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Purpose Numerous studies have demonstrated effectiveness for acupuncture in the treatment of seasonal allergic rhinitis (SAR). However, the underlying mechanism remains still unclear. Methods 29 SAR patients were recruited from a large randomized, controlled trial investigating the efficacy of acupuncture in SAR. 16 patients were treated by acupuncture plus rescue medication (RM, cetirizine), 6 patients received sham acupuncture plus RM and 8 patients RM alone over 8 weeks. Patients were blinded to the allocation to real or sham acupuncture. At baseline and different time-points during intervention, plasma and nasal concentration of mediators of various biological functions were determined in addition to validated disease-specific questionnaires. Results The concentration of biomarkers related to the Th1-, Th2-, and Treg-cluster was not changed in patients who received acupuncture, in neither plasma nor nasal fluid. However, with respect to eotaxin and some unspecific pro-inflammatory cytokines (IL-1b, IL-8, IP-10, MIP-1b, MCP-1), acupuncture led to a, partially significantly, lower nasal concentration than sham acupuncture or RM. Furthermore, the nasal symptom score was significantly reduced in patients only after real acupuncture. Conclusion In SAR, acupuncture reduces the intranasal unspecific inflammation, but does not seem to act immunologically on the Th1–Th2-imbalance.

Catalina Högerle, Marion San Nicolo, Donata Gellrich, Katharina Eder, Moritz Gröger Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maximilians-University Munich, München, GermanyCorrespondence: Catalina Högerle, Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maiximilians-Universität München, Marchioninistr. 15, München, D- 81377, Germany, Tel +49 89 4400 73892, Fax +49 89 4400 76892, Email catalina.hoegerle@med.uni-muenchen.dePurpose: Many plant food allergens contain homologs to the major birch allergen Bet v 1; therefore, the majority of patients with birch pollen allergy suffer from oral allergy syndrome. We studied the relevance of sensitization of Bet v 1 and co-sensitization with profilin concerning the clinical manifestations of an oral allergy syndrome.Patients and Methods: A total of 1119 patients with a positive skin prick test to birch and diagnostic for specific IgE to the allergen components Bet v 1 and profilin were analyzed retrospectively regarding complaints in the upper and lower airways, with demographic data as well as oral and gastrointestinal allergy symptoms.Results: Patients with simultaneous specific IgE to the allergen components Bet v 1 and profilin have to deal more often with an oral allergy syndrome and intestinal reactions. They also suffer more frequently and severely from rhinitis symptoms and show a higher tendency for asthma. No increased number of systemic reactions was seen.Conclusion: Patients with birch allergy recognizing both allergens have more probabilities of suffering from an oral allergy syndrome, and allergologists should be aware of this in order to give better advice to their patients.Keywords: oral allergy syndrome, clinical relevance of allergens, birch pollen sensitization, profilin co-sensitization, component resolved diagnostic

In recent studies, it has been assumed that vocal tract formants (Fn) and the voice source could interact. However, there are only few studies analyzing this assumption in vivo. Here, the vowel transition /i/-/a/-/u/-/i/ of 12 professional classical singers (6 females, 6 males) when phonating on the pitch D4 [fundamental frequency (ƒo) ca. 294 Hz] were analyzed using transnasal high speed videoendoscopy (20.000 fps), electroglottography (EGG), and audio recordings. Fn data were calculated using a cepstral method. Source-filter interaction candidates (SFICs) were determined by (a) algorithmic detection of major intersections of Fn/nƒo and (b) perceptual assessment of the EGG signal. Although the open quotient showed some increase for the /i-a/ and /u-i/ transitions, there were no clear effects at the expected Fn/nƒo intersections. In contrast, ƒo adjustments and changes in the phonovibrogram occurred at perceptually derived SFICs, suggesting level-two interactions. In some cases, these were constituted by intersections between higher nƒo and Fn. The presented data partially corroborates that vowel transitions may result in level-two interactions also in professional singers. However, the lack of systematically detectable effects suggests either the absence of a strong interaction or existence of confounding factors, which may potentially counterbalance the level-two-interactions.

Background: To improve the biocompatibility of porous polyethylene (PPE) implants and expand their application range for reconstructive surgery in poorly vascularized environments, implants were coated with tumor necrosis factor α (TNFα) inhibitor Etanercept. While approved for systemic application, local application of the drug is a novel experimental approach. Microvascular and mechanical integration as well as parameters of inflammation were analyzed in vivo. Methods: PPE implants were coated with Etanercept and extracellular matrix (ECM) components prior to implantation into dorsal skinfold chambers of C57BL/6 mice. Fluorescence microscopy analyses of angiogenesis and local inflammatory response were thrice performed in vivo over a period of 14 days to assess tissue integration and biocompatibility. Uncoated implants and ECM-coated implants served as controls. Results: TNFα inhibition with Etanercept led to a reduced local inflammatory response: leukocyte-endothelial cell adherence was significantly lowered compared to both control groups (n = 6/group) on days 3 and 14, where the lowest values were reached: 3573.88 leukocytes/mm-2 ± 880.16 (uncoated implants) vs. 3939.09 mm-2 ± 623.34 (Matrigel only) vs. 637.98 mm-2 + 176.85 (Matrigel and Etanercept). Implant-coating with Matrigel alone and Matrigel and Etanercept led to significantly higher vessel densities 7 and 14 days vs. 3 days after implantation and compared to uncoated implants. Mechanical implant integration as measured by dynamic breaking strength did not differ after 14 days. Conclusion: Our data show a reduced local inflammatory response to PPE implants after immunomodulatory coating with Etanercept in vivo, suggesting improved biocompatibility. Application of this tissue engineering approach is therefore warranted in models of a compromised host environment.

Introduction: Sensitization to Aspergillus fumigatus is a risk factor for severe asthma. However, little is known about its presence, appearance, and impact on allergic rhinitis. Herein, we investigated the usefulness of component resolved diagnostics in patients sensitized to Aspergillus fumigatus protein extract. Methods: Seventy-eight patients with suspected allergic rhinitis and elevated IgE levels toward Aspergillus fumigatus protein extract were retrospectively evaluated regarding their total and Aspergillus-specific IgE levels and their skin prick test. Furthermore, they were tested for specific IgE antibodies against Asp f 1, 2, 3, 4, and 6. Results: Skin prick test missed 6 patients (7.7%) with elevated IgE toward Aspergillus fumigatus protein extract. Fifty percent of patients (n = 39) were sensitized to at least one component. Even though monosensitization affected all components, all patients with positivity toward more than one component were sensitized to Asp f 1. There was a statistically significant increase of Aspergillus-specific IgE with increasing number of components affected by sensitization. Many patients were oligo- (34.6%) or polysensitized (51.3%). There was a high prevalence of sinusitis (61.8%). Conclusions: Component resolved diagnostic testing toward the major allergen Asp f 1 was less sensitive than skin prick test and serology to Aspergillus fumigatus protein extract. However, sensitivity of component resolved diagnostics might be underestimated. Diagnostics of the species-specific allergens Asp f 1, 2, and 4 might allow to differentiate between genuine and cross-reactive sensitization. In the clinical routine, skin prick test and serology to crude extract remain the methods of choice.

Regulatory and economic conditions drive the application of the concept of homologous groups on therapeutic and diagnostic formulations. In this context, a possible reduction of allergens in the skin prick test panel in the clinical routine should be investigated for the grass, birch and Dermatophagoides homologous group. Grass and cultivated rye skin prick test results of 1101 patients, birch/hazel/alder skin prick test results of 1131 patients and 1068 Dermatophagoides pteronyssinus and farinae skin prick tests were retrospectively evaluated with regard to sensitivity and false-negative rate detecting sensitization against cultivated rye with grass skin prick test, sensitization against hazel and/or alder with birch skin prick test and sensitization towards Dermatophagoides farinae with Dermatophagoides pteronyssinus skin prick test. Skin prick test results in all groups highly correlated in Spearman Rank Order correlation. Sensitivity of grass skin prick test detecting sensitization against cultivated rye was highest with 98.9%, sensitivity of birch skin prick test detecting sensitization toward hazel and alder was 95.6 and 90.0%, respectively. Sensitivity of skin prick test with Dermatophagoides pteronyssinus detecting sensitization towards Dermatophagoides farinae was 93.6%. Only 26 patients with positive rye, hazel, alder or Dermatophagoides farinae skin prick test that were overlooked by grass, birch or Dermatophagoides pteronyssinus skin prick test reported allergic symptoms. In routine clinical practice, sensitization against cultivated rye can safely be detected by skin prick test with grass allergen. In addition, the sensitivity of birch skin prick test is high in terms of sensitization towards hazel, but lower for alder. Sensitivity of Dermatophagoides pteronyssinus skin prick test also is high to detect sensitization towards Dermatophagoides farinae. Further research will indicate if several skin prick test allergens will disappear and be completely replaced by a single skin prick test based on the principle of homologous groups.

In current voice research, there is a growing interest in semi-occluded vocal tract exercises and their contribution to an increased vocal efficiency. However, there are only few studies on the lasting effects.Eight vocally healthy subjects were asked to sustain a phonation at a comfortable loudness on the vowel /i/, with a Fundamental Frequency of 250 Hz (females) or 125 Hz (males). During phonation the subjects were simultaneously recorded with transnasal High Speed Videoendoscopy (HSV, 20,000fps), electroglottography, and audio signals. The subjects then performed a water resistance therapy (WRT) for 10 min (tube: 30 cm length, 5 cm below water surface, diameter 9 mm). Repeated measurements of sustained phonation were performed 0, 5, 10, 20, and 30 min after exercising. From the HSV material the Glottal Area Waveform (GAW) was segmented and GAW parameters were computed.There were strong inter-individual differences concerning the changes of different measures over time after WRT. In general, directly after WRT there was a lowering of the GAW derived Period Perturbation Quotient, a lowering of the Closing Quotient and an increase of the Sound Pressure Level (SPL) in comparison to the pre-intervention measurement. However, only 5 min post WRT there was no longer a clear difference compared to baseline results before WRT. Other values such as Open Quotients exhibited no evident changes by WRT at any timepoint.WRT showed strong inter-individual effects concerning the changes in the evaluated measures post-intervention. General tendencies of some measures directly after the intervention showed a brief effect of only a few minutes.

Aspirin-exacerbated respiratory disease (AERD) is a severe form of chronic rhinosinusitis with nasal polyps (CRSwNP) accompanied by asthma and an aspirin intolerance. The underlying pathomechanism of AERD still remains unclear, recent data suggest a complex inflammatory imbalance. In the present study, we investigated the cytokine patterns in AERD, CRSwNP and healthy control patients. Furthermore, we describe the change in cytokine level in the course of aspirin desensitization (AD) with continuous intake of aspirin. The study included a total of 104 participants, 48 healthy controls, 45 patients with nasal polyps and 11 patients with AERD undergoing AD. Nasal secretions were analyzed for IL-1β, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17, THF-α, IFN-γ, eotaxin and ECP using Bio-Plex Human Cytokine Assay and Uni-CAP FEIA. Baseline measurements of cytokine levels were performed in all 104 patients; in patients with AERD, follow-up was performed 1–6 and 6–24 months after the initiation of AD. Our preliminary results show a TH2 dominated, eosinophilic milieu in AERD patients, which decreased in the first weeks of AD. However, after 6 months of AD, proinflammatory cytokines show a tendency to increase again. Also, TH1 as well as Treg associated cytokine seem to increase over time. For the first time, the present work shows the cytokine pattern in nasal secretions of AERD patients before and during AD. Further investigation of the complex interaction of inflammatory cytokines during AD might reveal important insights into the disease entity of AERD and open up new horizons for a targeted therapy.

Der Schluckakt ist ein hochkomplexer Vorgang, der auf vielen Ebenen storanfallig ist. Schluckstorungen kommen besonders haufig im hoheren Lebensalter vor. Zum einen nimmt die Inzidenz von Erkrankungen, die mit Dysphagie einhergehen, zu. Zum anderen ist das Schlucken aufgrund von altersphysiologischen Veranderungen weniger effizient.

Introduction: Weed pollen allergy is an important and in prevalence increasing cause of pollinosis in Europe and across the world. In this study we focus on the value of common diagnostic tools for detection of a sensitization to mugwort and English plantain, especially with regard to the clinical relevance of the sensitization. Methods: Eighty weed pollen sensitized patients (41 to mugwort and 39 to English plantain) were assessed retrospectively regarding their clinical anamnesis, in-vivo tests (skin prick test [SPT] and allergen specific provocation) and in-vitro tests (immunoglobulin E [IgE] reactivity to purified natural allergen extract and specific allergen components in serum). Results: 85% of mugwort and 83% of English plantain sensitizations could be diagnosed by SPT alone. Distinction between allergic and non-allergic patients could be made with clinical challenges solely. IgE serology revealed IgE antibodies against the native pollen extracts for mugwort in 98% and for English plantain in 90% of patients. Detection of major allergens nArt v 1, nArt v 3 and Pla l 1 did not add accuracy to the diagnosis. A vast majority of the weed pollen allergic patients was sensitized to >1 allergen. Minor allergens were found to be of less importance. Conclusion: The exact diagnosis of weed pollen allergy can be challenging due to confounding components in anamnesis and diagnostic tests. IgE-serology does not delineate allergic from sensitized patients. Component resolved diagnostics (CRD) can confirm, but not replace, extract based diagnostic methods, such as SPT, provocation tests or serology to native extracts. Hence, these are the gold standard diagnostic tools in weed pollen allergy up to now.

Purpose For perennial inhalant allergens such as house dust mite (HDM), the German guideline on allergen-specific immunotherapy explicitly recommends provocation testing. This procedure is time-consuming, expensive, and potentially dangerous for the patient. Recently it has been discussed whether provocation tests are really necessary for diagnosing allergy to Dermatophagoides species. Thus, our study aimed to analyze the concordance between nasal provocation tests with Dermatophagoides species and anamnestic data. Methods We retrospectively analyzed the concordance between patients’ histories including self-reported symptom scores and the results of provocation testing in 471 individuals with proven sensitization to Dermatophagoides species. Results 248 patients had a positive nasal provocation test (NPT) result to Dermatophagoides species and 223 individuals a negative NPT result. Patients allergic to HSM suffered significantly more often from atopic dermatitis (14% vs. 7%, p = 0.046) and more from asthma (20% vs. 19%, p = 0.851). Moreover, individuals with clinically silent sensitization complained less about nasal secretion (37% vs. 45%, p = 0.244) but significantly more about nasal dryness (46% vs. 34%, p = 0.046) whereas rates of nasal airway obstruction, ocular complaints and sleep quality were comparable in both groups. Allergic patients reported more often perennial (34% vs. 30%, p = 0.374) and location-dependent (39% vs. 31%, p = 0.090) symptoms. However, the discrepant prevalence of atopic dermatitis was the only statistically significant difference between both groups. Conclusion Despite slight differences between both patient groups, clinical data are not sufficient to distinguish between silent sensitization and clinically relevant allergic rhinitis to HDM. Therefore, nasal provocation testing remains the gold standard for assessing clinical relevance in patients sensitized to Dermatophagoides species.

Background: Recently, population-based birth-cohort studies provided an insight into the allergic march during childhood.Aims: Our study aimed to investigate sensitization pattern until advanced ag...

Introduction Diseases of the salivary glands are rare in children and adolescents, with the exception of viral-induced infections. Objective To determine the clinical course of the disease, the diagnostic procedures, the treatment and the outcome of all children and adolescents affected with salivary gland diseases at our clinic over a period of 15 years. Methods A retrospective chart review including a long-term follow-up was conducted among 146 children and adolescents treated for salivary gland disorders from 2002 to 2016. Results Diagnosing acute sialadenitis was easily managed by all doctors regardless of their specialty. The diagnosis of sialolithiasis was rapidly made only by otorhinolaryngologists, whereas diagnosing juvenile recurrent parotitis imposed difficulties to doctors of all specialties – resulting in a significant delay between the first occurrence of symptoms and the correct diagnosis. The severity-adjusted treatment yielded improvements in all cases, and a full recovery of 75% of the cases of sialolithiasis, 73% of the cases of juvenile recurrent parotitis, and 100% of the cases of acute sialadenitis. Conclusions Due to their low prevalence and the lack of pathognomonic symptoms, salivary gland diseases in children and adolescents are often misdiagnosed, resulting in an unnecessarily long period of suffering despite a favorable outcome following the correct treatment.

Introduction: House dust mite contains several allergen components and causes perennial allergy. Lately, a new major allergen, Der p 23, was described with relatively high sensitization rates in different European Countries. In addition, Der p 23 is supposed to cause asthmatic disease. Objective: We would like to question the prevalence and clinical impact of specific immunoglobulin E to Der p 23 in a large patient sample in southern Bavaria, Germany. Methods: 474 patients from southern Bavaria, who visited the allergy department within the Department of Oto-Rhino-Laryngology of a university hospital, with sensitization to Dermatophagoides pteronyssinus were retrospectively compared regarding their sensitization profile to Der p 1, Der p 2, and Der p 23 and their clinical characteristics. Results: Among D. pteronyssinus-sensitized patients, the overall sensitization rate to Der p 23 was 42% in southern Bavaria. Most likely, patients were simultaneously sensitized to Der p 1, Der p 2, and Der p 23. Der p 23-sensitized patients reported more frequently asthma and showed higher prevalence of poly-sensitization towards 3 additional allergen groups and higher prevalence of double-sensitization to Der p 1 and Der p 2 compared to patients with missing sensitization to Der p 23. Considering the results of allergen provocation tests, neither IgE sensitization against Der p 23 nor levels of specific immunoglobulin E to Der p 23 allow a clear prediction of the clinical relevance of the sensitization. Conclusion: With a sensitization rate of 42%, Der p 23 closely misses the criterion of a major allergen in our southern Bavarian patient collective. A higher prevalence of polysensitization and self-reported asthma was the only clinical feature found in Der p 23-sensitized patients.

Background Static magnetic fields (SMF) exhibit antitumoral activity and enhance the efficacy of chemotherapy by opening the tumor-blood barrier. This study aimed to analyze different SMF-exposure protocols on epidermal growth factor receptor (EGFR)-overexpressing tumors, as well as their combination with cetuximab. Materials and methods Experiments were performed in skinfold chamber preparations of C57Bl/6-and CD-1nu/nu mice bearing LLC-1 tumors. Animals were exposed to 587 mT magnetic field following different exposure protocols. A subgroup received additional cetuximab injections. Using in vivo-fluorescence microscopy and planimetry, tumor angiogenesis, growth and microcirculation were repeatedly analyzed for 13 days. Results In contrast to daily short SMF exposure, three-fold SMF exposure for 2 h led to a significant 46% reduction of tumor growth. Adding cetuximab to SMF exposure did not yield any benefit, although cetuximab monotherapy was highly effective (53% reduction of tumor growth), indicating a potential interference of SMF and EGFR signaling. No effects on microcirculation, angiogenesis or leukocyte-endothelium interactions were documented. Conclusion The use of SMF is promising in the treatment of solid tumors; however, it appears to interfere with EGFR-targeted therapy.

Die juvenile chronisch-rezidivierende Parotitis ist die zweithaufigste entzundliche Speicheldrusenerkrankung bei Kindern. Dennoch wird sie oft erst spat nach unnotig langem Leidensweg der Betroffenen erkannt. Der folgende Beitrag gibt eine Ubersicht uber die Erkrankung, deren Diagnostik sowie Therapiekonzepte und zeigt auf, wie sich Fehldiagnosen vermeiden lassen.

Background: Bet v 6, a minor birch pollen allergen, is commercially available for allergen-specific IgE antibody testing. However, there is hardly any literature on the clinical impact of Bet v 6. The aim of the present study was to analyze if testing specific IgE against Bet v 6 can add valuable benefit to the standard diagnostics of birch pollen-sensitized patients, especially in patients with unknown sensitization-eliciting allergens. Methods: Birch pollen-sensitized patients with missing IgE reactivity against Bet v 1, 2, and 4 were tested for specific IgE antibodies against Bet v 6. For comparison, an equal number of randomly selected patients with birch pollen sensitization, regardless of their individual sensitization patterns, were tested for specific anti-Bet v 6. Results: Of 57 cases with missing reactivity against the standard birch pollen allergens, 2 patients were positive for Bet v 6. In the representative sample, 3 patients showed specific IgE against Bet v 6 - resulting in a total prevalence of 5%. None of the Bet v 6-positive patients showed allergic symptoms after exposure to birch pollen or an oral allergy syndrome. An increased prevalence of asthma and a higher degree of sensitization were the only distinctive clinical features in Bet v 6-positive patients. Conclusions: Among birch pollen-sensitized patients, the prevalence of specific IgE against Bet v 6 is low. Further, sensitization to Bet v 6, which shows characteristics of a panallergen, remains clinically silent. Therefore, determination of anti-Bet v 6 is not considered useful in the clinical routine.

Since the beneficial implementation of allergen specific subcutaneous immunotherapy (SCIT), there are only a few studies on the risk of SCIT-induced neosensitizations. In 51 patients, we retrospectively analyzed sIgE and sIgG patterns by a multiplex ELISA as well as demographic and clinical features before and after SCIT. 33 allergic patients, who only received symptomatic treatment, served as controls. In 12 of 51 SCIT-treated patients (24%), we found new sIgE against allergen components of the allergen source treated by SCIT; eight of them were adults. Among controls, no adult patient showed neosensitization to components of the primarily affected allergen source. Only two children of the control group were affected by neosensitization, which was limited to major allergen components and rarely accompanied by sIgG. In the SCIT-treated group, neosensitization affected major and minor allergen components, and was accompanied by a strong induction of sIgG against major components. A clear clinical predictor of neosensitization during SCIT was not found. Comparing symptom scores, patients seem to profit more from SCIT, if neosensitization remained absent. Patients undergoing SCIT might carry an enhanced risk of neosensitization towards formerly unrecognized allergen components. According to anamnestic data, these neosensitizations might be of clinical relevance - supporting attempts towards personalized recombinant vaccines.

BACKGROUND AND OBJECTIVE An increasing number of studies have recently discussed whether provocation tests might be replaced by specific IgE serology in patients sensitized to airborne allergens. Objective: Our study aimed to analyze the concordance between a nasal provocation test with Dermatophagoides pteronyssinus and specific IgE measurements based on real-life data. METHODS We retrospectively analyzed concordance between the result of the provocation test and the IgE titer for house dust mite components and extracts in 223 patients with proven sensitization to D pteronyssinus. RESULTS In contrast to findings from other studies, the anti-Der p 1 level alone was not sufficient to distinguish between silent sensitization and allergy to D pteronyssinus. ROC curve analysis revealed that the sum of sIgE against Der p 1 and Der p 2 is-after adjustment for total serum IgE-the best parameter for discriminating between clinically silent and relevant sensitization. However, it does not have sufficient validity to confirm a diagnosis. CONCLUSIONS Despite the high correlation between sIgE levels and symptoms, no serologic parameter is sufficiently accurate to distinguish between silent sensitization and clinically relevant allergy. Therefore, nasal provocation tests remain the gold standard for assessing clinical relevance in sensitization to D pteronyssinus.

Objective— Pretubulysin (PT) is a novel, synthetically accessible myxobacterial compound that acts as a tubulin-depolymerizing agent and inhibits cancer cell growth in vitro and in vivo. Moreover, PT was found to attenuate tumor angiogenesis. Here, we hypothesized that PT could exert antivascular activities on existing tumor vessels. Approach and Results— We aimed to characterize the antivascular effects of PT and to elucidate the underlying mechanisms in endothelial cells. In vitro, PT rapidly induced endothelial hyperpermeability and a concentration-dependent disassembly of established endothelial tubes on Matrigel and in an ex vivo aortic ring model. It disrupted endothelial cell junctions and triggered F-actin stress fiber formation and cell contraction by the RhoA/Rho-associated protein kinase pathway without causing cell death. In vivo, using a hamster dorsal skinfold chamber preparation, PT significantly decreased blood flow and vessel diameter in hamster A-Mel-3 amelanotic melanoma tumors but not in the neighboring healthy tissue. In a second tumor model using mice with subcutaneous murine B16 melanoma tumors, a single dose of PT (10 mg/kg) caused a shut down of tumor blood flow and a strong central tumor cell necrosis within 24 hours. Repeated PT administration significantly decelerates tumor growth and seems to be well tolerated. Conclusions— In summary, we could show for the first time that the antitumor effect of PT is, at least in part, mediated via its antivascular activities on existing tumor vessels.

Background The purpose of this phase I/II clinical trial was to test safety and effectiveness of 2 doses of vascular targeting cationic liposomes encapsulating paclitaxel (EndoTAG-1 [ET]) in human head and neck squamous cell carcinoma (HNSCC). Methods Patients with nonresectable therapy-refractory HNSCC were recruited for both ET treatment groups (3 or 4 patients per group). In cutaneous metastases, laser Doppler blood flow measurements were conducted during infusions. Results Only adverse events of grade 1 or 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 3.0) – in particular fatigue, chills, and hypertension – occurred. Follow-up tumor volume measurements revealed stable disease in 4 of 5 cases. Reproducible dose-dependent blood flow reductions in skin metastases during ET infusions provide evidence of biological effectiveness. Conclusion Infusions of ET seem to be safe and further phase II and III studies are warranted to prove efficacy in the treatment of HNSCC. © 2013 Wiley Periodicals, Inc. Head Neck 36: 976–984, 2014

OBJECTIVES: This study aims to answer whether acoustic radiation force impulse imaging (ARFI) can reasonably be employed in initial examination and follow-up during therapy in patients with sialolithiasis, one of the most common non-malignant disorders of the salivary glands. METHODS: Mechanical tissue properties of affected and contralateral healthy salivary glands were analyzed by ARFI in 129 patients with sialolithiasis. In different subgroup analyses, ARFI shear wave velocity values were compared between healthy and diseased submandibular or parotid glands, salivary glands with calculi exhibiting different sizes, as well as before and after therapy. The patients’ symptoms were evaluated by a standardized questionnaire. The t-test (2 groups) or the One-way ANOVA test (>2 groups) was used for the estimation of stochastic probability in intergroup comparisons. RESULTS: Submandibular or parotid glands affected by sialolithiasis were found to exhibit significant lower ARFI values as compared to the healthy contralateral glands in the same individuals. ARFI values in submandibular glands with a single calculus of more than 5 mm in diameter or with multiple calculi as well as in parotid glands with calculi exhibiting diameters of more than 5 mm were significantly higher as compared to the respective healthy contralateral glands. No significant differences in ARFI values of affected salivary glands were detected between patients with low or high symptom perception. CONCLUSIONS: ARFI provides an easy, quick and reliable diagnostic tool for the objective assessment of disease severity and progression in patients with sialolithiasis that can simply be implemented in pre-existing ultrasound protocols.

Static magnetic fields (SMF) induce an intratumoral edema possibly by increasing microvessel permeability. The aim of this study was to evaluate the effects of SMF on tumor microvessel permeability and on treatment effects of conventional cytotoxic chemotherapy. Using intravital microscopy in skinfold chamber preparations in A-Mel-3-tumor-bearing hamsters, functional tumor microcirculation, microvessel permeability and leukocyte-endothelial cell interactions were measured under SMF-exposure (587 mT). Combining SMF-exposure with paclitaxel-chemotherapy, tumor growth was analyzed. SMF inhibited tumor angiogenesis and increased tumor microvessel permeability significantly. This was not mediated by inflammatory leukocyte-endothelial cell interactions. Further, SMF increased the effectiveness of paclitaxel-chemotherapy significantly. These findings support that SMF possibly open the blood-tumor-barrier to small molecular therapeutics.

The purpose of this phase I/II clinical trial was to test safety and effectiveness of 2 doses of vascular targeting cationic liposomes encapsulating paclitaxel (EndoTAG-1 [ET]) in human head and neck squamous cell carcinoma (HNSCC).Patients with nonresectable therapy-refractory HNSCC were recruited for both ET treatment groups (3 or 4 patients per group). In cutaneous metastases, laser Doppler blood flow measurements were conducted during infusions.Only adverse events of grade 1 or 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 3.0) - in particular fatigue, chills, and hypertension - occurred. Follow-up tumor volume measurements revealed stable disease in 4 of 5 cases. Reproducible dose-dependent blood flow reductions in skin metastases during ET infusions provide evidence of biological effectiveness.Infusions of ET seem to be safe and further phase II and III studies are warranted to prove efficacy in the treatment of HNSCC.