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Background: Due to the novel reimbursement policies, hospitals face substantial conflicts regarding best patient care and optimal utilization of resources. In order to optimize patient treatment, a central patients admission (CPA) unit has been established., Methods: All patients electively referred to the hospital were primarily treated by a medical specialist at the CPA unit. According to an appropriateness evaluation protocol established with the medical service of the health insurances of Bavaria ("MDK-Bayern"), patients were treated as inpatients or outpatients. The impact of this novel admission procedure was assessed for a period of 30 months., Results: Within 30 months following establishment of the CPA unit, 10% of the patients were treated as outpatients, whereas 90% of referred patients were admitted as inpatients. Nonetheless, numbers of inpatients increased by 20.7% after 24 months compared to 12 months following establishment of the CPA unit with a substantial increase of patients referred by external medical specialists. In addition, there were no cases of inappropriate admission., Conclusion: The CPA unit is an ideal instrument for treating patients cross-sectorally as well as more effectively and economically advocating reorganization. Establishment of a CPA unit leads to greater satisfaction among patients, referring physicians, and medical staff.

Background and Purpose: The presentation of scientific posters gives young scientists the opportunity to present their data in the setting of a medical congress. In preparation of the organization of the 116th Congress of the German Society of Internal Medicine (DGIM) 2010, the authors evaluated the poster rounds at the 115th Congress of the DGIM 2009 by using a questionnaire that was given to poster presenters, poster chairmen, and visitors. The authors sought to receive an instructive criticism for the organization in 2010., Methods: Distribution of questionnaires containing ten questions with preformulated response options and an additional field for further comments to all presenters, chairmen, and visitors of the poster rounds during the 115th Congress of the DGIM (April 2009)., Results: 159 questionnaires were returned and evaluated. Almost all respondents quoted the poster presentation as being important for their scientific work (98%). In general, they were satisfied with the discussion at the poster rounds (83%). The amount of posters within one round was criticized by 41%, as was the inadequate adherence to time constraints and time frame and room conditions themselves., Conclusion: The poster exhibition of the 115th Congress of the DGIM 2009 was evaluated positively by most of the respondents to the survey. Nevertheless, helpful hints were retrieved as how to further improve poster rounds. They should be respected when planning the exhibition at the congress in 2010.

A 17-year-old patient was transferred to the emergency room with an impacted food bolus by colleagues from the Department of Otorhinolaryngology. The examination of ear, nose and throat revealed significant amounts of saliva in both recessus piriformis, a radiologic examination of the esophagus showed a foreign body with a diameter of 1.6 cm in the region of the transitional zone of esophagus and stomach with a support level of the contrast medium. Clinical examination and laboratory tests showed no abnormalities. An emergency gastroscopy was performed. The foreign body, already evident in the barium swallow, was found in the distal esophagus. The foreign body was identified as a food bolus and gently advanced into the stomach with the aid of the gastroscope. In the stomach further food residues were detected and the examination was aborted because of increased risk of aspiration. On the next day, an elective gastroscopy was performed. Several biopsies were obtained from the esophagus because eosinophilic esophagitis (EE) was suspected due to clinical symptoms. Histological work-up showed a significant amount of eosinophilic granulocytes (> 15 eosinophils/HPF, 400 x) and reactive changes in the distal esophagus. Therefore, EE was diagnosed. Fluticasone therapy led to amelioration of symptoms and there was no evidence of recurring bolus impaction during follow-up.

Case Report: A 28-year-old woman was referred to hospital with a spontaneous femoral neck fracture. Dual energy X-ray absorptiometry showed severe osteoporosis without apparent cause or risk factors. The basic endocrinologic evaluation revealed hypercortisolism, and the diagnosis of Cushing's disease could be made following biochemical test and magnetic resonance imaging. A transsphenoidal resection of the pituitary gland tumor was performed and led to a cure of the disease. The patient received calcium and vitamin D substitution as well as biphosphonates., Conclusion: Glucocorticoid-induced osteoporosis is the most frequent cause of secondary osteoporosis. Only few cases with occult endogenous Cushing's syndrome and osteoporosis as the main manifestation of the disease have been reported. Nevertheless, hypercortisolism should be excluded whenever osteoporosis without apparent cause is diagnosed.

A 52-year-old male patient was admitted to the emergency department with dyspnea and hypertensive urgency. During the previous 6 months, the patient had noticed leg edema, weight gain (particularly in the face and abdomen), and impotence. 1.5 years ago, he was diagnosed with hypertension resistant to medication. After an accident at work 1 year ago, osteoporosis was diagnosed with vertebral and rib fractures. Measurement of sleeping midnight salivary cortisol levels together with 24-h urine free cortisol excretion and an overnight low-dose 1-mg dexamethasone suppression test proved overt hypercortisolism. The high-dose 8-mg dexamethasone suppression suggested an adrenal or ectopic source of hypercortisolism. By contrast, elevated adreno-corticotropic hormone (ACTH) levels and a corticotropin-releasing hormone stimulation test gave evidence for a pituitary source of hypercortisolism. However, pituitary magnetic resonance imaging failed to reveal a pituitary adenoma. Moreover, computed tomography scans of thorax and abdomen were negative. In this situation, an inferior petrosal vein sampling was performed and revealed an ACTH gradient (central-systemic) >3 with lateralization to the right side. The patient underwent a selective, partial, transsphenoidal resection and was cured from clinical signs and symptoms caused by hypercortisolism. Subsequent hormonal replacement therapy of postoperative pituitary insufficiency was necessary.

Background: Muscle weakness with or without elevation of serum creatine kinase (CK) is a common complaint, which is a diagnostic challenge for the treating physician. Either infectious, neurologic, iatrogenic, genetic or endocrinologic and rheumatologic causes should be considered., Case Report: A 66-year-old female patient with a history of systemic lupus erythematosus (SLE) currently in remission presented herself with muscle weakness, myalgias and elevated CK (1618 U/l) to the authors' hospital. A flare of the SLE as cause of the symptoms could be ruled out diagnostically. Instead, a Hashimoto's-associated hypothyroidism was detected. Treatment with L-thyroxine resulted in rapid improvement of symptoms, and CK levels returned to normal., Conclusion: Although a myositis can be observed in SLE patients suffering from muscle weakness with elevated CK levels, a careful evaluation is warranted. In the presented case, hypothyroidism due to Hashimoto's thyroiditis was the real culprit of the symptoms.

Background and Purpose: Sepsis still represents a major medical challenge despite several advances in therapy. Most published data on sepsis have been derived from clinical trials evaluating new drugs and from international cohort studies. The aim of this study was to analyze risk factors, mortality and causative pathogens in a cohort of unselected patients with severe sepsis at a German university hospital and to compare the data with international cohorts and recently published therapeutic trials., Patients and Methods: Between May 1999 and December 2002, all patients of the surgical and internal medicine intensive care units of a university medical center with newly manifested severe sepsis and at least one organ failure were recruited into the prospective observational study "Unicenter Sepsis Survey Regensburg" (USSR)., Results: 182 patients were included. The median age of the patients studied was 58 years, the median SAPS II amounted to 42, mortality at day 14 and day 30 was 25% and 34%, respectively. 48% of the patients developed sepsis due to an internal disease, 33% after surgical emergency interventions, and 19% after planned surgical interventions. Patients with surgical emergencies had higher SAPS II values and a worse outcome. 35% of all patients developed acute renal failure. 85% of the patients were treated with vasopressors, and 90% had to be ventilated mechanically. 58% of the patients had a probable and 38% a confirmed focal infection; in the final retrospective analysis, an infectious genesis proved to be unlikely in 4% of the patients., Conclusion: The characteristics of unselected patients with severe sepsis at the authors' institution are comparable to data from recently published sepsis studies with respect to mortality, severity of disease, and range of causative pathogens.

Due to the fatal prognosis of pancreatic carcinoma, great efforts have been made to investigate precursor lesions of invasive neoplasia during the last few years. Pancreatic intraepithelial neoplasias (PanIN) have been recognized as precursor lesions of ductal adenocarcinoma, and are classified into different grades from PanIN-1A, -1B, -2, to -3. Molecular analyses have helped to define a progression model for pancreatic neoplasia. The most important step seems to be the occurrence of a PanIN-3 lesion defining a high risk of malignant transformation. As in PanINs, different types of intraductal papillary-mucinous neoplasms (IPMN) can be discriminated ranging from benign to invasive lesions. Becoming invasive, some of these tumors appear as ductal adenocarcinoma, others as colloid carcinoma with a much better prognosis. In this review, the characteristics of these two precursor lesions and their genetic alterations are summarized.

History and Findings on Admission: A 63-year-old female patient was admitted to the authors' hospital for further diagnostic work-up for suspected reactivation of a previously successfully treated lymph node tuberculosis, which had been diagnosed 1 year prior to the current admission. The clinical signs consisted of worsening of the patient's general condition, negacervical lymphadenopathy, night sweats, dyspnea, and superficial inflammation of the right mamma., Findings: A contrast-enhanced CT scan of the neck, thorax and abdomen revealed a generalized enlargement of the cervical, axillar, mediastinal and retroperitoneal lymph nodes, multiple intrapulmonary nodular lesions with a diameter of up to 6 mm, and a substantial right-sided pleural effusion., Course of Disease: Under the assumption of reactivation of a lymph node tuberculosis, the patient was initially treated with an extended tuberculostatic therapy. Because of disease progression another lymph node biopsy was performed revealing Hodgkin's disease of mixed-cellularity type with a partly histiocytic necrotizing, partly tuberculoid reaction. The biopsy was negative for acid-fast bacilli. Thereupon initiated chemotherapy according to the ABVD protocol led to a rapid amelioration of the clinical symptoms., Conclusion: In the clinical setting of suspected or confirmed lymph node tuberculosis malignant lymphoma should always be considered. This consideration is particular important since Hodgkin's disease is typically associated with a cellular immunosuppression predisposing the subject to tuberculosis.

The competence network chronic inflammatory bowel disease (KN-CED) is one of 17 networks of competence initiated by the German Federal Ministry of Education and Research (BMBF). These networks are concerned with disease patterns which are characterized by their high frequency, high mortality rate or which present a large expense factor. The project-executing organization is the German Center for Air and Space Travel (DLR e. V.). The central structure of organization is the Telematic Platform for medical Networks (TMF e. V.). Aim of the KN-CED is to investigate, in their complexity, the incurable chronic diseases ulcerative colitis and Crohn's disease, particularly with regard to the causes of disease, the establishment of new therapy standards as well as patient care. To achieve this goal, the competence network is integrated into both national and international research associations and is also backed by the national self-help group DCCV and the pharmaceutical industry. Principal items of the competence network are the core facilities and their main focus on molecular genetics, animal and cell models and serum markers. Having stored the data of more than 4,000 patients so far, the central database of the competence network is one of the largest databases worldwide with regard to inflammatory bowel disease (IBD). The successful cooperation within the network is reflected in numerous publications. Thus, two of the three known genes of Crohn's disease were identified. Also with the participation of the competence network national guidelines for the diagnosis and therapy of IBD were generated.Furthermore, the competence network operates study centers where significant therapeutic developments in the field of biotechnological drugs are taking place. The analysis of existing structures of care as well as the development of standards of organization for patients with IBD top the research within the competence network and emphasize the claim to find comprehensive answers to the questions connected with IBD.

Case Report: A 17-year-old female was admitted to the hospital with epigastric pain radiating into the chest and neck. The patient had a known, long-standing history of systemic lupus erythematosus (SLE) with predominantly renal involvement. Diagnostic examinations including left heart catheterization showed acute myocardial infarction based on a coronary three-vessel disease. Percutaneous transluminal coronary angioplasty (PTCA) with dilatation of the left marginal branch and the left posterolateral branch was performed. 8 weeks after PTCA, the patient was admitted again showing occlusion of the same coronary artery. A coronary stent was implanted which, after 8 weeks, also showed signs of occlusion. This case report describes premature myocardial infarction in a young woman with SLE and addresses and discusses the problem that myocardial infarction in SLE can be caused by atherosclerosis and/or arteritis of the coronary arteries.

Not long ago forensic aspects where the major driving force to complete and correct medical documentation. Diagnosis related groups becoming basic data for billing of hospital treatment in Germany now extremely extend the need for complex administrative documentation over-ruling all medical documentary needs. Due to unchanged personnel resources in hospitals and due to a lack of comfortable tools supporting these documentary needs medical personnel in most hospitals is confronted with an annoying effort to fulfill these needs. As a result innumerable hours of working time have to be shifted from patient focused to administrative work. This paper introduces a computer system based on a hospital-wide documentation concept and clinical workflow allowing to derive administrative data straight from medical documents so that redundant documentation and discrepancies between medical and administrative documentation can be avoided.

History and Physical Examination: A 43-year-old, cachectic, alcohol-addicted patient was admitted to the hospital due to hemoptysis and fever of up to 40 degrees C for the last 4 days. Physical examination revealed pleural rubs in the right lower lung and a diffuse pain in the right upper quadrant of the abdomen. The right upper quadrant of the abdomen also showed scars from several surgical interventions on the small intestine, the liver and the biliary tract and deformed caudal ribs due to an accident 23 years earlier., Diagnostics, Therapy, and Clinical Course: Chest X-ray, ultrasound and computed tomography (CT) showed abscess cavities in lung and liver communicating through the diaphragm. Under antibiotic therapy the abscess was drained. Cultures showed Klebsiella pneumoniae and Streptococcus viridans. Continuous lavage of the abscess cavities and antibiotic therapy led to an improvement in parameters of inflammation and clinical status. Imaging after 10 days of treatment showed a contrast enrichment in the abscess cavities and a bronchobiliary fistula accounting for temporary biliptysis. The drainage was removed after 29 days, when similar imaging revealed no further sign of an abscess cavity and a previous CT follow-up had proven a distinct decrease of the abscesses., Conclusion: Bronchobiliary fistulas are very rare. In most cases they are caused by hepatic or subphrenic abscesses, resulting from different conditions. The development of an bronchobiliary fistula originating from a Klebsiella pneumoniae pneumonia, as indicated by this report, has not been described so far. In the patient presented here, treatment was achieved due to continuous drainage despite the large extent of the abscess.

Extraintestinal manifestations of Crohn's disease and ulcerative colitis are found in > 50% of all patients. These extraintestinal manifestations sometimes impair the overall life quality much more than the bowel-related symptoms. Extraintestinal manifestations need to be distinguished from secondary diseases or complications of inflammatory bowel diseases, as they require a different and specific therapy. Complications of the intestinal disease, such as vitamin deficiency or osteoporosis, can be treated specifically by substitution of vitamin D, calcium, or other vitamins. However, extraintestinal manifestations of Crohn's disease and ulcerative colitis, such as primary sclerosing cholangitis, arthritis or granulomatous inflammation of the skin, lung, or liver, are much more difficult to treat sufficiently. Almost every organ can be a localization of extraintestinal symptoms of inflammatory bowel diseases. It is important to acquire knowledge on these extraintestinal manifestations of Crohn's disease and ulcerative colitis to start the respective treatment early. Perhaps even more important, these extraintestinal symptoms can be the primary manifestation of Crohn's disease and ulcerative colitis. Therefore, they have to be recognized as extraintestinal manifestations to adequately treat the intestinal disease.

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.

Not too long ago, obtaining a patient's history and performing a physical examination was the beginning of every doctor-patient interaction. Today, impressing technical methods--extending the human "diagnostic horizon" to an unbelievable level of astonishing perception--are easily available in most places. So the question comes up whether clinical findings still have relevance in common medical practice. This article critically discusses the value of apparently "established" clinical signs, but also points out why taking a precise patient's history and performing a skilled physical examination is still essential-today and tomorrow.

Background and Purpose: The growing relevance of continuous medical education is evident. Also information retrieval helping to solve clinical problems yet at the patient's bedside becomes more and more important. This study challenges common and coming methods of information retrieval applied by German physicians. It helps answering the question which advantage or disadvantage due to the chosen method of information acquisition may arise. It also shows which practical relevance and which grade of quality the information seeking doctor may anticipate., Methods: A questionnaire was sent out to all registered clinicians in hospital and practice in Germany. Not only traditional means of information retrieval were analyzed. Also, a lot of the questions posed focused on the acceptance and use of new media in the professional context. About 16,000 colleagues answered by filling in the complete form therewith allowing a deep insight into their informational needs and habits., Results: While traditional media like books and scientific papers enjoy wide public confidence, the acceptance and estimated reliability of virtual sources of information today still remain restrained. The lack of transparency of the virtual sources and ways of information within the web according to often imprecise rules for quality assurance lead to major complaint. Information offered directly by the industry has a very low rate of acceptance., Conclusion: To gain higher confidence in electronic media presenting professional knowledge and advanced medical training, the development of technological advantages today seems to be less relevant. Work on the transparency of the informational structures including clear definition of resources and clear indication of possible conflicts of interest are just as important as a comprehensible quality of forthcoming medical content.

Background: The hyper-IgE syndrome is a rare primary immunodeficiency characterized by recurrent staphylococcal infections and high levels of serum IgE., Case Report: The case of a 28-year-old man with epidural and paravertebral abscesses and a markedly elevated serum IgE level of 2,609 U/ml is reported. There was no allergic diathesis, nor had the patient a history of other diseases, which might explain the high serum IgE level. In a blood culture, Staphylococcus aureus was detected. Since early childhood, the patient has suffered from recurrent skin infections., Conclusion: The presented study case discusses the diagnosis of a Job's syndrome in this patient and reviews previously published cases. It also summarizes the current knowledge about pathogenesis and diagnostic criteria of this rare syndrome.

Background: Local innate and adaptive immune processes are of importance during the acute phase of rheumatoid arthritis (RA). In the advanced inflammatory phase alterations of systemic anti-inflammatory feedback mechanisms might be important features which may support chronic inflammation., Alterations: Similarly, like in other chronic inflammatory diseases, inadequately low cortisol and androgen serum levels can be detected in RA patients. In addition, there is a marked reduction of anti-inflammatory sympathetic nerve fibers in the inflamed joints paralleled by an enhanced number of pro-inflammatory sensory nerve fibers. Thus, an uncoupling of synergistically acting endocrine and neuronal, anti-inflammatory mechanisms (cortisol, dehydroepiandrosterone, androgens, sympathetic neurotransmitters) and a preponderance of pro-inflammatory mechanisms (estrogens, sensory neurotransmitters) may lead to chronic inflammatory disease., Conclusion: From this pathogenetic point of view new therapeutic strategies could be developed for the treatment of patients with RA.

Background: The antiphospholipid (Huges) syndrome is a complication of connective tissue diseases characterized by thromboembolic occlusions of arterial and venous blood vessels., Case Report: At the age of 13, the patient developed connective tissue disease with arthritis and myositis. The course of her disease was characterized by frequent relapses despite immunosuppressive treatment. She developed deep venous thrombosis of her right leg as a manifestation of secondary antiphospholipid antibody syndrome at the age of 15 and was subsequently started on oral anticoagulation therapy. Approximately 10 months later, however, she decided to try alternative medicine and stopped both anticoagulation and immunosuppressive therapy. Only after 4 weeks she developed seizures followed by respiratory arrest with the need for cardiopulmonary resuscitation. Despite intensive care she died 2 days later with the signs of severe cerebral edema causing herniation of the brainstem. Autopsy confirmed the diagnosis of severe edema of the brain as a result of extensive thrombosis of all sinus veins., Conclusion: A complete sinus vein thrombosis is a rare manifestation of antiphospholipid antibody syndrome. The lethal thrombosis in this case occurred during a period of reactive hypercoagulability after termination of immunosuppressive and/or anticoagulation therapy. This case report underlines the need for long-term anticoagulation in patients with the antiphospholipid syndrome.

Background: In 1983 the antiphospholipid syndrome was first described as an independent clinical entity by Graham Hughes and characterized by thrombosis, thrombocytopenia and recurrent fetal losses. In the following years evidence accumulated from various studies that the thrombotic events in the antiphospholipid syndrome correlate with elevated serum titers of antiphospholipid antibodies. These autoantibodies represent a very heterogeneous group as multiple specificities against various negatively charged phospholipids are found. Most commonly described are antibodies against cardiolipin, but also cross-reactivities between the different phospholipids are observed. Moreover, efficient binding of antiphospholipid antibodies against a phospholipid requires the presence of certain protein-cofactors which on the other hand can be antigens themselves., Pathogenesis: Although numerous animal models strongly indicate that antiphospholipid antibodies play a causal role in the pathogenesis of the disease, the exact pathogenetic mechanisms are still to be elucidated. There is accumulating evidence from in vitro studies with poly- and monoclonal antiphospholipid antibodies that these autoantibodies are able to interfere with all aspects of the hemostatic balance. Influences of antiphospholipid antibodies on plasmatic processes of the coagulation cascade as well as antithrombotic and fibrinolytic mechanisms are described. Furthermore, antiphospholipid antibodies are able to exert prothrombotic effects on cells participating in hemostasis, mainly platelets and endothelial cells., Therapeutic Approaches: Therapeutic approaches to the antiphospholipid syndrome today are mainly restricted to the prevention of further thrombosis by permanent anticoagulation. Although 30-50% of all patients, according to the literature, with moderately to highly elevated antiphospholipid antibody titers develop the clinical symptoms of the syndrome, there are only few studies investigating the benefits of a prophylactic anticoagulation of the affected patients. There is an urgent need for prospective clinical studies to clarify this question. Therapy of nonthrombotic manifestations of the antiphospholipid syndrome are scarcely standardized. In obstetrics, treatment with aspirin, heparin and steroids is the main approach. Here also controlled studies are restricted to small numbers of patients and are therefore of limited validity.

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.

Background: Barrett's esophagus is a complication of gastroesophageal reflux disease (GERD) characterized by specialized columnar epithelium that contains goblet cells and replaces the squamous epithelium of the distal esophagus. It is found in about 10% of patients with symptomatic reflux disease and more importantly has been associated with the development of esophageal cancer. Adenocarcinoma arises from dysplasia, which is usually not visible during routine endoscopy, therefore extensive random sampling of the entire Barrett's segment should be performed with biopsies in the 4 quadrants every 1 to 2 cm and of any macroscopic abnormality., Case Report: We report the history of a 60-year-old man who was admitted to hospital because of an ulcer in Barrett's esophagus not healing despite conservative treatment. He has suffered from gastroesophageal reflux disease for more than 30 years and an antireflux surgical procedure had not resulted in regression of Barrett's esophagus. However, close surveillance could not reveal any dysplastic or malignant lesion. Endoscopic fluorescence detection (EFD) after sensitization with 30 mg/kg 5-aminolevulinic acid (5-ALA) in this patient demonstrated a selective red fluorescence in a macroscopically normal appearing area near the already known ulcer. Biopsies from this fluorescent area showed an adenocarcinoma. Esophagectomy confirmed the presence of intramucosal adenocarcinoma without lymph node metastases.

Background and Aim: According to the German consensus statement, the indication for treatment of HCV-RNA-positive chronic hepatitis C is not derived from histopathology but from elevated aminotransferases. The indication for liver biopsy has been discussed controversely. This study aimed at investigating the correlation between different biochemical and virological parameters and histological scores of inflammation and fibrosis in chronic hepatitis C., Patients and Methods: In a retrospective study, data of 126 patients with chronic hepatitis C who had undergone liver biopsy between January 1994 and March 1998 were analyzed. Histology was interpreted according to a defined numerical score of inflammation and fibrosis by a single pathologist. Scores of fibrosis and inflammation were correlated with biochemical and virological parameters., Results: Inflammatory grading showed a moderate but significant correlation with ALT (r = 0.33, p < 0.001), whereas staging of fibrosis did not correlate with ALT (r = 0.15). There was no association between grading or staging and HCV genotype (n = 110) or serum viral load (n = 57). Grading and staging showed a significant association with each other (p < 0.0001)., Conclusion: Aminotransferases as "surrogate markers" reflect more or less the histological inflammatory activity but do not allow any estimation of the extent of fibrosis. Some patients may have a high inflammatory activity with low aminotransferases or high aminotransferases with low inflammatory activity. Virological parameters such as HCV genotype or viral load do not allow an estimation of histological findings. If prior to treatment of chronic hepatitis C liver biopsy is omitted and the decision for treatment depends solely on the measurement of surrogate markers, considerable misjudgement of the actual status of liver inflammation or fibrosis may result.

Background: Recently, increasing antibiotic resistance has been observed among gram-positive bacteria. However, only few isolates were found to be resistant against glycopeptides. Therefore, internationally accepted guidelines recommend a restricted use of vancomycin and other glycopeptide antibiotics in order to prevent the development of resistance against these clinically important antibiotics. In many countries, the hospital pharmacies play a key role in control and reinforcement of antibiotic formulary restrictions. In Germany, however, the hospital pharmacies usually do not take over such control functions, and most wards keep a stock of regularly used drugs including antibiotics, which makes reinforcement of restrictions difficult., Methods: In an attempt to achieve a restriction of vancomycin use, the pharmacy of our university hospital was advised to deliver vancomycin to the wards only on request with a special order form signed by an attending, individually for every patient who should receive vancomycin. The efficacy of this restriction measure was evaluated in 3-month periods before and after the restriction became effective., Results: Hospitalwide, this led to a 20.1% reduction of i.v. vancomycin and an 85.7% reduction of oral vancomycin use per 1000 patient days. If the hematology/oncology units were not considered, the reduction of i.v. vancomycin use was 41.8%, and the total use after the restriction 24.2 g per 1000 patient days. Microbiology results which justified the use of vancomycin decreased by 8.3% (10.9% hematology/oncology units not considered) between the 2 observation periods. Assuming a 7-day mean course of i.v. vancomycin therapy, the empirical use of i.v. vancomycin decreased from 39.9% to 8% after the restriction had been instituted., Conclusion: Allowing only experienced physicians (attendings) to decide on the use of vancomycin therapy, proved in our experience to be an effective measure to reduce unnecessary vancomycin use.

Background: Rheumatoid arthritis is a chronic systemic disorder of unknown etiology, that is characterized by inflammation, synovial hyperplasia and destruction of the affected joints. Novel molecular biology techniques have identified important cellular and molecular pathways in the pathogenesis of rheumatoid arthritis during the last years., Results: The cellular activation of aggressively growing, matrix-degrading synovial fibroblasts is a key event in the pathogenesis of rheumatoid arthritis. The cellular activation results in an altered expression of apoptosis regulating molecules (for example CD 95 and Sentrin) as well as of protooncogenes (for example RAS and MYC). Important extracellular stimuli such as the pro-inflammatory cytokines interleukin-1 and TNF-alpha are overexpressed in the rheumatoid arthritis synovium. First clinical trials with cytokine inhibiting molecules (interleukin-1 receptor antagonist, recombinant soluble TNF-alpha receptor/Etanercept and monoclonal TNF-alpha antibodies/Remicade) revealed promising results. Etanercept is now available for the treatment of rheumatoid arthritis in the USA. In addition, gene transfer methods could help to overcome the problem of a continuous expression of therapeutic molecules in the affected joints; gene delivery of the interleukin-1 receptor antagonist is currently tested in a human trial. Finally, the inhibition of matrix degrading enzymes such as matrix metalloproteinases, that mediate the joint destructive features of the activated synovial fibroblasts, could be another therapeutic approach., Conclusions: The elucidation of important molecular and cellular pathways in the pathogenesis resulted in novel concepts in the therapy of rheumatoid arthritis. Gene transfer methods are of importance in studying the pathogenesis of the disease, however, their clinical safety and usefulness have to be proven in additional studies.

Objective: Destruction of articular cartilage and bone by invading synovial fibroblasts is a typical histopathologic feature in rheumatoid arthritis (RA). However, little is known about specific up- or downregulation of genes leading to this aggressive phenotype. Thus, our aim was to identify genes, which are differentially expressed in RA synovial fibroblasts as compared to synovial fibroblasts derived from patients with osteoarthritis (OA) using RAP-PCR for differential display., Methods: After extraction of total RNA, the first step of RAP-PCR was performed using various different arbitrary 10-12-base primers for first-strand cDNA synthesis. Second-strand synthesis was achieved by cycling at low stringency conditions for 35 cycles using different arbitrary 10-base primers, followed by electrophoretic separation and sequence analysis of the amplified fingerprint products., Results: On average, approximately 70 different RNAs were obtained per primer, of which most were expressed both by RA and OA synovial fibroblasts. Using 26 different primer combinations, in total 12 cDNAs were differentially expressed between RA and OA synovial fibroblasts. In the RA group strong amplification of distinct PCR products suitable for sequencing could be observed. Sequence analysis identified these PCR products as highly homologous to various genes involved in regulation of cell cycle and metabolism., Conclusion: The data indicate that RAP-PCR is a suitable method to identify differentially expressed genes in rheumatoid synovial fibroblasts potentially involved in the specific pathophysiology of RA.

Budesonide in the pH-dependent and time-dependent release preparation is at a dose of 9 mg/day useful for treatment of mild to moderate active Crohn's disease. Although the remission rates are somewhat lower as compared to systemic steroids, the number of side effects is significantly decreased. Differences between both preparations based on theoretical and pharmacological considerations have not yet been proven in clinical practice. With regard to maintenance of steroid-induced remission the data available do not justify continuous treatment. This is also true for postoperative remission maintenance. It is not clear at the moment if higher doses could possibly be effective for this indication. It has to be expected, however, that side effects than will increase as well.

Background: In many cases inflammatory bowel disease is accompanied by extraintestinal manifestations. This results in lowering of live quality. The aim of this study was to gather data retrospectively about initial symptoms, extraintestinal manifestations and course of pregnancy in a large unselected population with inflammatory bowel disease in South Germany., Patients and Methods: Data from 1975 to 1989 (392 patients) were analyzed and partially compared with data from 1992 to 1995 (211 patients)., Results: Patients with Crohn's disease in average have been 25 years old at the time point of initial symptoms, whereas the age of ulcerative colitis patients was 30 years (p < 0.0001). The number of Crohn's disease patients with a long interval between initial symptoms and diagnosis (> 1 year) was significantly decreased in the second population (50% vs 38%; p < 0.05). Dominant initial symptoms in Crohn's disease were indisposition, abdominal pain and nonbloody diarrhea in contrast to ulcerative colitis which manifested mostly with bloody diarrhea. Extraintestinal manifestations occurred in 76% of patients with Crohn's disease and 64.6% with ulcerative colitis. Complications during the course of pregnancy have been detected in 40.5% in Crohn's disease and 60% in ulcerative colitis., Conclusion: A better knowledge of initial symptoms and extraintestinal manifestations in inflammatory bowel disease can help to decrease the interval between initial symptoms and the diagnosis. Pregnancy in patients with inflammatory bowel disease needs to be treated with special care.

Background: Deficiencies of vitamins and trace elements are frequent in inflammatory bowel disease. Aim of this study was to evaluate retrospectively the prevalence of these deficiencies and of liver complications in a large population., Patients and Methods: The records from 392 out-patients, 279 with Crohn's disease (160 female, 119 male) and 113 with ulcerative colitis (56 female, 57 male) were analyzed., Results: Deficiencies were found in 85% of patients with Crohn's disease vs 68% with ulcerative colitis during the course of the disease, predominantly a deficiency of iron and of calcium. Less frequently deficiencies of zinc, protein, cyanocobalamin, and folic acid were found. Elevated liver enzymes were seen in 38% of patients with Crohn's disease vs 27% with ulcerative colitis. In order of frequency: gamma-glutamyl-transferase, ALAT, AP, ASAT, and bilirubin. Gallstones were present in 12% of patients with Crohn's disease and 4% with ulcerative colitis. 6% of patients with Crohn's disease and 4% with ulcerative colitis had kidney stones., Conclusions: In view of the high frequency of deficiencies in patients with inflammatory bowel disease it seems to be important to check frequently for extraintestinal complications.

Background: During the last years, examination of autonomic nervous function and of autonomic neuropathy has attracted attention not only in diabetes mellitus research but also in other areas of internal medicine. However, patients with various chronic diseases with autoimmune phenomenons have never been investigated in a comparative study with standardized examination techniques. Hence, the aim of the study was to examine the prevalence and the severity of autonomic neuropathy in patients with the following chronic diseases., Patients and Methods: We investigated 28 patients with Crohn's disease (CD: age: 32.4 +/- 2.0 y), 17 patients with ulcerative colitis (UC: 39.7 +/- 3.6 y), 39 patients with systemic lupus erythematosus (SLE: 34.9 +/- 2.0 y), 38 patients with progressive systemic sclerosis (pSS; 51.5 +/- 2.4 y) and 65 patients with insulin-dependent diabetes mellitus (IDDM: 35.5 +/- 1.6 y). Cardiovascular autonomic (cANP), pupillary autonomic (pANP), and sensorimotor (ssNP) neuropathy were assessed by standardized techniques., Results: Prevalence rates for cANP, pANP and ssNP were found to be 0%, 19%, and 7% in CD, 6%, 25%, and 18% in UC, 5%, 29%, and 10% in SLE, 11%, 16%, and 32% in pSS, and 26%, 66%, and 29% in IDDM, respectively., Conclusion: The study demonstrated patients with IDDM to have the highest prevalence rates of cANP and pANP. Patients with other chronic diseases, particularly SLE, pSS and UC, had high prevalence rates of pANP. This may be due to alterations of structures of the central nervous system in these patients. cANP was rare in patients with inflammatory bowel disease and ssNP was found very often in patients with pSS, probably due to local fibrotic lesions. The various disease groups differ in the pattern and severity of autonomic and sensorimotor neuropathy, which indicates that different structures and neuropathogenic mechanisms may be involved.

Background: Between 1972 and 1984 the diagnostic arsenal has much changed due to wide application of endoscopy, sonography and computed tomography., Patients and Method: Using the data from patients undergoing autopsy in the years 1972, 1977, 1981, and 1984, it was assessed how many of the diagnostic techniques had been used and to what extent the premortal diagnosis of abnormalities found at autopsy improved during this period., Result: While the number of autopsies declined from 113 in 1977 to 66 in 1984, the number of diagnostic techniques used increased continuously (94, 107, 118, and 140, amounting to 0.83, 1.34, 1.76 and 2.12 per patient). The premortal detection of abdominal abnormalities increased globally from 16.8 to 32.5%. This increase was largely due to better diagnosis of liver and gallbladder abnormalities which were in most cases of little relevance., Conclusion: Thus, the massive increase of the application of technical diagnostic tools leads only to a limited premortal diagnostic gain while costs are significant.

Background: Glucocorticoids are an effective treatment of ulcerative colitis. The occurrence of steroid side effects depends on dosage and duration of steroid treatment. It may be a high as 80%. A rare side effect of glucocorticoid therapy is steroid induced myopathia. There exists an acute and a chronic form of steroid induced myopathia. Chronic steroid myopathia affects mainly the proximal musculature of the lower and upper extremities and leads to proximal muscle weakness. Histologically, an atrophy of type IIb-muscle fibers can be found. Chronic steroid myopathia occurs after prolonged treatment with higher doses of glucocorticoids., Case Report: The case report describes a 25 year old male patient with left-sided ulcerative colitis who developed chronic steroid myopathia after several months of glucocorticoid treatment. After switching from systemic steroids to budesonide the symptoms of myopathia disappeared. Left-sided ulcerative colitis remained in remission., Conclusion: The case documents the disappearance of a severe steroid side effect after switching from a systemic steroid to budesonide.

Background: In the recent years several investigations focused on the diagnostic value of abdominal ultrasonography in pancreatic disorders. However, the diagnostic accuracy in these studies ranged between 40 and 90% probably related to variations in study design and other methodologic criteria., Patients: We examined retrospectively 585 patients subdivided into six subgroups. 385 patients had a clinical question aimed at the pancreas and the remaining 200 functioned as screening patients., Results: Using laboratory tests, CT, ERCP, surgery and autopsy as reference methods the positive predictive value for all pancreatic disorders was 85% with the best results for chronic pancreatitis (86% versus 77.5% for acute pancreatitis and 79.5% for malignant tumors). The prevalence of pancreatic disease in symptomatic patients was 28.6% versus only 2.5% in the screening groups. Therefore no significant differences could be detected in groups where the pancreas was not clearly visualized and groups with negative sonographic findings (4% false negative findings versus 1%, respectively). In groups with suspected pancreatic disease the negative predictive value was 86% which was independent of the visualization of the pancreas., Conclusion: In summary positive sonographic findings have a high predictive value for pancreatic disorders and negative results are not more reliable than missing visualization of the pancreas. The positive predictive value is independent from the kind of pancreatic disease and in screening examinations negative findings and findings without clearly visualization of the pancreas have both high negative predictive values.

The present study was aimed to determine the vitamin status of vitamins A, E, beta-carotene, B1, B2, B6, B12 and folate in plasma using HPLC and vitamins B1, B2 and B6 in erythrocytes using the apoenzyme stimulation test with the Cobas-Bio analyzer in 29 elderly type II diabetic women with (G1: n = 17, age: 68.6 +/- 3.2 years) and without (G2: n = 12, age: 71.8 +/- 2.7 years) diabetic polyneuropathy. The basic parameters as age, hemoglobin A1c, fructosamine and duration of the disease did not differ in both groups. Furthermore, retinopathy was assessed with fundoscopy and nephropathy with creatinine clearance. The creatinine clearance (G1: 50.6 +/- 3.4 vs. G2: 63.6 +/- 3.7 ml/min, 2p < 0.025) and the percentage of retinopathy (G1: 76.5% vs. G2: 16.7%, 2p = 0.002) were different indicating that G1 had significantly more severe late complications than G2. Current plasma levels of all measured vitamins (A, E, beta-carotene, B1, B2, B6, B12 and folate) and the status of B1, B2 and B6 in erythrocytes did not vary between the two groups (2p > 0.1). In summary, we found a lack of association between the actual vitamin condition in plasma and erythrocytes and diabetic neuropathy.