Comparative efficacy and safety of azelastine and levocabastine nasal sprays in patients with seasonal allergic rhinitis.

The aim of the present investigation was to compare the efficacy and tolerability of azelastine (CAS 58581-89-8) (1.12 mg/day) and levocabastine (CAS 79547-78-7) (0.4 mg/day) nasal spray administered twice daily to patients with seasonal allergic rhinitis. A total of 180 patients participated in a 4-week, double-blind, parallel group (n = 90 each) study. Symptom severity of nasal, ocular and other symptoms were recorded, out of which a total symptom score (TSS) was calculated. Physicians assessed symptoms at baseline and at days 7, 14, and 28, patients and physicians evaluated the efficacy and tolerability. After 4 weeks of treatment with azelastine the mean overall TSS was reduced from a baseline score of 18.7 to 4.2, after levocabastine from 17.8 to 5.9. Patients morning scores for treatment days 1 to 28 gave a mean total score of 212.4 for the azelastine group and 230.6 for the levocabastine group; the equivalent evening scores yielded a mean total score of 115.5 and 175.6 respectively. Global efficacy was judged by physicians as either 'very good' or 'good' for 90% of azelastine patients and for 74% of the levocabastine group; 92% of azelastine patients and 76% of levocabastine patients judged treatment to be either 'very good' or 'good'. No serious adverse events were reported, all adverse events were related to nasal symptoms. Both azelastine and levocabastine administered twice daily as a nasal spray provide effective and well tolerated symptomatic treatment of seasonal allergic rhinitis. Azelastine, however, was statistically superior in efficacy as well as in safety (PWei-Lachin < 0.0001, combined results).

Determination of soluble CD21 as a parameter of B cell activation.

In this study we established a novel solid-phase immunoassay for CD21 using the time-resolved fluorescence of lanthanide chelates. The capture assay was able to detect concentrations of as low as 100 pg of CD21 antigen per millilitre of sample and was used for quantitative determination of CD21 in lysates of different cell lines as well as in patient serum specimens. CD21 was measured in lysates of tonsils and cell lines of B, T cell and myelomonocyte lineage, and appeared to consist of monomeric antigen under the detergent conditions used. Elevated levels of soluble CD21 were observed in serum of patients with Epstein-Barr virus (EBV) infection, a disease known to be associated with polyclonal B cell activation, and in infection with the lymphotropic rubella virus. Significantly increased levels were also found in malignancies which are associated with EBV. In patients with nasopharyngeal carcinoma (NPC), a correlation with the titre of EBV-specific IgA was observed, thus supporting a possible role of soluble CD21 as a marker for disease activity in certain malignancies. Our data suggest that measurement of soluble CD21 could serve as a marker for activation of the immune system and diseases involving the B cell lymphoid system. Possible mechanisms and functions of soluble CD21 are discussed.

[Viral origin of postnatally acquired inner ear damage]. / Zur viralen Genese postnatal erworbener Innenohrschäden.

Experimental and clinical data exist which point at a possible role of herpes virus infections in postnatally acquired inner ear disturbances. The presence of viral DNA in the inner ear and vestibular organ of experimentally infected mice and pigs suggests that not only primary infections but also the reactivation of latent herpes viruses can cause severe inner ear damage. Serological examinations are presented and therapeutic considerations discussed.

Antibacterial treatment of otitis and sinusitis with ciprofloxacin and penicillin V--a comparison.

80 adult outpatients suffering from otitis media, sinusitis (maxillaris or frontalis) or peritonsillitis were treated with 500 mg ciprofloxacin b.i.d. (n = 40) or with 2 g penicillin V t.i.d. (n = 40). The patients were randomly allocated. Three groups of patients resulted, clinically and bacteriologically evaluable, or only clinically evaluable because the isolated strains were resistant to ciprofloxacin or penicillin V or because no strains were isolated. Ciprofloxacin was superior to penicillin V; there were fewer resistant strains (one compared to 11), and the eradication rate (57% compared to 43%) as well as the clinical efficacy (60% compared to 48%) of ciprofloxacin were better than those of penicillin V--even in a daily dose of 6.0 g. Both treatments were well tolerated; side effects were neither reported nor found.

Ciprofloxacin concentrations in tonsils following single or multiple administrations.

Penetration of ciprofloxacin into human tonsils was studied in 20 adult humans undergoing tonsilectomy. Ten patients received a single intravenous infusion of 200 mg ciprofloxacin within 15 min (group A) and 14 patients were treated orally for three days with 500 mg ciprofloxacin b.i.d. prior to a preoperative infusion of 200 mg (group B). Ciprofloxacin concentrations in serum and tonsils were determined microbiologically. Mean ciprofloxacin serum concentrations did not differ significantly between both groups. Similarly, mean distribution ratios between tonsils and serum were not dissimilar, being on average 150% irrespective of whether the drug was administered once or repeatedly. Thus, a significant accumulation of ciprofloxacin was not observed either in the intravascular or in the extravascular space.

The role of acute and latent virus infections in the pathogenesis of inner ear disturbances.

The possible role of herpesviral infections of the inner ear in suddenly appearing inner ear disturbances was investigated. Experimental pseudorabies virus (PRV, Herpes sui 1) infection of mice and swine was used as a model system. Infected mice represented the productive cycle of PRV infection (acute phase), whereas the latent phase of infection could be tested in swine. From the acutely infected mice the virus could be reisolated from perilymphatic fluid and various parts of the brain. Massive histopathologic alterations and signs of total cell damage to the organ of Corti and the vestibular organ were found. Accordingly, in all of the cells of the inner ear multiple copies of the PRV genome could be demonstrated. We therefore suggest that the disturbances of the inner ear were induced by the acute virus infection. In two latently infected swine (sixty weeks after infection), PRV could not be recovered either from the perilymphatic fluid or from a variety of different neural and extraneural tissues. However, histopathologic changes similar to those found in the acutely infected mice were observed. The presence of viral DNA could be demonstrated by in situ cytohybridization in both sensory and supportive cells of the inner ear and vestibular organ, but not in the corresponding nerve fibers, which is in contrast to the acutely infected mice. The distribution of the viral genome was further analyzed in adjacent areas of the central nervous system. An involvement of acute and latent herpes virus infection in inner ear dysfunction including sudden deafness and vestibular neuronitis in man, might be suggested from the results described. The presented animal model system, PRV-infected swine, should permit further studies on a possible role of herpetic recurrences, particularly with regard to inner ear disturbances.

Demonstration of pseudorabies virus DNA in the mouse inner ear by an in situ nucleic acid hybridization technique in plastic embedded bony material.

This investigation is concerned with the possibility of identifying viral DNA using the in situ DNA hybridization method in methylmethacrylate-embedded material. As an experimental model we chose viral labyrinthitis produced by intranasal infection of the mouse with pseudorabies virus. Fixation and embedding methods specially adapted to this procedure and bony histology preparation technique (specimens by grinding or micromilling) made it possible to identify viral DNA directly morphologically and virologically in the inner ear. Quantitative microphotometric analyses of trans-sagittal sections of the entire skull after in situ DNA hybridization are presented and discussed here as an explicit method of investigating the path of distribution of viral DNA in the brain and the inner ear.

Detection of pseudorabies virus DNA in the inner ear of intranasally infected BALB/c mice with nucleic acid hybridization in situ.

Evidence for the pathogenicity of pseudorabies virus for the auditory and vestibular organs of experimentally infected mice is presented. We demonstrate viral genomes in cells of the peripheral sensory organs, the nerve structures, and the affected areas of the brain in single sections from an entire cranium of an adult mouse. The data were obtained by an in situ hybridization technique adapted for use with fixed, plastic-embedded materials. In contrast to conventional methods which use frozen sections, we were able to analyze cartilaginous and bony materials with high resolution.

Ciprofloxacin concentrations in tonsils following a single intravenous infusion.

Penetration of ciprofloxacin into human tonsils was studied following an intravenous infusion of 200 mg over 15 minutes to adult humans undergoing tonsillectomy. Samples were taken one-and-a-half to four hours after dosing. Generally, tissue levels exceeded corresponding serum concentrations by 50% (range of intraindividual ratios between tonsil and serum concentrations 100% to 288%). Ciprofloxacin distribution was homogeneous and independent of sampling time.

[Nasal infection of the domestic cat with feline herpesvirus as an animal model of experimental viral labyrinthitis]. / Nasale Infektion der Hauskatze mit felinem Herpesvirus als Tierversuchsmodell der experimentellen viralen Labyrinthitis.

Looking for a suitable animal model of experimental labyrinthitis we performed in vivo infections of the domestic cat with feline rhinotracheitis virus. After instillation of the virus suspension into the nose of the anaesthetized cat we could find the complete virus particles in so-called virus factories in the nasal mucosa four days later by means of electron-microscopy. The adjacent ganglia of the olfactory nerve were stained by immunohistochemical methods and showed positive viral antigen. After embedding of the cochlea for electron microscopy virus particles could be demonstrated in the inflammatory cell material in the scala tympani. Our experimental model seems to be suitable for further studies of the rhinogenic way of infection in experimental viral labyrinthitis.

New developments in nucleic acid hybridization.

Nucleic acid hybridization is widely used for scientific applications in specialized laboratories. This paper describes hybridization probes that can be prepared with less specialized equipment. A new indirect 'sandwich' hybridization test is described which allows the use of only one universally usable labelled probe for hybridization tests with specificities for various sequences. The use of different labels and hybridization techniques is also discussed and critically compared. For in situ hybridization, the usability of fixed and embedded materials is tested and evaluated.

The capsid antigen of Epstein-Barr virus in nasopharyngeal carcinomas: comparison of serum antibody titre, cellular antigen content and histopathology.

In a retrospective study of 21 patients with nasopharyngeal malignancies (lymphoepithelial carcinomas, both undifferentiated and dedifferentiated serological and immunohistological methods were used to examine the significance of the IgG- and IgM-antibody against the capsid antigen of Epstein-Barr virus for early detection and follow-up, and the findings compared with those from a control group. Furthermore, the IgA-antibody is taken into account and presented with examples from the literature. Other possible forms of therapy (combined radio- and polychemotherapy) are also discussed.

Fungal infection of the ear. Etiology and therapy with bifonazole cream or solution.

Fungal infections of the auditory canal and middle ear are usually left unnoticed and regarded as a harmless saprophytic growth. However, these infections may become clinically significant in immunocompromised patients or patients undergoing long-term antibiotic treatment. This is demonstrated by characteristic case reports and confirmed by light and electron microscopic findings. Moreover, studies on animals with experimentally induced fungal infections have furnished evidence for the risk of the infection's spreading to the inner ear and causing serious damage to the organ of Corti; indirect damage to these structures by mycotoxins cannot be ruled out. To avoid complications of such severity of an allegedly harmless otomycosis we consider a quick and clinically easy to perform local treatment of high-risk patients as absolutely necessary. Such a treatment using bifonazole solution or cream was carried out on a number of patients and proved to be effective and free from side effects.

[Mycotic infection of the ear: a harmless saprophyte or pathognomonic risk factor?]. / Pilzbefal des Ohres--Harmloser Saprophyt oder pathognomonischer Risikofaktor?

The mycotic infection of the auditory canal and middle ear in patients with special risks (transplantation, extensive ear surgery, immunosuppression) and long term antibiotic treatment is discussed as a possible pathogenetic factor for inner ear lesions and generalization. This problem was also studied by experimental investigations with artificially infected guinea pigs. Further on we report about a clinical study with a new antimycotic substance which was used for local therapy.

[Anomalies of kinocilia in Kartagener's Syndrome]. / Kinozilienanomalien beim Kartagener-Syndrom.

A family with Kartagener's Syndrome, under investigation in our clinic, was subjected to clinical and electron microscopic studies about possible anomalies of kinocilia in the upper respiratory tract. The results are discussed as whether there are typical abnormalities in the ultrastructure or pathological variations of the mucosa which can also be seen in other diseases, such as mucoviscidosis or chronical alterations.

Experimental infection of the guinea pig inner ear with Toxoplasma gondii.

Based on the question whether toxoplasma gondii is a potential pathogenetic factor in sudden deafness and vertigo (especially in the acquired form of Toxoplasmosis) we started a series of investigations, dealing with direct, local, hematogenous, and intracisternal infection of the guinea pig cochlea with toxoplasma gondii. Three of ten directly inoculated and one of five hematogenously infected guinea pigs showed a severe labyrinthitis in electron and light microscopy. Thus, we could demonstrate that toxoplasma gondii is a potent pathogenetic factor in acute inner ear disturbances in laboratory animals. Toxoplasmosis should always be considered in cases with sudden deafness and vertigo without obvious other cause. With a specific therapy the labyrinthine disturbances can apparently be successfully treated.

[Otitis nigra: etiologic pathogenetic and clinical aspects (author's transl)]. / Otitis nigra: ätiologische, pathogenetische und klinische Gesichtspunkte.

The clinical picture of otitis nigra (idiopathic sero-hemmorrhagic otitis media) as independent clinical entity is shown, presenting 5 cases requiring mastoid surgery. Samples of mastoid mucosa were investigated by light- and electron-microscopy employing histochemical, immunofluorescent and virological techniques. Pathological changes of the small vessels in the subepithelial connective tissue with increased vascular permeability and extravasation of red blood cells and serum play a central role in the pathogenetic course of the disease. Disintegration of erythrocytes leads by catabolism of hemoglobin to formation of hemosiderin and ferretin, whereas by processing of phospholipids of the cell-membrane cholesterin cristals are deposited in the connective tissue. These cholesterin deposits in turn induce a foreign body reaction with formation of typical cholesterol granulomas. The mucosa shows secretory activity in intraepithelial secretory cells and glandlike structures in the subepithelial connective tissue. Neutral and acidic mucopolysaccharides are demonstrated in the secretory product. As possible cause for the vascular lesion that in turn sets off the pathomechanisme of otitis nigra a subclinical viral infection is discussed. This conjecture is supported by demonstration of virus-like inclusion bodies in macrophages and fibrocytes and of virus-like particles in antral smears. In addition myxoviruses of the parotitis-epidemica group could be identified in these smears by serological methods. Furthermore, the stimulation of the local immunological defense system, evidenced by the presence of numerous immunoglobulin-producing plasmacells in the tissue, is in concord with a viral infection. Therapy requires mastoidectomy in combination with posterior tympanotomy in order to eradicate completely the intractably diseased mastoid mucosa.

Effects and side effects of radiosynovectomy with Yttrium 90 on rheumatic joint cartilage.

8 and 12 weeks after Synovectomy with Yttrium 90, cartilage specimens from the femoral condyle of 8 patients with R.A. were examined. Cellular and matrix damage could be detected. Intracellular particles containing Circonium, an Yttrium decay-product could be found using microprobe X-ray analysis. This was verified in experimentally induced arthritis in the rat.

[Papilloma of the larynx. Immunology (author's transl)]. / Zur Immunologie des Larynxpapilloms.

Electron-microscopic and immunohistological studies show the cross-reactivity of an antigen in verruca plana, condyloma acuminatum and laryngeal papilloma. If this antigen is identical with papova virus or a tumor-performed antigen, cannot be distinguished definately. The fact that sera of patients bearing condylomata acuminata show strong antigen-antibody-reaction with tissue-sections of laryngeal papilloma by means of immunofluorescence microscopy, is discussed in a probably therapeutical point of view.