American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force Report on omalizumab-associated anaphylaxis

The American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma and Immunology Executive Committees formed the Omalizumab Joint Task Force with the purpose of reviewing the Genentech Xolair (omalizumab) clinical trials and postmarketing surveillance data on anaphylaxis and anaphylactoid reactions. Using the definition of anaphylaxis proposed at a 2005 multidisciplinary symposia, the Omalizumab Joint Task Force concluded that 35 patients had 41 episodes of anaphylaxis associated with Xolair (omalizumab) administration between June 1, 2003, and December 31, 2005. With 39,510 patients receiving Xolair (omalizumab) during the same period of time, this would correspond to an anaphylaxis-reporting rate of 0.09% of patients. Of those 36 events for which the time of reaction was known, 22 (61%) reactions occurred in the first 2 hours after one of the first 3 doses. Five (14%) of the events after the fourth or later doses occurred within 30 minutes. Considering the timing of these 36 events, an observation period of 2 hours for the first 3 injections and 30 minutes for subsequent injections would have captured 75% of the anaphylactic reactions. The OJTF report provides recommendations for physicians who prescribe Xolair (omalizumab) on (1) the suggested wait periods after administration and (2) patient education regarding anaphylaxis.     

Respiratory controversies in the critical care setting. Should heliox be used for mechanically ventilated patients?

Helium is an inert gas with a very low density (0.18 g/L), which allows it to pass through narrowed passages with less turbulence than nitrogen or oxygen. For many years, helium-oxygen mixture (heliox) has been used for patients with severe airway obstruction. However, the data supporting the clinical application of heliox are few and clearly nondefinitive. This article reviews the medical literature on whether heliox should be used for mechanically ventilated patients. No definitive randomized studies have attempted to answer this question. Studies both support and contest the benefit of heliox during mechanical ventilation. Most studies agree that heliox is extremely safe; no adverse effects have been reported. However, heliox must be administered with vigilance and continuous monitoring to avoid technical complications. As is the case with all therapies that have not been definitively studied, the risk/benefit ratio for an individual patient must be assessed by the clinical care team.     

Side effects of proton beam therapy of choroidal melanoma in dependence of the dose to the optic disc and the irradiated length of the optic nerve

Graefe's Archive for Clinical and Experimental Ophthalmology - To analyze the impact of the dose to the optic disc and the irradiated length of the optic nerve on radiation-induced optic...     

New immunotoxins targeting CD123, a stem cell antigen on acute myeloid leukemia cells

The specific alpha subunit of the interleukin-3 receptor (IL-3Ralpha, CD123) is strongly expressed in various leukemic blasts and leukemic stem cells and seems to be an excellent target for the therapy of leukemias. In this study, immunotoxins were developed to target CD123 only, which bypasses the dependence on other subunits to form intact IL-3R. Three anti-CD123 hybridomas (26292, 32701, and 32716) were selected on the basis of their affinity for CD123. Total RNAs were extracted from the 3 anti-CD123 hybridomas and used to clone the fragment of variable region (Fvs). The Fvs were assembled into single chain Fvs and fused to a 38-kd fragment of Pseudomonas exotoxin A to make recombinant immunotoxins. 26292(Fv)-PE38 was found to have the highest cytotoxic activity on the CD123 expressing leukemia cell line TF-1. It bound the cells with a kd of 3.5 nM. Another immunotoxin, 32716(Fv)-PE38, belonging to a different epitope group, had a similar binding ability but was less active, demonstrating the role of epitope selection in immunotoxin action. The cytotoxic activity of 26292(Fv)-PE38 was increased from 200 to about 40 ng/mL by mutating the REDLK sequence at the C terminus to KDEL. 26292(Fv)-PE38-KDEL was specifically cytotoxic to several CD123 expressing cell lines (TF-1, Molm-13, and Molm-14) with good CD123 expression but not to ML-1 or U937 with low or absent expression. In conclusion, 26292(Fv)-PE38-KDEL shows good cytotoxic activity against CD123 expressing cell lines, and merits further development for the possible treatment of acute myeloid leukemia and other CD123 expressing malignancies.     

Presentation of cauda equina syndrome due to an intradural extramedullary abscess: a case report

Background contextCauda equina syndrome is caused by compression or injury to the nerve roots distal to the level of the spinal cord. This syndrome presents as low back pain, motor and sensory deficits in the lower extremities, and bladder as well as bowel dysfunction. Although various etiologies of cauda equina syndrome have been reported, a less common cause is infection.PurposeTo report a case of cauda equina syndrome caused by infection of an intradural extramedullary abscess with Staphylococcus aureus.Study design/settingCase report and review of the literature.MethodsThe literature regarding the infectious causes of cauda equina syndrome was reviewed and a case of cauda equina syndrome caused by infection of an intradural extramedullary abscess with Staphylococcus aureus was reported.ResultsA 37-year-old woman, with history of intravenous drug abuse, hepatitis C, and hepatitis B, presented with low back pain lasting 2 months, lower extremity pain, left greater than right with increasing weakness and difficulty ambulating, and urinary and fecal incontinence. Her presentation was consistent with cauda equina syndrome. The patient underwent a T12–L2 laminectomy, and intradural exploration revealed an abscess. Methicillin-resistant Staphylococcus aureus was found on wound culture.ConclusionsCauda equina syndrome, presenting as a result of spinal infection, such as the case reported here, is extremely rare but clinically important. Surgical intervention is generally the recommended therapeutic modality.     

Species of <Emphasis Type="Italic">Lasiodiplodia</Emphasis> associated with papaya stem-end rot in Brazil

The last decade has revealed an unexpected fungal diversity associated with natural rocks, often collected in environments influenced by harsh climatic conditions. Yet the phylogenetic affiliations and the taxonomy of many of these extreme fungi, mainly within Dothideomycetes, the largest class of Ascomycota, have only partially been described. In the present study we confirm that most rock inhabiting-fungi (RIF) are highly polyphyletic among Dothideomycetidae, mainly within the order Capnodiales, an order otherwise incorporating several families of major plant pathological importance. Novel taxa were identified within the two major and distinct clades of Teratosphaeriaceae, both comprising meristematic black fungi. Thirty one novel species and 13 new genera are proposed, based on ITS and partial nucLSU, RPB2 and BT2 sequences.     

Genetic alterations of IL-1 receptor antagonist in mice affect plasma cholesterol level and foam cell lesion size

Inflammatory cytokines have been linked to atherosclerosis by using cell culture models and acute inflammation in animals. The goal of this study was to examine lipoprotein levels and early atherosclerosis in chronic animal models of altered IL-1 physiology by using mice with deficient or excess IL-1 receptor antagonist (IL-1ra). IL-1ra knockout C57BL/6J mice fed a cholesterol/cholate diet for 3 mo had a 3-fold decrease in non-high-density lipoprotein cholesterol and a trend toward increased foam-cell lesion area compared to wild-type littermate controls. IL-1ra transgenic/low-density lipoprotein receptor (LDLR) knockout mice fed a cholesterol-saturated fat diet for 10 wk showed a 40% increase in non-high-density lipoprotein cholesterol, consistent with the IL-1ra knockout data, although there was no change in lesion size. When these IL1-ra overexpressing transgenic mice on the LDLR knockout background were fed a high-cholesterol/high-fat diet containing cholate, however, a statistically significant 40% decrease in lesion area was observed compared to LDLR knockout mice lacking the transgene. By immunohistochemistry, IL-1ra was present in C57BL/6J and LDLR knockout aortae, absent in IL-1ra knockout aortae, and present at high levels in LDLR knockout/IL-1ra transgene aortae. In summary, IL-1ra tended to increase plasma lipoprotein levels and, when fed a cholate-containing diet, decrease foam-cell lesion size. These data demonstrate that in selected models of murine atherosclerosis, chronic IL-1ra depletion or overexpression has potentially important effects on lipoprotein metabolism and foam-cell lesion development.