Th2-mediated atopic disease protection in Th1-mediated rheumatoid arthritis.

OBJECTIVE: The balance between CD4+ T-helper (h) cell subsets (Th1 and Th2) plays an important role in the pathogenesis of rheumatoid arthritis (RA) and atopy. While RA is believed to be a Th1 mediated disease, Th2 cells predominate in atopic disorders. The purpose of this study was to investigate differences in the occurrence of allergy, hay fever, house dust mite sensitivity and asthma, as well as total serum IgE levels in RA patients and controls. METHODS: The case history of atopic disorders was assessed in 134 RA patients and compared to those found in 305 healthy blood donors. RA patients also answered clinical questions concerning disease activity and severity. Total serum IgE levels were measured in both groups, taking into consideration disease modifying therapy. RESULTS: A significantly lower occurrence of medical history of hay fever (2.3%) and house dust mite sensitivity (3.1%) was found among RA patients compared to controls (24.2% and 12.2%, respectively; p < 0.0001 and p < 0.003 respectively). Moreover, RA patients had significantly lower total serum IgE levels than control subjects (p < 0.0001). RA was less severe in patients with atopy compared to non-atopic RA patients. CONCLUSION: These results support the concept that RA and atopy antagonize each other and that a change in the cytokine patterns of Th1 and Th2 cells could provide an indication for curative effects on RA.

Analysis of interleukin-4 receptor alpha chain variants in multiple sclerosis.

A recent candidate gene study employing microsatellite markers suggested a possible linkage of multiple sclerosis (MS) with the interleukin-4 receptor (IL4R) gene. Consequently, we investigated the association of different IL4R variants with MS in 341 German MS patients and 305 healthy controls. Analysis of the first 100 MS patients for six IL4R variants showed an increased frequency of the R551 variant in MS patients versus healthy controls and carriage of the same IL4R variant was weakly associated with myelin oligodendrocyte glycoprotein (MOG) autoantibody production. However, further analysis of all 341 MS patients did not confirm the finding that this IL4R variant represents a general genetic risk factor for MS but revealed an increased frequency of the R551 variant in MS patients with primary progressive MS (PPMS, n=48) as compared to patients with relapsing remitting MS or secondary progressive MS (RR/SPMS n=284; P=0.005 for genotype differences) and to 305 healthy controls (P=0.001 for genotype differences). This association was statistically independent of the presence of the well-known MS susceptibility allele HLA-DRB1*15. After correction for multiple comparisons only the genotype differences between PPMS patients and healthy controls remained statistically significant. These results indicate, that the IL4R variant R551 may influence the genetic predisposition for PPMS but does not represent a general genetic risk factor for MS.

What is the optimal dose of botulinum toxin A in the treatment of cervical dystonia? Results of a double blind, placebo controlled, dose ranging study using Dysport. German Dystonia Study Group.

OBJECTIVES: Botulinum toxin injections have become a first line therapeutic approach in cervical dystonia. Nevertheless, published dosing schedules, responder rates, and frequency of adverse events vary widely. The present prospective multicentre placebo controlled double blind dose ranging study was performed in a homogenous group of previously untreated patients with rotational torticollis to obtain objective data on dose-response relations. METHODS: Seventy five patients were randomly assigned to receive treatment with placebo or total doses of 250, 500, and 1000 Dysport units divided between one splenius capitis (0, 175, 350, 700 units) and the contralateral sternocleidomastoid (0, 75, 150, 300 units) muscle. Assessments were obtained at baseline and weeks 2, 4, and 8 after treatment and comprised a modified Tsui scale, a four point pain scale, a checklist of adverse events, global assessment of improvement, and a global rating taking into account efficacy and adverse events. At week 8 the need for retreatment was assessed and then the code was unblinded. For those still responding, there was an open follow up until retreatment to assess the duration of effect. RESULTS: Seventy nine per cent reported subjective improvement at one or more follow up visits. Decreases in the modified Tsui score were significant at week 4 for the 500 and 1000 unit groups versus placebo (p<0.05). Additionally positive dose-response relations were found for the degree of subjective improvement, duration of improvement, improvement on clinical global rating, and need for reinjection at eight weeks. A significant dose relation was also established for the number of adverse events overall and for the incidence of neck muscle weakness and voice changes. CONCLUSION: Magnitude and duration of improvement was greatest after injections of 1000 units Dysport; however, at the cost of significantly more adverse events. Therefore a lower starting dose of 500 units Dysport is recommended in patients with cervical dystonia, with upward titration at subsequent injection sessions if clinically necessary.

A randomized study comparing fluconazole with amphotericin B/5-flucytosine for the treatment of systemic Candida infections in intensive care patients.

In this prospective, randomized study fluconazole and amphotericin B/5-flucytosine were compared in the treatment of systemic candidiasis. Seventy-two non-neutropenic intensive care patients with systemic Candida infections were enrolled. Thirty-six patients were randomly assigned to receive fluconazole (400 mg on the first day then 200 mg) and 36 were randomized to amphotericin B/5-flucytosine (1.0-1.5 mg/kg body weight every other day and 3 x 2.5 g flucytosine/day) for 14 days following the diagnosis. There was no statistically significant difference in clinical outcome in regard to the treatment of pneumonia and sepsis: 18/28 of the patients were treated successfully with fluconazole and 17/27 with amphotericin B/5-flucytosine. For the treatment of peritonitis, however, amphotericin B/5-flucytosine was more effective than fluconazole (55% vs. 25%). Furthermore, amphotericin B/5-flucytosine was found to be superior to fluconazole with regard to pathogen eradication (86% vs. 50%). Fluconazole was associated with less toxicity than amphotericin B/5-flucytosine.

[Endocarditis from Erysipelothrix rhusiopathiae]. / Endokarditis durch Erysipelothrix rhusiopathiae.

Erysipelothrix rhusiopathiae only seldom causes cases of endocarditis. Contact with infectious animals leads to endocarditis of the left heart with high lethality. Vancomycin and aminoglycosides, which are often used in gram-positive endocarditis, show no effect.

[Pelvic vein thrombosis in protein C deficiency after infectious mononucleosis]. / Beckenvenenthrombose bei Protein-C-Mangel nach infektiöser Mononukleose.

Subsequent to an infectious mononucleosis a 15 year old girl developed a thrombosis of the iliaca vein. Laboratory evaluation revealed a heterozygous form of protein C deficiency. An infusion with r-tPA (= recombinant tissue plasminogen activator) at a rate of 0.02 mg/kg BW/h over 96 hours failed to reopen the vessel. After intermittent heparin therapy longterm treatment with coumarin began. Three months later the iliaca vein was partially recanalised.

[Progressive left ventricular dilatation following anterior myocardial infarct as a determinant for the development of heart failure]. / Progrediente linksventrikuläre Dilatation nach Vorderwandinfarkt als Determinante für die Entwicklung einer Herzinsuffizienz.

35 consecutive patients were studied prospectively with respect to echocardiographic left ventricular size after anterior myocardial infarction. In 25 patients sufficient follow-up was possible. Another 57 patients and volunteers were examined to prove accuracy in comparison to angiocardiography and nuclear magnetic resonance imaging and reproducibility as well as to define normal values. While two-thirds of all patients did not develop left ventricular dilation, one-third showed marked dilation with left ventricular size being 41% above mean normal value. All patients who subsequently developed congestive heart failure or died were in this group. Two-thirds showed no left ventricular dilation and had an uneventful follow-up. Mean left ventricular dilation for all infarcts was 22% within 4 weeks and 26% within 6.3 months, but some patients showed marked left ventricular dilation beyond 4 weeks. We conclude that serial echocardiography is very useful for stratification of risk for CHF after myocardial infarction, and left ventricular dilation is a major risk factor for CHF.