Influencing factors on the safety and effectiveness of venom immunotherapy.

BACKGROUND AND OBJECTIVE: The safety profile of venom immunotherapy (VIT) is a relevant issue and considerable differences in safety and efficacy of VIT have been reported. The primary aim of this study was to evaluate the safety of ACE inhibitors and beta-blockers during VIT, which has already been published. For a second analysis, data concerning premedication and venom preparations in relation to systemic adverse events (AE) during the up-dosing phase and the first year of the maintenance phase were evaluated as well as the outcome of field stings and sting challenges. METHODS: The study was conducted as an open, prospective, observational, multicenter study. In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. RESULTS: Premedication with oral antihistamines was taken by 52.1% of patients during the up-dosing and 19.7% of patients during the maintenance phase. Taking antihistamines had no effect on the frequency of systemic AE (p=0.11) but large local reactions (LLR) were less frequently seen (OR: 0.74; 95% CI: 0.58-0.96; p=0.02). Aqueous preparations were preferentially used for up-dosing (73.0%) and depot preparations for the maintenance phase (64.5%). The type of venom preparation neither had an influence on the frequency of systemic AE nor on the effectiveness of VIT (p=0.26 and p=0.80, respectively), while LLR were less frequently seen when depot preparations were used (p<0.001). CONCLUSION: Pretreatment with oral antihistamines during VIT significantly reduces the frequency of LLR but not systemic AE. All venom preparations used were equally effective and did not differ in the frequency of systemic AE.

Dipolar Quantum Mixtures of Erbium and Dysprosium Atoms.

We report on the first realization of heteronuclear dipolar quantum mixtures of highly magnetic erbium and dysprosium atoms. With a versatile experimental setup, we demonstrate binary Bose-Einstein condensation in five different Er-Dy isotope combinations, as well as one Er-Dy Bose-Fermi mixture. Finally, we present first studies of the interspecies interaction between the two species for one mixture.

Scaffolds in a shell-a new approach combining one-photon and two-photon polymerization.

We report on a laser system combining one-photon and two-photon polymerization for precise and fast fabrication of macroscopic three-dimensional structures featuring microscale and nanoscale characteristics. This single-stage process significantly reduces the production time as demonstrated by scaffolds in a shell application. Porous scaffolds with different pore sizes are surrounded by a ring so that cells can be seeded directly to the scaffolds kept in a shell and do not spread over the whole substrate expecting a saving of cell suspension, faster growth on the scaffolds, and a more controllable environment. Compared to a two-photon polymerization process, the ring is fabricated about 500 times faster using one-photon polymerization. The presented hybrid process qualifies for further applications illustrated by a fluidic system.

Freshly squeezed: anaphylaxis caused by drone larvae juice.

Summary: Drone larvae are mostly considered a by-product of beekeeping, but have recently been advo-cated as a high-protein source of food. There are as yet no data concerning their allergenic potential. We report on a 29-year old bee keeper who experienced an anaphylactic reaction following the consumption of a freshly prepared beverage from raw drone larvae. Larvae-specific sensitization was confirmed by prick-to-prick and basophil activation testing. Bee stings and classical bee products including honey and royal jelly were tolerated. This is the hitherto first report on IgE-mediated allergy to drone larvae. We suggest that a certain awareness towards the allergenicity of bee larvae is required.

General anaesthesia-induced anaphylaxis: impact of allergy testing on subsequent anaesthesia.

BACKGROUND: Immunoglobulin E-mediated allergy to drugs and substances used during general anaesthesia as well as non-allergic drug hypersensitivity reactions may account for anaesthesia-induced anaphylaxis. As IgE-mediated anaphylaxis is a potentially life-threatening reaction, identification of the culprit allergen is essential to avoid anaphylaxis recurrence during subsequent general anaesthesia. OBJECTIVE: To study whether preventive recommendations derived from allergy testing after intraoperative anaphylaxis were followed in subsequent general anaesthesia. METHODS: Results of standardized allergy testing after anaesthesia-induced anaphylaxis and outcome of subsequent general anaesthesia were analysed retrospectively. RESULTS: Fifty-three of 107 patients were diagnosed with IgE-mediated allergy to a drug or substance used during general anaesthesia, and 54 patients were test negative. Twenty-eight of 29 allergy patients tolerated subsequent general anaesthesia uneventfully. One patient with cefazolin allergy suffered from anaphylaxis recurrence due to accidental reapplication of cefazolin. Twenty-two of 24 test-negative patients tolerated subsequent general anaesthesia, whereas two patients again developed anaphylaxis despite pre-medication regimens. CONCLUSION AND CLINICAL RELEVANCE: Our results confirm the practical impact of allergy testing in general anaesthesia-induced anaphylaxis. By identification of the allergen, it is possible to avoid allergic anaphylaxis during subsequent anaesthesia. In most cases, recommended pre-medication seems to prevent the recurrence of non-allergic drug hypersensitivity reactions.

Electrochemical degradation of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in groundwater.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) represent hazardous pollutants and are frequently detected in the environment, e.g. in contaminated groundwater. PFASs are persistent to biodegradation and conventional oxidation processes such as ozonation. In this study electrochemical degradation of PFASs on boron-doped diamond (BDD) electrodes is demonstrated. Experiments were performed with model solutions and contaminated groundwater with a dissolved organic carbon (DOC) content of 13 mg/L. The perfluorinated carboxylic acids (PFCAs) perfluorobutanoate, perfluoropentanoate, perfluorohexanoate, perfluoroheptanoate and perfluorooctanoate, and the perfluorinated sulfonic acids (PFSAs) perfluorobutane sulfonate, perfluorohexane sulfonate, perfluorooctane sulfonate and 6:2 fluorotelomer sulfonate were detected in the groundwater samples. At PFAS concentrations ranging from 0.26 to 34 mg/L (0.7 to 79 µM), the degradation of PFASs was achieved despite of the high DOC background. Pseudo first-order kinetic constants of PFSA degradation increased with the increase of carbon chain length. Fluoride formation as well as the generation of PFCAs with shortened chain lengths was observed. Inorganic byproducts such as perchlorate were also formed and have to be considered in further process optimization.

Relief of photoallergy: atorvastatin replacing simvastatin

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Aminopenicillin-associated exanthem: lymphocyte transformation testing revisited.

BACKGROUND: The lymphocyte transformation test (LTT) has been promoted as in-vitro test for diagnosis of drug hypersensitivity. For determination of statistical LTT sensitivity, series of patients with clinically uniform reactions followed by complete drug hypersensitivity work-up are mandatory. Assessment of LTT specificity requires control patients who tolerated exposure to the drug studied. OBJECTIVE: To prospectively determine the diagnostic value of the LTT in a clinically and diagnostically well-defined series of patients. METHODS: Patients with exanthematous skin eruptions after ampicillin (AMP) intake were included in this study. After exclusion or confirmation of delayed-onset allergic AMP hypersensitivity by skin and provocation testing, two independent LTTs were performed: one standard LTT and a modified LTT with additional anti-CD3/anti-CD28 monoclonal antibody stimulation. RESULTS: By testing, delayed-onset allergic AMP hypersensitivity was diagnosed in 11 patients and definitely ruled out in 26. The standard LTT reached a diagnostic sensitivity of 54.5% while the modified LTT yielded 72.7%. However, the methodical test modification resulted in a decline of specificity from 92.3% (standard LTT) to 76.9%. CONCLUSIONS AND CLINICAL RELEVANCE: In cases of AMP-associated exanthems, the diagnostic value of the LTT compared with routine allergy testing is limited. When evaluating such exanthems, provocation testing remains the gold standard. Delayed reading of intradermal skin tests remains most useful to avoid positive provocation reactions.

[Differential diagnose of angioedema. Acute edematous scleromyxedema]. / Differenzialdiagnose Angioödem. Akut ödematöses Skleromyxödem.

A woman presented in the emergency room with the diagnosis of angioedema refractory to treatment. She had soft, compressible periorbital edema, as well as edema of her hands and lower arms. She also complained of severe pain in her hands including sensations of numbness and tingling. The history, course and examination results eliminated several possible differential diagnostic considerations like an acute histamine- or bradykinin-mediated angioedema or superior vena cava syndrome. Histological examination confirmed the diagnosis of scleromyxedema.

Angiotensin-converting enzyme inhibitors do not impair the safety of Hymenoptera venom immunotherapy build-up phase.

BACKGROUND: There is an ongoing debate on whether angiotensin-converting enzyme inhibitors (ACEI) should be substituted prior to initiation of venom immunotherapy (VIT) for safety reasons. OBJECTIVE: We aimed to assess the influence of ACEI medication on the incidence of systemic reactions (SR) during the build-up phase of VIT in a large and homogeneous cohort of patients. METHODS: The frequency of SR during 775 consecutive cycles of VIT initiation was analyzed in relation to cardiovascular medication, age, sex, venom, reactivity in diagnostic tests, severity of preceding sting-induced anaphylaxis, comorbidities, latency before the initiation of VIT, and treatment protocols. ACEI were routinely maintained throughout VIT, beta-blockers replaced if appropriate. RESULTS: During VIT-initiation, 190 (24.5%) patients were on some kind of cardiovascular treatment, 90 (11.6%) on ACEI, 23 (3.0%) on beta-blockers. VIT-related SR rates were 11.7% (any documented reactions including subjective symptoms) and 3.0% (reactions fulfilling objective diagnostic criteria of anaphylaxis). Medication with ACEI (P = 0.097) or beta-blockers (P = 1.0) was not significantly related to the incidence of SR. A reduced rate of SR in patients taking cardiovascular drugs was not statistically significant in the final multivariate regression model. A prolonged latency before the initiation of VIT (P = 0.018, odds ratio = 1.010), and use of 5-day compared to 3-day rush protocols (P = 0.008, odds ratio = 3.522) increased the frequency of SR. CONCLUSIONS AND CLINICAL RELEVANCE: Study data do not provide evidence of an ACEI-mediated increase of VIT-related SR, supporting the continued use of these valuable and hard-to-replace substances throughout VIT.

Motional coherence of fermions immersed in a Bose gas.

We prepare a superposition of two motional states by addressing lithium atoms immersed in a Bose-Einstein condensate of sodium with a species-selective potential. The evolution of the superposition state is characterized by the populations of the constituent states as well as their coherence. The latter we extract employing a novel scheme analogous to the spin-echo technique. Comparing the results directly to measurements on freely evolving fermions allows us to isolate the decoherence effects induced by the bath. In our system, the decoherence time is close to the maximal possible value since the decoherence is dominated by population relaxation processes. The measured data are in good agreement with a theoretical model based on Fermi's golden rule.

Skin test concentrations for systemically administered drugs -- an ENDA/EAACI Drug Allergy Interest Group position paper.

Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity.

[Aspirin desensitization: therapy options in patients with aspirin-exacerbated respiratory disease]. / ASS-Toleranzinduktion: Therapieoption bei Patienten mit analgetikainduzierter Erkrankung der Atemwege.

Aspirin desensitization has established itself as an additional therapy option in the treatment of aspirin- exacerbated respiratory disease, recurrent chronic rhinosinusitis and nasal polyps. Inpatient treatment is strongly recommended due to the risk of life-threatening side effects. In addition, the necessary requirements, indications and contraindications should be carefully considered from a medicolegal perspective. A maintenance dose of 300 (-500) mg ASS is currently recommended. Indications include persisting symptoms despite intensive medical care and/or recurrent nasal polyps, leading to recurrent sinus operations and/or the need to take systemic corticosteroids in order to control nasal symptoms or asthma. If ASS intake is interrupted for more than 48 h, aspirin desensitization should be resumed to prevent renewed intolerance reactions.

[Maculo-papular exanthem with acute renal failure. Drug-induced hypersensitivity syndrome]. / Makulopapulöses Exanthem mit akuter Niereninsuffizienz. Arzneimittelinduziertes Hypersensitivitätssyndrom.

Acute renal failure caused by interstitial nephritis as part of a drug hypersensitivity syndrome constitutes a rare, but potentially life-threatening adverse drug reaction. We describe a patient with a mild maculo-papular rash accompanied by eosinophilia after prolonged treatment with meropenem, vancomycin, and moxifloxacin. Subsequently, a rapidly progressing renal failure developed which dominated the clinical picture. Upon cessation of all suspected drugs and therapy with high-dose steroids for 6 weeks, the renal function slowly returned to normal.

Decisive role of tumor necrosis factor-α for spongiosis formation in acute eczematous dermatitis.

Apoptosis of single keratinocytes (KC) is a characteristic feature of spongiosis formation, the histopathologic hallmark of acute eczematous dermatitis. In acute eczema, activated dermis-infiltrating T cells secrete several proinflammatory cytokines which might be decisive for KC apoptosis or survival. We analyzed the role of tumor necrosis factor alpha (TNF-α) in the determination of KC fate during spongiosis formation in acute eczematous dermatitis. Supernatants of activated human CD4(+) T cells induced apoptosis in primary KC, which could be fully inhibited by individual blockade of interferon-γ (IFN-γ) and CD95 but not by neutralization of TNF-α activity. As compared to CD95-triggering alone, synchronous CD95 and TNF receptor cross-linking in the presence of IFN-γ only marginally enhanced KC apoptosis. Importantly, pre-treatment of KC with TNF-α followed by CD95 stimulation, but not vice versa, significantly amplified KC apoptosis as compared to CD95 stimulation alone. This TNF-α-mediated sensitization to CD95-induced KC cell death could be abrogated by blocking TNF receptor 1 (TNF-R1) but not TNF-R2 mAb. In eczematous dermatitis, the CD95 receptor was expressed throughout the epidermis, whereas immunohistological detection of TNF-R1 was rather restricted to KC around spongiotic vesicle formation. Thus, TNF-α primes KC for CD95-mediated signals which results in an increased susceptibility to apoptosis. TNF-R1 expression and spatial action of TNF-α restricted to spongiotic vesicles promote both CD95-induced KC apoptosis and limitation of spreading KC damage.

[Dithiols as chelators. A cause of bullous skin reactions]. / Chelatbildner mit Thiolaktivität. Auslöser bullöser Hautreaktionen.

Chelation therapy with (RS)-2,3-Bis(sulfonyl)propane-1-sulfonic acid (DMPS) after an occupational lead exposure led to the development of a severe bullous drug eruption. Skin tests and histology/immunohistology of the test reactions indicated a T-cell-mediated immune response against DMPS. Metal-binding thiol groups as in DMPS are chemically highly reactive and therefore effectively mediate the development of immunogenic hapten (DMPS)-protein complexes. Therefore, the pharmacological effects and sensitization potential of dithiols are tightly connected. Cross-reactivity of DMPS to other chelators like D-penicillamine is possible; the indications for chelation therapy should be weighed carefully.