Syphilis is back: presentation of three cases at the ENT department.

PROBLEM: Syphilis is a sexually-transmitted disease caused by the spirochete Treponema pallidum, and is transmitted either through sexual contact or vertically across the placenta. Rates of infection were at a low point in the early 1990s. Since then, increasing numbers of new cases of infections have been observed in all Western countries. AIM: Presentation of three patients with syphilis who presented within a short period of time in an ENT outpatient clinic. CONCLUSIONS: One must be aware of the increasing incidence of syphilis, even in head and neck disciplines. Typical symptoms of an early infection are an ulcerous lesion in the mouth, with or without cervical lymphadenopathy. The main therapy is high doses of penicillin G administered intramuscularly. Other simultaneous sexually-transmitted diseases, especially HIV infection, must be excluded. Unnoticed and untreated patients may develop late and life-threatening complications.

A novel antagonist of prostaglandin D2 blocks the locomotion of eosinophils and basophils.

BACKGROUND: Chemoattractant receptor homologous molecule of Th2 cells (CRTH2) has been shown to mediate the chemotaxis of eosinophils, basophils and Th2-type T lymphocytes. The major mast cell product prostaglandin (PG) D(2) is considered to be the principal ligand of CRTH2. MATERIALS AND METHODS: We developed a novel CRTH2 antagonist, AZ11665362 [2,5-dimethyl-3-(8-methylquinolin-4-yl)-1H-indole-1-yl]acetic acid, and characterized its efficacy in binding assay in HEK293 cells, eosinophil and basophil shape change assay and migration assay, platelet aggregation and eosinophil release from guinea pig bone marrow. The effects were compared with ramatroban, the sole CRTH2 antagonist clinically available to date. RESULTS: AZ11665362 bound with high affinity to human and guinea pig CRTH2 expressed in HEK293 cells and antagonized eosinophil and basophil shape change responses to PGD(2). AZ11665362 was without effect on the PGD(2)-induced inhibition of platelet aggregation. In contrast, AZ11665362 effectively inhibited the in vitro migration of human eosinophils and basophils towards PGD(2). The release of eosinophils from the isolated perfused hind limb of the guinea pig was potently stimulated by PGD(2), and this effect was prevented by AZ11665362. In all assays tested, AZ11665362 was at least 10 times more potent than ramatroban. CONCLUSIONS: AZ11665362 is a potent CRTH2 antagonist that is capable of blocking the migration of eosinophils and basophils, and the rapid mobilization of eosinophils from bone marrow. AZ11665362 might hence be useful for the treatment of allergic diseases.

Problems in the differential diagnosis of Kartagener's syndrome and ATP-ase deficiency.

Two cases of Kartagener's syndrome with a partial loss of the dynein arms and the central spokes within the cilia are presented. In light microscopic examination the predominant cell types were mast cells within the stroma and the epithelium and plasma cells and lymphocytes in the stroma. The reaction for the magnesium-activated ATP-ase located in the apical cytoplasm of ciliated cells was negative in one case and slightly positive in the same case on year later; in our second case, the ATP-ase reaction was variable, slightly to moderately positive, in the same biopsy. Besides the dynein arm defect this is a second defect of another ATP-ase, located in the apical region of the ciliated and mucus producing epithelial cells. Based on histological examination of nasal mucosal biopsies a differential diagnosis has been established for Kartagener's syndrome, the more common cystic fibrosis and the relative frequent allergic rhinitis.

[Quality control in the allergy laboratory--4 years "Allergy Ring Trial" in Austria]. / Qualitätskontrolle im Allergielabor--4 Jahre "Ringversuch Allergie" in Osterreich.

In 1988 the Austrian Society for Allergology and Immunology initiated an external quality control program for the in vitro allergy diagnosis. In 12 mailings, 62 sera from allergic patients were sent to selected laboratories in order to determine total and antigen specific IgE according to the laboratory-specific methods. The values for total IgE varied considerably (73.9% were within +/- 1 SD, 94.3% within +/- 2 SD and 99.1% within +/- 2 SD, but only 0.9% beyond that). Sources of error were mainly attributable to inappropriate equipment and low quality reagents, but also bad test performance, with respect to personnel and the routines. In contrast, antigen specific IgE against pollen, mites, moulds, insect venoms, animal danders, drugs, parasites, environmental and food antigens revealed quite homogeneous results. Out of 1492 data, only 46 (3.1%) had to be declared as "wrong", and the variability of the RAST-classes was low. Whereas the quality of the reagents from all the different suppliers was not absolutely reliable at the beginning of the study, it improved considerably with time, as consequence of our complaints. The comparability of the methods for detecting total-IgE were non-satisfactory, whereas those for antigen specific IgE were generally good. The variety of methods employed (radio- and enzyme immunologic, fluoro- and nephelometric methods, etc.) should entail appropriate consequences, especially critical comparisons within one and the same laboratory; in addition, international standardization of the "normal" values should replace company-standards, and quality control programs for each test system before it is marketed should be mandatory. Our results confirm, that external control should be obligatory for any laboratory.(ABSTRACT TRUNCATED AT 250 WORDS)

[Immediate reaction in native tests with red chironomid larvae]. / Sofortreaktion bei Nativtestung mit roter Zuckmückenlarve.

Growing numbers of pet animals in households go along with increasing sensitisation hazards by various, partially highly aggressive allergens. Even running an aquarium can be risky for atopic humans, if the fishes are fed chironomid larvae. This is illustrated by a case of inhalation allergy in a patient who showed severe reactions to skin testing with native chironomidae.

[Usefulness of Phadiatop as a screening parameter in inhalation allergies]. / Einsetzbarkeit des Phadiatop als Screeningparameter bei Inhalationsallergien.

After IgE had been identified as the key mediator of type-I-allergies, laboratory tests to measure total-IgE (PRIST) and specific IgE (RAST) were developed. Since 1986 a new screening method based on the RAST-technique has been introduced: Phadiatop. We evaluated the usefulness of Phadiatop for the allergologist compared to the information provided by total IgE-measurement (PRIST). Despite a statistically significant difference in favour of Phadiatop over PRIST, Phadiatop alone does not seem to be sufficient parameter for allergy screening. In its current conception it can neither rule out false negative findings, nor does it allow a precise determination as to which inhalation allergy prevails.

[A new rapid test for the detection of IgE antibodies in inhalation allergies]. / Neuer Schnelltest zum Nachweis von IgE-Antikörpern bei Inhalationsallergien.

We compared the results of the Skin-Prick-Test, Phadezym-RAST and IgE-Quick, developed by QUIDEL, obtained from 75 patients suffering from an inhalant allergy and 25 controls. The IgE-Quick is a qualitative EIA dipstick test designed for the rapid visual detection of allergen-specific IgE. The IgE-Quick contained nine test pads coated with one of the following purified allergens: Betula pendula, Phleum pratense, Secale cereale, Artemisia vulgare, Felis domestica, Canis familiare, D. pteronyssinus and D. farinae. The results of the Phadezym-RAST and IgE-Quick correlated very well (r = 0.96) and both in-vitro methods corresponded to the Skin-Prick-Test (greater than 90%). The IgE-Quick is the simplest, fastest and easiest in-vitro allergy screen available.

[Mycologic analyses of house dust in patients with mycotic infections of the paranasal sinuses and in healthy probands]. / Mykologische Analysen des Hausstaubes von Patienten mit Nebenhöhlenmykosen und gesunden Probanden.

Dust samples from 30 patients suffering from an aspergillus sinusitis and from 20 healthy persons were analysed for moulds as a possible cause of mycotic sinusitis. Questionnaires were also distributed to assess the ecological environment of the patients. Mycological analyses of the dust samples showed no statistical difference in the presence of moulds, especially those of Aspergillus fumigatus and Aspergillus niger. Both moulds were found to roughly the same extent in 75%-95% of subjects. The questionnaires showed that most patients were exposed to moulds during work as well as in their spare time. The case history always showed a chronic sinusitis. Thus it appears that the development of a mycotic sinusitis is caused by many factors.

[Changes in nasal volume flow following local administration of neuropeptide substance P and capsaicin]. / Anderungen des nasalen Volumsstromes nach lokaler Applikation des Neuropeptides Substanz-P und von Capsaicin.

In a recently published paper, the author discovered the neuropeptide Substance-P (SP) in human nasal mucosa. SP is the transmitter substance of sensory neurons in the central and peripheral nervous system. The influence of SP and CAPSAICIN on the vascular system of human nasal mucosa is investigated. The application of these substances on the nasal mucosa of volunteers leads to a significant decrease of nasal air flow which can be registered by anterior rhinomanometry. The pathogenetic importance of vascular protein leakage and vasodilatation caused by the neuropeptide SP is discussed.

Control of vascular permeability and vascular smooth muscle in the respiratory tract by multiple neuropeptides.

Recent evidence suggests that a population of primary afferent neurons which terminate in the upper and lower airways contains several coexisting peptides. Thus, substance P was found to coexist with at least three structurally related tachykinins, viz. neurokinin A, neuropeptide K and an eledoisin-like peptide. Furthermore, calcitonin gene-related peptide which is structurally not related to tachykinins is also present in the same neurons which innervate a variety of peripheral tissues. Substance P, neurokinin A, eledoisin-like peptide and calcitonin gene-related peptide can simultaneously be released from central and peripheral branches of primary sensory neurons, whereas a release of neuropeptide K could not be demonstrated. Local inflammatory mediators like bradykinin or histamine also released multiple peptides in the airways and caused vascular protein leakage which is partly dependent on intact sensory nerves. In experimental animals, tachykinins as well as calcitonin gene-related peptide caused vasodilatation, whereas tachykinins but not calcitonin gene-related peptide caused an increase in vascular protein leakage. In humans, intranasally administered substance P (but not calcitonin gene-related peptide) lead to nasal obstruction as measured by rhinomanometry, and to secretion. It is suggested that activation of peripheral endings of perivascular primary sensory neurons causes vasodilatation and increase in vascular protein leakage by simultaneous action of several neuropeptides including tachykinins and calcitonin gene-related peptide.

In vivo and in vitro suppression of lymphocyte function in Aspergillus sinusitis.

In about 10% of patients who are operated on for chronic sinusitis, an aspergilloma is found in the affected paranasal sinus. In order to detect possible underlying immune defects, 25 patients with aspergillomas were subjected to an immunological screening program. The data obtained were compared with those of patients with non-mycotic chronic sinusitis and healthy controls. Total lymphocyte counts and immunoglobulin levels were normal in both groups with sinusitis. However, leukocyte subset analyses using membrane fluorescence revealed a significant decrease of CD11+ cells (macrophages, monocytes and natural killer-cells) in both types of sinusitis. Furthermore, a markedly enhanced frequency of CD25+ cells (interleukin 2-receptor-bearing cells), was observed in patients with the aspergillomas. Additionally, peripheral blood lymphocytes in both groups of patients showed a significant reduction in the proliferative response to both T- and B-cell mitogens, with the values for the mitogens ConA and PHA being significantly lower in the aspergilloma patients as compared to those with non-mycotic sinusitis. This lack of lymphocyte stimulation in the aspergilloma group was also manifest in skin tests to recall antigens. These first data suggest that there is an immune deficiency in patients with chronic sinusitis caused by Aspergillus fumigatus. Further studies are needed to clarify if this defect is the cause or the result of the mycotic infection.

[In vivo and in vitro suppression of lymphocyte function in paranasal sinus mycoses]. / In-vivo- und In-vitro-Suppression der Lymphozytenfunktion bei Nebenhöhlenmykosen.

In about 10% of patients operated on a chronic sinusitis, an aspergilloma is found in the paranasal sinus. To detect possible underlying immunodeficiencies, patients with aspergilloma were subjected to an immunological screening programme. The data were compared with those of patients suffering from non-mycotic chronic sinusitis and healthy controls. Totale lymphocyte counts and immunological levels were normal in both groups of sinusitis. Leukocyte subset analyses by membrane fluorescence revealed a significant decrease of CD11+ cells, i.e. macrophages/monocytes and NK cells, in both types of sinusitis. Furthermore, a markedly enhanced frequency of CD25+-cells, i.e. IL 2-receptor bearing cells, was observed in patients with aspergilloma. Peripheral blood lymphocytes of both groups of patients showed a significant reduction in the proliferative response to both T and B-cell mitogens, the values for the mitogens ConA and PWM being significantly lower in aspergilloma patients than in those with non-mycotic sinusitis. This lack of lymphocyte stimulation in the aspergilloma group was also manifest in skin tests to recall antigens. These first data suggest an immunodeficiency in association with chronic sinusitis caused by Aspergillus fumigatus. Further studies are needed to clarify if this defect is cause or result of the mycotic infection.

[Suppression of lymphocyte function 2 years following surgical treatment of paranasal sinus mycosis]. / Suppression der Lymphozytenfunktion zwei Jahre nach operativer Behandlung einer Nebenhöhlenmykose.

Prior investigations showed that acutely diseased patients with an aspergillus sinusitis manifested immune dysfunctions in respect of both T and B lymphocytes. In contrast to patients with nonmycotic sinusitis reduced in vitro and in vivo responsiveness was observed. The aim of this study, carried out after removal of the fungus ball and endoscopic surgery in clinically healthy patients, was to ascertain whether this reduced responsiveness was to be regarded as the effect or cause of an Aspergillus fumigatus infection. Two years later, the in vivo response to recall antigens was normal in both groups of patients, whereas the response to mitogens (ConA, PHA and PWM) was still decreased in the aspergillus sinusitis groups. The data suggest that the reduced immune response is a consequence of the Aspergillus fumigatus infection. Depressed skin reactivity is only present during acute infection, while proliferative capacity, as measured in the "whole blood stimulation" assay is depressed for a long time after healing the acute infection.

[The clinical significance of anti-IgE antibodies in the treatment of allergic rhinopathy]. / Die klinische Bedeutung von Anti-IgE-Antikörpern für die Behandlung der allergischen Rhinopathie.

A simple assay, based on monoclonal antibodies, was used to measure "free" anti-IgE antibodies or anti-IgE antibodies in immune complexes of IgE and anti-IgE. No significant correlation was found between serum IgE levels and the concentration of anti-IgE antibodies. Furthermore, patients who were successfully treated by hyposensitization therapy showed only unmeasurable or extremely low anti-IgE antibody levels in their serum. However, patients who were unsuccessfully treated by hyposensitization had elevated anti-IgE serum titers. Thus, determination of anti-IgE antibodies might become a tool for predicting the success of hyposensitization therapy.

Trichophyton rubrum in the external auditory meatus.

We report the case of a 28-year-old immunocompetent male suffering from otitis externa. The right external auditory meatus was filled with cerumen and detritus, the tympanic membrane covered wallpaper-like with layers of fungi. Mycological analysis revealed Trichophyton rubrum. With further examination tinea pedis of plantar and interdigital type and concomitant onychomycosis of the toenails due to T. rubrum could be detected. The auditory meatus was cleaned and treated topically with clotrimazole. Two weeks later the auditory meatus and the tympanic membrane were bare of fungi and the inflammation was resolved. Treatment of tinea pedis and onychomycosis with terbinafine (systemically and topically) is still lasting.

Intrathyroidal dendritic cells, epitheloid cells, and giant cells in iodine deficient goiter.

Immunohistochemistry and immunofluorescence were performed on thyroid sections of 44 consecutive patients undergoing thyroid surgery for goiter due to iodine deficiency. Sections were compared with specimens from ten individuals without goiters from the same endemic area, with specimens from ten sporadic nontoxic goiter patients, and with specimens from an area with sufficient iodine supply from nine healthy subjects. Cells were characterized using monoclonal antibodies to the CR3 receptor (CD11b) and the p150/95 antigen (CD11c) present on macrophages, to HLA-DR, to antigen presenting cells (RFD1), to T helper (CD4) and to T suppressor/cytotoxic cells (CD8), and with a polyclonal antibody to human cytokeratin. In iodine deficient goiters, focal aggregates were found of RFD1-positive dendritic cells. Furthermore, RFD1-positive epitheloid cells were seen. In 27% of cases, these epitheloid cells completely filled the thyroid follicles. Within the epitheloid cell clusters, multinucleated giant cells could be detected that carried the macrophage markers. Dendritic cells, epitheloid cells, and giant cells were strongly HLA-DR positive. In nongoitrous thyroids from the endemic area such aggregates could also be seen but they were more sparse and were RFD1 negative. Giant cells were absent there. In normal thyroids with sufficient iodine supply, only a few isolated dendritic cells were seen. All except RFD1, which was negative, showed the same marker pattern. In sporadic nontoxic goiters from an area with sufficient iodine supply, dendritic cells occurred in much higher numbers than in the normal thyroids from that area, and they were RFD1 positive. They never aggregated as in iodine deficiency, and giant cells were not observed. These observations on iodine deficient goiter strongly suggest involvement of active antigen-presenting cells in this disorder. However, the immunohistologic difference between this disease and sporadic goiter suggests different underlying mechanisms.

Thyroid infiltrating dendritic cells, epitheloid cells and giant cells in iodine deficiency.

This study describes dendritic cells in thyroid sections of iodine deficient goiters. Cells were characterized by monoclonal markers and detected by immunohistochemistry and double labelling immunofluorescence. We observed dendritic cells located in focal aggregates in the interstitium and epitheloid cells as well as multinucleated giant cells filling thyroid follicles. All these cells showed strong positivity for the MHC class II molecules HLA-DR, -DQ, -DP and RFD1, a monoclonal marker for active antigen presenting cells.

HLA patterns in patients with nasal polyposis.

The etiology of nasal polyposis is still unknown, although risk factors include Aspirin intolerance, asthma, cystic fibrosis and primary ciliary dyskinesia. We studied frequencies of HLA A, B, DR and DQ in patients with nasal polyposis in order to determine a possible genetic component in the multifactorial pathogenesis of nasal polyps. Previous work has suggested an association of HLA-A1B8 with nasal polyposis and Aspirin intolerance. We investigated 89 patients with nasal polyposis, 11 of whom had Aspirin-intolerance, 19 asthma and 22 allergies to inhalation allergens. HLA patterns of these patients were compared to the ones of 1,070 healthy controls. No significant association of HLA-A1B8 was found with nasal polyps in the Aspirin-sensitive subgroup of our patients, but a significant association was seen with HLA-A74 and nasal polyposis.