. We also present a review of the literature with respect to the CD4 negative NK-cell lymphomas with blastic morphological features.     

Clinical and developmental aspects of cardiac involvement in infant of diabetic mother

The authors evaluated the main clinical and evolutive aspects of heart involvement in the newborn of diabetic mother (IDM). We studied the files of 35 IDM in a 4 years period; they were investigated the first week of life and at 6-12 months (18 cases). Most of the patients were asymptomatic/signs of extracardiac suffering; 15 had a systolic murmur. ECG: left ventricle (LV) hypertrophy (8) and LV repolarization disturbances (19 cases). Chest X-ray: cardiomegaly (9 cases). Echocardiography: hypertrophic cardiomyopathy (HCM), especially septal (25 cases, 71%); LV diastolic dysfunction (19-35) and normal systolic function; pulmonary hypertension (3), other congenital heart diseases (8 cases). The control revealed the alleviation of the LV walls size and LV diastolic function. The high incidence of the cardiac manifestations in IDM and the risk of occurrence of some severe problems, require a complete cardiological exam from the first few days of life and a follow-up schedule until the normalization of the cardiac parameters.     

Antitumor activity of erlotinib (OSI-774, Tarceva) alone or in combination in human non-small cell lung cancer tumor xenograft models

Our objective was the preclinical assessment of the pharmacokinetics, monotherapy and combined antitumor activity of the epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor erlotinib in athymic nude mice bearing non-small cell lung cancer (NSCLC) xenograft models. Immunohistochemistry determined the HER1/EGFR status of the NSCLC tumor models. Pharmacokinetic studies assessed plasma drug concentrations of erlotinib in tumor- and non-tumor-bearing athymic nude mice. These were followed by maximum tolerated dose (MTD) studies for erlotinib and each chemotherapy. Erlotinib was then assessed alone and in combination with these chemotherapies in the NSCLC xenograft models. Complete necropsies were performed on most of the animals in each study to further assess antitumor or toxic effects. Erlotinib monotherapy dose-dependently inhibited tumor growth in the H460a tumor model, correlating with circulating levels of drug. There was antitumor activity at the MTD with each agent tested in both the H460a and A549 tumor models (erlotinib 100 mg/kg: 71 and 93% tumor growth inhibition; gemcitabine 120 mg/kg: 93 and 75% tumor growth inhibition; cisplatin 6 mg/kg: 81 and 88% tumor growth inhibition). When each compound was given at a fraction of the MTD, tumor growth inhibition was suboptimal. Combinations of gemcitabine or cisplatin with erlotinib were assessed at 25% of the MTD to determine efficacy. In both NSCLC models, doses of gemcitabine (30 mg/kg) or cisplatin (1.5 mg/kg) with erlotinib (25 mg/kg) at 25% of the MTD were well tolerated. For the slow growing A549 tumor, there was significant tumor growth inhibition in the gemcitabine/erlotinib and cisplatin/erlotinib combinations (above 100 and 98%, respectively), with partial regressions. For the faster growing H460a tumor, there was significant but less remarkable tumor growth inhibition in these same combinations (86 and 53% respectively). These results show that in NSCLC xenograft tumors with similar levels of EGFR expression, the antitumor activity of erlotinib is robust both as monotherapy and in combination with chemotherapies.     

Membrane-bound and releasable nucleotidase activities: differences in canine mesenteric artery and vein

1. At least two enzymatic activities are proposed to degrade the extracellular ATP: (i) ubiquitously expressed membrane-bound enzymes (ecto-nucleotidases); and (ii) soluble (releasable) nucleotidases that are released during stimulation of sympathetic nerves and break down neuronal ATP. No quantitative data have placed the magnitude of these nucleotidase activities into a physiological perspective of neurovascular control. 2. We studied comparatively the membrane-bound and releasable nucleotidase activities in canine isolated inferior mesenteric arteries and veins using 1,N6-etheno(epsilon)-nucleotides (i.e. epsilon-ATP, epsilon-ADP, epsilon-AMP and epsilon-adenosine) as exogenous substrates. The enzymatic activities were estimated by measuring the disappearance of the epsilon-substrate and appearance of epsilon-products by means of HPLC-fluorescence detection during either stimulation of sympathetic perivascular nerves (releasable activity) or in the absence of nerve stimulation (ecto-nucleotidase activity). 3. Incubation of vascular segments with 50 nmol/L epsilon-ATP for 60 min resulted in a decrease of the epsilon-ATP substrate by 63.5 +/- 4.6 and 91.2 +/- 6.2% in the artery and vein, respectively. In contrast, the decrease of the epsilon-ATP during electrical field stimulation (EFS; 16 Hz, 0.3 msec, 2 min) was 39.8 +/- 4.2% in the artery and 13.1 +/- 7.3% in the vein. Therefore, the mesenteric arteries demonstrate a greater releasable ATPase activity and a weaker ecto-ATPase activity than mesenteric veins. 4. The degradation of epsilon-ADP and epsilon-AMP was similar in both blood vessels under either experimental protocol. The epsilon-adenosine was not significantly degraded in the absence or presence of EFS. 5. These data implicate a differential removal of extracellular ATP as a potential mechanism of serving resistance and capacitance in the splanchnic circulation.     

Clinical value of antineutrophil cytoplasmic antibodies

This article presents a brief review of the clinical value of antineutrophil cytoplasmic antibodies (ANCA) in the diagnosis and management of patients with various forms of vasculitis. ANCA assay methodology and testing recommendations are reviewed. The patterns of reactivity of ANCA observed by indirect immunofluorescence, the antigens recognized by ANCA, and the sensitivity, specificity, and positive predictive value of ANCA for diagnosis of different vasculitides are described. In addition, the spectrum of drugs and nonvasculitic diseases that are associated with ANCA and need to be differentiated from true ANCA-positive vasculitides are reviewed. When properly utilized and cautiously interpreted, ANCA are a useful, noninvasive diagnostic tool in the differential diagnosis of vasculitis.