Apoptose bei multipler Sklerose Ätiopathogenetische Relevanz und Perspektiven für neue therapeutische Strategien

Apoptosis, or programmed cell death, is a physiological cell suicide program mainly leading to selective elimination of useless cells. This mechanism is important for the homeostasis of the immune system and presumably plays a two-sided role in the pathogenesis of multiple sclerosis (MS). On the one hand, evidence has been provided that impaired apoptosis might result in increased numbers or persistence of activated myelin-specific T cells, thus inducing the pathophysiologic processes in MS. On the other hand, local tissue damage might involve apoptosis of glial and neuronal cells and lead to the clinical symptoms. Here, an overview is presented on the current knowledge of the role of apoptosis in the pathogenesis of MS, and implications for related therapeutic strategies are discussed.     

Expression of receptor activator of nuclear factor kappaB ligand on bone marrow plasma cells correlates with osteolytic bone disease in patients with multiple myeloma.

PURPOSE: Increased bone resorption is a hallmark of multiple myeloma and is attributable to osteoclast activation. Recent studies showed that the receptor activator of nuclear factor kappaB ligand (RANKL) is the key mediator of osteoclastogenesis and plays a crucial role in bone destruction in malignant bone disease. We found that human myeloma cells express RANKL and analyzed the association of the RANKL expression with the presence of osteolytic bone disease in patients with multiple myeloma. EXPERIMENTAL DESIGN: Flow cytometry was performed on bone marrow samples derived from controls and multiple myeloma patients with or without osteolytic bone lesions on conventional radiography. Plasma cells were identified as CD38++/CD138+ cells. The level of RANKL expression on the surface of bone marrow plasma cells was correlated with the bone status of the patients. RESULTS: The bone marrow plasma cells from controls showed no or only a weak surface expression of RANKL, and the median mean fluorescence index (MFI) was 6. In contrast, expression of RANKL could be detected on bone marrow plasma cells from all of the patients with multiple myeloma, and median MFI was 47. The difference in MFI for RANKL expression of bone marrow plasma cells from controls and myeloma patients was highly significant (P < 0.0005). Myeloma patients with osteolytic bone lesions showed a significantly higher expression of RANKL (median MFI = 60; range, 16-2494) compared with patients without osteolysis (median MFI = 16; range, 6-229; P < 0.0005). CONCLUSIONS: These results show for the first time that the level of RANKL expression by myeloma cells correlates significantly with osteolytic bone disease.     

Delayed Diagnosis of Tuberculous Arthritis

Monoarticular tuberculosis （TB） affecting the knee is rare in all forms of TB （0.1-0.3%）. We present the case of a patient with tuberculous arthritis in whom the diagnosis was belated due to a lack of familiarity with the disease; here, we emphasize the difficulties associated with the diagnosing joint TB. A 20-year-old man was referred to our department due to swelling of the right knee and the presence of persistent, mild pain for 4 years. The lack of systemic evidence of this disease, the indolent course of disease, and the presence of non- specific symptoms renders early recognition of this disease difficult. Furthermore, in cases in which a diagnosis cannot be reached simply by culturing the synovial fluid, synovial biopsy cultures should be considered m the diagnostic process, due to the high rate of positivity of such cultures. The diagnosis and treatment of articular TB are both urgent matters; surgical debridement and strict adherence to antituberculous chemotherapy tend to yield a satisfactory functional outcome.     

Acetylcholinesterase inhibitory and antioxidant properties of Cyclotrichium niveum, Thymus praecox subsp. caucasicus var. caucasicus, Echinacea purpurea and E. pallida

The dichloromethane, ethyl acetate, ethanol, and aqueous extracts of Cyclotrichium niveum (CN) and Thymus praecox subsp. caucasicus var. caucasicus (TP), Echinacea purpurea (EPU), and E. pallida (EPA) along with the essential oils of CN and TP were assessed for their anti-acetylcholinesterase (AChE) and antioxidant activities. AChE inhibition was estimated using spectrophotometric method of Ellman. Antioxidant activity was evaluated by 2,2-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and ferrous ion-chelating power tests. Ferric-reducing antioxidant power (FRAP) of CN and TP were also tested. CN essential oil was found to contain isomenthone (56.21%) and pulegone (19.76%). The ethyl acetate (83.11–87.98%) and dichloromethane (73.45–84.02%) extracts of CN showed the highest AChE inhibition. The ethyl acetate and ethanol extracts of TP exerted significant DPPH scavenger effect. The water extracts of CN and TP and the chloroform extract of the aerial parts of EPU displayed the highest ferrous ion-chelating effect. The leaf and flower essential oils of TP had the best FRAP.     

Mean Platelet Volume is Associated with Diabetic Macular Edema in Patients with Type-2 Diabetes Mellitus

Aim: To evaluate the effect of the platelet indices on the stage of diabetic retinopathy (DR) and diabetic macular edema (DME). Methods: In this retrospective study, the mean platelet valume (MPV), Plateletcrit (PCT), platelet (PLT), and platelet distribution width (PDW) of 199 diabetic patients and 76 healthy subjects were enrolled. The participants were divided into four groups. The first group was healthy control; the second group consisted of diabetic patients without DR; the third group was nonproliferative DR (NPDR); and the fourth group was proliferative DR (PDR). Results: Significant differences were found only in MPV and PCT values between patients with diabetes and healthy participants (8.6±0.96 fL vs 8.32±0.9 fL, P=0.011, 0.216± 0.58 vs 0.202±0.52, P=0.038). Comparing the groups, a statistically significant difference in MPV values was found between groups 4 and 1 (8.91±.7 fL vs 8.32±0.9 fL P=0.001) and between groups 4 and 3 (8.91±.7 fL vs 8.42±0.9 fL P=0.014). The MPV values of patients with DME were significantly higher than those of diabetic patients without DME (8.87±0.80 fL vs 8.45±0.97 fL). Conclusion: High MPV values may be an important risk factor for the development of PDR and DME in patients with diabetic retinopathy.     

One-stage vs. two-stage adjustable sutures for the correction of esotropia

BACKGROUND The aim of this study was to evaluate the stability and the level of postoperative consciousness, nausea and vomiting, ocular pain, starting oral intake and activity, and cost-effectiveness in patients undergoing medial rectus recession surgery using an adjustable suture technique that was performed by two different methods. METHOD In this prospective study, we evaluated 78 patients undergoing medial rectus recession surgery. Thirty-eight patients were operated by a one-stage technique in which the whole operation was done under topical anesthesia and adjustment was done on the operating table, while 40 patients were operated by a two-stage technique in which the operation was done under general anesthesia and adjustment was done the following day at the patient’s bedside. The results were recorded and compared according to the parameters given above. A scoring system was used to assess all these parameters except for stability. The stability of the procedures was evaluated according to the degrees of squint immediately after the adjustment and at least three months thereafter. RESULTS There was no significant difference between the procedures with regard to stability and ocular pain. During the early postoperative period, the level of consciousness was better and nausea and vomiting occurred less frequently in the patients operated by the one-stage procedure. Postoperative activity and oral intake returned to normal status more quickly in the one-stage group and the one-stage procedure was cost-effective. CONCLUSION We conclude that although both procedures provide satisfactory and stable results, the one-stage procedure has significant advantages over the two-stage procedure for medial rectus recession surgery in suitable cases.     

Prognostic impact of circulating tumor cells assessed with the CellSearch System? and AdnaTest Breast? in metastatic breast cancer patients: the DETECT study

Introduction

There is a multitude of assays for the detection of circulating tumor cells (CTCs) but a very limited number of studies comparing the clinical relevance of results obtained with different test methods. The DETECT trial for metastatic breast cancer patients was designed to directly compare the prognostic impact of two commercially available CTC assays that are prominent representatives of immunocytochemical and RT-PCR based technologies.

Methods

In total, 254 metastatic breast cancer patients were enrolled in this prospective multicenter trial. CTCs were assessed using both the AdnaTest Breast Cancer and the CellSearch system according to the manufacturers' instructions.

Results

With the CellSearch system, 116 of 221 (50%) evaluable patients were CTC-positive based on a cut-off level at 5 or more CTCs. The median overall survival (OS) was 18.1 months in CTC-positive patients. (95%-CI: 15.1-22.1 months) compared to 27 months in CTC-negative patients (23.5-30.7 months; p<0.001). This prognostic impact for OS was also significant in the subgroups of patients with triple negative, HER2-positive and hormone receptor-positive/HER2-negative primary tumors. The progression free survival (PFS) was not correlated with CTC status in our cohort receiving different types and lines of systemic treatment (p = 0.197). In multivariate analysis, the presence of CTCs was an independent predictor for OS (HR: 2.7, 95%-CI: 1.6-4.2). When the AdnaTest Breast was performed, 88 of 221 (40%) patients were CTC-positive. CTC-positivity assessed by the AdnaTest Breast had no association with PFS or OS.

Conclusions

The prognostic relevance of CTC detection in metastatic breast cancer patients depends on the test method. The present results indicate that the CellSearch system is superior to the AdnaTest Breast Cancer in predicting clinical outcome in advanced breast cancer.

Trial registration

Current Controlled Trials Registry number ISRCTN59722891.     

CYP1A1 gene polymorphism and polycystic ovary syndrome

The aim of this study was to assess the rates of variant alleles of cytochrome P4501A1 (CYP1A1) in patients with polycystic ovary syndrome (PCOS). It was designed as a case-control study in Hacettepe University, Faculty of Medicine, Department of Obstetrics and Gynecology and Genetics. Forty-eight patients with PCOS served as the study group. Ninety-six regularly cycling women with no clinical and biochemical evidence of hyperandrogenism and polycystic ovary appearance served as the controls. The CYP1A1 variant alleles of all patients were determined via polymerase chain reaction. The rate of the CYP1A1 isoleucine (Ile)/valine (Val) allele was significantly higher in patients with PCOS than in the controls (OR: 7.8, 95% CI: 3.45-17.52, P < 0.001). However, there was no statistically significant difference in the distribution of Val/Val genotype (OR: 4.0, 95% CI: 0.60-26.73). The rate of any Val genotype (Ile/Val or Val/Val) was significantly higher in patients with PCOS compared with the control group (OR: 7.4, 95% CI: 3.33-16.46, P < 0.001). In conclusion, the patients with PCOS had a 7.8-fold higher frequency of CYP1A1 Ile/Val genotype and a 7.4-fold higher frequency of CYP1A1 of any Val genotype (Ile/Val or Val/Val).