Peter Komericki

Histamine intolerance: lack of reproducibility of single symptoms by oral provocation with histamine: A randomised, double-blind, placebo-controlled cross-over study

ZusammenfassungHINTERGRUND: Der Terminus Histamin-Intoleranz steht für eine ganze Reihe von Symptomen an unterschiedlichen Effektororganen, die nach dem Genuss Histamin-reicher Nahrung auftreten. Das Studienziel war, Histamin-assoziierte Beschwerden durch die Provokation mit einer standardisierten Menge an Histamin zu objektivieren und zu quantifizieren und zu prüfen, ob oral verabreichte Diaminoxidase (DAO) das Beschwerdeausmaß beeinflusst. PATIENTEN UND METHODEN: Vier Institutionen in Österreich nahmen teil. Es wurden Patienten rekrutiert, die den Verdacht auf Histamin-Intoleranz äußerten. Zunächst erfolgte eine offene orale Provokation mit 75 mg Histamin in Tee. Alle Probanden, die dabei Beschwerden entwickelten, wurden in den verblindeten Teil der Studie eingeschlossen und erhielten in drei weiteren verblindeten, einem crossover Design folgenden Provokationsschritten Kombinationen aus Histamin-freiem und Histamin-hältigem Tee mit Diaminoxidase- und Placebo-Kapseln. Es wurden Haupt- und Nebensymptome (stärkste und weniger starke Beschwerden an den einzelnen Effektororganen auf einer 10-Punkte-Skala) definiert, die Reproduzierbarkeit dieser Beschwerden in Bezug auf die jeweiligen Effektororgane geprüft, die Beschwerden weiters in ihrer Gesamtheit (Summe der Beschwerdepunkte aller Effektororgane) erfasst und Veränderungen nach Supplementation von DAO beurteilt. ERGEBNISSE: 39 von 56 Patienten reagierten in der offenen Provokation und wurden in den verblindeten Studienabschnitt eingeschlossen. Haupt- und Nebensymptome waren dabei nicht zu reproduzieren, die Probanden reagierten quasi zufällig. Allerdings brachte die Einnahme von DAO eine statistisch signifikante Reduktion von Beschwerden (definiert durch den Rückgang der aufsummierten Gesamtpunkte) im Vergleich zur Placebo-Gruppe. SCHLUSSFOLGERUNG: Die Ergebnisse erscheinen kontrovers. Möglicherweise reagieren Histamin-intolerante Personen zu unterschiedlichen Zeiten mit unterschiedlichen Symptomen. Die Reproduzierbarkeit definierter Symptome allein würde dann nicht genügen, um eine Histamin-Intoleranz zu bestätigen. Am Kollektiv zeigte sich weiters, dass die Einnahme von DAO-Kapseln im Vergleich mit Placebo-Kapseln zu einer statistisch signifikanten Abschwächung von Beschwerden nach Histamin-Provokation führte.SummaryOBJECTIVES: The term histamine intolerance stands for a range of symptoms involving various effector organs after the consumption of histamine-rich food. Our intention was to objectify and quantify histamine-associated symptoms and to analyse whether oral administration of the histamine-degrading enzyme diamine oxidase (DAO) caused a reduction of symptoms. PATIENTS AND METHODS: Four Austrian centres participated. Patients suspected to be histamine intolerant were recruited. The first step consisted in the open oral provocation of these patients with 75 mg of liquid histamine. Patients who developed symptoms were tested in a randomised double blind crossover provocation protocol using histamine-containing and histamine-free tea in combination with DAO capsules or placebo. Main and secondary symptoms (strongest and weaker symptoms based on a ten-point scale) were defined, the grand total of all symptoms of the individual provocation steps was determined and changes in symptoms after administration of DAO were measured. RESULTS: Thirty nine patients reacted to the open histamine provocation and were enrolled in the blinded part. Here, both the main and secondary symptoms were not reproducible. Subjects reacted sometimes unexpectedly and randomly. Regarding the total symptom scores, the differences between the three treatment groups were statistically significant. The intake of DAO demonstrated a statistically significant reduction of histamine-associated symptoms compared to placebo (P = 0.014). CONCLUSIONS: Oral provocation with 75 mg of liquid histamine failed to reproduce histamine-associated single symptoms in many patients. One may suggest that histamine-intolerant subjects reacted with different organs on different occasions. As a consequence, reproducibility of single symptoms alone may not be appropriate to diagnose histamine-intolerance whereas a global symptom score could be more appropriate. The fact, that the intake of DAO capsules compared to placebo led to a statistically significant reduction of total symptom scores, may indirectly point in the same direction.

Origin of modern syphilis and emergence of a pandemic Treponema pallidum cluster

The abrupt onslaught of the syphilis pandemic that started in the late fifteenth century established this devastating infectious disease as one of the most feared in human history1. Surprisingly, despite the availability of effective antibiotic treatment since the mid-twentieth century, this bacterial infection, which is caused by Treponema pallidum subsp. pallidum (TPA), has been re-emerging globally in the last few decades with an estimated 10.6 million cases in 2008 (ref. 2). Although resistance to penicillin has not yet been identified, an increasing number of strains fail to respond to the second-line antibiotic azithromycin3. Little is known about the genetic patterns in current infections or the evolutionary origins of the disease due to the low quantities of treponemal DNA in clinical samples and difficulties in cultivating the pathogen4. Here, we used DNA capture and whole-genome sequencing to successfully interrogate genome-wide variation from syphilis patient specimens, combined with laboratory samples of TPA and two other subspecies. Phylogenetic comparisons based on the sequenced genomes indicate that the TPA strains examined share a common ancestor after the fifteenth century, within the early modern era. Moreover, most contemporary strains are azithromycin-resistant and are members of a globally dominant cluster, named here as SS14-Ω. The cluster diversified from a common ancestor in the mid-twentieth century subsequent to the discovery of antibiotics. Its recent phylogenetic divergence and global presence point to the emergence of a pandemic strain cluster.

Simultaneous intradermal testing with hymenoptera venoms is safe and more efficient than sequential testing.

According to current guidelines, skin testing for hymenoptera venom allergy should be performed in a stepwise manner, maintaining 15‐ to 20‐min intervals between the injections of venom. Given the long‐winded procedure of sequential skin testing, we retrospectively explored the safety of simultaneous intradermal testing.

Determination of sIgE to rPhl p 1 is sufficient to diagnose grass pollen allergy

New diagnostic tools such as the basophil activation test (BAT) and component‐resolved diagnosis (CRD) are promising for hymenoptera venom or food allergy. A clear benefit for inhalant allergens has not yet been shown. Our aim was to compare new and established tests for grass pollen allergy.

Maculopapular exanthem from propolis: case report and review of systemic cutaneous and non-cutaneous reactions.

Propolis is increasingly used in cosmetics and for self-treatment of various diseases as a ‘cure-all’(1). It is sold in many health food stores in various forms for ingestion. Unfortunately, it is a known contact allergen and may seldom induce immediate type reactions. This is the first report of a maculopapular exanthema after ingestion of propolis capsules. Following, a Medline search using the terms ‘propolis’ and ‘allergy’ or ‘adverse reaction’ or ‘adverse event’, reports of systemic cutaneous and non-cutaneous reactions after propolis consumption are listed (Table 1).

Ratio of marked and excised sentinel lymph nodes and scintigraphic appearance time in melanoma patients with negative sentinel lymph node

AIM Metastases can occur in up to 15% of all melanoma patients with negative sentinel lymph node examination (SN -). We retrospectively investigated the number of preoperatively marked sentinel lymph nodes (SNs) with lymphoscintigraphy and effectively surgically removed SNs in SN--patients with cutaneous melanoma >or=0.5 mm. Ratio of these parameters was calculated and impact of this ratio as well as impact of scintigraphic appearance time (SAT) on disease progression was studied. MATERIALS AND METHODS Data on 122 SN--patients--70 women (58%), mean age 56.5 years--were analyzed. Mean follow-up time was 58 months. RESULTS Mean tumour thickness of all patients was 2.3 mm. In 51 patients (42%) the number of SNs marked in lymphoscintigraphy was higher than excised in surgery, in 47 patients (38%) the same number as marked was excised and in 24 patients (20%) a lower number was marked than excised. Metastases occurred in 17 patients (14%) after a mean time of 24.8 months. Mean tumour thickness (5.4 mm) was significantly higher in these patients than in the other patients (p = 0.000). Ratio of marked and excised SNs had no influence on disease progression; the only parameter influencing outcome was tumour thickness (p = 0.000). Short SAT was significantly associated with higher tumour thickness (p = 0.004). CONCLUSION Our study indicates that, in routine clinical practice, it suffices to harvest the first SN, as the ratio of marked and excised SNs has no impact on disease progression.

Differentiation Between Balanitis and Carcinoma In Situ Using Reflectance Confocal Microscopy

IMPORTANCE Zoon plasma cell balanitis is a benign inflammatory disease of genital skin. It may be difficult to clinically distinguish between balanitis and carcinoma in situ (CIS); thus, a biopsy may be needed to exclude malignant disease. Reflectance confocal microscopy (RCM) is an in vivo imaging method to get morphologic information about architecture and single cells in the skin. OBJECTIVE To evaluate the ability of RCM to differentiate between balanitis and CIS compared with the gold standard histopathologic methods. DESIGN Observer blinded study. SETTING A referral center. PARTICIPANTS Fifteen patients with balanitis or CIS. INTERVENTION Patients were assessed by clinical, histologic, and RCM findings. All lesions were imaged with the Vivascope 1500. In 5 cases of balanitis, the surrounding, noninvolved skin also was evaluated. MAIN OUTCOME MEASURES Local recurrence, nodal metastasis, disease-specific death, overall death. RESULTS The clinical diagnoses showed 9 cases of balanitis and 6 cases of CIS. With histopathologic analysis, 12 cases of balanitis and cases of CIS were diagnosed, and RCM evaluation confirmed these diagnoses. The most relevant RCM criteria for CIS were atypical honeycomb pattern, disarranged epidermal pattern, and round nucleated cells. Balanitis showed a nucleated honeycomb pattern and vermicular vessels. Scattered small bright cells and round vessels were present in all lesions. The adjacent normal skin showed a typical honeycomb pattern and round papillary vessels. CONCLUSIONS AND RELEVANCE We were able to differentiate between balanitis and CIS. Reflectance confocal microscopy may help to avoid biopsies at this sensitive site.

Near-fatal anaphylaxis caused by human serum albumin in fibrinogen and erythrocyte concentrates

A 40‐year‐old man developed anaphylactic shock during surgical replacement of a prolapsed mitral valve during general anaesthesia and an attenuated reaction (Grade 2), three days later during a blood transfusion. Human serum albumin, a component of the fibrinogen concentrate used postoperatively with the erythrocyte concentrate, was identified as the trigger, confirmed by positive skin prick and intradermal tests. Any anaphylaxis during the peri‐operative period should cause the clinician to perform allergy tests for identification of the culprit drug and, sometimes, culprit additive. Testing of human serum albumin, acting as hidden allergen, should be included, especially where there has been a blood transfusion.

Impact of Mental and Physical Stress on Blood Pressure and Pulse Pressure under Normobaric versus Hypoxic Conditions

Objective Hypobaric hypoxia, physical and psychosocial stress may influence key cardiovascular parameters including blood pressure (BP) and pulse pressure (PP). We investigated the effects of mild hypobaric hypoxia exposure on BP and PP reactivity to mental and physical stress and to passive elevation by cable car. Methods 36 healthy volunteers participated in a defined test procedure consisting of a period of rest 1, mental stress task (KLT-R), period of rest 2, combined mental (KLT-R) and physical task (bicycle ergometry) and a last period of rest both at Graz, Austria (353 m asl) and at the top station Dachstein (2700 m asl). Beat-to-beat heart rate and BP were analysed both during the test procedures at Graz and at Dachstein and during passive 1000 m elevation by cable car (from 1702 m to 2700 m). Results A significant interaction of kind of stress (mental vs. combined mental and physical) and study location (Graz vs. Dachstein) was found in the systolic BP (p = .007) and PP (p = .002) changes indicating that during the combined mental and physical stress task sBP was significantly higher under hypoxic conditions whereas sBP and PP were similar during mental stress both under normobaric normoxia (Graz) and under hypobaric hypoxia (Dachstein). During the passive ascent in cable car less trivialization (psychological coping strategy) was associated with an increase in PP (p = .004). Conclusion Our data show that combined mental and physical stress causes a significant higher raise in sBP and PP under hypoxic conditions whereas isolated mental stress did not affect sBP and PP under hypoxic conditions. PP-reaction to ascent in healthy subjects is not uniform. BP reactions to ascent that represents an accumulation of physical (mild hypobaric hypoxia) and psychological stressors depend on predetermined psychological traits (stress coping strategies). Thus divergent cardiovascular reactions can be explained by applying the multidimensional aspects of the biopsychosocial concept.

Origin of modern syphilis and emergence of a contemporary pandemic cluster

Syphilis swept across the world in the 16th century as one of most prominent documented pandemics and is re-emerging worldwide despite the availability of effective antibiotics. Little is known about the genetic patterns in current infections or the evolutionary origins of the disease due to the non-cultivable and clonal nature of the causative bacterium Treponema pallidum subsp. pallidum. In this study, we used DNA capture and next generation sequencing to obtain whole genome data from syphilis patient specimens and from treponemes propagated in laboratory settings. Phylogenetic analyses indicate that the syphilis strains examined here share a common ancestor after the 15th century. Moreover, most contemporary strains are azithromycin resistant and members of a globally dominant cluster named here as SS14-Ω. This cluster diversified from a common ancestor in the mid-20th century and has the population genetic and epidemiological features indicative of the emergence of a pandemic strain cluster.