Medizin - Open Access LMU - Teil 13/22 Ludwig-Maximilians-Universität München

Toll-like receptor (TLR)-9 recognizes CpG motifs in microbial DNA. TLR9 signalling stimulates innate antimicrobial immunity and modulates adaptive immune responses including autoimmunity against chromatin, e.g., in systemic lupus erythematosus (SLE). This review summarizes the available data for a role of TLR9 signalling in lupus and discusses the following questions that arise from these observations: 1) Is CpG-DNA/TLR9 interaction involved in infection-induced disease activity of lupus? 2) What are the risks of CpG motifs in vaccine adjuvants for lupus patients? 3) Is TLR9 signalling involved in the pathogenesis of lupus by recognizing self DNA?

Objective: The purpose of this pilot study was to evaluate the feasibility and toxicity of concurrent chemotherapy with vinorelbine and mitomycin C in combination with accelerated radiotherapy (RT) in patients with locally advanced cancer of the head and neck. Patients and Methods: Between January 2003 and March 2004, 15 patients with T4/N2-3 squamous cell carcinoma (12/15) and with N3 cervical lymph node metastases of carcinoma of unknown primary (3/15) were treated with chemotherapy and simultaneous accelerated RT. Results: 11 patients completed therapy without interruption or dose reduction. Grade 3 - 4 acute mucosal toxicity was observed in 9/15 patients, grade 4 hematologic toxicity in 6/15 patients. At a median follow-up of 7.5 months, 2 patients have died of intercurrent disease, 2 patients have experienced local relapse; 5 patients are alive with no evidence of disease at the primary tumor site. Discussion: The described regimen is highly effective, but led to remarkable side effects.

Background/Aims
The apical sodium dependent bile acid transporter ASBT (SLC10A2) contributes
substantially to the enterohepatic circulation of bile acids by their reabsorption from
the intestine. In the rat, its adaptive regulation was observed in the kidneys,
cholangiocytes and terminal ileum after bile duct ligation. Whether an adaptive
regulation of the human intestinal ASBT exists during obstructive cholestasis is not
known.
Methods
Human ASBT mRNA expression along the intestinal tract was analyzed by real time
PCR in biopsies of 14 control subjects undergoing both gastroscopy and
colonoscopy. Their duodenal ASBT mRNA expression was compared to 20 patients
with obstructive cholestasis. Additionally, in 4 patients with obstructive cholestasis,
duodenal ASBT mRNA expression was measured after reconstitution of bile flow.
Results
Normalized ASBT expression in control subjects was highest (mean arbitrary units±
SEM) in the terminal ileum 1010 ± 330. Low ASBT expression was found in the
colonic segments (8.3±5, 4.9±0.9, 4.8±1.7 and 1.1±0.2, ascending, transverse,
descending, and sigmoid colon, respectively). Duodenal ASBT expression of control
subjects was found with 171.8±20.3 at about four fold higher levels when compared
to 37.9±6.5 (p0.0001) in patients with obstructive cholestasis. Individual ASBT
mRNA expression was inversely correlated with bile acid and bilirubin plasma
concentrations. In 4 cholestatic patients average ASBT mRNA increased from 76±18
before to 113±18 after relief of cholestasis (NS). Immunohistochemical assessment
indicates that ASBT protein is expressed on the apical surface of the duodenal
epithelial cells.
Conclusion
Obstructive cholestasis in humans leads to down-regulation of ASBT mRNA
expression in the distal part of the human duodenum.

Purpose:
To investigate retinal thickness and optic disc parameters by the Retinal Thickness Analyzer (RTA) glaucoma program in older normal subjects and to determine any age effect.
Methods:
Subjects over 40 years of age without any prior history of eye diseases were recruited. Only subjects completely normal on clinical ophthalmologic examination and on visual field testing by Humphrey Field Analyzer (HFA) using the SITA 24-2 program were included. A total of 74 eyes from 74 subjects with even age distribution over the decades were enrolled and underwent topographic measurements of the posterior pole and of the optic disc by RTA. The `glaucoma full' program in software version 4.11B was applied.
Results:
Mean patient age was 59.9 +/- 10.3 years with a range from 40 to 80 years. The only parameter intraocular pressure (IOP) correlated with was retinal posterior pole asymmetry (r=0.27, p=0.02). IOP itself increased significantly with age (r=0.341, p=0.003). Mean defect and pattern standard deviation of the HFA did not correlate with any of the retinal or optic disc measurements. Increasing age correlated significantly with some of the morphologic measurements of the RTA: decreasing perifoveal minimum thickness (r=-0.258, p=0.026), increased cup-to-disc area ratio (r=0.302, p=0.016) and increased cup area (r=0.338 p=0.007).
Conclusions:
An age effect exists for some of the retina and optic disc measurements obtained by the RTA. Copyright (C) 2005 S. Karger AG, Basel.

Previous studies showed that mitoxantrone can reduce disability progression in patients with multiple sclerosis (MS). There is, however, concern that it may cause irreversible cardiomyopathy with reduced left ventricular (LV) ejection fraction (EF) and congestive heart failure. The aim of this prospective study was to investigate cardiac side effects of mitoxantrone by repetitive cardiac monitoring in MS patients. The treatment protocol called for ten courses of a combined mitoxantrone (10 mg/m(2) body surface) and methylprednisolone therapy. Before each course, a transthoracic echocardiogram was performed to determine the LV end-diastolic diameter, the end-systolic diameter and the fractional shortening; the LV-EF was calculated. Seventy-three patients participated (32 males; age 48 +/- 12 years, range 20-75 years; 25 with primary progressive, 47 with secondary progressive and 1 with relapsing-remitting MS) who received at least four courses of mitoxantrone. Three of the 73 patients were excluded during the study (2 patients discontinued therapy; 1 patient with a previous history of ischemic heart disease developed atrial fibrillation after the second course of mitoxantrone). The mean cumulative dose of mitoxantrone was 114.0 +/- 33.8 mg. The mean follow-up time was 23.4 months (range 10-57 months). So far, there has been no significant change in any of the determined parameters (end-diastolic diameter, end-systolic diameter, fractional shortening, EF) over time during all follow-up investigations. Mitoxantrone did not cause signs of congestive heart failure in any of the patients. Further cardiac monitoring is, however, needed to determine the safety of mitoxantrone after longer follow-up times and at higher cumulative doses. Copyright (C) 2005 S. Karger AG, Basel.

Background: The increasing demand for complementary medicine indicates a change in attitudes regarding treatment understanding. Objectives: To investigate the role of attitudes in treatment motivation. (1) Can the study sample be subdivided into homogenous groups as regards attitudes toward complementary treatment? (2) How do these groups relate to motivational variables? Patients and Methods: Four questionnaires on motivation and attitudes were administered to 203 patients of two clinics for complementary medicine. Results were interpreted following Petry's motivational process model that distinguishes treatment disposition, preparedness for treatment and treatment activity. Results: According to a cluster analysis, 3 patient groups could be identified: `Not- convinced' patients (cluster 1, n = 24) demonstrated little conviction regarding any aspect of complementary treatment. `Convinced' patients (cluster 2, n = 103) showed a high degree of agreement on all three scales, being highest on `Role of patient'. `Partially- convinced' patients (cluster 3, n = 70) also evaluated `Role of patient' highest, but aspects of the `Physician- patient relationship' and the `Treatment method' were only partly regarded as important. In all clusters, the pragmatic motive of treatment acceptance was central for the treatment choice, but was highest in cluster 2. As compared to cluster 1, a complementary treatment understanding was higher in patients of clusters 2 and 3 ( highest in cluster 2). Discussion: Even if the pragmatic treatment motivation was high in all groups, the central role of treatment attitudes in the motivational process could be verified. Despite differing attitude structures, a majority of patients displayed a complementary treatment comprehension.