[Prevention of road accidents involving non-motorized traffic participants (pedestrians and cyclists) in Germany]. / Prävention von Verkehrsunfällen äußerer Verkehrsteilnehmer (Fußgänger und Fahrradfahrer) in Deutschland.

During a 1-day workshop organized by the German Society of Orthopaedics and Traumatology (DGOU) 15 German accident researchers used different approaches to improve the effectiveness of accident prevention for pedestrians and bicyclists on German roads. The main results of this analysis show: Fatal injuries of pedestrians have been significantly reduced by 82% between 1970 (n=6.056) and 2007 (n=695). Similarly, fatalities of bicyclists have been reduced during the same time period from 1,835 to 425 which amount to almost 80%. However, the total number of injured cyclists increased almost twice, i.e. from 40,531 (in 1979) to 78,579 (in 2007) a fact that needs to be analyzed in more detail. Although scientifically proven to provide protection against severe head injuries, helmets are worn less frequently by adolescents and women as compared to younger children and men. Fatalities of bicyclists might be reduced by using Dobli mirrors which allow the truck driver to see the bicyclist when turning right. Recently developed sensors are able to detect pedestrians walking closely (<2.5 m) and warn the truck driver acoustically. Bicycle lanes should be planned for one direction only, separated from the pedestrian way and large enough (2.0 m are safer than 1.6 m). Traffic education for school beginners and younger children should be repeated to be effective. Training for elderly bicyclists in cities with heavy traffic would also be reasonable. Active security systems in cars like ESP (electronic stability program), BAS (brake assist system), special light systems for curves, and night vision utilities are most effective to prevent collision with pedestrians and bicyclists. TV spots for bicyclists could help to point out dangerous situations and the proven benefits of wearing a helmet in the same way as previous campaigns, e.g."The 7th Sense" for car drivers.

Prospective, randomised, double blind trial of prophylaxis with single dose of co-amoxiclav before percutaneous endoscopic gastrostomy.

OBJECTIVE: To determine the efficacy of antibacterial prophylaxis in preventing infectious complications after percutaneous endoscopic gastrostomy. DESIGN: Prospective, randomised, placebo controlled, double blind, multicentre study. SETTING: Departments of internal medicine at six German hospitals. SUBJECTS: Of 106 randomised adult patients with dysphagia, 97 received study medication, and 84 completed the study. The median age of the patients was 65 years. Most had dysphagia due to malignant disease (65%), and many (76%) had serious comorbidity. INTERVENTIONS: A single intravenous 2.2 g dose of co-amoxiclav or identical appearing saline was given 30 min before percutaneous endoscopic gastrostomy performed by the thread pull method. MAIN OUTCOME MEASURES: Occurrence of peristomal wound infections and other infections within one week after percutaneous endoscopic gastrostomy. RESULTS: The incidence of peristomal and other infections within one week after percutaneous endoscopic gastrostomy was significantly reduced in the antibiotic group (8/41 (20%) v 28/43 (65%), P<0.001). Similar results were obtained in an intention to treat analysis. Several peristomal wound infections were of minor clinical significance. After wound infections that required no or only local treatment were excluded from the analysis, antibiotic prophylaxis remained highly effective in reducing clinically important wound infections (1/41 (2%) v 11/43 (26%), P<0.01) and non-wound infections (2 (5%) v 9 (21%), P<0.05). CONCLUSIONS: Antibiotic prophylaxis with a single dose of co-amoxiclav significantly reduces the risk of infectious complications after percutaneous endoscopic gastrostomy and should be recommended.

Interleukins and their antagonists but not TNF and its receptors are released in post-ERP pancreatitis.

OBJECTIVE: Usually it is not possible to study the initial systemic response in patients with acute pancreatitis in the first hours after onset of the disease. We used postendoscopic retrograde pancreatography (ERP) pancreatitis as a model to study cytokine and anticytokine release in the early phase of human acute pancreatitis. METHODS: Post-ERP pancreatitis was defined as a threefold increase in serum amylase and at least two of the following clinical symptoms: abdominal pain, nausea, vomiting or peritonism 24 h after ERP. Serum levels of pro-inflammatory cytokines interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor alpha (TNF), as well as endogenous antagonistic mediators of the systemic inflammatory response such as soluble tumour necrosis factor alpha receptors p55 (TNFR p55) and p75 (TNFR p75), and IL-1-receptor antagonist (IL-1-RA) and interleukin-2-receptor (IL-2R) as indicators of lymphocyte activation were measured before and 0, 1, 4, 12, 24 and 48 h after ERP. In nine patients with acute post-ERP pancreatitis, these parameters were monitored daily until C-reactive protein (CRP) was within normal ranges and were compared to patients without pancreatitis after ERP. RESULTS: IL-1beta was not detectable in five patients with and four patients without post-ERP pancreatitis. The values of the remaining patients in both groups were lower than 3.9 pg/ml. IL-8 and IL-1-RA serum concentrations peaked 12 h after ERP (132.9 and 3245.0 pg/ml respectively) compared to patients without post-ERP pancreatitis (25.8 and 389.9 pg/ml respectively). The IL-6 concentration increased to 81.6 pg/ml (8.0 pg/ml in control patients) 24 h after ERP, while the peak values for CRP were measured 72 h after ERP (164.0 versus 7.7 mg/l). IL-2R content was maximally elevated 144 h after ERP (688.8 versus 255.9 U/ml), while concentrations of TNF and its receptors showed no significant change over time. CONCLUSION: The initial response of the cytokine network to damage of the human pancreas leading to acute pancreatitis includes the release of IL-8 and the IL-1 antagonist IL-1-RA, while IL-1beta is not found in the systemic circulation. The TNF system does not seem to be involved as indicated by the lack of detectable changes in TNF and the soluble TNFR p55 and p75 serum concentrations. Lymphocyte activation as indicated by elevated IL-2R levels occurred days after the initial trauma. Even mild post-ERP pancreatitis leads to significant systemic release of cytokines and their biological counterparts.

Effect of programmed endoscopic follow-up examinations on the rebleeding rate of gastric or duodenal peptic ulcers treated by injection therapy: a prospective, randomized controlled trial.

BACKGROUND AND STUDY AIMS: A second-look endoscopy is often performed to evaluate the efficacy of a prior injection therapy in patients with bleeding peptic gastric or duodenal ulcers. Although this strategy is widely established, it does not rely on unequivocal data from controlled studies. In a prospective, randomized, controlled multicenter trial we assessed the effect of programmed endoscopic follow-up examinations with eventual retreatment on the outcome of bleeding ulcers in these patients. PATIENTS AND METHODS: One hundred and five patients with gastric or duodenal peptic ulcers presenting with active (Forrest type I) or recent (Forrest type IIa and IIb) bleeding upon endoscopy within four hours after admission were included in the study. Emergency treatment consisted of the sequential injection of both epinephrine (1:10,000 v/v) and up to 2 ml of fibrin/thrombin around the ulcer base. Fifty-two patients were randomized to receive programmed endoscopic monitoring with eventual retreatment in cases of Forrest type I, IIa, or IIb ulcers beginning within 16-24 hours after the index bleed. Follow-up endoscopies were continued until the macroscopic appearance revealed a Forrest type IIc or III ulcer. Fifty-three patients in the control group were closely monitored, and only received a second endoscopy when there was clinical or biochemical evidence of recurrent bleeding. The groups did not differ with respect to age, sex, site and severity of bleeding. RESULTS: The numbers of patients with recurrent bleeding were similar whether they were endoscopically monitored or not (21% versus 17%, P=0.80 chi-squared test). In addition, there was no statistically significant difference between the two groups with respect to the number of blood units transfused, need for surgical intervention, hospital stay or number of deaths (Mann-Whitney U-test). Improving local ulcer stigmata was not related to a better outcome. CONCLUSIONS: Programmed endoscopic follow-up examinations with eventual retreatment in patients locally injected for an acute or recent hemorrhage from a gastric or duodenal ulcer did not influence their outcome when compared to patients receiving only a second endoscopic intervention upon evidence for recurrent hemorrhage. Scheduled control endoscopies cannot be recommended after an initial successful endoscopic treatment of peptic ulcer bleeding when selection of the patients for second-look endoscopy is directed by the Forrest criteria.

[Time requirements of medical and non-medical personnel for ultrasound studies]. / Zeitaufwand von ärztlichen und nichtärztlichen Mitarbeitern für Ultraschalluntersuchungen.

To assess the time needed for ultrasound examinations for physicians and assistants we carried out a survey among members of the German Association of Ultrasound in Medicine (DEGUM) in hospitals and practices. The physician's examination time for the investigation of the upper abdomen and kidneys was 12.3 min with additional time for preparation (2.9 min), for work up (2.3 min) and written documentation (3.6 min), together 21.3 min. The examination times in practices (18.9 min) are shorter than in ultrasound labs in hospitals. Assistants in ultrasound laboratories need for organisation, upkeep of equipment, to filing the images in archives etc. medium 15.2 min per patient. Assistants with exclusive employment in the ultrasound laboratory need 17.6 min (4-57 min), whereas assistants employed in the ultrasound laboratory and other departments need 12.7 min (1.6-31 min). In internal practices the desired time is 7.9 min (3.5-20 min). Because of the different organisation in the ultrasound laboratories in several hospitals and in practices a comparison of times needed by assistant personnel (or, in many cases, by the physicians who perform such work themselves) is very difficult. The examination time really needed by physicians and the time for assistant personnel are shorter than presumed earlier, but are longer than estimated in the recent discussion about money saving in medicine.

Spontaneous rupture of liver in a patient with Ehlers Danlos disease type IV.

Ehlers-Danlos syndrome (EDS) type IV is an autosomal dominant connective tissue disease caused by mutations in the type III collagen gene resulting in extreme tissue fragility. Affected individuals are at risk of dramatic and often fatal complications, mostly spontaneous arterial, uterine, or colonic ruptures. Phenotypic expression of EDS type IV is variable and clinical signs are generally quite subtle, thus making a prompt diagnosis difficult. The case of a 33-year-old woman is described who presented with a wide range of clinical features and sequelae that eventually led to the diagnosis of EDS type IV. She presented with spontaneous liver rupture, renal infarction, and pneumothorax, all representing rare complications of EDS type IV. Prior history revealed a uterine rupture in advanced pregnancy associated with ischemic necrosis of the descending and sigmoid colon. EDS type IV should be suspected in young individuals who present with such unusual complications. Early diagnosis is essential if severe or even lethal complications are to be avoided in the diagnostic and therapeutic management of such patients.

[Association of bone marrow mastocytosis with extremely immature extramedullary mast cell sarcoma]. / Assoziation einer Knochenmarksmastozytose mit extrem unreifem extramedullärem Mastzellsarkom.

The case of a 63-year-old man with a widespread retroperitoneal tumor and two tumor nodules in the left testis is described. Histopathological and cytopathological examination of tissue from the retroperitoneal tumor led to a diagnosis of lymphoreticular neoplasia. The patient died in acute cardiac failure, five weeks after initial presentation. Autopsy revealed another tumor nodule in the right atrium. Macroscopically, the bone marrow appeared normal. The tumor cells were reactive for CD45, vimentin and chloroacetate esterase, but were uncreative with a broad spectrum of antibodies against myelomonocytic and lymphocytic antigens and antibodies against tryptase and c-kit (CD117), characteristic markers for mast cells. However, the bone marrow exhibited the typical picture of mastocytosis. A diagnosis of bone marrow mastocytosis with an associated secondary extramedullary mast cell sarcoma was established. The cause of death was heart failure due to arrhythmia caused by an exophytic atrioseptal tumor nodule.

Post-ERP pancreatitis as a model for cytokine induced acute phase response in acute pancreatitis.

BACKGROUND/AIMS: By contrast with animal models, in most cases it is not possible to examine the systemic response in patients in the first hours after onset of acute pancreatitis. The aim was to determine whether endoscopic retrograde cholangiopancreaticography (ERP)-induced pancreatitis can be used as a human model for the study of cytokine release and acute phase response in the first hours of the disease. PATIENTS AND METHODS: Seventy consecutive patients undergoing ERP for different reasons were prospectively evaluated by sampling blood before and 0, 1, 4, 12, 24, and 48 hours after ERP and, in patients who developed an acute post-ERP pancreatitis, daily until C reactive protein (CRP) was within normal range. A post-ERP pancreatitis was defined as a three-fold increase of amylase or lipase and at least two of the clinical symptoms: abdominal pain, nausea, vomiting, and peritonism during 24 hours after ERP. RESULTS: Nine out of 70 patients developed an acute pancreatitis. Cytokines and other biochemical variables were measured in those nine and in 34 patients out of the 61 not developing pancreatitis. In the nine patients amylase and lipase increased within the first hour after ERP with maximum values between four and 12 hours. Interleukin-6 increased to maximal concentrations after 24-48 hours and the highest CRP concentrations were found 72 hours after ERP. Tumour necrosis factor did not change. CONCLUSION: Post-ERP pancreatitis is an ideal model in which to examine the initial cytokine and acute phase response in the first hours after the initiation of the disease.

[Nephrotic syndrome as the initial symptom of Crohn disease]. / Nephrotisches Syndrom als Erstsymptom eines M. Crohn.

In february 1993, a now 54-year-old man presented with an increased serum-creatinine of 1.7 mg/dl known since september 1992 associated with peripheral edema. He reported painless and infrequent diarrhea during the previous 15 years. Clinically, he showed typical symptoms of a nephrotic syndrome. A renal biopsy revealed an amyloidosis. By further investigations the diagnosis of underlying Crohn's disease could be established. An ileocecal resection and a subsequent immunosuppressive therapy with azathioprine was performed. Following this procedure the serum-creatinine has meanwhile increased to 3.2 mg/dl with the proteinuria remaining stable. Furthermore, the patient developed a renal hypertension. However, at present the patient is otherwise asymptomatic and in a good general condition.

[Diagnostic imaging in acute pancreatitis]. / Bildgebende Verfahren bei akuter Pankreatitis.

With a sensitivity of 90% in the diagnosis of necrotic pancreatic tissue contrast-enhanced computed tomography is the most reliable imaging tool for classifying acute pancreatitis. ERCP is essential for the diagnosis of stones in the common bile duct and in the pancreatic ducts and of tumors of the duodenal papilla and the pancreatic head and thus for clarifying the etiology of acute pancreatitis. Sonography as the only imaging tool would not be sufficient, because its sensitivity for necrotizing pancreatitis is only 33% and stones in the common bile duct are often missed.

Diagnostic approach to acute pancreatitis: diagnosis, assessment of etiology and prognosis.

The aims of initial diagnostic procedures leading to early treatment in an appropriate setting in acute pancreatitis are: initial diagnosis and differential diagnosis, assessment of etiology and assessment of prognosis. Etiology can be assessed with certainty only by endoscopic retrograde cholangiopancreaticography. This method allows us to differentiate between pancreatic duct abnormalities as seen in so-called alcoholic pancreatitis as an exacerbation of chronic pancreatitis and biliary causes of the disease. Contrast-guided computed tomography is useful for detecting necroses and their infection. As in other inflammatory diseases, the prognosis in acute pancreatitis seems to be determined by mediators leading to "whole body inflammation", confirmed by high concentrations of interleukin-8 as a major attractant of neutrophils, by interleukin-6 preceding high levels of CRP, as well as by leukocyte immigration into the pancreas. Besides these determinants of the course of acute pancreatitis the prognosis can be assessed by simple clinical means. A clinical score based on physical examination seems to be the best standard for assessing prognosis. Measurement of PMN-elastases and CRP may be additionally helpful.

Inflammatory mediators and cytokines--new aspects of the pathophysiology and assessment of severity of acute pancreatitis?

Most attacks of acute pancreatitis are mild and self-limiting. In 10-20% of the cases, however, severe disease with multiple systemic complications develops. During the last few years it has been recognized that activated leukocytes have an important role in the multisystem involvement during acute pancreatitis. Activated leukocytes are thus a pathogenetic factor in the severity of the disease. Activation of polymorphonuclear granulocytes (PMNs) and of monocytes/macrophages is an early event during severe acute pancreatitis. Factors released by activated leukocytes therefore reflect the severity of the disease. Three independent studies have shown that released PMN-elastase is a reliable early prognostic marker that permits correct classification of 80-95% of the patients within the first 24-48 hours. Interleukin-6 (IL-6), mainly secreted by activated monocytes/macrophages, is also an early prognostic parameter (shown in one study), but is not superior to PMN-elastase. Leukocyte activation markers are more reliable than multiple scoring systems in the assessment of the severity of acute pancreatitis. Compared with PMN-elastase or IL-6, increased plasma concentrations of such acute-phase proteins as alpha-1-antitrypsin or CRP, and consumption of the protease inhibitor alpha-2-macroglobulin, are later events that can be detected only 1 to 4 days later. Comparison of the various inflammatory parameters suggests that PMN-elastase is the best early and reliable prognostic marker in acute pancreatitis. The reviewed data underscore the role of activated leukocytes in the pathogenesis of complicated acute pancreatitis.

[A severe course of leptospirosis with acute kidney failure and extensive icterus (Weil disease)]. / Schwerer Verlauf einer Leptospirose mit akutem Nierenversagen und ausgeprägtem Ikterus (Morbus Weil).

A 77-year-old man developed a fever up to 38.4 degrees C, with diarrhoea, acute renal failure (creatinine up to 8.7 mg/dl; urea up to 308 mg/dl) and marked jaundice (total bilirubin up to 24.3 mg/dl). In addition there was thrombocytopenia, conjunctivitis and epistaxis, as well as cerebral symptoms with somnolence and general slowing up. At first he was thought to have cholangitis resulting from previously diagnosed gall-stones, and he was therefore treated with ampicillin, 2 g two times daily, and metronidazole, 0.5 g two times daily. The fewer regressed, but the renal failure required haemodialysis and haemofiltration under strict fluid control. Endoscopy excluded obstructive jaundice, but a suspicion of inflammatory liver disease or possibly cirrhosis was raised in the differential diagnosis. Serology revealed an increased titre for Leptospira interrogans var. sejroe (1:200, later 1:1600). Liver biopsy finding was compatible with the diagnosis of leptospirosis. Because of the high inflammatory activity in the liver, 2 mega units of penicillin G were administered three times daily for six days. Gradually the renal functions and jaundice improved and, on discharge on the 36th day, the patient was again in generally good health, although creatinine and bilirubin values were still slightly elevated (1.7 mg/dl each).

Value of endoscopic retrograde cholangiopancreatography in determining the cause but not course of acute pancreatitis.

We have recently shown that ERCP is the most useful technique for detecting a biliary origin of acute pancreatitis and can be done without side effects. We now report on a second series of 50 patients with acute pancreatitis in whom ERCP, computed tomography (CT), ultrasound (US), and clinical and laboratory assessment were performed within the first 24 to 48 hours of hospitalization. A score for ERCP, CT and US was used to assess the severity of the disease. Patients were followed up until discharge or death and their condition classified according to outcome as mild (less than or equal to 1 complication), severe (greater than 1 complication) or fatal. ERCP was superior in detecting choledochal stones (ERCP 100%, US 25%, CT 50%) and dilated intrahepatic ducts (ERCP 75%, US 75%, CT 37%) but not gallbladder stones (ERCP 70%, US 100%, CT 60%). When the ERCP severity score was calculated there was no relevant difference between patients thereafter having a mild course (0.66 +/- 0.91, range 0-3), a severe course (1.3 +/- 0.80, range 0-3), or a fatal outcome (1.0 +/- 1.1, range 0-3). In contrast, the CT score was different in all three groups (mild: 3.0 +/- 1.9; severe: 5.3 +/- 3.2; lethal: 6.3 +/- 3.1) as was the US score (mild: 1.5 +/- 1.3; severe: 3.2 +/- 2.3; lethal: 4.4 +/- 1.4). It is concluded from these results that ERCP is of value in defining the origin of acute pancreatitis. When a biliary origin is detected this can lead to immediate treatment using endoscopic sphincterotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Interleukin-8 and neutrophil activation in acute pancreatitis.

It has been suggested that leucocytes play an important role in the pathogenesis of complicated pancreatitis. Indeed, increased plasma concentrations of neutrophil elastase as a marker of neutrophil activation could be detected in patients with a severe course of the disease. Recently, interleukin-8 (IL-8) has been described as a novel neutrophil activating peptide. To determine the role of IL-8 in acute pancreatitis we measured its serum concentrations by a specific enzyme-linked immunosorbent assay in 10 patients with acute pancreatitis daily during the first week of hospitalization. IL-8 levels were compared with plasma concentrations of neutrophil elastase and the clinical course of the disease. Three of the patients had uncomplicated pancreatitis, while seven showed various extrapancreatic complications. Patients with complicated pancreatitis had statistically significant (P less than 0.05) higher mean values of IL-8 (121 +/- 41 pg/ml-1 vs. 13 +/- 6 pg ml-1, mean +/- SEM) and neutrophil elastase (547 +/- 35 ng ml-1 vs. 250 +/- 20 ng ml-1) than patients with uncomplicated disease. There was a positive correlation (r = 0.52, P less than 0.0001) between IL-8 and neutrophil elastase in the lower concentration range of IL-8 (less than 100 pg ml-1). At IL-8 levels greater than 100 pg ml-1 neutrophil elastase was always greatly elevated; however, under these conditions the relationship between IL-8 and elastase was no longer linear. No measurable IL-8 concentrations were found when plasma elastase was less than 200 ng ml-1. During follow-up, initially elevated IL-8 concentrations decreased in correlation with clinical improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

[Papillotomy in acute pancreatitis: more benefits than risks]. / Papillotomie bei akuter Pankreatitis: Mehr Nutzen als Risiken.

The pathogenesis of acute pancreatitis is still unclear. OPIE's theory that obstruction of the Ampulla of Vater can be an important etiological factor in acute pancreatitis is still relevant for the ongoing discussion whether endoscopic papillotomy can improve acute pancreatitis. Patients with severe acute pancreatitis have to undergo an early ERCP for the detection of the biliary origin of the disease. In case of the detection of choledocholithiasis endoscopic papillotomy should be performed. The rate of complications and the duration of hospitalization can be significantly reduced in contrast to conservative treatment. Controlled clinical studies are necessary to answer the question if endoscopic papillotomy should be carried out in all patients with severe acute pancreatitis.

Inflammatory mediators in chronic inflammatory bowel diseases.

Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) of unknown etiology. They are characterized by an activation of intestinal mononuclear cells. Cytokines play a crucial role in the regulation of the functions of these cells. An increased synthesis of the cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha), which are primarily synthesized by activated monocytes/macrophages has been described in patients with IBD. The synthesis of interleukin-2 (IL-2) and of interferon gamma (IFN gamma), which are produced by lymphocytes, on the other hand, has been found to be decreased. The published data are, however, not quite consistent. In patients with IBD there is not only a stimulation of the local cytokine production in the gut. The blood levels and the synthesis of the cytokines IL-1, IL-6 and TNF alpha by peripheral blood mononuclear cells are also increased, in particular in patients with Crohn's disease. Drugs, which are commonly used for the treatment of IBD impair the synthesis of these cytokines in monocytes/macrophages.