Plasma histamine and tumour necrosis factor-alpha levels in Crohn's disease and ulcerative colitis at various stages of disease.

Mast cells secrete numerous mediators and this study investigated plasma levels of histamine, and tumor necrosis factor alpha (TNF-α) in chronic inflammatory bowel disease (IBD). Plasma levels of histamine were determined in 68 patients with Crohn's disease (CD), 22 with ulcerative colitis (UC) and 13 controls. TNF-α levels were assessed in 29 CD patients, 11 UC patients, and in 11 controls. Plasma histamine levels in the control group were 0.25 ng (0.14 - 0.33) and showed no difference to CD (0.19 ng, 0.09 - 0.35) or UC (0.23 ng, 0.11 - 0.60). Significantly lower histamine levels were only found in CD patients on 5-aminosalicylic acid treatment (P ≤ 0.04). Plasma TNF-α levels in the control group were significantly lower 0.44 ml/m(2) (0 - 1.15) than in CD patients (4.62 ml/m(2), 1.82 - 9.22, P = 0.005) or UC (3.14 ml/m(2); 0.08 - 11.34, P = 0.01). In CD disease activity, fistula, and extraintestinal manifestations (EM) were associated with significantly higher plasma TNF-α values, but not the type of treatment. We concluded that in contrast to TNF-α, histamine levels were normal in CD and UC. There is no correlation with histamine and thus the proportion of TNF-α secreted from mast cells in the plasma in patients with IBD is less important.

Mast cell tryptase levels in gut mucosa in patients with gastrointestinal symptoms caused by food allergy.

BACKGROUND AND AIMS: Mast cells, which are important effector cells in food allergy, require a special histologic treatment for quantification in endoscopic gastrointestinal samples. The objective of this study was to investigate whether mast cell tryptase (T), a typical mast cell-associated marker, may help to detect patients with food allergy. METHODS: Mast cell T was investigated from 289 colorectal samples of 73 controls, 302 samples from 43 patients with food allergy and gastrointestinal symptoms, and 72 samples from 12 patients with partial or complete remission of allergic symptoms. Endoscopically taken samples were immediately put into liquid nitrogen, mechanically homogenized by a micro-dismembrator with three homogenization steps and tissue T content (ng T/mg wet weight) was measured by fluoroenzyme immunoassay. RESULTS: Tissue T levels from the lower gastrointestinal tract were significantly elevated (p < 0.0001) in patients with manifest gastrointestinal allergy (median: 55.7, range: 9.3-525.0) compared with controls (median: 33.5, range: 8.0-154.6). A subgroup of 12 patients with remission of allergy showed markedly decreased symptom scores and mucosal T levels after more than 1 year of antiallergic therapy (pretreatment median: 54.1, range: 37.0-525.0 and posttreatment median: 28.4, range: 19.8-69.1; p = 0.01). CONCLUSIONS: High T levels in the gut of food-allergic patients support the role of stimulated mast cells or an increased mast cell number.

[Integrative and personalized health care--requirements for a timely health-care system]. / Integrative und personalisierte gesundheitsversorgung--forderungen für ein zeitgemässes gesundheitssystem.

In medical and public debates, the concept "personalized" or "individualized" medicine (PM) is increasingly used for the orientation of medicine towards individual genetic, molecular and biological characteristics. However, this tunnel view neglects that the human "person" or "individual" encompasses more than just the molecular and biological side, and that patients increasingly call for a more holistic and more person-centred form of health care. Therefore the authors propose to extend the concept of PM in the framework of an integrative health-care concept, so that with respect to a modern and patient-centred health-care system not only the biological, but also the relevant psychological, mental, social, cultural, spiritual, and economic aspects of the human individual are accounted for in health care. The Faculty of Health of Witten/Herdecke University proposes the term "integrative and personalised health care" for such a holistic form of PM.

Analysis of immediate ex vivo release of nitric oxide from human colonic mucosa in gastrointestinally mediated allergy, inflammatory bowel disease and controls.

Nitric oxide (NO) is a local mediator in inflammation and allergy. The aim of this study was to investigate whether live incubated colorectal mucosal tissue shows a direct NO response ex vivo to nonspecific and specific immunological stimuli and whether there are disease-specific differences between allergic and chronic inflammatory bowel disease (IBD). We took biopsies (n=188) from 17 patients with confirmed gastrointestinally mediated food allergy, six patients with inflammatory bowel disease, and six control patients. To detect NO we employed an NO probe (WPI GmbH, Berlin, Germany) that upon stimulation with nonspecific toxins (ethanol, acetic acid, lipopolysaccharides), histamine (10(-8)-10(-4)M), and immune-specific stimuli (anti-IgE, anti-IgG, known food allergens) directly determined NO production during mucosal oxygenation. Non-immune stimulation of the colorectal mucosa with calcium ionophore (A23187), acetic acid, and ethanol induced a significant NO release in all groups and all biopsies. Whereas, immune-specific stimulation with allergens or anti-human IgE or -IgG antibodies did not produce significant release of NO in controls or IBD. Incubation with anti-human IgE antibodies or allergens produced a ninefold increase in histamine release in gastrointestinally mediated allergy (p<0.001), but anti-human IgE antibodies induced NO release in only 18% of the allergy patients. Histamine release in response to allergens or anti-human IgE antibodies did not correlate with NO release (r(2)=0.11, p=0.28). These data show that nonspecific calcium-dependent and toxic mechanisms induce NO release in response to a nonspecific inflammatory signal. In contrast, mechanisms underlying immune-specific stimuli do not induce NO production immediately.

The measurement of leukotrienes in urine as diagnostic option in systemic mastocytosis.

Clinical symptoms of patients with mastocytosis may include skin reactions, but also gastrointestinal symptoms with hyperacidity and dysmotility (e.g. ulcer, diarrhea, pain). They are mostly caused by mediators derived from activated mast cells. In order to investigate the impact of leukotrienes on the clinical symptoms excretion of leukotriene B4 (LTB4) and leukotrienes C4-D4-E4 (cysteinyl-leukotrienes) into urine was studied in 9 patients with indolent systemic mastocytosis divided into a group with high and low intensity of symptoms and in 11 healthy volunteers. Leukotriene excretion was determined by ELISA and correlated with methylhistamine excretion. Patients with systemic mastocytosis with high and low intense symptoms showed significantly higher urinary excretion of cysteinyl-leukotrienes than controls. There was a positive correlation of cysteinyl-leukotriene excretion and urinary methylhistamine excretion. LTB4 excretion was also significantly increased in patients with systemic mastocytosis compared to healthy volunteers. No correlation of urinary LTB4 excretion with urinary methylhistamine was observed. The present study demonstrates that urinary excretion of LTB4 and cysteinyl-leukotrienes LTC4-D4-E4 is clearly enhanced in indolent systemic mastocytosis Hence, determination of leukotriene excretion into urine can be used as a tool in the diagnostic and in the therapeutic monitoring of systemic mastocytosis.

Modern enteroscopic interventions and characterization of nonmalignant postsurgical biliary anastomosis by double-balloon endoscopy.

BACKGROUND: Endoscopic access to strictured biliodigestive anastomoses often is difficult and may require percutaneous transhepatic biliary drainage or reoperation. METHODS: Push- or push-and-pull enteroscopy was used to diagnose disease and treat 24 postsurgical patients with suspected strictured biliodigestive anastomosis. Endoscopic retrograde cholangiography and biliary interventional procedures were used. Endoscopic accessibility, diagnosis of disease, therapeutic success, and complication rates were investigated at a single tertiary university gastroenterology center. RESULTS: Push enteroscopy reached biliary enteroanastomoses in 5 of the 24 patients (20.8%), whereas push-and-pull enteroscopy found choledocho- or hepaticojejunostomies in 17 of the remaining 19 postsurgical patients (89.4%). In all, successful enteroscopic intervention was achieved for 21 of the 24 patients (87.5%), whereas only 3 patients had to undergo percutaneous cholangiodrainage (12.5%). Cicatricially changed biliodigestive anastomoses were found in 14 of 21 patients (66.6%) including a mucosal type stricture in 7 patients (50%), an intramural type stricture in 5 patients (35.7%), and a ductal type stricture in 2 patients (14.2%). The remaining seven patients (33.3%) were normal. Enteroscopic interventions at strictured biliodigestive anastomosis included ostium incision for 8 (57.1%) and endoprosthesis insertion for 13 (92.8%) of the 14 patients, with prompt resolution of cholestasis and cholangitis. The major complications for the 24 patients involving 68 double-balloon enteroscopy (DBE) examinations comprised 2 perforations (8.3% per patient), 1 mild peritonitis (4.1%), and 1 cholangitis (4.1%), whereas minor complications were experienced by up to 20.8% of the patients. CONCLUSIONS: Modern interventional enteroscopy yields a high rate of successful interventions for strictured biliodigestive anastomosis, requires ostium incision for mucosal and intramural types of strictures, and helps to reduce percutaneous approaches.

Efficacy of contrast-enhanced US versus CT or MRI for the therapeutic control of percutaneous radiofrequency ablation in the case of hepatic malignancies.

PURPOSE: The goal of this study was to assess the informative value of contrast-enhanced ultrasound after radiofrequency ablation (RFA). Patients who had undergone RFA of malignant liver tumors were followed up with contrast-enhanced sonography (CEUS), computed tomography (CT) and/or magnetic resonance tomography (MRI), and the outcomes were compared. MATERIALS AND METHODS: 76 patients undergoing 194 RFAs for 118 hepatic neoplasms (n = 55 HCC, n = 63 metastases) in the course of a 7-year period were examined post-interventionally using CEUS and CT or MRI. During follow-up (gold standard of evaluation), contrast agent rim accumulations with a diameter greater than 5 mm and a growth rate of at least 25 % were counted as a recurrence. RESULTS: CEUS-CT comparison group: A total of 65 scan pairs were compared. In 54 cases (83.1 %) the findings were the same with either method. In 7 cases (10.8 %) CEUS confirmed the correct diagnosis, and in 2 cases (3.1 %) only CT was correct. In 2 cases (3.1 %) both methods yielded incorrect results. Diagnostic accuracy (DA): CEUS 93.8 %, CT 86.2 %. CEUS-MRI comparison group: In 23 cases (88.5 %) of a total of 26 scan pairs, the findings were the same for both CEUS and MRI. In 3 discordant cases only CEUS confirmed the correct diagnosis (3 cases, 11.5 %). Diagnostic accuracy DA (n = 26): CEUS 100 %, MRI 88.4 %. CONCLUSION: CEUS performs equally to CT and MRI in the follow-up of patients treated for liver tumors by RFA.

[38 year-old patient with suspected congenital hormonal dysfunction]. / 38-jähriger Patient mit Verdacht auf eine angeborene hormonelle Störung.

We present the case of a patient with suspected congenital hypopituitarism first diagnosed at the age of 38 years. Despite partial insufficiency of all pituitary-regulated hormonal axes, the patient never suffered from severe health problems. However, the patient was disfigured, and his intellectual and physical capacities were clearly impaired. The initiation of a hormone replacement therapy with hydrocortisone and thyroid hormones is essential in such a patient, but the substitution of sex hormones can create ethical problems.

[33-year-old male patient with recurrent syncopes and orthostatic hypotension]. / 33-jähriger Patient mit rezidivierenden Synkopen und orthostatischer Hypotension.

We describe the case of a 33 year old male patient with severe orthostatic hypotension, which was at times even in upright (sitting) position not tolerated, thus leading to complete immobilisation. The diagnostic measurements pointed to the group of primary autonomic degenerative disorders, the so-called "synucleinopathies". The clinical presentation und laboratory values confirmed the diagnosis of "pure autonomic failure". Finally, we describe the differential diagnosis of autonomic dysfunction.

Mice lacking cannabinoid CB1-, CB2-receptors or both receptors show increased susceptibility to trinitrobenzene sulfonic acid (TNBS)-induced colitis.

This study was performed to assess whether mice lacking the cannabinoid receptor CB1, CB2 or both receptors show increased susceptibility to TNBS colitis in comparison to wildtype mice. Previously, activation of CB1 and CB2 receptors showed attenuation of TNBS colitis in mice. The aim of the study was to investigate the susceptibility of three mouse strains CB1-, CB2- and CB1+2 double knockout mice in the model of TNBS colitis. The different knockout mice were given each a single enema with TNBS 7 mg, volume 150 microl (in 50% ethanol solution) on day 1. Control group (C57BL/6 mice) received the same concentration of TNBS enema and each strain received vehicle application of 150 microl 50% ethanol solution. After a 3-day period, the animals were sacrificed and their colon excised. A scoring system was used to describe macroscopical and histological changes. Messenger RNA-expression of TNF-alpha and IL-1beta as pro-inflammatory markers was measured by RT-PCR. All three knockout strains showed increased susceptibility to TNBS colitis quantified by macroscopical and histological scoring systems and pro-inflammatory cytokine expression in comparison to the TNBS control group (wild type C57BL/6 animals). Mice lacking the CB1-, CB2-receptor or both receptors showed aggravation of inflammation in the model of TNBS colitis. Lacking of both cannabinoid receptors did not result in potentiation of colitis severity compared to lacking of each CB1 or CB2, respectively. These results suggest that the endocannabinoid system may have tonic inhibitory effects on inflammatory responses in the colon.

[A comparative study of the hepatic transit time (HTT) of different ultrasound contrast agents in patients with liver metastases and healthy controls]. / Vergleich der hepatischen Transitzeit (HTT) verschiedener Ultraschallkontrastmittel (USKM) bei Patienten mit Lebermetastasen und gesunden Probanden.

PURPOSE: Liver metastases lead to a shortening of the HTT of an echo enhancer. Studies using SonoVue™ also showed a shortening of the HTT in healthy controls. Hence the HTT depends on the applied contrast agent. We examined whether the HTT of SonoVue™, Luminity™ und Levovist™ is useful to discriminate between patients with and without liver metastases. MATERIALS AND METHODS: We compared the arteriovenous HTT of Levovist™, Sonovue™ und Luminity™ in 20 patients with liver metastases and in 15 controls. An Acuson Sequoia™ ultrasound system was used. The HTT results from the difference of the arrival time of the microbubbles in the hepatic artery and a hepatic vein. RESULTS: Using Levovist™ six patients and three controls had to be excluded from further analysis. The arrival time was undetectable. The mean HTT values in healthy controls were: Levovsit™ 14.75 sec (SD ± 2.53 sec), SonoVue™ 9.27 sec (SD ± 2.41 sec) and Luminity™ 9.2 sec (SD ± 2.34 sec). In patients the mean HTT values were: Levovist™ 9.89 sec (SD ± 1.04 sec), SonoVue™ 6.28 sec (SD ± 2.41 sec) and Luminity™ 6.33 sec (SD ± 1.37 sec). Using a cut off of 8 sec for SonoVue™ and Luminity™, the sensitivity to exclude liver metastases was 75% and 80%. CONCLUSION: The mean HTT values of all contrast agents were shorter in patients. Levovist™ showed a longer HTT in patients and controls than Luminity™ and SonoVue™. Levovist™ showed the best separation between patients and controls but some patients and controls had to be excluded. The HTT could still be a useful tool to exclude liver metastases but the HTT depends on the contrast agent and the applied contrast technique.

Clinical significance of lymphoid hyperplasia of the lower gastrointestinal tract.

Lymphoid hyperplasia of the intestine has been associated with multiple diseases and symptoms. This study was undertaken to analyze the number and topographical distribution of the lymphoid follicles. A total of 302 adult consecutive patients were enrolled when they underwent elective colonoscopy. Standardized pictures from terminal ileum and colon were taken using video colonoscopes. In each picture, the number, size, and mucosal elevation of lymphoid follicles were analyzed in relation to histological and immunological findings and medical history. Lymphoid hyperplasia was found to be most extensive in the terminal ileum and cecum. Patients with untreated gastrointestinally mediated allergy (GMA) showed the highest number of lymphoid follicles per visible field in the terminal ileum ( P < 0.001) and cecum ( P = 0.003) vs. the control group. Patients with infectious colitis also showed a high number of lymphoid follicles per endoscopic visible field in the transverse colon ( P = 0.020). The presence of lymphoid hyperplasia is a frequent finding during colonoscopy. It may indicate an enhanced immunological mucosal response to antigenic stimulation such as GMA or infection.

[Unexplained weight gain in a 41-year-old woman]. / Unklare Gewichtszunahme bei einer 41-jährigen Frau.

A 41-year-old female was admitted to our clinic due to weight gain and facial edema. The patient also reported hair loss, amenorrhea and the formation of striae. The laboratory diagnostics ensured the diagnosis of Cushing's syndrome. Unfortunately, the patient was among the 5-10% of patients in whom neither laboratory testing nor imaging revealed the source of the cortisol excess. Due to the dramatic decrease of her general condition, and the appearance of hypertension and diabetes mellitus we chose to refer the patient to bilateral minimally invasive adrenalectomy. The advantage of this therapeutic approach is, that it is a definitive treatment that provides immediate control of hypercortisolism. As disadvantage, the resultant permanent hypoadrenalism requires a lifelong glucocorticoid and mineralocorticoid replacement therapy. Furthermore, given that the problem was caused by occult pituitary microadenoma, Nelson's syndrome has to be considered. As only one adrenal could be excised due to technical reasons, the underlying pathology is thus not solved. In spite of this, the patient's general condition improved dramatically without need for replacement therapy. As the mortality of patients with persistent moderate hypercortisolism is increased 3,8- to 5 fold, mainly due to cardiovascular reasons, thorough surveillance for signs of recurrence is mandatory to be ready for quick intervention.

Gender-based differences in drug prescription: relation to adverse drug reactions.

BACKGROUND/AIM: The female gender appears to suffer from more adverse drug reactions (ADRs) than the male gender. So far, there has been no epidemiologic study analyzing gender-based differences in drug prescribing and its ADR risks. The aim of the present study was to establish a drug risk stratification adjusted to age, number of prescriptions and drug classes with respect to gender differences based on intensive data acquisition methods. METHOD: A prospective multicenter study was conducted in several departments in Germany and Israel (pediatrics, medicine and geriatrics) enclosing 2,371 inpatients. RESULTS: A total of 25,532 drug prescriptions during hospitalization were evaluated. At least 1 ADR was found in 774 patients (32.6%). Drugs for the cardiovascular system, nervous system, alimentary tract and musculoskeletal system were prescribed most often in females. The following drug classes led significantly more often to ADRs in women as compared to men: alimentary tract (OR 0.5; p = 0.0002), cardiovascular system (OR 0.72; p = 0.0140), musculoskeletal system (OR 0.31; p = 0.0004) and nervous system (OR 0.62; p = 0.0023). After adjustment to age, total number of prescriptions and drug class, only anti-infectives (antibacterials) and musculoskeletal system (anti-inflammatory) drugs stand out as causing more ADRs in women. CONCLUSION: Antibacterials and anti-inflammatory agents cause more ADRs in females as compared to males.

Liver function under interferon/ribavirin therapy of chronic hepatitis C.

BACKGROUND: Quantitative testing of liver function (QTLF) is one way to show the efficacy of antiviral treatment of Hepatitis C. Data on liver function in patients with chronic Hepatitis C during antiviral therapy are lacking. We therefore investigated if and to what extent antiviral therapy influenced quantitative testing of liver function (QTLF). METHODOLOGY: One hundrend seven patients with chronic Hepatitis C (genotype 1) were treated with pegylated-interferon 2alpha/ribavirin for 48 weeks. Quantitative testing of liver function, including aminopyrine breath test (ABT), galactose elimination capacity (GEC), sorbitol clearance (SCl) and indocyanine green clearance (ICG) was performed before and 12 weeks after initiation of antiviral therapy. QTLF was repeated at the end of the therapy (week 48) and 6 months after therapy. RESULTS: After 3 months of treatment, 97 patients showed normal transaminases and were negative for HCV-RNA. ABT and GEC as parameters of microsomal and cytosolic liver function were reduced in all patients before therapy initiation and returned to normal values in the therapy responders after 3 months. Parameters of liver perfusion (SCl and ICG) require one year of treatment before returning to normal levels. In non-responders, QTLF did not change during therapy, in relapsers, QTLF results deteriorated after ending the therapy. CONCLUSION: All liver tests return to normal within one year after eradication of the Hepatitis C virus. Parameters measuring the liver plasma flow (SCI and ICG) require more time to become normal, most likely due to tissue remodelling processes.

Percutaneous endoscopic jejunostomy and jejunal extension tube through percutaneous endoscopic gastrostomy: a retrospective analysis of success, complications and outcome.

BACKGROUND: Percutaneous access to the jejunum is an important approach if gastrostomy feeding is not possible. OBJECTIVE: To analyze success, short- and long-term complications (STCs, LTCs) in patients with percutaneous endoscopic jejunostomy (PEJ) and jejunal access through percutaneous endoscopic gastrostomy (Jet-PEG). METHODS: A retrospective analysis of endoscopically placed PEJs and Jet-PEGs. Success rates, mortality, STCs and LTCs were investigated for risk factors comprising demographic data, underlying disease, previous surgery and experience of the endoscopist. RESULTS: 205 PEJ and 58 Jet-PEG placements were included in the study. PEJs and Jet-PEGs were successfully placed in 65.4 and 89.7%, respectively. Billroth II surgery predisposed in favor of a significantly higher success rate for PEJ placement (p = 0.014, OR = 2.27). Inexperienced examiners have a significantly (p = 0.040) lower success rate for tube insertion than examiners with a medium level of experience. STCs and LTCs occurred evenly in PEJ and Jet-PEG patients. Dislocation of the tube occurred significantly more frequently in Jet-PEG patients (33.3%, p = 0.005). Aspiration was most common for bedridden patients. CONCLUSION: PEJ has a significantly lower success rate for insertions, but fewer LTCs. The experience of the endoscopist correlates with the success rate of tube insertion.

[Spectrum and bleeding complications of sonographically guided interventions of the liver and pancreas]. / Spektrum und Blutungskomplikationen sonografisch gesteuerter Interventionen an Leber und Pankreas.

PURPOSE: Sonographically guided fine-needle punctures (p.) are considered to be a low risk procedure. Interventions with needles with a larger diameter seem to cause more complications. In search of potential complications, we examined 1923 sonographically guided interventions of the liver and pancreas in a retrospective analysis. MATERIALS AND METHODS: We examined the coherence of the kind of intervention and complications. We considered bleeding with a need for transfusion and/or a need for surgical treatment as complications. Diseases and medication increasing the probability of post-interventional bleeding were also detected. RESULTS: 1923 sonographically guided interventions in the abdomen (1800 in the liver, 123 in the pancreas) were analyzed (n = 1696 diagnostic interventions, n = 227 therapeutic interventions). Needles with diameters > 1 mm were primarily used. Drainage and radiofrequency ablation (RFA) (12 % of all interventions) were performed with devices with diameters between 2 - 3.96 mm. A need for transfusion was found in 8 / 1923 patients (0.4 %), predominantly in the first 24 h. There was no significant correlation between coagulation preventing drugs (heparin, NSAIDs, antiaggregants) and bleeding events. Patients who suffered from liver cirrhosis with a thromboplastin time of < 50 % had a higher risk of post-interventional bleeding than patients with liver cirrhosis and a thromboplastin time > 50 %. Furthermore, therapeutic interventions showed higher complication rates than diagnostic procedures. CONCLUSION: Severe bleeding complications with a need for transfusion in sonographically guided procedures are rare (0.4 %). Our results showed that liver cirrhosis with a low thromboplastin time (< 50 %) seems to be the most important risk factor for patients. Overall, sonographically guided interventions are safe and have low complication rates considering careful performance and contraindications.