Individual invitation letters lead to significant increase in attendance for screening colonoscopies: Results of a pilot study in Northern Hesse, Germany.

BACKGROUND: Colorectal cancer (CRC) is the second most common cancer in Germany. Screening colonoscopies are considered an effective tool for early detection and prevention of CRC and are recommended in Germany for citizens over the age of 55. To increase the participation rate for screening colonoscopies, an invitation procedure was initiated in parts of Germany for patients between the ages of 55 and 75 who had never undergone a screening colonoscopy before. METHODS: We examined the number of participating patients before, during, and after the invitation procedure and compared the number of the participating patients who received a cover letter with the participating patients from the control group. Additionally, we classified the findings of the colonoscopies including CRC, advanced adenomas, and polyps. RESULTS: During the invitation period, the participation rate of the invitation group increased from 220 patients to 531 patients compared to 1256 to 1693 in the control group. The increase was significantly greater in patients with cover letters (+141% vs.+35%, p < 0.0001). Also, significantly more polyps and adenomas were found in patients from the invitation letter group (254 (+102%) vs. 679 (-9%), p < 0.0001). CONCLUSIONS: Our study clearly indicates that personal invitation letters are an effective measure to increase overall participation rates in screening colonoscopies.

[Integrated management of patients with chronic inflammatory bowel disease in the Rhine-Main Region: results of the first integrated health-care project IBD in Germany]. / Integrierte Versorgung von Patienten mit chronisch-entzündlichen Darmerkrankungen im Rhein-Main-Gebiet: Ergebnisse der ersten integrierten Versorgung CED in Deutschland.

INTRODUCTION: In our previous studies investigating the drug therapy in patients suffering from inflammatory bowel disease (IBD) in the Rhein-Main region, Germany, we detected serious discrepancies between treatment reality and treatment guidelines. Consecutively, patient outcome in this cohort was compromised. Following this pilot project a network between primary deliverers of care for IBD patients and one large health-care insurance company [BKK Taunus (Gesundheit), the second largest insurance company in Hessen, Germany] was established. PATIENTS AND METHODS: An analysis of treatment and socioeconomic data from 220 IBD patients (Crohn's disease - CD = 96, ulcerative colitis - UC = 124) entering the integrative health-care programme between 1.1.-30.9.2009 was performed. RESULTS: Remission rates for CD and UC in the integrated health-care programme could be improved from 60 - 73 % (CD) and from 61 - 79 % (UC). Guideline-conform treatment was observed in 81 % of patients with CD and 85 % with UC, respectively. Although medication costs increased, total costs could be cut by 162 304.- €, as secondary costs for hospitalisation and days off work could be reduced. CONCLUSION: The study shows that networking of deliverers of care for IBD patients with health insurances provides an excellent possibility to optimise medical treatment and can cut down costs significantly.

[Knee joint infections]. / Das infizierte Kniegelenk.

Knee joint infection represents an emergency case at every age. Joint infection occurs frequently after trauma or joint surgery. The infection can be caused by numerous bacteria, viruses, or yeasts; however, Staphylococcus aureus is identified as the cause in 85-95 % of joint infections. Early treatment is important for patient outcome. In addition to synovectomy and therapeutic arthroscopy, antibiotic therapy is essential and should be started after sample recovery.

Female patients suffering from inflammatory bowel diseases are treated less frequently with immunosuppressive medication and have a higher disease activity: a subgroup analysis of a large multi-centre, prospective, internet-based study.

BACKGROUND: The introduction of immunosuppressants and biologic agents has led to active debate and research about optimal therapeutic strategies considering risk factors and predictors of clinical outcome in inflammatory bowel disease (IBD). Data about gender-specific treatment differences and risk factors is lacking for IBD. The aim of the present study was to evaluate gender-related differences in the treatment of a distinct IBD patient population treated in the Rhein-Main region, Germany. METHODS: Data about past medical history, disease status and medical treatment of 986 outpatients treated in ten gastroenterological practices and three hospitals were collected from November 1st 2005-July 31st 2007 and analyzed with regard to gender-related differences in therapy and disease management. RESULTS: With the exception of an extended disease duration in women, no significant gender-related differences in demographic and clinical characteristics were observed. Men showed a significantly higher remission rate than women (p=0.025), while women received significantly less immunosuppressive medication compared to men (p=0.011). In addition, treatment with immunosuppressants was not different in women with child-bearing potential compared to menopausal women. CONCLUSION: Our investigation demonstrates for the first time gender-specific differences in the therapeutic management in a large cohort of IBD patients.

Rapid discovery and optimization of therapeutic antibodies against emerging infectious diseases.

Using a comprehensive set of discovery and optimization tools, antibodies were produced with the ability to neutralize SARS coronavirus (SARS-CoV) infection in Vero E6 cells and in animal models. These anti-SARS antibodies were discovered using a novel DNA display method, which can identify new antibodies within days. Once neutralizing antibodies were identified, a comprehensive and effective means of converting the mouse sequences to human frameworks was accomplished using HuFR (human framework reassembly) technology. The best variant (61G4) from this screen showed a 3.5-4-fold improvement in neutralization of SARS-CoV infection in vitro. Finally, using a complete site-saturation mutagenesis methodology focused on the CDR (complementarity determining regions), a single point mutation (51E7) was identified that improved the 80% plaque reduction neutralization of the virus by greater than 8-fold. These discovery and evolution strategies can be applied to any emerging pathogen or toxin where a causative agent is known.

Health care and cost of medication for inflammatory bowel disease in the Rhein-Main region, Germany: a multicenter, prospective, internet-based study.

BACKGROUND: Studies examining the treatment reality of IBD patients in Germany have been limited, as networking among deliverers of care and reliable documentation of medical, demographic, and economic data are lacking. The aim of the present study was to establish an internet-based treatment registry in order to evaluate treatment of IBD patients in Germany. METHODS: Between November 1(st), 2005, and January 31, 2007, 1024 outpatients with prevalent IBD from 10 gastroenterological private practices and 3 hospitals (UC = 439, CD = 567, ID = 18) were enrolled in the study. An internet-based registry was established that included data about medical history, disease status, diagnostic procedures, laboratory test results, and medical treatment. Data for private practices and hospitals were pooled in order to compare treatment habits between these types of medical facilities. The cost of medication was determined according to medications prescribed. RESULTS: There was no significant difference between the 2 patient groups in demographic and clinical characteristics. Marked differences were observed in medical treatment. The most frequently prescribed medications in the private practices for patients in remission and those with active disease were aminosalicylates and corticosteroids. Immunomodulators played a marginal role. In contrast, in the hospitals azathioprine/6-MP was predominantly used for the maintenance of remission. Patients with fistulizing CD were treated with infliximab. The mean annual cost of medications was 1826 +/- 1331euro/patient (median 1353euro) in the private practices and 1849euro +/- 2897euro/patient (median 960euro) at the University Hospital. CONCLUSIONS: The registry provides the first detailed data about the reality of treatment of IBD patients in Germany and reveals the necessity for networking among attending physicians in order to implement guidelines-conformed treatment.

Prospective evaluation of faecal neutrophil-derived proteins in identifying intestinal inflammation: combination of parameters does not improve diagnostic accuracy of calprotectin.

BACKGROUND: Differentiating symptoms of irritable bowel syndrome from those of organic intestinal disease is a common clinical problem. Several neutrophil-derived proteins have been proposed as a marker of inflammatory bowel disease. AIM: To compare the diagnostic value of faecal calprotectin, lactoferrin and polymorphonuclear neutrophil-elastase in distinguishing inflammatory bowel disease from irritable bowel syndrome. METHODS: Eighty-eight adult patients with a history of chronic diarrhoea of unknown origin were screened. All patients underwent a complete work-up to identify the underlying cause. In addition, a single stool sample was assayed for faecal calprotectin, lactoferrin and polymorphonuclear neutrophil-elastase by enzyme-linked immunosorbent assay. RESULTS: Within the study cohort inflammatory bowel disease was diagnosed in 45 patients and irritable bowel syndrome in 31 patients. The sensitivity and specificity of calprotectin for inflammatory bowel disease were 93% and 100%, respectively. In contrast, the respective diagnostic values for lactoferrin and polymorphonuclear neutrophil-elastase were 82% and 100% and 84% and 87%, respectively. Neither combination of markers did improve the diagnostic power compared with calprotectin alone. CONCLUSIONS: Although all faecal biomarkers studied provide a reliable and simple non-invasive means in the differentiation of inflammatory bowel disease and irritable bowel syndrome, calprotectin appears to represent the most accurate marker to discriminate between these two common causes of chronic diarrhoea.

[Antibiotic-associated diarrhea]. / Die Antibiotika-assoziierte Diarrhö.

The incidence of antibiotic-associated diarrhea (AAD) differs with the antibiotic and varies from 15 - 25 %. Most cases of AAD are directly or indirectly caused by alterations of gut microflora by the antibiotics resulting in clinically mild AAD cases due to functional disturbances of intestinal carbohydrate or bile acid metabolism. Alternatively, changes in the gut flora allow pathogens to proliferate. Clostridium difficile is responsible for 10 - 15 % of all cases of AAD and almost of all cases of antibiotic-associated pseudomembraneous colitis. There is also a growing body of evidence which supports the responsibility of Klebsiella oxytoca for the development of antibiotic-associated hemorrhagic colitis. Diagnosing Clostridium difficile-associated diarrhea should be based both on fecal-cytotoxin detection and culture. With respect to specific therapy, metronidazol has become the first choice whereas treatment with oral vancomycin should be reserved for patients who have contraindications or intolerance to or who have failed to respond to metronidazole. Probiotics such as Sacharomyces boulardii can reduce the risk of development. Restrictive antibiotic policies (e. g. restricting clindamycin and cephalosporins) and the implementation of a comprehensive hospital infection control have also been shown to be effective in reducing the incidence of AAD.

Microsomal glutathione S-transferases: selective up-regulation of leukotriene C4 synthase during lipopolysaccharide-induced pyresis.

Cysteinyl-leukotrienes (cys-LTs) are potent smooth muscle contracting agents, which play key roles in inflammatory and allergic diseases. The committed step in cys-LT biosynthesis is catalyzed by leukotriene C(4) synthase (LTC4S) as well as microsomal glutathione S-transferase type 2 (MGST2) and type 3 (MGST3). Here we report that intraperitoneal injections of lipopolysaccharide in rats lead to a strong increase of LTC4S messenger RNA (mRNA) levels after approximately 1 h, particularly in the heart, brain, adrenal glands and liver, without any significant effect on MGST2 and MGST3 mRNA levels. After 6 h, LTC4S mRNA returns to basal levels, concomitant with a 4.9-, 4.0-, 2.9- and 2.3-fold induction of LTC4S protein in brain, heart, liver and adrenal gland, respectively. Hence, challenge with lipopolysaccharide in vivo causes an organ-selective, local priming for leukotriene C(4) synthesis. Moreover, these data suggest that LTC4S and cys-LTs may be involved in acute systemic inflammatory responses such as fever and tachycardia.

Enteral nutrition by endoscopic means; I. Techniques, indications, types of enteral feed.

Enteral nutritional support plays a major role in the management of patients who are critically ill in intensive care units (ICU), those with poor volitional intake, persons with chronic neurological or mechanical dysphagia, and individuals with gut dysfunction. Part I of this review will briefly discuss the principles governing nasoenteral feeding and will describe in detail the endoscopic-assisted methods for placing enteral feeding tubes. These include percutaneous endoscopic gastrostomy, jejunal extension through a percutaneous endoscopic gastrostomy or direct endoscopic jejunostomy, and the "one-step button". In addition, the types of enteral food with focus on disease-specific enteral diets will be discussed. Finally, the latest innovations in enteral feeding including immune-enhancing nutrients such as arginine, omega-3 fatty acids, glutamine, and nucleotides advocated for critically ill patients will be discussed. Questions regarding possible complications and long-term results of the various methods of enteral feeding will be discussed separately in part II.

Enteral Nutrition by Endoscopic Means; II. Complications and Management.

Despite the benefits and the widespread use of enteral and tube feeding (ETF) some patients experience complications, which can be divided in three categories: mechanical, e. g., tube blockage or removal; gastrointestinal, e. g., vomiting, diarrhea; and metabolic, e. g., re-feeding syndrome, hyperglycemia. The type and frequency of complications related to tube feeding varies considerably in accordance with the access to the intestinal tract (e. g., nasoenteric vs. percutaneous gastric vs. small bowel), the composition of the formula diet used, and the severity of the underlying disease. For example, tube-related complications have been reported to occur in 0-20 % and gastrointestinal complications in 8-65 % of patients during early postoperative feeding via a needle catheter jejunostomy (NCJ) using comparable techniques. The complication rate can be reduced by careful observance of guidelines on tube feeding including those related to food composition, administration rate, portion size, food temperature, and supervision of the patient. Gastrointestinal side effects (including diarrhea) are without doubt the most frequent.

A study for the evaluation of safety and tolerability of intravenous high-dose iron sucrose in patients with iron deficiency anemia due to gastrointestinal bleeding.

INTRODUCTION: The provision of adequate iron to support erythropoiesis in iron deficient patients is a time-consuming process which may present compliance problems for patients in the outpatient setting. The aim of the present study was to evaluate the safety and tolerability of intravenous high-dose iron sucrose therapy specifically in patients with iron deficiency anemia (IDA) due to gastrointestinal blood loss. METHODS: A single dose of iron sucrose of 7 mg iron/kg body weight (not exceeding 500 mg) was infused over 3.5 hours in 31 consecutive patients with IDA due to gastrointestinal blood loss. Safety and tolerability of the therapy was assessed by the occurrence of adverse events under therapy and up to one week after completion of the study. Further examinations comprised vital parameters, ECG, and clinical chemistry including iron indices. RESULTS: A total of 14 adverse events were observed in 10 patients, of which two adverse events in two patients were considered as being definitely related to drug administration. None of the patients had to be withdrawn from therapy. Significant changes in vital parameters and ECG during therapy and follow-up were not observed and clinical chemistry remained unchanged. DISCUSSION: A single intravenous high-dose iron sucrose therapy in patients with IDA due to gastrointestinal blood loss appears to be safe and therefore is a therapeutic option which may save time and improve patient compliance.

Combining infliximab and methotrexate in fistulizing Crohn's disease resistant or intolerant to azathioprine.

BACKGROUND: Crohn's disease is complicated by fistulas in 20-40% of patients at some time during the course of their illness. Azathioprine has been reported to heal fistulas in 30-40% of cases. Long-lasting effects by the anti-tumour necrosis factor-alpha antibody infliximab most often require repeated infusions. Methotrexate has been shown to be an effective drug in maintaining remission in Crohn's disease. AIM: To evaluate the combination of infliximab and methotrexate as therapy for fistulas in patients with Crohn's disease. METHODS: Twelve consecutive patients (mean age, 29.5 years) with fistulizing Crohn's disease resistant or intolerant to azathioprine were followed prospectively. Patients received three infusions of infliximab (5 mg/kg) and long-term methotrexate (20 mg/week). Therapy success was defined as sustained closure of fistulas > or = 6 months after fistula closure. RESULTS: In four of the 12 patients, complete closure of fistulas that persisted for > or = 6 months (median follow-up, 13.25 months) was observed. In three further patients, a partial response was noted. In five patients, persistent therapy success could not be achieved or therapy had to be stopped due to side-effects. CONCLUSIONS: A combination of infliximab with long-term methotrexate may be a promising concept in fistulizing Crohn's disease. Our data indicate the need for larger controlled trials.

The value of routinely performed ultrasonography in patients with Crohn disease.

BACKGROUND: In active Crohn disease (CD), abdominal ultrasound can demonstrate morphological changes in the bowel wall. By contrast, the role of ultrasonography in periods with no disease activity has never been evaluated. In this prospective study we investigated the outcome of routinely performed abdominal ultrasonography in CD patients irrespective of symptoms and disease activity. METHODS: 255 consecutive patients with chronic CD (117 M, 138 F, mean age (+/-s) 38 +/- 14) were evaluated by high-resolution ultrasonography of the bowel wall and abdomen. The findings were graded with respect to further diagnostic and/or therapeutic implications. In addition, the CD activity index (CDAI) was determined. In patients with pathological sonographic findings, complementary procedures (e.g. endoscopy, computed tomography, biopsy or operation) were performed to validate the suspected diagnosis. RESULTS: In 46/255 (18%) patients with CD, the diagnosis of a transmural inflammatory reaction (TMR) with or without fistula was made by ultrasonography. In respect of CDAI, 29/46 (63%) of these patients were graded as active disease (CDAI > 150) and 17/46 (37%) as inactive disease (CDAI < or = 150). Of the 17 patients with a TMR and CDAI < or = 150, 4 patients revealed interenteric fistula, 7 patients mesenteric or perirectal fistula, whereas 6 patients presented with a transmural mesenteric inflammatory reaction without fistula. All fistulae were confirmed by radiography. Ultrasonography of the remaining abdominal organs revealed pathological findings with further diagnostic implications in 25/255 (10%) patients and with therapeutic implications in 9/255 (4%) patients. CONCLUSION: Routinely performed ultrasonography of the abdomen reveals pathological findings with therapeutic implications not only in symptomatic but also in asymptomatic patients with CD. It can therefore be recommended as a screening tool for this group of patients.

Expression of microsomal glutathione S-transferase type 3 mRNA in the rat nervous system.

Microsomal glutathione S-transferase type 3 (MGST3) is a recently identified member of a large superfamily of enzymes involved in biotransformation of xenobiotics and biosynthesis of eicosanoids, including prostaglandins and leukotrienes. Using in situ hybridization histochemistry and reverse transcription polymerase chain reaction, we characterized the expression of MGST3 mRNA in the rat nervous system based on the cloned rat MGST3 gene, under normal conditions and after systemic administration of lipopolysaccharide (LPS). The MGST3 mRNA seemed to be confined to neurons. The broad distribution in the brain was characterized by a strong signal in the hippocampal formation and in the nuclei of the cranial nerves. A moderate signal was found in the cortex, thalamus, amygdala and substantia nigra and a weak signal in the hypothalamus. Motoneurons in the spinal cord and sensory neurons in dorsal root ganglia displayed strong MGST3 mRNA signal. No significant changes in the level of expression of MGST3 mRNA in the brain were found 1, 3 or 6 h after LPS administration. The pattern of distribution of MGST3 mRNA in the rat nervous system and the lack of response to LPS do not support a role for MGST3 in the biosynthesis of proinflammatory eicosanoids but rather suggest other functions, perhaps in metabolic detoxication and neuroprotection.

A new immunological test strip device for the rapid, qualitative detection of faecal occult blood.

OBJECTIVE: Guaiac tests for faecal occult blood are still the most commonly performed screening procedure for colorectal cancer. Because both sensitivity and specificity of faecal occult blood testing are critical to cost-effective colorectal cancer screening programs, we investigated a rapid immunological test strip device for bedside detection of faecal occult blood. METHODS: Stool specimen from 100 patients were chosen for this study based on the presence (n = 50) or absence (n = 50) of faecal occult blood as measured with a human haemoglobin ELISA (cut-off level

[Vomiting in pregnancy. When is it more than only a bothersome nuisance?]. / Erbrechen in der Schwangerschaft. Wann ist es mehr als nur ein lästiges Ubel?

In industrial countries more than half of women complain of nausea and vomiting during the first trimenon. Morning sickness, the common term of gestational nausea and vomiting, is usually temporary and harmless, it persists in less than 20% of all pregnancies. Maternal and fetal prognosis of uncomplicated emesis gravidarum is good. The responsible hormone as the pathogenetical trigger has not been defined yet, genetical and psychosocial factors may influence the intensity and duration of disease. The uncomplicated emesis has to be distinguished from hyperemesis gravidarum, a disorder which occurs in 0.3-2% of all pregnancies and is potentially of life-threatening character. While the uncomplicated form generally does not need any special therapy, hyperemesis gravidarum requires immediate compensation of fluid- and electrolyte loss, adequate supplementation of calories and vitamins as well as antiemetic therapy. Prospective studies have demonstrated that antihistamines are safe and effective for treatment of nausea and vomiting of pregnancy, in addition, also metoclopramide posses a high efficacy and safety profile.

Toward the three-dimensional structure of the Escherichia coli DNA-binding protein H-NS: A CD and fluorescence study.

The DNA-binding protein H-NS compacts DNA and acts as a specific transcription factor regulating the expression of various bacterial genes. The small abundant protein binds to curved DNA without apparent sequence specificity and the exact nature of its DNA interaction is still unknown. H-NS lacks any common DNA-binding or oligomerization motif and except for a C-terminal fragment of the protein no high resolution structural information is available today. Since the complete structure of H-NS is of considerable interest for understanding its versatile regulatory features, and in lack of high-resolution data for the complete molecule, we have combined circular dichroism (CD) and fluorescence measurements to collect secondary- and higher-order structural information on H-NS. Comparison of CD analyses of wild type H-NS and functional defective mutants allowed assigning secondary structure elements to the N-terminal oligomerization domain of the protein. Moreover, according to fluorescence energy-transfer data we calculate a 45 A distance between the DNA-binding and the oligomerization domain of H-NS.