Following the bite in August, 2001, the reaction developed rapidly, and he immediately lost consciousness and went into cardiac arrest before the ambulance arrived. Because of delayed resuscitation, ...he had hypoxic brain damage to the basal ganglia, resulting in spastic tetraplegia. Despite having only slightly raised serum tryptase of 11·5 ?g/L (normal range <11·4 ?g/L), bone marrow examination showed spindle shaped mast cells expressing CD25, and the typical Kit-mutation (D816V) was detected by PCR of peripheral blood leucocytes.1 From the patient's description of the appearance of the mosquitoes that bit him, and knowledge of the geographic region where the incidents occurred, Culex pipiens was identified by an expert from the Bernhard Nocht Institute, Hamburg, Germany, as the most likely of the 100 known mosquito species in central Europe to be responsible for inducing such reactions.
To evaluate the efficacy of craniospinal irradiation (CSI) in the management of recurrent infant medulloblastoma after surgery and chemotherapy alone.
Seventeen pediatric medulloblastoma patients ...registered in the HIT-REZ 1997 and 2005 studies underwent CSI as salvage treatment at first recurrence. All patients had achieved complete remission after first-line treatment consisting of surgery and chemotherapy. Eleven patients showed metastatic disease at relapse. Five patients underwent surgery prior to radiation therapy, which resulted in complete resection in 1 case. In 1 patient, complete resection of the residual tumor was performed after CSI. Eleven patients received chemotherapy prior, 6 patients during and 8 patients after CSI. All patients received CSI with a median total dose of 35.2 Gy, and all but 1 received a boost to the posterior fossa (median total dose, 55.0 Gy). Metastases were boosted with an individual radiation dose, depending on their location and extent.
During a median follow-up time of 6.2 years since recurrence, 11 patients showed progressive disease and died. Median progression-free (overall) survival was 2.9 ± 1.1 (3.8 ± 0.8) years. Progression-free survival (PFS) rates at 1, 3, and 5 years were 88% ± 8%, 46% ± 12%, and 40% ± 12%, respectively. Overall survival (OS) rates at 1, 3, and 5 years were 94% ± 6%, 58% ± 12%, and 39% ± 12%, respectively. For 11 patients with classic medulloblastoma, 3-year (and 5-year) PFS and OS were 62% ± 15% and 72% ± 14% (52% ± 16% and 51% ± 16%), respectively. On univariate analysis, metastatic disease was not associated with poorer progression-free and overall survival.
Our results suggest that salvage treatment of relapsed medulloblastomas consisting of CSI and chemotherapy offers a second chance for cure, even for patients with classic histological findings. Metastatic disease at relapse did not have an impact on survival. However, this may be explained by the small number of patients.
Background Mast cells (MCs) and nerves can induce cutaneous inflammatory responses, both independently and by interacting with each other. However, little is known about the role of skin nerves and ...neuropeptides in the regulation of MC-mediated skin inflammation, and the contribution of MCs in neurogenic inflammation is still controversial. Objective The aim of this study was to investigate the effects of cutaneous sensory nerves on MC-driven inflammatory responses. Methods Passive cutaneous anaphylaxis, a model for type I allergic skin responses, was studied in the presence or absence of sensory nerves by using a murine model of selective cutaneous denervation. Results Passive cutaneous anaphylaxis was significantly impaired in the absence of sensory nerves. This effect was not a result of an alteration of mast cell numbers in denervated skin. Moreover, IgE-mediated activation of mast cells was markedly decreased in denervated compared with normal skin. Notably, pretreatment of mice with selective antagonists of the neuropeptides substance P and/or calcitonin gene-related peptide also resulted in decreased inflammatory responses after MC activation. Conclusion These data suggest that sensory skin nerves augment MC-driven inflammatory responses by releasing neuropeptides that increase MC degranulation.
In 154 patients the severity of symptoms was recorded by using the weekly urticaria activity score (UAS 7), and impairment in quality of life was assessed in 156 patients by using the Dermatology ...Life Quality Index (DLQI), as described previously.6 In confirmation of previously published findings, skin reactivity to autologous serum (positive ASST result) was found in 37.5% of all 200 patients with CU tested (Fig 1), and only slightly higher numbers of patients exhibited skin reactivity to autologous plasma (positive APST result, 43.0%), which is in contrast to a previous report in which up to 86% of patients with CU were found to have positive APST results.4 The results for skin autoreactivity were found to be comparable in all 3 study centers and ranged from 42.9% to 43.8% (positive APST result) and 32% to 50% (positive ASST result).
Patients with acquired cold urticaria (ACU) show itchy wheals during cold exposure. This disturbing condition involves histamine and platelet-activating factor in its pathogenesis. Rupatadine is a ...dual antagonist of both histamine and platelet-activating factor.
To assess rupatadine efficacy in preventing reactions to cold challenge in patients with ACU.
A crossover, randomized, double-blind, placebo-controlled study in which 21 patients with ACU received rupatadine, 20 mg/d, or placebo for 1 week each is presented. The main outcome was the critical stimulation time threshold (CSTT) determined by ice cube challenge. Secondary outcomes included CSTT and the critical temperature threshold assessed by a cold provocation device (TempTest 3.0), as well as scores for wheal reactions, pruritus, burning sensations, and subjective complaints after cold challenge.
After rupatadine treatment, 11 (52%) of 21 patients exhibited a complete response (ie, no urticaria lesions after ice cube provocation). A significant improvement in CSTT compared with placebo was observed after ice cube and TempTest 3.0 challenge (P = .03 and P = .004, respectively). A significant reduction of critical temperature threshold (P < .001) and reduced scores for cold provocation-induced wheal reactions (P = .01), pruritus (P = .005), burning sensation (P = .03), and subjective complaints (P = .03) after rupatadine treatment were also found. Mild fatigue (n = 4), somnolence (n = 1), and moderate headache (n = 1) were reported during active treatment.
Rupatadine, 20 mg/d, shows high efficacy and is well tolerated in the treatment of ACU symptoms.
Disease burden is particularly high in Chronic Spontaneous Urticaria (CSU) patients with angioedema, and patients whose signs and symptoms are inadequately controlled by H1-antihistamines need new ...treatment options. Here we report an exploratory analysis, from the ligelizumab Phase 2b study, investigating angioedema occurrence in patients with CSU and describe the changes in angioedema following treatment with ligelizumab, omalizumab, or placebo.
Data from the ligelizumab Phase 2b core (ligelizumab 72 mg, 240 mg, omalizumab 300 mg and placebo) and extension study (ligelizumab 240 mg) were used. Changes in Weekly Angioedema Activity Score (AAS7), the Dermatology Life Quality Index (DLQI), and Weekly Urticaria Activity Score (UAS7) among each time point were analyzed for each treatment arm.
From a total of 297 patients analyzed, 165 (55.6%) reported angioedema occurrence at baseline, with mean AAS7 ranging 30.6—42.2 across treatment arms. At Week 12 of the core study 87.5%, 84.6%, 75.0%, and 61.0% of patients were angioedema free for ligelizumab 72 mg, 240 mg, omalizumab 300 mg, and placebo arms, respectively. In CSU patients with angioedema at baseline, the largest change from baseline in AAS7 score was observed with ligelizumab 72 mg (−31.9) at week 16 in the core study. Patients with angioedema had a higher mean DLQI at baseline (14.9—16.1) vs. patients without angioedema (10.6—12.0). In patients with angioedema, low AAS7 was significantly associated with complete response on UAS7 (UAS7 = 0) and complete normalization of DLQI (DLQI 0—1).
In the Phase 2b study, ligelizumab effectively reduced angioedema and urticaria symptoms, and improved health related quality of life in patients with moderate-to-severe CSU.
NCT02477332; NCT02649218.
...many allergic patients exhibit high levels of circulating antigen-specific IgE but never have anaphylaxis, whereas other subjects with low concentrations of specific IgE in the blood can ...experience anaphylactic shock.1 Endothelin-1 (ET-1), a 21-amino-acid naturally occurring peptide with potent vasoconstrictor activity, has been reported to exacerbate certain allergic reactions in rodents. MCs are thought to represent a critical effector cell in IgE-dependent anaphylaxis.1 Prior functional assays and expression analyses of various MC populations demonstrated that ETA can be expressed by connective tissue-type MCs, including peritoneal MCs.5,6,9 However, immature bone marrow-derived cultured mouse mast cells (BMCMCs), which have some similarities to mucosal-type MCs, are largely unresponsive to ET-1 and have very low levels of receptor expression.6 We confirmed, using flow cytometric analysis, the substantial expression of ETA and weak expression of ETB on C57BL/6 mouse peritoneal MCs (Fig 1, A), as well as the absence of detectable surface ETB and very weak expression of ETA on C57BL/6 mouse BMCMCs (Fig 1, B).
Purpose To observe the effect of a topical anesthetic on pain and corneal clarity in premature infants undergoing eye examinations for retinopathy of prematurity (ROP). Methods ROP examinations were ...performed on premature infants who were randomized to receive either proparacaine 0.5% or an artificial tear solution in the right eye. All infants received an artificial tear solution in the left eye. Assessment of discomfort was performed by use of the Premature Infant Pain Profile (PIPP) during examination of the right eye, with a painful event defined as a PIPP score ≥11. The left eye was then examined and a comparison of corneal clarity was made between the 2 eyes. Results A total of 39 examinations were performed on 34 infants: artificial tear solution was administered 17 times and topical proparacaine anesthetic 22 times. The mean PIPP score for those receiving artificial tears was 10.4 compared with 8.8 for the anesthetic group ( p = 0.17). Of the examinations without anesthetic, 65% were painful, compared with 27% with anesthetic ( p = 0.04). No effect on corneal clarity was observed in any examination. Conclusions The use of a topical anesthetic appears to marginally decrease pain and has no adverse effect on subjectively assessed corneal clarity during examination of premature infants for ROP.
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