Gustatory and olfactory function in patients with granulomatosis with polyangiitis (Wegener's).

OBJECTIVES: Recent findings suggest that autoimmune disorders predispose to a diminished capacity to taste and smell. This has been shown for patients with systemic lupus erythematosus as well as for patients with rheumatoid arthritis (RA). Granulomatosis with polyangiitis (GPA), with its particular manifestations in the upper respiratory tract, may therefore have an even higher impact on these senses. The aims of this study were to evaluate the gustatory and olfactory function in patients with GPA, to compare them to sex- and age-matched healthy controls, and to correlate these findings with their GPA disease severity. METHOD: Patients with established GPA were analysed by standardized assessments for gustatory and olfactory functions and examined for disease activity, stage of disease, and treatment. RESULTS: Forty-four GPA patients were tested for their chemosensory functions. Compared to age- and sex-matched healthy controls, GPA patients showed significantly decreased olfactory scores along with diminished scores for their gustatory functions. The diminished sense of smell in GPA patients correlated significantly with elevated C-reactive protein (CRP) values whereas the gustatory impairment correlated with the duration and extent of the disease. CONCLUSIONS: Our results indicate that olfactory and gustatory functions are significantly decreased in GPA. As the olfactory function of these patients was comparable to patients with RA, chemosensory impairment may not simply be a consequence of the involvement of the upper respiratory tract, but rather a common complication of systemic autoimmune diseases.

[Adult-onset Still's disease]. / Adulter Morbus Still.

Adult-onset Still's disease is a rare inflammatory systemic disease. Cardinal symptoms/manifestations are fever, arthralgias or arthritis, myalgias, the typical skin rash, sore throat, hepatosplenomegaly, lymphadenopathy and serositis. Several other symptoms and organ involvements are possible. The clinical picture is variable with mild to life-threatening courses. The disease is self-limiting, intermittently active or chronic. Because of the lack of a defined diagnostic test the diagnosis of AOSD can only be made after exclusion of several differential diagnoses in particular of infectious, malignant and autoimmune origin. For therapy non-steroidal anti-inflammatory drugs, glucocorticoids, disease modifying antirheumatic drugs and biologics can be used.

[Longterm outcome of TNF blockade in adult-onset Still's disease]. / Langzeitergebnisse einer TNF-Blockade beim Morbus Still im Erwachsenenalter.

BACKGROUND AND OBJECTIVE: Adult-onset Stills disease (AOSD) is a rare entity. The course of the disease can be mild or severe, acute or chronic. The intention of this survey was to evaluate the longterm efficacy of TNF blockade in patients with severe and active AOSD. PATIENTS AND METHODS: Eight patients with the diagnosis of AOSD, according to the diagnostic criteria developed by Yamaguchi in 1992, and pretreatment with either high dosage steroid or more intensive immunosuppressive therapy were treated with infliximab in a dosage of 3 - 5 mg/kg at time pointsduring week 0, 2 and 6. Later on, the treatment regimen was adapted to the individual needs of the patients. The follow-up period was between one and five years. RESULTS: Seven patients responded to treatment with infliximab. Symptoms like fever, arthralgia, hepato-splenomegaly and serological parameters instantly improved. Five of these patients remained in remission over years after discontinuation of therapy. One of the responding patients needed permanent intensive treatment with TNF-blockers to control his severe chronic arthritis. Three patients experienced infusion reactions. One responding patient was therefore switched to etanercept and kept on this therapy. The one patient, who had not responded to infliximab also had no benefit from consecutive treatment with etanercept or adalimumab. CONCLUSION: Anti-TNF therapy can have a lasting beneficial effect on the course of AOSD. Five of eight patients remained in remission even after termination of therapy.

Treatment of psoriatic arthritis with antitumour necrosis factor-alpha antibody clears skin lesions of psoriasis resistant to treatment with methotrexate.

BACKGROUND: In inflamed skin, keratinocytes and inflammatory cells both produce large amounts of tumour necrosis factor (TNF) -alpha, a cytokine with broad effects that are relevant to inflammation. Blockade of this proinflammatory cytokine by a monoclonal anti-TNF-alpha antibody might be effectively used in the treatment of inflammatory skin diseases. OBJECTIVES: To gather information about the efficacy of an anti-TNF-alpha antibody (infliximab) in the treatment of skin lesions of psoriatic arthritis. METHODS: Six patients with progressive joint disease and psoriatic skin lesions unresponsive to methotrexate therapy were treated with anti-TNF-alpha antibody. The Psoriasis Area and Severity Index was determined before and 10 weeks after initiation of therapy. RESULTS: Improvement of psoriatic skin lesions was observed in all patients. In addition, a marked improvement of the joint disease was noted. CONCLUSIONS: Therapy with anti-TNF-alpha antibody may be an effective treatment regimen for both psoriatic arthritis and psoriatic skin lesions.

Positive influence of the Delta32CCR5 allele on response to highly active antiretroviral therapy (HAART) in HIV-1 infected patients.

The heterozygous 32 base pair deletion of the chemokine receptor 5 (Delta32CCR5) has been associated with a more benign course of HIV-1-infection. To study the influence of Delta32CCR5 on the response to antiviral therapy we analyzed the presence of Delta32CCR5 by PCR in PBMC from 107 randomly selected HIV-1-infected patients treated with HAART for at least three months. 24 of 107 patients were heterozygous for Delta32CCR5 (22.4%). Before initiation of HAART Delta32CCR5 heterozygous patients (d/w) did not differ from homozygous CCR5 wild-type patients (w/w) regarding viral load and CD4 counts. After a median treatment time on HAART of 17.5 months (d/w, range 6-31 months, p = n.s.) or 19 months (w/w, range 3-33 months) all 24 patients (100%) with the Delta32CCR5 mutation, but only 58/83 patients (69.9%) with wild-type CCR5 showed a suppression of HIV-1-viremia below 500 copies/ml (p = 0.0020). Furthermore, 20/24 (83.3%) of the Delta32CCR5 heterozygous patients achieved CD4 counts above 200/microliter, but only 57/83 (68.7%) of the patients homozygous for CCR5 wild-type (p = 0.011). Our data indicate that the presence of heterozygous Delta32CCR5 is associated with a better response to HAART suggesting that therapeutic strategies targeting CCR5 could be of value for a sustained suppression of HIV-1 by HAART.

Carnosic acid in green callus and regenerated shoots of Rosmarinus officinalis.

Rooted regenerated shoots obtained from leaf and nodal segments of Rosmarinus officinalis were grown on a basal nutrient medium for 9 weeks. The regenerants were shown by means of HPLC and mass spectrometry to contain carnosic acid, a diterpenoid with antioxidant and medicinal properties. Five-week-old nodular green callus also contained carnosic acid, whereas non-green, undifferentiated callus maintained in the dark did not.

Phagocytes from both vertebrate and invertebrate species use "coiling" phagocytosis.

Coiling phagocytosis has been observed previously only by chance, and there has been no systematic investigation of this uptake mechanism. Therefore, a comparative electron microscopical study was performed. Different human and murine cell populations, phagocytes from various vertebrate and invertebrate species, and predatory amoebae were incubated with Borrelia burgdorferi, one of the microbes known to induce coiling phagocytosis, to study the uptake mechanisms used. In this model, coiling phagocytosis was observed with both vertebrate and invertebrate species but not with amoebae. With cells from humans and mice, this uptake mechanism was restricted to phagocytic cells of myeloid origin. The coiled membrane gaps did not give rise to phagosomes; instead, membrane fusion was followed by membrane dissipation. Thus, coiling of B. burgdorferi apparently is an alternative uptake mechanism used by metazoan phagocytes, involving special membrane processing. However, coiling phagocytosis may show different features with different microbes.

Estimation of the male and female mutation rates in Duchenne muscular dystrophy (DMD).

We present the results of an international collaborative study aimed at estimating the ratio of male to female mutation rates in Duchenne muscular dystrophy based on the method of C. Müller and T. Grimm. With a sample size of 295, this ratio is found to be very close to 1, thus giving evidence for equal mutation rates in males and females in Duchenne muscular dystrophy.