Medizin - Open Access LMU - Teil 15/22 Archiv

Background/Aims: Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been shown to inhibit growth and to induce apoptosis in human hepatocellular carcinoma (HCC) cells. However, the potential benefit of pravastatin in HCC patients has still not been characterized, which prompted us to test the efficacy of pravastatin in patients with advanced HCC. Methods: We investigated prospectively a cohort of 183 HCC patients who had been selected for palliative treatment by transarterial chemoembolization (TACE). Fifty-two patients received TACE combined with pravastatin (20-40 mg/day) and 131 patients received chemoembolization alone. Six independent predictors of survival according to the Vienna survival model for HCC were equally distributed in both groups. Results: During the observation period of up to 5 years, 31 (23.7%) out of 131 patients treated by TACE alone and 19 (36.5%) out of 52 patients treated by TACE and pravastatin survived. Median survival was significantly longer in HCC patients treated by TACE and pravastatin (20.9 months, 95% Cl 15.5-26.3, p = 0.003) than in HCC patients treated by TACE alone (12.0 months, 95% Cl 10.3-13.7). Conclusion: Combined treatment of chemoembolization and pravastatin improves survival of patients with advanced HCC in comparison to patients receiving chemoembolization alone. Copyright (C) 2008 S. Karger AG, Basel

Background/ Aims: So far, surgical and interventional therapies for muscular ventricular septal defects ( mVSDs) beyond the moderator band have had their limitations. Thus, alternative therapeutic strategies should be developed. We present a new animal model for the evaluation of such strategies. Methods: In a pig model ( n = 9), anterolateral thoracotomy was performed for exposure of the left ventricle. mVSDs were created under two- and three- dimensional echocardiography with a 7.5- mm sharp punch instrument, which was forwarded via a left ventricular puncture without extracorporeal circulation. Results: Creation of mVSDs was successful in all animals ( n = 9) confirmed by echocardiography, hemodynamic measurements and autopsy. The defects were located in the midmuscular ( n = 4), apical ( n = 1), inlet ( n = 2) and anterior part ( n = 2) of the muscular septum. All animals were hemodynamically stable for further procedures. The diameter and shunt volume of the mVSDs were 4.8 - 7.3 mm ( mean: 5.9 mm) and 12.9 - 41.3% ( mean: 22.1%), respectively. Autopsy confirmed in all animals the creation of a substantial defect. Conclusion: The described new technique for creation of an mVSD on the beating heart in a pig model is suitable for the evaluation of new therapeutic strategies for mVSD closure. Copyright (C) 2008 S. Karger AG, Basel.

Background: Whereas various molecular working mechanisms of shock waves have been demonstrated, no study has assessed in detail the influence of varying energy flux densities (EFD) on new bone formation in vivo. Methods: Thirty Chinchilla bastard rabbits were randomly assigned to 5 groups (EFD 0.0, 0.35, 0.5, 0.9 and 1.2 mJ/mm(2)) and treated with extracorporeal shock waves at the distal femoral region (1,500 pulses; 1 Hz frequency). To investigate new bone formation, animals were injected with oxytetracycline at days 5-9 after shock wave application and sacrificed on day 10. Histological sections of all animals were examined using broad-band epifluorescent illumination, contact microradiography and Giemsa-Eosin staining. Results: Application of shock waves induced new bone formation beginning with 0.5 mJ/mm(2) EFD and increasing with 0.9 mJ/mm(2) and 1.2 mJ/mm(2). The latter EFD resulted in new bone formation also on the dorsal cortical bone; cortical fractures and periosteal detachment also occurred. Conclusion: Here, for the first time, a threshold level is presented for new bone formation after applying shock waves to intact bone in vivo. The findings of this study are of considerable significance for preventing unwanted side effects in new approaches in the clinical application of shock waves. Copyright (c) 2008 S. Karger AG, Basel.

Objective: The aim of our study was the evaluation of sonographic fetal weight estimation taking into consideration 9 of the most important factors of influence on the precision of the estimation. Methods: We analyzed 820 singleton pregnancies from 22 to 42 weeks of gestational age. We evaluated 9 different factors that potentially influence the precision of sonographic weight estimation ( time interval between estimation and delivery, experts vs. less experienced investigator, fetal gender, gestational age, fetal weight, maternal BMI, amniotic fluid index, presentation of the fetus, location of the placenta). Finally, we compared the results of the fetal weight estimation of the fetuses with poor scanning conditions to those presenting good scanning conditions. Results: Of the 9 evaluated factors that may influence accuracy of fetal weight estimation, only a short interval between sonographic weight estimation and delivery (0-7 vs. 8-14 days) had a statistically significant impact. Conclusion: Of all known factors of influence, only a time interval of more than 7 days between estimation and delivery had a negative impact on the estimation.

Objective: To determine maternal serum placental protein 13 (PP13) in normal pregnancy and preeclampsia. Methods: A prospective, longitudinal study with 41 normal pregnant women, 18 cases with preterm delivery or cervix insufficiency and 4 with developing late-onset preeclampsia. Six hundred and sixty-six maternal blood samples were obtained every 2-4 weeks starting at 5-8 weeks gestation (10-12 samples/patient) and tested for serum PP13 by ELISA. Results: In normal pregnant women delivering at term, median maternal serum PP13 levels were growing from 166 to 202 pg/ml and 382 pg/ml in the first, second and third trimester, respectively. Preeclamptic women had significantly reduced PP13 levels in the first trimester (multiples of median of 0.14 at 7-8 weeks; p = 0.005 compared to normal). PP13 in the third trimester was significantly higher compared to normal at 35-36 weeks with PP13 multiples of median of 1.79. Conclusion: This preliminary study indicates that low levels of PP13 in early pregnancy identify at-risk pregnancies, whereas high levels precede the syndrome in late pregnancy and suggest syncytiotrophoblast necrosis. Copyright (C) 2008 S. Karger AG, Basel.

Objective: Developmental disorders in childhood are generally assumed to have stigmatizing effects. The goal of the present study was to assess whether parents of children with speech-language impairment perceive stigmatization of their child or themselves and which variables influence the degree of negative labeling. Subjects and Methods: The study was based on 362 questionnaires completed by parents of children with speech-language impairment. The questionnaires concerned perceived stigmatization by other children, other adults and family members as a result of the child's developmental problems. Results: In our sample, about 50% of the parents reported negative labeling of their child and about 30% felt they were involved in the stigmatizing process. Parents whose children also had behavioral problems more often reported negative labeling than parents whose children did not. Conclusion: The findings suggest that parents of children with speech-language disorders often perceive stigmatization of their children or themselves. In counseling such families, professionals should therefore address stigmatization and its consequences as a separate and important issue. Copyright (c) 2008 S. Karger AG, Basel

We present the case of a 76-year-old female patient with complex psychosomatic complaints. The patient suffered from depression, panic attacks, chronic pain and dyspepsia with nausea and loss of appetite. In addition to the conventional psychosomatic care, the patient received individual homeopathic treatment for her dyspepsia, resulting in complete remission. The therapeutic value of homeopathy in the present case is discussed in the context of recent findings from placebo research.

Based on resource-oriented conceptions of successful life-span development, we propose three principles for evaluating assistive technology: (a) net resource release; (b) person specificity, and (c) proximal versus distal frames of evaluation. We discuss how these general principles can aid the design and evaluation of assistive technology in adulthood and old age, and propose two technological strategies, one targeting sensorimotor and the other cognitive functioning. The sensorimotor strategy aims at releasing cognitive resources such as attention and working memory by reducing the cognitive demands of sensory or sensorimotor aspects of performance. The cognitive strategy attempts to provide adaptive and individualized cuing structures orienting the individual in time and space by providing prompts that connect properties of the environment to the individual's action goals. We argue that intelligent assistive technology continuously adjusts the balance between `environmental support' and `self-initiated processing' in person-specific and aging-sensitive ways, leading to enhanced allocation of cognitive resources. Furthermore, intelligent assistive technology may foster the generation of formerly latent cognitive resources by activating developmental reserves (plasticity). We conclude that `lifespan technology', if co-constructed by behavioral scientists, engineers, and aging individuals, offers great promise for improving both the transition from middle adulthood to old age and the degree of autonomy in old age in present and future generations. Copyright (C) 2008 S. Karger AG, Basel.

Introduction: Eczematous reactions to type I allergy-inducing antigens are documented in a subgroup of patients with atopic eczema. Yet, the underlying immunological mechanisms are not well understood. Material and Methods: To delineate the effect of native pollen grains on human skin of healthy and atopic individuals we performed patch tests (atopy patch test with native pollen grains, PPT). Nickel patch tests (NPT) served as an established model of contact dermatitis. Skin site biopsies were taken 6 - 96 h after allergen application and investigated immunohistochemically. Results: Histology of positive patch tests showed an influx of mononuclear cells (predominantly CD4+, CD25+, CD45RO+). This influx was detected earlier in the PPT reaction than in the immune response to nickel. A biphasic cytokine response could be detected in the PPT: IL-5 dominated in the early, IFN-gamma in the late phase. The NPT was continuously dominated by IFN-gamma. Dendritic cell subpopulations imitated the earlier kinetics of the mononuclear infiltrate. Discussion: Thus, pollen grains induce eczematous reactions in susceptible individuals. This reaction appears clinically and immunohistochemically similar to the contact hypersensitivity reaction to nickel but follows a faster kinetic and a biphasic course: Th2 and IgE in the early (24 h) and Th1 predominance in the late (96 h) phase. Copyright (c) 2007 S. Karger AG, Basel.

Hyper IgE syndromes (HIES) are primary immunodeficiency disorders of unknown pathogenesis. Patients are typically affected with `cold' abscesses of the skin, recurrent cyst-forming pneumonia, chronic mucocutaneous candidiasis and other less frequent features such as progressive skeletal abnormalities. Defective signaling in the Toll-like receptor (TLR) pathways has been suggested as a responsible pathologic mechanism, however, in previous reports, 10 patients revealed no defect in inflammatory cytokine responses to different TLR ligands. Here, we report the increase in pro-inflammatory cytokines TNF-alpha and IL-8, following TLR2 and TLR4 stimulation in a larger cohort of 25 additional patients with HIES, and provide a meta-analysis of the TLR data in HIES. Copyright (C) 2008 S. Karger AG, Basel.

We report on a 33-year-old female patient with indolent systemic mastocytosis and urticaria pigmentosa who died of an anaphylactic reaction after a yellow jacket sting. As she had no history of previous anaphylactic sting reaction, there was no testing performed in order to detect hymenoptera venom sensitization. But even if a sensitization had been diagnosed, no venom immunotherapy (VIT) would have been recommended. It is almost certain that VIT would have saved her life and it is most likely that VIT is indicated in some patients with mastocytosis with no history of anaphylactic sting reaction. However, no criteria have been established in order to allow a selection of mastocytosis patients eligible for such a `prophylactic' VIT. Copyright (C) 2008 S. Karger AG, Basel.

Methanogenic archaea accumulate glycine betaine in response to hypersalinity, but the regulation of proteins involved, their mechanism of activation and regulation of the corresponding genes are largely unknown. Methanosarcina mazei differs from most other methanoarchaea in having two gene clusters both encoding a potential glycine betaine transporter, Ota and Otb. Western blot as well as quantitative real-time PCR revealed that Otb is not regulated by osmolarity. On the other hand, cellular levels of Ota increased with increasing salt concentrations. A maximum was reached at 300-500 m M NaCl. Ota concentrations reached a maximum 4 h after an osmotic upshock. Hyperosmolarity also caused an increase in cellular Ota concentrations. In addition to osmolarity Ota expression was regulated by the growth phase. Expression of Ota as well as transport of betaine was downregulated in the presence of glycine betaine. Copyright (c) 2007 S. Karger AG, Basel.