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Summary   Infection with Varicella zoster virus (VZV) usually occurs in children up to 15 years with mild symptoms. We present a case of a 22-year old man with a fatal varicella zoster infection. He developed fulminant hepatitis with acute liver failure and an acute respiratory distress syndrom (ARDS). In this article the general aspects of VZV infection are discussed. Treatment options and previous publications are reviewed. [ABSTRACT FROM AUTHOR]

Summary Up to now, strategies for the verification of the correct localization of gastric tubes have not been internationally standardized. In Germany, most units rely on the auscultation method, whereas in the United States a radiological control after tube placement is considered mandatory. In this pilot study, the feasibility of a simple sonographic method for the correct localization of a gastric tube in intensive care units is evaluated. In 60 gastric tube insertions (with 50 patients being on artificial ventilation) performed on a medical intensive care unit, the correct placement of the tube was controlled by 1) auscultation, 2) pH measurement of the aspirate, and 3) sonography. In sonography, correct placement of the tip of the tube in the stomach was ascertained by detecting a 50 ml air jet applied with a syringe via the gastric tube. Results of ultrasound and the other control methods were compared to radiological control of the tube. In 43 patients (72%), the correct placement of the gastric tube was documented by ultrasound, compared to only 23% of patients in which a pH value of less than 4 allowed the proof of correct localization. In 2/20 patients without a detectable air jet on sonography, the gastric tube was located in the esophagus. We conclude that ?bedside? sonography is a fast and easy to perform method for the ascertainment of the correct positioning of a gastric tube and may in most cases be able to replace radiology for this indication. [ABSTRACT FROM AUTHOR]

The interdisciplinary guidelines at the S3 level on the diagnosis of and therapy for hepatocellular carcinoma (HCC) constitute an evidence- and consensus-based instrument that is aimed at improving the diagnosis of and therapy for HCC since these are very challenging tasks. The purpose of the guidelines is to offer the patient (with suspected or confirmed HCC) adequate, scientifically based and up-to-date procedures in diagnosis, therapy and rehabilitation. This holds not only for locally limited or focally advanced disease but also for the existence of recurrences or distant metastases. Besides making a contribution to an appropriate health-care service, the guidelines should also provide the foundation for an individually adapted, high-quality therapy. The explanatory background texts should also enable non-specialist but responsible colleagues to give sound advice to their patients concerning specialist procedures, side effects and results. In the medium and long-term this should reduce the morbidity and mortality of patients with HCC and improve their quality of life., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim: Deep vein thrombosis (DVT) is an insidious disease wherein more than 15 different clinical signs are described. The aim of this work was to focus on these clinical signs and to test them for their importance in making a diagnosis of DVT., Methods: All patients treated with a tentative diagnosis of DVT in the emergency department were asked to take part in the study. Out of the 254 patients who were examined in order to exclude DVT, 204 patients agreed to participate in the study. The patients who agreed to take part were tested for fifteen clinical examination signs. The Wells score was then determined., Results: Sixty-two were diagnosed with DVT. For 142 patients, DVT could be ruled out. The probability of DVT for 9 signs together is 88%, and for 3 signs is 78%. The negative predictive values are 91-95%. The combination of the clinical signs showed a specificity of 100%, independent if the patients were old, comorbid, and were diagnosed with the thrombosis in the lower limbs. The determination of the Wells score resulted in no convincing evidence for or against the diagnosis of DVT., Conclusion: We suggest a modified Wells score integrating missing clinical signs with more reliable predictive values. Even with the availability of ultrasound, clinical signs have not become superfluous. They are quick to carry out, safe, cheap and an important addition to the Wells score, particularly for multimorbid and elderly patients.

Introduction: The localisation of focal liver lesions is usually performed according to the Couinaud classification system. The exact description of localisation and size of liver lesions is especially important for surgical procedures. The aim of this prospective study was the evaluation of differences and agreements in the localisation and size of hepatic lesions as found by ultrasound (US), computed tomography (CT) and according to the intraoperative status (OP)., Material and Methods: 32 patients (21 male, 11 female) were enrolled in the study. The results obtained from sonography, computed tomography and surgery were classified into 5 categories for localisation and for size, respectively., Results: According to the agreement between sonography and computed tomography, 25 % of all hepatic lesions were classified into category 1 (exact agreement), whereas 40.6 % were ranked into category 2 (almost exact agreement). Correlating sonography and intraoperative results, 31.3 % of the lesions were classified into category 1 and 46.9 % into category 2. In the comparison of CT with OP, 34.4 % of the lesions were found to be in category 1 and 43.8 % in category 2. Concerning the size of the lesions, almost half of the tumours (46.9 %) were classified into category 1 on the basis of the correlation between US and CT and 21.9 % on the basis of the correlation between US and OP., Discussion: The localisation and description of the size of hepatic lesions is mainly similar or even identical on the basis of the different methods. Further improvements might be achieved by the introduction of a consistent nomenclature.

Objective: Although often recommended, it is unclear whether fasting enhances the imaging quality of abdominal sonography examinations. The aim of this study was to produce experimental evidence of the effect of fasting on the imaging quality of abdominal organs., Material and Methods: Formally consenting medical inpatients who underwent elective abdominal sonography examinations at a university medical center were randomized to either a fasting or a non-fasting preparation. Blinded examiners evaluated the imaging quality of 11 anatomical regions. The primary end-point was the proportion of completely evaluable patients for each region. In secondary analyses, values of an imaging index reflecting the mean imaging quality of all regions (range 0-1) were compared. RESULTS. Of 280 screened patients, 102 (36%) met the exclusion criteria and 35 (13%) declined participation. Of the 143 randomized patients, 130 (91%) were included in the primary analyses (66 fasting, 64 non-fasting). The proportion of completely evaluable patients did not differ significantly for any of the 11 regions, but a large nominal difference occurred for the gallbladder (45/66 (73%) fasting versus 34/64 (56%) non-fasting patients, p=0.051). The median (range) imaging index was 0.57 (0.14-0.95) for fasting and 0.43 (0.00-1.00) for non-fasting subjects (p =0.078). A significant (p=0.002) difference favoring fasting was detected in the post-hoc subgroup analyses for male patients., Conclusions: For examinations of the gallbladder and for male patients, fasting might improve the sonographic imaging quality to some extent. Overall, no significant improvement in the imaging quality of abdominal organs was reached with a fasting preparation.

The case of a 58-year-old female patient with well-differentiated breast cancer (T1 stadium) without axillar lymphadenopathy and with multiple suspect liver lesions is described. Liver metastases of the breast cancer could be excluded histologically, however, serologic testing for echinococcosis was negative. After contrast-enhanced sonography and because of the complex B-mode appearance of the liver lesions, cystic echinococcosis was suspected. This could be verified histologically after hemihepatectomy.

The role of diagnostic imaging in the assessment of liver disease continues to gain in importance. The classic techniques used for liver imaging are ultrasonography, CT and MRI. In the past decade, there have been significant advances in all three techniques. In this article, we discuss the advances in ultrasonography, CT and MRI that have improved assessment of focal and diffuse liver disease, including the development of hardware, software, processing algorithms and procedural innovations.

Objective: High-frequency ultrasound transducers have been helpful in certain settings of transabdominal ultrasound examination, and their role in the evaluation of the liver surface in patients with cirrhosis is well documented. However, their value in the routine assessment of the liver has not yet been analysed systematically. The aim of this pilot study was to clarify whether the additional use of high-frequency ultrasound as compared to the standard 3.5 MHz-transducer is of any benefit., Material and Methods: A total of 999 patients from a tertiary care medical centre were examined with a wideband 3.5 MHz- and a high-frequency transducer (band width 4.5 to 10 MHz) with tissue harmonic imaging using one of two high-end ultrasound machines (Siemens Sonoline Elegra or Hitachi EUB-8500). Findings on hepatic pathologies were collected on a standardized documentation sheet and were evaluated using descriptive statistics., Results: In all, 948 patients showed a plain liver surface when the 3.5 MHz transducer was used, whereas this was only true for 862 patients examined with the high-frequency probe. Using the 7.5 MHz probe, the structure of the liver parenchyma appeared to be homogeneous (n=800; 80.1%) less often than when the 3.5 MHz probe (n=822; 82.3%) was used. More cases of liver cirrhosis were suspected with the high-frequency probe (n=66; 6.6% as compared with n=49; 4.9%). In 85 patients (8.5%) new hepatic pathologies were described which had not been detected with the 3.5 MHz probe. The examiners judged the high-frequency examination to be helpful in 284 cases. The time needed for the additional examination ranged between 0.5 and 10 min (mean: 2.2 min)., Conclusions: This study demonstrates that the additional use of a high-frequency transducer during routine abdominal examinations reveals new hepatic pathologies in a significant proportion of examined patients, without substantial prolongation of the overall examination period.

Aims: The aim of the present study was to evaluate the 6-month survival rate of patients with inoperable or metastatic pancreatic cancer treated with irinotecan and gemcitabine plus 5-fluorouracil. Secondary efficacy end points included response rate, time to progression (TTP), overall survival (OS) and toxicity., Patients and Methods: 30 patients with histologically proven pancreatic carcinoma and at least one bidimensionally measurable lesion were enrolled. Of the patients, 83% had metastatic and 17% locally advanced disease. One cycle, lasting 21 days, comprised treatment on days 1 and 8 consisting of 75 mg/m(2) irinotecan i.v. for 90 min, 1,000 mg/m(2) gemcitabine i.v. for 30 min and 2,000 mg/m(2) fluorouracil (5-FU) for 24 h. A total of six cycles was planned for each patient., Results: 28 patients competed at least one treatment cycle and were therefore assessable for efficacy, and 75% of them achieved the primary end point of the study (survival after 6 months). One-year survival was 25%. Stabilization (partial response and stable disease) was observed in 35.7% (10/28) and partial remission in 7.1% (2/28). The objective response rate was 7.1% (2/28) after completion of the six cycles. Median TTP was 3.4 months (1.2-11.5), and median OS was 8.3 months (2.1-36.2). Regarding severe hematological toxicities, only neutropenia was observed (grade 3 20.7%, 6/29, and grade 4 3.5%, 1/29). In spite of anti-emetic supportive care, nausea affected most of the patients: 79.3% (23/29). Grade 3 vomiting was observed in 4 of the 29 patients (13.8%) and grade 4 in 1 patient (3.5%). Only 1 patient experienced diarrhea grade 3 (3.5%) and 1 patient (3.5%) suffered from a grade 3 peroneal nerve enervation., Conclusions: A combination of irinotecan, gemcitabine and 5-FU is feasible and shows considerable efficacy in patients with inoperable or metastatic pancreatic cancer. Due to its low toxicity, this combination might be an interesting cytotoxic regimen in addition to targeted therapies., (Copyright (c) 2008 S. Karger AG, Basel)

Background and Aims: To evaluate the benefit of the additional use of a high frequency ultrasound probe (7.5 MHz) in finding suspicious liver lesions compared to the examination using a 3.5-MHz transducer only., Patients and Methods: One hundred and fifty-seven patients with underlying malignant disease were examined with both transducers using one of three ultrasound machines (Siemens Sonoline Elegra, GE Healthcare Logic 9, or Hitachi EUB-8500). Findings on hepatic lesions were collected on a standardised documentation sheet and evaluated by descriptive statistics., Results: Ninety-three patients (59.2% of all patients) showed no evident liver lesion on conventional ultrasound with the 3.5 MHz probe. In 29 patients (18.5%) new suspicious liver lesions were found by using the high frequency transducer. Thirteen of these 29 patients (44.8%) were suspected to suffer from diffuse infiltration of the liver with malignant lesions or at least 10 additional visible lesions. In 14 patients, no liver lesion had been known before high frequency ultrasound examination. The size of newly described liver lesions ranged from 2 mm to 1.5 cm. Time needed for the additional examination with the high frequency transducer ranged between 1 and 15 min with an average of 4.0 min., Conclusion: The additional use of a high frequency transducer in patients with underlying malignant disease slightly extends the examination time, but reveals new, potentially malignant hepatic lesions in almost every fifth patient.

Percutaneous endoscopic catheter gastrostomy (PEG) is a convenient way to supply enteral nutrition for patients with swallowing disorders. One rare complication of PEG is the buried bumper syndrome where gastric mucosa overgrows the internal bumper and prevents free flow of the feeding solution. As a consequence, the application of enteral feeding has to be stopped until a free outflow is re-established. We report a case of buried bumper where symptoms were misinterpreted for several months as PEG stoma infection by the homecare service. This led to a vastly delayed diagnosis and treatment. As endoscopic intervention was unsuccessful, surgical PEG removal was required. In consequence, we recommend early endoscopic exploration in cases with prolonged inflammatory signs at the PEG stoma site in order to avoid misdiagnosis of buried bumper syndrome and to allow timely endoscopic intervention.

Infection with Varicella zoster virus (VZV) usually occurs in children up to 15 years with mild symptoms. We present a case of a 22-year old man with a fatal varicella zoster infection. He developed fulminant hepatitis with acute liver failure and an acute respiratory distress syndrom (ARDS). In this article the general aspects of VZV infection are discussed. Treatment options and previous publications are reviewed., (© Steinkopff-Verlag 2006.)

Background and Study Aims: The diagnosis of Barrett's esophagus at present requires endoscopic and histological confirmation of specialized intestinal metaplasia. This study prospectively analyzed the endoscopic and histological prevalence of Barrett's esophagus and the risk factors for the presence of Barrett's esophagus among patients being treated in an endoscopy unit., Patients and Methods: A total of 474 unselected patients (58% men; mean age 52 y) were included in the study. Two biopsy specimens each were taken from below and above the squamocolumnar junction and from the antrum and gastric body. Four-quadrant biopsies were taken every 1-2 cm to confirm a macroscopic suspicion of Barrett's esophagus., Results: Barrett's esophagus was suspected at endoscopy in 109 patients (23%). Of the 109 patients with endoscopically suspected Barrett's esophagus, only 46 (42%) had the finding confirmed histologically. The sensitivity and specificity for the endoscopic diagnosis of Barrett's esophagus were 62% and 84%, respectively. A multivariate logistic regression analysis identified age (P = 0.0001; odds ratio per life-year 1.087; 95% CI, 1.046-1.139), male sex (P = 0.0020; OR 6.346; 95% CI, 2.094-22.314), and the number of biopsies (P = 0.0025; OR 1.661; 95% CI, 1.247-2.392) as factors associated with evidence of intestinal metaplasia on biopsy., Conclusion: The striking discrepancy between the endoscopic findings and the histological diagnosis may be due to the focal distribution of intestinal metaplasia. This emphasizes the importance of an adequate biopsy protocol. In addition, better methods of detecting focal islands of intestinal metaplasia that are not visible at conventional endoscopy are needed.

Background and Aims: Depending on their physico-chemical characteristics, bile acids can be potent inducers of apoptosis in colon cancer cells. This observation contrasts with bile acids being promoters of colorectal cancer carcinogenesis. Our recent observation of caspase activation in deoxycholate (DC)-treated colon cancer cell lines prompted us to analyze the mechanisms of bile acid-induced colon cancer cell death., Methods: CD95 expression was correlated to DC-induced cell death in four colon cancer cell lines. Mitochondrial transmembrane potential (MTP) was determined in whole cells as well as in isolated mitochondria., Results: On 2 of the 4 human colon cancer cell lines investigated, no CD95 was detected. These data were supported by a lack of CD95 mRNA in those cell lines that did not express CD95 on their surface. The apoptotic response to bile acids did not correlate with CD95 receptor expression on the respective cell lines. Therefore, we analyzed the MTP after the addition of toxic bile acids. MTP was destabilized early after the addition of deoxycholate to SW480 cells. These data were confirmed in isolated mitochondria, which showed strong swelling after the addition of DC. Accordingly, release of cytochrome-c from the mitochondrial intermembrane space into the cytosol, indicating dissipation of the MTP, and subsequent caspase-3 cleavage were detectable as early as 3 min after the addition of DC., Conclusion: In contrast to hepatocytes and hepatic carcinoma cell lines, DC induces apoptosis in colon cancer cell lines via a CD95 receptor-independent mechanism. Direct induction of the mitochondrial permeability transition by toxic bile acids is suggested as the apoptosis-inducing mechanism in colon cancer cells.

Doppler sonography is part of the entire sonographic evaluation of intestinal diseases. It can help in estimating disease activity, although as the sole method to assess the patients situation it is not acceptable. New methods to quantify disease activity, such as contrast enhanced sonography, are at an experimental level and have to be evaluated in more detail.

With regard to acute or chronic pancreatitis various complications involving the spleen can occur, hematoma of the spleen being a rare complication. We describe the case of a patient in reduced general condition with elevated pancreatic enzymes and signs of inflammation. During multiple examinations, hematoma of the spleen, as well as hematomas close to the left adrenal gland and a larger hematoma close to the gastric wall were detected. In computed tomography and due to the laboratory parameters a pancreatitis was diagnosed. After CT-controlled puncture a communication between both formations was considered possible which was in retrospect CT-assisted not successful. Subsequently an ultrasound controlled drainage was performed, finally resulting in a restitutio ad integrum, thereby avoiding splenectomy. The described percutaneous puncture of a fluid formation in the splenic area represents a non-surgical option in the therapy of intrasplenic pancreatic fluid formations.

Background: In acute or chronic inflammatory bowel disease (IBD) interferon gamma (IFNgamma) is still considered to be an important pro-inflammatory mediator. In the present study we investigated the impact of IFNgamma on interleukin-8 (IL-8) production as a read-out for cell activation in intestinal epithelial cell (IEC) lines and primary human colonic epithelial cells (CEC)., Methods: Primary cultures of human CEC were established from the mucosa of patients without inflammatory disease. CEC, HT-29 or Caco-2 cells were incubated with either IFNgamma, tumor necrosis factor (TNF)alpha or IL-10. IL-8 and IL-1Ra secretion was determined by ELISA. Competicon PCR was used for quantification of IL-8mRNA. Apoptosis was quantified by propidium iodine incorporation and fluorescence activated cell sorting (FACS) analysis., Results: In contrast to HT-29 cells in primary human CEC 100 U/ml IFNgamma inhibited IL-8 secretion significantly to 70+/-15% of unstimulated primary CEC (p<0.005) more effectively than IL-10 (87+/-21% versus unstimulated cells, n.s.). In HT-29 cells, IL-8 secretion was induced to 405+/-101% of unstimulated cells. In Caco-2 cells, IFNgamma had no significant effect on IL-8 secretion. The effect in HT-29 and CEC was concentration dependent. In primary CEC, 200 U/ml IFNgamma further reduced IL-8 secretion to 48+/-18% of unstimulated CEC (p<0.05). Whereas IL-8 mRNA was strongly upregulated in HT-29 cells, no upregulation or even a downregulation was found in CEC. Pre-incubation with 100 U/ml IFNgamma did not increase the susceptibility to apoptosis mediated by anti-Fas antibody (CH-11) in primary CEC, whereas HT-29 cells showed increased rates of apoptosis after priming with IFNgamma., Conclusion: In contrast to HT-29, IFNgamma downregulated IL-8 secretion and did not induce IL-8 mRNA expression in primary human CEC. This effect was not due to induction of apoptosis., (Copyright 2004 Springer-Verlag)

Squamous cell carcinomas account for more than 80 % of esophageal malignancies in Germany. Alcohol and tobacco smoke are two of the most important risk factors. In superficial esophageal squamous cell carcinoma, endoscopic mucosal resection (EMR) is a very useful and effective treatment modality. However, in patients with submucosal esophageal cancer, radical esophageal resection is regarded as the gold standard for treatment at present. We report the case of a 71-year-old female patient with alcohol-induced liver cirrhosis with esophageal varices and a - therefore inoperable - early esophageal squamous cell carcinoma. Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) seemed not to be an effective treatment modality due to its limited penetration depth (< 2 mm) and the liver toxicity of 5-ALA. PDT using Photofrin(R) with a higher penetration depth seemed to be associated with a high risk of bleeding due to the esophageal varices. Furthermore, this sensitizer is associated with a high rate of strictures and a long-lasting skin sensitivity. In contrast, arguments against an endoscopic mucosal resection (EMR) were endosonographically suspected submucosal tumor growth and a high risk of bleeding. Nevertheless, with respect to the lack alternatives we decided to perform an EMR after ligation of esophageal varices. The tumor could be resected in sano without major bleeding complication. Histology demonstrated a carcinoma in situ without submucosal invasion. After 3 months a second EMR was necessary due to recurrence. Meanwhile after a follow-up period of 18 months only low grade intraepithelial neoplasia without macroscopically suspicious lesions was observed.

Background and Aims: Contrast harmonic imaging significantly increases the detectability of liver lesions which are invisible on conventional B-mode sonography. With the introduction of contrast agents, which can be visualized at low mechanical index (low-MI), continuous real time observation of liver lesions under contrast conditions is possible. We addressed the question whether contrast-enhanced sonography allows for intervention of hepatic lesions impossible to detect on conventional B-mode imaging., Patients and Methods: We evaluated twelve patients with hepatic tumors or abscesses, which could not be analyzed and punctured under fundamental B-mode guidance. The ultrasound contrast agent BRI was used for detection of the hepatic lesions under contrast harmonic imaging (CHI) conditions with phase inversion at low-MI., Results: In eleven out of twelve patients interventions under CHI conditions were successful, as proven by histological, microbiological or tumor marker analysis. The puncture needles were visible in all cases. With an algorithm for optimizing the puncture conditions at low-MI CHI the biopsies can be performed in two steps., Conclusions: Our results show that biopsies of liver lesions under real-time continuous CHI at low-MI are feasible.

A tissue-protective effect of interleukin-11 (IL-11) for the intestinal mucosa has been postulated from animal models of inflammatory bowel disease (IBD). Despite the fact that the clinical usefulness of the anti-inflammatory effects of this cytokine is presently investigated in patients with IBD, there are no data available regarding the target cells of IL-11 action and the mechanisms of tissue protection within the human colonic mucosa. IL-11 responsiveness is restricted to cells that express the interleukin-11 receptor alpha-chain (IL-11Ralpha) and an additional signal-transducing subunit (gp130). In this study, we identified the target cells for IL-11 within the human colon with a new IL-11Ralpha monoclonal antibody and investigated the functional expression of the receptor and downstream effects of IL-11-induced signaling. Immunohistochemistry revealed expression of the IL-11Ralpha selectively on colonic epithelial cells. HT-29 and colonic epithelial cells (CEC) constitutively expressed IL-11Ralpha mRNA and protein. Co-expression of the signal-transducing subunit gp130 was also demonstrated. IL-11 induced signaling through triggering activation of the Jak-STAT pathway without inducing anti-inflammatory or proliferative effects in colonic epithelial cells. However, IL-11 stimulation resulted in a dose-dependent tyrosine phosphorylation of Akt, a decreased activation of caspase-9, and a reduced induction of apoptosis in cultured CEC. In HLA-B27 transgenic rats treated with IL-11, a reduction of apoptotic cell numbers was found. This study demonstrates functional expression of the IL-11Ralpha restricted on CEC within the human colonic mucosa. IL-11 induced signaling through triggering activation of the Jak-STAT pathway, without inducing anti-inflammatory or proliferative effects. The beneficial effects of IL-11 therapy are likely to be mediated by CEC via activation of the Akt-survival pathway, mediating antiapoptotic effects to support mucosal integrity.

Background and Purpose: Early detection of metastases of malignant melanoma has therapeutic implications. The aim of this study was to evaluate palpation and ultrasound examination in the diagnostics of lymph node metastases in locally advanced melanoma., Patients and Methods: 83 patients suffering from melanoma (Clark level IV or V) were examined for lymph node metastases by palpation and sonography. Findings were compared to histopathologic results after lymph node extirpation if available or the findings at the next follow-up visit., Results: Lymph node metastases were confirmed histopathologically in 14 patients at the first study visit, in three others at the control visit. Sensitivity, specificity, positive and negative predictive values of palpation for the detection of metastases or suspicious nodes with increasing volume at follow-up in this population were 65%, 81%, 48%, and 89%, and of ultrasound 100%, 66%, 45%, and 100%, respectively., Conclusion: Sonography of lymph nodes should be included as a standard procedure in the detection of metastases of locally advanced malignant melanoma.

Objective: In a prospective study we analysed the quality of ICD-coding in clinical everyday life of a department for internal medicine., Methods: A skilled intern--the so-called DRG assistant--was temporarily released from clinical work. Over nine weeks he had to control all diagnoses contemporaneously that were ICD-coded by his colleagues on admission and discharge of their patients. The DRG-assistant had to ask for missing or correct implausible diagnoses, or inappropriate ICD-coding and with it also train his colleagues in appropriate coding. The effects of the DRG-assistant's correction of coding, on DRG-consistent grouping and on the potential financial loss or benefit generated by his work were recorded. After stoppage of this control in a subsequent phase of the study the effect of the absence of the DRG-assistant, the absence of reminders and coding control and the changes of the clinic's revenue were determined., Results: Corrections of ICD-coding by the DRG-assistant alone caused a remarkable increase in case-mix-index (CMI). CMI's mean value increased from 1.76 to 1.84 and the clinic's revenue increased by 180 Euro per patient (a total of about 80,000 Euro in nine weeks). After the end of the control, the case-mix-index dropped within three weeks down to 1.14, corresponding with a potential loss of 1200 Euro per patient (assuming that patients' morbidity was the same over the time of the study). Coding corrections could not improve CMI in this situation., Conclusion: Contemporaneous control of ICD-coding by physicians seems to be essential in DRG based accounting.

Photodynamic therapy (PDT) is a new treatment modality for solid tumors as well as for flat lesions of the gastrointestinal tract. Although the use of 5-aminolevulinic acid-induced protoporphyrin IX (PPIX) shows important advantages over other photosensitizers, the main mechanisms of phototoxicity induced are still poorly understood. Three human colon carcinoma cell lines with variable degrees of differentiation and a normal colon fibroblast cell line were used to generate a suitable in vitro model for investigation of photosensitizer concentration as well as the applied light dose. Also, the effects of intracellular photosensitizer localization on efficiency of PDT were examined, and cellular parameters after PDT (morphology, mitochondrial transmembrane potential, membrane integrity and DNA fragmentation) were analyzed to distinguish between PDT-induced apoptosis from necrosis. The fibroblast cell line was less affected by phototoxicity than the tumor cells to a variable degree. Well-differentiated tumor cells showed higher toxicity than less-differentiated cells. After irradiation, cell lines with cytosolic or mitochondrial PPIX localization indicate a loss of mitochondrial transmembrane potential resulting in growth arrest, whereas membrane-bound PPIX induces a loss of membrane integrity and consequent necrosis. Although the absolute amount of intracellular photosensitizer concentration plays the main determining role for PDT efficiency, data indicate that intracellular localization has additional effects on the mode of cell damage.

Background/aims: Ultrasonographic determination of gallbladder motility is sparsely performed in clinical practice as the examination is considered to be time consuming and there is uncertainty about a number of parameters possibly influencing the results. The aims of this study were a) to establish normal values for a simple ultrasonographic test and b) to evaluate the influence of different parameters on gallbladder motility., Methodology: In 62 systematically age- and sex-matched healthy volunteers, ultrasonographic measurements of gallbladder volume (ellipsoid method, planimetry and sum-of-cylinders method) were performed fasting and 5, 10, 20, 30, 40, 50, 60, 70 and up to 75 min after stimulation with a standardized high-caloric liquid meal., Results: Using the ellipsoid method, gallbladder fasting volume (V0) reached a mean value (+/- SD) of 24.6 +/- 10.0 mL with an ejection fraction of 65.9 +/- 19.1%. Age, gender and hair color did not influence parameters of gallbladder contraction. Body mass index showed a weak correlation with V0 but not with ejection fraction. There was a highly significant correlation between the ellipsoid method and longitudinal planimetry and the sum-of-cylinders method, respectively., Conclusions: Ultrasonographic measurement of gallbladder motility in healthy volunteers shows a very wide scattering of normal values. In the interpretation of gallbladder emptying, age, gender and body mass index do not have to be considered. Determination of gallbladder motility may be performed by a rather simple approach with oral stimulation and ellipsoid method or longitudinal planimetry as easily applicable ultrasonographic measurements.

Thioredoxin and thioredoxin reductase 1 (TR1) are redox proteins that have been implicated in cellular events such as proliferation, transformation, and apoptosis. Analysis of the expression and localization of TR1 in different normal and cancer cell lines and in colon tissues (normal, neoplastic, or inflamed) was performed using reverse transcription-PCR and in situ hybridization. TR1 mRNA was expressed in all analyzed tissues with TR mRNA-positive cells restricted to the stroma of colon crypts, partly being CD3 or CD56 positive. In neoplastic areas of colonic cancer tissue, a loss of TR was obvious. None of the epithelial cells in colonic mucosa expressed TR mRNA, whereas more than 70% of HT-29 cells grown in monolayer were positive for TR. In contrast, HT-29 cells, grown as spheroids or as tumors in SCID mice, were negative for TR. In contrast to these in vitro findings and previous studies, there is no evidence that TR plays a significant role in vivo in normal cell growth in colonic epithelial cells. The mechanism underlying the loss of TR1-positive/CD3-positive/CD56-positive cells or the biologic consequence of this phenomenon observed in neoplastic colonic tissue remains to be clarified.

Bile acids have been suggested to play an important role in the etiology of colon and gastric cancer after gastrectomy, but the molecular biology of these effects is poorly understood. We evaluated the effect of different bile acids on human gastric and colon carcinoma cells and identified genes by RNA arbitrarily primed PCR for differential display that are modulated following treatment with hydrophobic bile acids. Thioredoxin reductase (TR) mRNA was upregulated after treatment with taurochenodeoxycholic acid (TCDCA) in St 23132 cells. This raised the question whether deoxycholic acid (DCA) would have regulative effects on TR in HT-29 cells. After an incubation time of 6 h with DCA, TR mRNA expression was increased up to threefold. Ursodeoxycholic acid had no influence on TR mRNA expression. The upregulation of TR after DCA incubation was almost identical to incubation with 12-O-tetradecanoylphorbol-13-acetate. This implies that hydrophobic bile acids mediate oxidative stress in gastrointestinal cancer cells, which was confirmed by measurement of oxidative burst after treatment with DCA. The results suggest that hydrophobic bile acids induce oxidative stress in gastrointestinal cancer resulting in a compensatory upregulation of TR mRNA, one of the key components in the complex anti-oxidant defense system within eukaryotic cells. The activation of at least parts of the redox signaling system is potentially related to the cytotoxicity and the stimulation of the cell death machinery induced by toxic bile acids.

Background: Diagnostic or therapeutic paracentesis of ascites or pleural effusions is part of the daily routine on many hospital wards and in outpatient clinics. In Germany, paracentesis is usually performed with angiocaths. However, the therapeutic large volume paracentesis of ascites and paracentesis of pleural effusions with angiocaths is often cumbersome and quite often paracentesis fails, forcing the physician to repuncture. This is mainly due to the fact that angiocaths are not designed for such interventions., Patients and Method: 45 patients with ascites or pleural effusions were treated with a new needle specially designed for paracentesis, or with an angiocath. The new paracentesis needle was compared with the angiocath needle under the following aspects: necessity and number of positional corrections of the needle, necessity of and reasons for repuncture, duration of puncture, flow capacity, subjective practicability of paracentesis and patient acceptance of the paracentesis needle., Results: The paracentesis needle was superior to the angiocath in all investigated respects. Significantly, the paracentesis needle had a much higher success rate in the complete drainage than had the angiocath., Conclusion: The paracentesis needle was objectively superior as compared to the angiocath. It might help to avoid additional complications due to repuncture and it will increase the patients' comfort.

Progress in instrumentation and clinical research continues to expand the potential utility of endoscopic ultrasound (EUS) in the treatment of esophageal and gastric cancer. This review focuses on the role of EUS in the staging and treatment planning of patients with esophageal and gastric cancer., (Copyright 2001 Wiley-Liss, Inc.)

The prevalence of hepatitis B virus markers was investigated in 5305 individuals considered to be representative for the adult German population. After adjustment of the data according to the age and sex distribution in the whole German population an anti-HBc prevalence of 8.71% (95% confidence interval, 7.94-9.48%) and an HBsAg carrier rate of 0.62% (95% confidence interval, 0.40-0.84%) were calculated. Anti-HBc prevalence increased with age from 4.12% in the youngest group to 15.66% in the 61-70-year-old. The percentage of HBsAg carriers showed a maximum of 1.12% in the 41-50-year-old individuals and decreased significantly in the older age groups. 1.40% (95% confidence interval, 1.08-1.72%) of individuals had anti-HBc only. There was a trend to higher rates of this pattern in males than in females; a significantly higher percentage of persons with anti-HBc only was found in anti-HBc-positive individuals below 31 years than in older individuals. Five participants with anti-HBc only (7.7%, or about 0.1% of the whole population) showed HBV-DNA despite the absence of HBsAg. 3.1% of anti-HBc positive individuals where also positive for anti-HCV, that was significantly higher than the percentage of anti-HCV-positives among persons without any HBV marker (0.46%). This study provides a comprehensive picture of the current hepatitis B situation in Germany, showing new data especially on the distribution of HBsAg in the general population and on the subgroup of individuals with anti-HBc only., (Copyright 2001 Wiley-Liss, Inc.)

STATs act as second messenger after binding of a signaling molecule to its receptor. IL-4 STAT is directly involved in the IL-4-dependent gene transcription in the nucleus. We examined the expression and activation of IL-4 STAT and its related kinase Jak-1 in rheumatoid synovium. Rheumatoid arthritis (RA) synovial frozen sections of patients with short-term (<1 year) and long-term disease (>2 years) were examined using in situ hybridization and immunohistochemistry. IL-4 STAT mRNA could be detected in synovium of patients with short-term and long-term RA. The most intensive expression of IL-4 STAT mRNA could be seen in follicular inflammatory infiltrates. In the synovial lining, both fibroblasts and macrophages expressed IL-4 STAT mRNA. IL-4 STAT and Jak-1 protein was expressed by synoviocytes, and up-regulation could be induced after stimulation with IL-4. Activation of IL-4 STAT was reflected by phosphorylation of IL-4 STAT. The results indicate that IL-4 STAT is involved in key pathomechanisms in RA synovium and that IL-4 STAT-dependent pathways operate in early and late stages of the disease and presumably contribute to inhibitory immune mechanisms in RA synovium.

Objective: The prevalence of anti-HCV in Germany has been determined for blood donors and certain risk groups, but the burden of disease in the general population remains unknown. The aim of this study was to determine the prevalence of anti-HCV in a study group representing the normal adult German population., Design: A total of 5312 individuals aged 18-70 years were randomly selected from small, middle-sized and big cities in five different German states. Sera were tested for anti-HCV by enzyme immunoassay and immuno dot assay, as well as for anti-HBc and, in the case of a positive result, for anti-HBs and HBsAg. Serological typing was performed in anti-HCV-positive persons., Results: Thirty-nine individuals were anti-HCV positive; indeterminate results (with antibodies against the viral core protein only) were obtained in 20. There was a tendency to higher prevalence rates with increasing age as well as to a higher prevalence in women. Serological typing revealed the presence of genotype 1 in the vast majority of participants (82%); only a minority showed genotype 3 (7.2%) or other genotypes (7.2%). Markers of HBV were seen in 43.6% of the anti-HCV positive individuals, with nearly one third (29.4%) of the double-infected showing anti-HBc as the only marker for HBV., Conclusions: According to our data, an anti-HCV prevalence of 0.63% (95% confidence interval, CI, 0.42-0.84%) can be assumed in the general adult German population, with higher values in older people and women. Nearly half of the anti-HCV positive individuals also show markers of hepatitis B virus.

C-reactive protein (CRP) is a unique serum pentraxin and the prototype acute phase reactant. CRP is a ligand for specific receptors on phagocytic leukocytes, and mediates activation reactions of monocytes/macrophages, but inhibits the respiratory burst of neutrophils (PMN). Since CRP selectively accumulates at inflammatory sites in which IL-8 is also produced, we tested the effects of CRP on the responsiveness of PMN to IL-8 and the bacterial chemotactic peptide, FMLP-phenylalanine (FMLPP). Purified human CRP inhibited the chemotactic response of PMN to IL-8 and FMLPP. A mouse IgM mAb that was generated against the leukocyte CRP receptor (CRP-R) also inhibited the chemotactic response. Incubation of purified CRP with activated PMN generated CRP-derived peptides that also inhibited chemotaxis. A synthetic CRP peptide (residues 27-38) that binds to the CRP-R had weak chemotactic activity, whereas two other CRP synthetic peptides (residues 174-185 and 191-205) inhibited chemotaxis of PMNs to both IL-8 and FMLPP. CRP did not alter receptor-specific binding of IL-8, but exerted its effect at the level of signaling. CRP augmented both IL-8- and FMLPP-induced mitogen-activated protein kinase (extracellular signal-regulated kinase-2) activity. CRP at acute phase levels increased both agonist-induced and noninduced phosphatidylinositol-3 kinase activity. The results suggest a role for CRP as a regulator of leukocyte infiltration at inflammatory sites.

Fas induces apoptosis in lymphocytes via a poorly defined intracellular signaling mechanism. We and others have previously demonstrated the involvement and significance of a signaling cascade from the Fas receptor via sphingomyelinases and ceramide to Ras in apoptosis (Gulbins, E., Bissonette, R., Mahboubi, A., Nishioka, W., Brunner, T., Baier G., Baier-Bitterlich, G., Byrd, C., Lang, F., Kolesnick, R., Altman, A., and Green, D. (1995) Immunity 2, 341; Cifone, M. G., DeMaria, R., Roncali, P., Rippo, M. R., Azuma, M., Lanier, L. L., Santoni, A., and Testi, R. (1994) J. Exp. Med. 180, 1547-1552; Gill, B. M., Nishikata, H., Chan, G., Delovitch, T. L., and Ochi, A. (1994) Immunol. Rev. 142, 113-126). Here, we demonstrate an activation of the small G-proteins Rac 1 and Rac 2 after Fas receptor triggering. Expression of a transdominant inhibitory Ras mutant (N17Ras) prevents Rac 1 and Rac 2 stimulation, suggesting a signaling cascade from the Fas receptor via Ras to Rac 1 and Rac 2. Genetic and pharmacological inhibition of Ras or Rac 1 and Rac 2 stimulation blocks Fas-induced apoptosis, pointing to an important function of a Ras and Rac protein-regulated signaling pathway in Fas-mediated programmed cell death.

The CD40 receptor is an important molecule regulating B lymphocyte proliferation, maturation, Ab class switching, and cell survival. In the present study, we identified signal transduction events triggered by cross-linking the CD40 receptor. Stimulation of Daudi B cells with anti-CD40 resulted in activation of p21ras, an important switch point in the regulation of cell growth and differentiation. Ras activation correlated with a stimulation of Rac1 and MEK-1 as well as tyrosine phosphorylation of phosphatidylinositol 3-kinase. Inhibition of endogenous Ras by transfection of transdominant inhibitory Ras prevented tyrosine phosphorylation or stimulation of phosphatidylinositol 3-kinase, Rac1, or MEK-1 upon CD40 receptor triggering, proving an activation of the Ras pathway by CD40. Ras activation was partially inhibited by either herbimycin A or calphostin pretreatment and completely inhibited by preincubation with a combination of both inhibitors, indicating a synergistic role for protein tyrosine kinases and diglycerides in Ras activation after CD40 stimulation. In support of a role for diglycerides, we detected a 30 +/- 5% decrease of cellular phosphatidylcholine content, correlating with a threefold increase of diacylglycerol synthesis induced by CD40. Supporting a role for protein tyrosine kinase, we measured a five- to eightfold stimulation of p56lyn and p58blk kinase activity. These results suggest the activation of the Ras pathway via an additive function of src kinases and phospholipases that may be important in the mediation of biologic effects after CD40 receptor engagement.