Histone deacetylase inhibitors in lymphoma and solid malignancies

Histone deacetylase inhibitors (HDACi) are a new class of antineoplastic agents with demonstrable preclinical antitumor activity in both in vitro and in vivo studies in a wide range of malignancies. Based on these preclinical findings, in recent years HDACi have undergone a rapid phase of clinical development with many HDACi entering Phase I-III clinical trials, both as single agents and in combination with other therapies. Favorable clinical responses have been demonstrated in cutaneous T-cell lymphoma with emerging evidence of clinical activity in other types of lymphoma and, to date, a good toxicity profile. Solid tumor responses to single agent and combination therapies have also been reported, paving the way for larger studies in this field. In this review we discuss the recent advances in the clinical development of HDACi and their current therapeutic role in lymphoma and solid malignancies.     

Cerebral abscess associated with meningococcal meningitis

Purulent fluid collections, including brain abscess and subdural empyema, are exceedingly rare in association with meningococcal meningitis. We present a 5-month-old infant with meningococcal meningitis and sepsis complicated by an intracerebral abscess.     

Hyperoxia and apoptosis in developing mouse lung mesenchyme

Hyperoxia contributes to the development of bronchopulmonary dysplasia in former premature infants. Injurious environmental factors such as hyperoxia may disrupt distal airway branching and alveolar septation, as these critical stages in lung development occur following birth in extremely premature infants. To test if hyperoxia directly inhibited distal airway branching, we cultured E16 fetal mouse lung explants in either 20% (control) or 95% oxygen (hyperoxia). Hyperoxia reduced the number of distal airways to less than 50% of controls. Explants cultured in 95% oxygen also had fewer complex distal airways compared with controls. Mesenchymal cells adjacent to distal airways in hyperoxic explants appeared apoptotic by phase microscopy. Consistent with increased apoptosis, explants cultured in hyperoxia had increased caspase 3/7 activity compared with controls. Hyperoxia also increased mesenchymal caspase 3 expression and annexin V binding within cultured explants as visualized by fluorescence microscopy. We measured increased annexin V binding in isolated primary fetal lung mesenchymal cells cultured in 95% oxygen suggesting a direct effect on cells within the mesenchyme. Hyperoxia can lead to NF-kappaB activation, which mediates inflammatory cascades and may protect cells from apoptosis. We detected NF-kappaB activation and nuclear p65 localization in explants exposed to 48 h of hyperoxia. Inhibition of NF-kappaB prevented the hyperoxia-induced activation of caspase 3. NF-kappaB activation may therefore contribute to apoptosis in the developing fetal mouse lung following hyperoxia exposure. Our data suggest hyperoxia inhibits distal airway branching and directly induces apoptosis of the fetal mouse lung mesenchyme.     

Short QT Syndrome in a Pediatric Patient

Short QT syndrome (SQTS) is a recently described genetic syndrome characterized by abnormally brisk ventricular repolarization. Similar to long QT syndrome, SQTS might result in ventricular arrhythmias, syncope, and sudden death. The clinical diagnosis of SQTS is supported by the finding of an abnormally short QT interval on the resting electrocardiogram in combination with a suggestive clinical or family history. To date, few pediatric cases have been reported and the ideal therapy is unknown. We report a teenage boy who suffered a witnessed ventricular fibrillation arrest and was subsequently diagnosed with SQTS. Additional data from nine other pediatric patients diagnosed with SQTS are presented.     

Left ventricle: automated segmentation by using myocardial effusion threshold reduction and intravoxel computation at MR imaging

This retrospective analysis of existing patient data had institutional review board approval and was performed in compliance with HIPAA. No informed consent was required. The purpose of the study was to develop and validate an algorithm for automated segmentation of the left ventricular (LV) cavity that accounts for papillary and/or trabecular muscles and partial voxels in cine magnetic resonance (MR) images, an algorithm called LV Myocardial Effusion Threshold Reduction with Intravoxel Computation (LV-METRIC). The algorithm was validated in biologic phantoms, and its results were compared with those of manual tracing, as well as those of a commercial automated segmentation software (MASS [MR Analytical Software System]), in 38 subjects. LV-METRIC accuracy in vitro was 98.7%. Among the 38 subjects studied, LV-METRIC and MASS ejection fraction estimations were highly correlated with manual tracing (R(2) = 0.97 and R(2) = 0.95, respectively). Ventricular volume estimations were smaller with LV-METRIC and larger with MASS than those calculated by using manual tracing, though all results were well correlated (R(2) = 0.99). LV-METRIC volume measurements without partial voxel interpolation were statistically equivalent to manual tracing results (P > .05). LV-METRIC had reduced intraobserver and interobserver variability compared with other methods. MASS required additional manual intervention in 58% of cases, whereas LV-METRIC required no additional corrections. LV-METRIC reliably and reproducibly measured LV volumes. Supplemental material: http://radiology.rsnajnls.org/cgi/content/full/248/3/1004/DC1.     

Rituximab for the treatment of the skin manifestations of dermatomyositis: a report of 3 cases

Three patients suffering from classic dermatomyositis (juvenile and adult-onset) with prominent recalcitrant skin manifestations are described. All patients demonstrated good control of muscle symptoms on immunosuppressive medications, but their cutaneous disease persisted despite treatment with at least 4 different systemic treatments and topical agents. They were given rituximab, a monoclonal anti-CD20 antibody, achieving a response with minimal side effects. We document our experience with this medication for the cutaneous lesions of dermatomyositis.