[A 59-year-old woman with upper abdominal pain and fever]. / 59-jährige Patientin mit Oberbauchschmerzen und Fieber.

A 59-year-old woman suffered from fever and upper abdominal pain. The computed tomography (CT) scan revealed a liver lesion. Conventional imaging techniques (CT, magnetic resonance imaging, contrast-enhanced ultrasonography) did not allow for a consistent diagnosis. Fine needle biopsy of the liver lesion was performed. Histologically, fibrotic inflammation was found and an inflammatory pseudotumor (IPT) diagnosed. Despite treatment with steroids and antibiotics, the size of the IPT increased; thus, surgical resection was necessary. In case of fever of unknown origin, IPT should be considered as a potential diagnosis.

[Diagnosis of and therapy for hepatocellular carcinoma]. / Diagnostik und Therapie des hepatozellulären Karzinoms.

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.

Toxicity of ingested cadmium to the nematode Caenorhabditis elegans.

Benthic organisms ingest dissolved and particle-bound contaminants together with their food, whereas it is not clear which fraction of the ingested suspension causes the toxic effects. In the standard toxicity test using the nematode Caenorhabditis elegans, the organisms are fed with bacteria that bind contaminants, thus influencing the bioavailability of the contaminants for the organisms. To unravel the role of food bacteria in the toxicity of contaminants in C. elegans, suspensions with varying densities of bacteria were spiked with the toxic metal cadmium (Cd), either via the water or via the bacteria. The toxicity of Cd to C. elegans was clearly related to the uptake of bacteria in the nematode's gut. An increase in the bacterial density resulted in a significant decrease in the toxicity of Cd such that toxic effects better correlated with the aqueous than with the bacterial-bound or total Cd concentrations. The results suggested that the aqueous Cd that was ingested together with the food was the best available fraction and thereby mainly caused the observed toxicity on the reproduction of C. elegans.

[Localisation of hepatic lesions to liver segments according to sonography (US), computed tomography (CT) and surgery (OP): a comparative study]. / Untersuchung der Segmentzugehörigkeit von Leberraumforderungen in Sonografie (US), Computertomografie (CT) und intraoperativ (OP): eine Vergleichsstudie.

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.

Irinotecan plus gemcitabine and 5-fluorouracil in advanced pancreatic cancer: a phase II study.

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.

Comparison of low and high frequency transducers in the detection of liver metastases.

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.

Barrett's esophagus: a discrepancy between macroscopic and histological diagnosis.

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.

Activation of Src-family tyrosine kinases during Fas-induced apoptosis.

Stimulation of several human and murine hematopoietically derived cell lines with anti-Fas antibodies induced increased tyrosine phosphorylation of a panel of proteins observed in whole-cell lysates. In the human T cell line Jurkat, the activity of a 56-kDa tyrosine kinase was likewise activated by anti-Fas antibodies. Immunoprecipitation studies of anti-Fas-stimulated human Jurkat and murine 2B4.11 T cells revealed activation of the Src-family tyrosine kinases Lck and Fyn. Fas receptor-induced tyrosine phosphorylation of p120 c-cbl proto-oncogene product was observed in Jurkat T cells. Pharmacological experiments demonstrated that pretreatment of Jurkat cells with tyrphostins inhibited Fas-induced apoptosis; likewise, Lck activity was inhibited by tyrphostins in a dose-dependent fashion. Finally, Lck derived from unstimulated Jurkat T cells formed stable complexes with the intracellular domain of the Fas receptor. These data are consistent with the notion that expression and activation of members of the Src-family kinases is required for Fas-induced cell death in T lymphocytes and consistent with recent findings demonstrating decreased Fas-mediated thymocytic death in Fyn-knockout mice.

Prevalence of antibodies against hepatitis C virus in the adult German population.

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.

[Evaluation of a new, portable ultrasound system in routine clinical use]. / Evaluation eines tragbaren Ultraschallgerätes im Routinebetrieb der Klinik.

AIM: Evaluation of a new, hand-carried ultrasound system (SonoSite 180) for routine use at a university hospital. METHODS: 101 routine ultrasound examinations were performed as bedside examinations on the wards or in the ultrasound centre by three experienced sonographers. The quality and results of examinations using the SonoSite 180 were evaluated in a standardized questionnaire. RESULTS: in 89 % of the ultrasound examinations, results were at least satisfactory. Even though the examiners felt some uncertainty due to the small screen, especially while performing abdominal scans, small lesions which were located far from the scanner were readily identified. CONCLUSION: Routine ultrasound examinations yield satisfactory results when performed with the new, hand-carried ultrasound system. The low size and weight of this ultrasound system and its good image quality makes it a very usefull tool, especially for examinations of patients at intensive care units and on hospital wards.

[A new paracentesis needle for ascites and pleural effusion compared with the venous indwelling catheter. A prospective, randomized study]. / Eine neue Parazentesenadel für Aszites und Pleuraerguss im Vergleich mit der Venenverweilkanüle. Eine prospektive, randomisierte Studie.

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.

Clinical signs in the diagnosis of deep vein thrombosis.

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.

[Fatal outcome of varicella zoster sepsis in a 22-year old patient]. / Letaler Verlauf einer Varizella-Zoster-Sepsis bei einem 22-jährigen Patienten.

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.

Role of endoscopy in the staging of esophageal and gastric cancer.

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.

Effects of rC5a on the circulation of normal and split hydronephrotic rat kidneys.

Systemic release of complement-derived anaphylatoxin C5a is suggested to be involved in the pathogenesis of renal failure during endotoxic or severe traumatic shock. In the present study we analyzed renal hemodynamic effects of recombinant human complement 5a (rC5a) and examined whether these effects are mediated by the secondary release of other inflammatory mediators. Intravenous infusion of rC5a (0.5 micrograms/min) in thiobarbital-anesthetized rats decreased renal blood flow (RBF) by 20 and 34% after 20 and 60 min, respectively. Glomerular filtration rate (GFR) was reduced by 45%, whereas filtration fraction and blood pressure were not significantly changed by rC5a. Hematocrit (Hct) increased by 11%, whereas white blood cell count decreased by 40%. Renal rC5a effects were completely inhibited by the competitive leukotriene D4/E4 antagonist ICI-198615, whereas the competitive thromboxane A2 (TxA2) antagonist daltroban only partly reversed rC5a effects on RBF and GFR. The competitive platelet-activating factor (PAF) antagonist L-695989 did not influence renal or systemic rC5a effects. These results point to an rC5a-mediated synthesis and release of cysteinyl leukotrienes and TxA2, whereas PAF does not seem to be released after intravenous rC5a in rats. To determine the cellular source of cysteinyl-leukotriene synthesis, rats were depleted of polymorphonuclear cells (PMN) by intraperitoneal injection of anti-rat PMN antibodies, which abrogated renal and systemic hemodynamic rC5a effects, suggesting that PMN participate in the synthesis and release of cysteinyl leukotrienes. The exact localization of renovascular rC5a effects was performed on the model of the split hydronephrotic rat kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of systemic complement activation on renal circulation of rats.

In a variety of immunopathological diseases activation of the complement cascade occurs either systemically or localized in the kidney. To elucidate the functional impact of complement activation upon the renal microcirculation, we administered cobra venom factor of Naja naja kaouthia (CVF) i.v. into thiobarbital anaesthetized female rats. CVF is a potent activator of the alternative pathway of complement by forming the C3-convertase CVF, Bb which cannot be downregulated by the natural inhibitor factors H and I and thereby leads to generation of the anaphylatoxins C3a and C5a and formation of the membrane attack complex (MAC). We utilized creatinine clearance and flowmeter measurements in the normal kidney and intravital microscopy of the split hydronephrotic rat kidney model to observe the microvascular changes. Bolus injection of CVF (100 U kg-1) resulted in an immediate reduction of RBF (-68% after 10 min), which remained decreased during the entire experiment (90 min). Systemic blood pressure was significantly reduced only in the early period (-23% of control: 126 mmHg after 10 min). After an initial anuric phase of 30 min duration, the glomerular filtration rate was significantly diminished by 47%. White cell count was decreased by about 50% after the experiments. Application of the competitive thromboxane A2-antagonist, BM 13505, reversed all renal and systemic CVF-effects. Continuous infusion of the competitive leukotriene D4-antagonist, ICI 198615, attenuated the late renal CVF-effects (i.e. 30 min after injection of CVF). Depletion of polymorphonuclear cells (PMN) attenuated the CVF-effects similar to BM 13505. Intravenous administration of CVF in the hydronephrotic kidney model resulted in a massive constriction of the interlobar and arcuate artery, with a fall in glomerular blood flow comparable to the reduction of RBF in the normal kidney. Diameters of the afferent arterioles--most sensitive to many vasoconstricting agents--were not significantly altered. Our results suggest that injection of CVF and the liberation of high amounts of the anaphylatoxins, C3a and C5a, induces the release of TXA2, which contributes to the early renal effects and the formation of cysteinyl-leukotrienes which play an important role in the late phase of systemic complement activation. Utilizing the split hydronephrotic kidney model we demonstrated the predominant action of complement activation on the large preglomerular vessels for the first time. PMN are seemingly involved in the liberation of secondary mediators which appear to reduce renal blood flow and glomerular filtration.

[Intercostal percutaneous ultrasound guided decompressive gastrostomy (PUG)--a case report]. / Die interkostal angelegte perkutane ultraschallgesteuerte Entlastungsgastrostomie (PUG)--Ein Fallbericht.

Percutaneous gastrostomies (PG) are nowadays usually placed endoscopically (PEG). Due to stenoses in the pharynx or the esophagus or in case of a lack of diaphany, other methods for the placement of PG such as computed tomography (CT-) guided or ultrasound-guided PG (PUG) are performed. We present a case of a 63-year old male patient with a retroperitoneal liposarcoma and multivisceral resection who presented with the symptoms and signs of an ileus due to metastatic occlusion of the small bowel. The placement of a decompression-PEG was impossible due to interposition of colon between the stomach and the abdominal wall. After filling the stomach with water via a naso-gastral decompression tube, the stomach could be visualized at the left thoracic wall, since the spleen and the left kidney had been removed at prior surgery. A transcostal decompression-PUG was inserted. The intervention described is the first published ultrasound guided transcostal decompression gastrostomy and is an example for the growing significance of interventional ultrasound.

Negative signaling via FcgammaRIIB1 in B cells blocks phospholipase Cgamma2 tyrosine phosphorylation but not Syk or Lyn activation.

Crosslinking of the B cell antigen receptor surface immunoglobulin induces tyrosine phosphorylation and activation of the Src family and Syk tyrosine protein kinases, tyrosine phosphorylation of phospholipase Cgamma2 (PLCgamma2) and increases in intracellular second messengers inositol phosphates and Ca2+. These activation events, in conjunction with other pathways, culminate in the induction of B cell proliferation and differentiation. In contrast, co-crosslinking surface Ig with the B cell IgG Fc receptor prevents many of these activation events, including B cell proliferation and differentiation. The precise nature of the negative signal(s) derived from Fc receptors that prevent B cell activation is not known. Here, early activation events were examined in B cells stimulated via the antigen receptor alone or under co-crosslinking conditions. The data indicated a selective block in the tyrosine phosphorylation and activation of PLCgamma2 but not in activation of the upstream kinases, Syk and Lyn, under co-crosslinking conditions. We conclude that the negative signal acts directly on PLCgamma2 and is consistent with recent studies describing an activation-induced association of a phosphotyrosine phosphatase with tyrosine-phosphorylated B cell Fc receptor.