[Upper abdominal pain: a frequent and multifaceted leading symptom in primary care internal medicine]. / Oberbauchschmerz ­ ein häufiges und facettenreiches Leitsymptom in der internistisch-hausärztlichen Praxis.

Upper gastrointestinal symptoms are among the most common reasons for medical consultation and represent a challenge for general practitioners in the outpatient care setting. History taking, symptom evaluation and physical examination are the crucial steps toward establishing an initial working diagnosis. The subsequent abdominal ultrasound and laboratory analyses are essential tools for the differential diagnosis.

Genetic and epigenetic insights into uveal melanoma.

Uveal melanoma (UM) is the most frequent primary intraocular tumor in Caucasian adults and is potentially fatal if metastases develop. While several prognostic genetic changes have been identified in UM, epigenetic influences are now getting closer attention. Recent technological advances have allowed to exam the human genome to a greater extent and have improved our understanding of several diseases including malignant tumors. In this context, there has been tremendous progress in the field of UM pathogenesis. Herein, we review the literature with emphasis on genetic alterations, epigenetic modifications and signaling pathways as well as possible biomarkers in UM. In addition, different research models for UM are discussed. New insights and major challenges are outlined in order to evaluate the current status for this potentially devastating disease.

Kit transduced signals counteract erythroid maturation by MAPK-dependent modulation of erythropoietin signaling and apoptosis induction in mouse fetal liver.

Signaling by the stem cell factor receptor Kit in hematopoietic stem and progenitor cells is functionally associated with the regulation of cellular proliferation, differentiation and survival. Expression of the receptor is downregulated upon terminal differentiation in most lineages, including red blood cell terminal maturation, suggesting that omission of Kit transduced signals is a prerequisite for the differentiation process to occur. However, the molecular mechanisms by which Kit signaling preserves the undifferentiated state of progenitor cells are not yet characterized in detail. In this study, we generated a mouse model for inducible expression of a Kit receptor carrying an activating mutation and studied its effects on fetal liver hematopoiesis. We found that sustained Kit signaling leads to expansion of erythroid precursors and interferes with terminal maturation beyond the erythroblast stage. Primary KIT(D816V) erythroblasts stimulated to differentiate fail to exit cell cycle and show elevated rates of apoptosis because of insufficient induction of survival factors. They further retain expression of progenitor cell associated factors c-Myc, c-Myb and GATA-2 and inefficiently upregulate erythroid transcription factors GATA-1, Klf1 and Tal1. In KIT(D816V) erythroblasts we found constitutive activation of the mitogen-activated protein kinase (MAPK) pathway, elevated expression of the src kinase family member Lyn and impaired Akt activation in response to erythropoietin. We demonstrate that the block in differentiation is partially rescued by MAPK inhibition, and completely rescued by the multikinase inhibitor Dasatinib. These results show that a crosstalk between Kit and erythropoietin receptor signaling cascades exists and that continuous Kit signaling, partly mediated by the MAPK pathway, interferes with this crosstalk.

Susceptibility variants on chromosome 7p21.1 suggest HDAC9 as a new candidate gene for male-pattern baldness.

BACKGROUND: Male-pattern baldness (androgenetic alopecia, AGA) is the most common form of hair loss among humans. Research has shown that it is caused by genetic factors. Numerous studies have unequivocally identified two major genetic risk loci for AGA: the X-chromosomal AR/EDA2R locus, and the PAX1/FOXA2 locus on chromosome 20. OBJECTIVES: To identify further candidate genes for AGA, and thus gain further insights into this phenotype. METHODS: A German sample of 581 severely affected cases and 617 controls was used to perform a genome-wide association study. The identified associated locus was further analysed by fine-mapping, and then independently replicated in an Australian sample. Expression and pathway analyses were performed to characterize the susceptibility gene identified. RESULTS: The most significant association signal was obtained for rs756853 (P = 1·64 × 10(-7) ), which is located intronically in the histone deacetylase 9 (HDAC9) gene. Fine-mapping and a family-based analysis revealed that rs756853 and the 6-kb distal rs2249817 were the most highly associated single nucleotide polymorphisms. The association finding was replicated in an independent Australian sample, when the analysis was restricted to severely affected cases and unaffected controls (P = 0·026). Analysis of rs2249817 in a combined sample of severely affected German and Australian cases and unaffected controls revealed a strong association signal (P = 9·09 × 10(-8) ). Tissue expression studies demonstrated HDAC9 expression in various tissues, including tissues of relevance to AGA. No strong genotypic effects were observed in genotype-specific expression or splice studies. Pathway analyses supported the hypothesis that HDAC9 plays a functional role in AGA via interaction with the AR gene. CONCLUSIONS: The present study suggests that HDAC9 is the third AGA susceptibility gene.

Irradiation of DNA loaded with platinum containing molecules by fast atomic ions C(6+) and Fe(26+).

PURPOSE: In order to study the role of the Linear Energy Transfer (LET) of fast atomic ions in platinum-DNA complexes inducing breaks, DNA Plasmids were irradiated by C(6+) and Fe(26+) ions. MATERIAL AND METHODS: DNA Plasmids (pBR322) loaded with different amounts of platinum contained in a terpyridine-platinum molecule (PtTC) were irradiated by C(6+) ions and Fe(26+) ions. The LET values ranged between 13.4 keV/microm and 550 keV/microm. In some experiments, dimethyl sulfoxide (DMSO) was added. RESULTS: In all experiments, a significant increase in DNA strand breaks was observed when platinum was present. The yield of breaks induced per Gray decreased when the LET increased. The yield of single and double strand breaks per plasmid per track increased with the LET, indicating that the number of DNA breaks per Gray was related to the number of tracks through the medium. CONCLUSIONS: These findings show that more DNA breaks are induced by atomic ions when platinum is present. This effect increases for low LET heavy atoms. As DSB induction may induce cell death, these results could open new perspectives with the association of hadrontherapy and chemotherapy. Thus the therapeutic index might be improved by loading the tumour with platinum salts.

Fast He2+ ion irradiation of DNA loaded with platinum-containing molecules.

PURPOSE: The association of radiotherapy and chemotherapy is an attractive approach to improve the therapeutic index of the treatment of tumors. A lot of work has been devoted to investigate the effects of X-ray, gamma-ray and neutron irradiation of DNA or living cells loaded with different chemical compounds containing heavy atoms like platinum. No such studies exist presently when fast atomic ions are chosen as ionizing particles. In the present work, we investigate quantitatively the increase of DNA breaks in complexes of plasmid-DNA loaded with platinum atoms under irradiation by fast atomic He2+ ions. MATERIALS AND METHODS: DNA Plasmids (pBR322) are incubated in solutions containing different concentrations of terpyridine platinum (PtTC). In some preparations, dimethyl sulfoxide (DMSO), a free radical scavenger, has been added in order to investigate the role of the free radicals. The complexes of DNA plasmids loaded with high-Z atoms are irradiated under atmospheric conditions by He2+ ions at an energy of 143 MeV/amu and a linear energy transfert (LET) of 2.24 keV/microm. Analysis of DNA damage--single and double strand breaks--is made by electrophoresis on agarose gels. RESULTS: The results show a significant increase in DNA strand breaks when platinum is present, indicating a radiosensitization by the high Z atoms. The increase in DNA damages is attributed to inner-shell ionization of a platinum atom by secondary electrons emitted along the He2+ tracks followed by an Auger deexcitation, leading, thus, to a local amplification of the radiative effects close to the DNA. The contributions of scavengeable--solvant mediated--indirect effects and non-scavengeable effects (direct ionization) are quantitatively evaluated. CONCLUSION: Enhancement of DNA breaks in plasmids loaded with heavy atoms like platinum and irradiated by atomic ions are observed. This finding suggests an enhancement of cell death rate will occur under irradiation by atomic ions when the cells contain high-Z atoms located close to DNA due to the increase of the DNA breaks.

[Peranal passage of a surgical sponge: fortunate outcome of an intraoperative oversight]. / Glücklicher Ausgang einer intraoperativen Unterlassung.

Four years after cholecystectomy and recurrent epigastric pain, a surgical sponge passed per anum in a 39-year-old man. Diagnostic procedures including clinical and laboratory examinations, ultrasound, coloscopy, and abdominal CT did not reveal any noteworthy residual changes by the foreign body. After 4 years in situ, the surgical sponge showed no alterations in structure. The representatives of the hospital concerned had to satisfy the patient's claims for damages. Pathology, technical diagnostic methods, and prognosis in cases of retained gauzes are presented. It is essential to count instruments and towels and advisable to use only single sponges in forceps in order to prevent intraoperative loss.

Enhancement of X-ray-induced breaks in DNA bound to molecules containing platinum: a possible application to hadrontherapy.

Complexes made of DNA and chloroterpyridine platinum (PtTC) bound to plasmid DNA were placed in aqueous solution and irradiated with monochromatic X rays tuned to the resonant photoabsorption energy of the L(III) shell of the platinum atom. The number of single- and double-strand breaks (SSBs and DSBs) induced by irradiation on a supercoiled DNA plasmid was measured by the production of the circular-nicked and linear forms. To distinguish the contribution of the direct effects of ionization from the indirect effects due to a free radical attack, experiments were also performed in the presence of a hydroxyl free radical scavenger, dimethyl sulfoxide (DMSO). An enhancement of the number of SSBs and DSBs was observed when the plasmids contained the platinum intercalating molecules. A quantitative analysis was made to evaluate the respective contributions of the direct effects (Auger effect) and the indirect effects (free radical attack) to the number of DNA strand breaks. Even when off-resonant X rays were used, the strand break efficiency remained higher than expected based upon the absorption cross section, suggesting that the platinum bound to DNA might be increasing the yield of strand breaks. A mechanism is suggested that involves photoelectrons generated from the ionization of water which efficiently ionize platinum atoms. If this mechanism is correct, then heavy atoms, with a large cross section for ionization by electrons that are bound to the DNA, should behave as a radiosensitizer. This observation may provide insight into understanding the effects of new radiotherapy protocols, related chemotherapeutic agents such as cisplatin, and conventional radiotherapy for the treatment of tumors. A possible way to deliver the dose selectively in a well-defined volume, which uses the properties of the linear energy transfer of atomic ions interacting with matter, is suggested.

Enhanced strand break induction of DNA by resonant metal-innershell photoabsorption.

We determined the number of single and double strand breaks (ssb and dsb) in a DNA-chloroterpyridine platinum complex induced by resonant photoabsorption in the L(III) innershell of a platinum atom. The number of ssb and dsb were measured in supercoiled plasmids (AG30) versus the chloroterpyridine platinum concentration, i.e., the ratio of intercalated molecules to the number of phosphate sites in DNA. A significant increase in the number of ssb and dsb was observed when the DNA contained intercalated molecules. This technique is an efficient way to induce ssb and dsb triggered by the atomic Auger effect.

Strand break induction by photoabsorption in DNA-bound molecules.

Dried samples of a DNA-chloroterpyridine platinum complex were irradiated with monochromatic X rays tuned to the photoabsorption resonance of the L(III) inner shell of the platinum atom. The number of single- and double-strand breaks (SSBs and DSBs) triggered by the Auger effect in supercoiled DNA plasmids was measured by the production of circular nicked and linear forms. To probe the specific contribution of the L(III) inner-shell excitation of the platinum atom, photon wavelengths were tuned on the resonance energy (on peak) and below (off peak). The quantum yields of the resonance radiation were typically found to be 11 for the SSBs and 1 for the DSBs. The DSB-to-SSB ratio increased by 20% when switching from off-resonance to on-resonance irradiation.

[Acute heart arrest during urologic routine interventions in 2 cases. Interdisciplinary crisis management assures tumor-free survival despite fulminant lung embolism with acute heart arrest during thoraco-abdominal tumor nephrectomy and radical cystoprostatovesiculectomy]. / Akuter Herzstillstand während urologischer Routineeingriffe in 2 Fällen. Interdisziplinäres Krisenmanagement sichert tumorfreies Uberleben trotz fulminanter Lungenembolie mit akutem Herzstillstand während einer thorakoabdominalen Tumornephrektomie und einer radikalen Zystoprostatovesikulektomie.

Intraoperative pulmonary embolism with acute cardiac arrest can successfully be managed by immediate open cardiac massage followed by rt-PA injection, an inter-disciplinary approach is mandatory. The scheduled tumor nephrectomy was performed 6 weeks after the initial event. The tumor was embolised with intravascular coils placed in a supraselective manner by the radiologist. During the secondary procedure it was found to be necrotic. In the second case the event occurred at the end of a radical cystectomy. Instead of an ileal conduit cutaneous ureterostomies were used for urinary drainage after cardiac output had been restored and rt-PA had been administered.

DNA breakage upon K-shell excitation of phosphorus as a model for direct effects in radiation biology.

Single-strand breaks (SSBs) and double-strand breaks (DSBs) induced in DNA under phosphorus K-shell resonant absorption have been studied using supercoiled plasmids. The kinetics of the production of SSBs and DSBs exhibits a linear and a quadratic dependence, respectively, on photon fluence. Cross sections and quantum yields have been measured. The resonant photoexcitation of the phosphorus atoms was found to increase the DSB/SSB ratio compared to the off-resonance excitation. This enhancement factor can be related to the measured enhancement of the rate of cellular death and gene mutation in yeast under similar experimental conditions reported previously in the literature. Such resonant excitation of a specific atom belonging to DNA turns out to be an elegant method to investigate pure direct effects.

[Decreasing the surgical risk of laparoscopy by using a newly developed, blunt trocar]. / Senkung des operativen Risikos in der Laparoskopie durch den Einsatz eines neuentwickelten, stumpfen Trokars.

Laparoscopy is one of the most frequent interventions used in operative gynaecology. Because of the possible, occasionally grave complications through the use of the trocar forms applied so far, we have developed a new blunt trocar. By using this trocar throughout 1889 interventions, we have had no complications which could be ascribed to the use of this blunt instrument. The advantage of this trocar lies in the avoidance of the possible and feared injuries to the intestines and vessels. Even though overall complication rates in laparoscopy are low and there is no evidence of a statistically significant reduction compared with the use of the sharp trocar, the advantages of the blunt trocar are obvious. There is only one disadvantage, namely the slightly prolonged training time of the younger colleagues, as well as the theoretical possibility of a prolapse of the omentum. Nevertheless, in our opinion, the use of the blunt trocar is advisable to reduce the complication rate in laparoscopy.

[The spontaneous regression of a dissection of the descending aorta]. / Die spontane Rückbildung einer Dissektion der Aorta descendens.

The outcome of an aortic dissection is either endothelialisation of the false lumen forming a so-called double aorta, or thrombosis of the sack leading to fibrosis. Healing of an aortic dissection, particularly if thrombosis and organisation have obliterated the dissected segment, is rare and there are only a few case reports on this finding. We report on a case where spontaneous resolution of the false lumen of Type B aortic dissection was demonstrated by serial contrast enhanced computed tomography after antihypertensive medical treatment.

[A realistic cardiovascular model for evaluating clinical applicability of duplex and color-Doppler equipment]. / Ein realitätsnahes Kreislaufmodell zur Beurteilung der klinischen Anwendbarkeit von Duplex- und Farbdopplergeräten.

To evaluate the accuracy and reliability of colour-coded Doppler devices (CCDD) for practical use, a circulatory phantom with in vivo characteristics was developed. The experimental design consists of a piston-diaphragm metering pump with an adjustable piston volume and frequency of stroke as well as silicone tubings with different elasticity and diameters comparable with cadaver arteries. Depending on physiological conditions, blood as a circulating fluid and the surrounding soft tissues of the artery near the Doppler probe should be employed. The transducer should be manually guided. Thus, comparable to physiological frequency spectral displays, different types of wave forms (e.g. monophasic, triphasic) were initiated to analyze the reliability of CCDDs for practical use.

[Computed tomographic detection of a polypous form of eosinophilic gastroenteritis in the duodenum]. / Computertomographische Darstellung einer polypösen Form der eosinophilen Gastroenteritis im Duodenum.

The eosinophilic granuloma of the intestine is a relatively uncommon lesion which is unrelated to the eosinophilic granuloma of lung or bone. We describe one case of this disease in the duodenum evaluated by hypotonic duodenography and computed tomography (CT). The radiographs showed sharply delineated circular intra-luminal filling defect. CT demonstrated a homogeneous soft tissue mass and excluded an extraluminal extension of the lesion. Histological examination is essential for confirming the diagnosis.