Integrative medicine and health in undergraduate and postgraduate medical education.

Background and objective: Integrative Medicine and Health (IMH) is a theory-based paradigm shift for health, disease and health care, which can probably only be achieved by supplementing medical roles and competences. Definition of IMH: The definitions of the Academic Consortium for Integrative Medicineand Health 2015 and the so-called Berlin Agreement: Self-Responsibility and Social Action in Practicing and Fostering Integrative Medicine and Health Globally are used. The basic features of evidence-based Integrative Medicine and Health (EB-IMH) are based on the recommendations on EBM by David L. Sackett. Global State of Undergraduate and Postgraduate Medical Education (UG-PGME) for IMH: The USA and Canada are most advanced in the development of IMH regarding practice, teaching and research worldwide. Despite socio-cultural peculiarities, they can provide guidance for Europe and especially for Germany. Of interest here are competences for UG-PGME in IMH in primary care and in some specialist disciplines (e.g. internal medicine, gynecology, pediatrics, geriatrics, oncology, palliative care). For these specialties, the need for an interprofessional UG-PGME for IMH was shown in the early stages of development. UG-PGME for IMH in Germany: In the course of the development of the new Medical Licensure Act in Germany (ÄApprO), based on a revision of the National Competence-based Catalogue of Learning Objectives for Medicine (NKLM 2.0) and new regulations for Postgraduate Medical Education in Germany, suggestions for an extension of UG-PGME are particularly topical. To some extent there are already approaches to IMH. Old and new regulations are set out and are partly compared. As a result, some essential elements of IMH are mapped in the new ÄApprO. The new regulations for Postgraduate Medical Education do not mention IMH. Conclusion: The development of medical competences for IMH in the continuum of the UG-PGME could be supported by the coordinated introduction of appropriate entrustable professional activities (EPA) and IMH sub-competences combined with appropriate assessment.

Additive antitumour response to the rabbit VX2 hepatoma by combined radio frequency ablation and toll like receptor 9 stimulation.

INTRODUCTION: Radiofrequency ablation (RFA), a palliative therapeutic option for solid hepatic tumours, stimulates localised and systemic antitumour cytotoxic T cells. We studied how far addition of CpG B oligonucleotides, toll like receptor (TLR) 9 agonists, would increase the antitumoural T cell response of RFA in the highly aggressive VX2 hepatoma. METHODS: Rabbits were randomised to receive RFA, CpG B, their combination or no therapy. The antitumour efficacy of RFA alone or in combination with CpG B was further tested by rechallenging a separate group with intravenously injected VX2 tumour cells after 120 days. Animals were assessed for survival, tumour size and spread, and tumour and immune related histological markers after 120 days. Peripheral blood mononuclear cells were tested for tumour-specific T cell activation and cytotoxicity. Immune modulatory cytokines tumour necrosis factor α, interleukin (IL)-2/IL-8/IL-10/IL-12 and interferon γ, and vascular endothelial growth factor were measured in serum. RESULTS: Mean survival of untreated animals was 36 days, as compared with 97, 78 and 114 days for RFA, CpG and combination therapy, respectively. Compared with untreated controls, antitumour T cell stimulation/cytotoxicity increased 26/16-fold, 32/17-fold and 50/38-fold 2 weeks after RFA, CpG and combination treatments, respectively. The combination inhibited tumour spread to lungs and peritoneum significantly and prohibited new tumour growth in animals receiving a secondary systemic tumour cell injection. RFA alone induced a Th1 cytokine pattern, while IL-8 and IL-10 were only upregulated in CpG treated animals and controls. CONCLUSIONS: The combination of TLR9 stimulation with RFA resulted in a potentiated antitumour T cell response and cytotoxicity in the VX2 tumour model. Only this combination prevented subsequent tumour spread and resulted in a significantly improved survival, justifying the need for further exploration of the combination of ablative therapies and TLR9 agonists in liver cancer.

Excretion of urinary histamine and N-tele methylhistamine in patients with gastrointestinal food allergy compared to non-allergic controls during an unrestricted diet and a hypoallergenic diet.

BACKGROUND: Patients with gastrointestinal food allergy are characterised by increased production of mast cell derived mediators upon allergen contact and present often with unspecific symptoms. The aim of this study was to evaluate urinary histamine and methylhistamine excretion in patients with food allergy and to compare their values with food-tolerant controls. METHODS: In a retrospective case control study the urinary excretion parameters were analysed from 56 patients (40.9, 19 - 58 years) in whom later food challenge tests confirmed food allergy. During their diagnostic work-up urine was collected during a 12-h period under an unrestricted diet with staple foods and a hypoallergenic potato-rice-diet (each 2 days). Healthy controls underwent the same diet types to define normal excretion parameters. Urinary histamine and n-methylhistamine were determined by ELISA or tandem mass spectrometry, respectively, and were expressed as median (25 - 75% range, µg/mmol creatinine x m(2)BSA). RESULTS: During unrestricted diet urinary histamine was significantly higher in gastrointestinal food allergy than healthy controls (1.42, 0.9 - 2.7 vs 0.87, 0.4 - 1.3; p < 0.0001), while the difference between both groups became marginal during potato-rice diet (1.30, 0.7 - 2.1 vs 1.05, 0.5 - 1.5; p = 0.02). N-methylhistamine was found to be significantly elevated in gastrointestinal food allergy both during unrestricted diet (7.1, 5.0 - 11.2) and potato-rice diet (5.7, 3.7 - 8.7) compared to controls (p < 0.0001). Interestingly, urinary methylhistamine excretion (p < 0.004) and clinical symptom score (p < 0.02) fell significantly when the diet was switched from unrestricted to hypoallergenic food, but was not correlated with symptom scores. CONCLUSIONS: In gastrointestinal food allergy significantly higher levels of urine histamine and methylhistamine excretion were found under unrestricted diet, reflecting an increased secretion of histamine due to offending foods. Measurement of urinary n-methylhistamine levels may help to find out patients with increased histamine production and/or food-allergen induced clinical symptoms, respectively.

Conventional endoscopic retrograde cholangiopancreaticography vs the Olympus V-scope system.

AIM: To compare the new Olympus V-scope (VS) to conventional endoscopic retrograde cholangiopancreaticography (ERCP). METHODS: Forty-nine patients with previous endoscopic papillotomy who were admitted for interventional ERCP for one of several reasons were included in this single-centre, prospective randomized study. Consecutive patients were randomized to either the VS group or to the conventional ERCP group. ERCP-naïve patients who had not undergone papillotomy were excluded. The main study parameters were interventional examination time, X-ray time and dose, and premedication dose (all given below as the median, range) and were investigated in addition to each patient's clinical outcome and complications. Subjective scores to assess each procedure were also provided by the physicians and endoscopy assistants who carried out the procedures. A statistical analysis was carried out using the Wilcoxon rank-sum test. RESULTS: Twenty-five patients with 50 interventions were examined with the VS ERCP technique, and 24 patients with 47 interventions were examined using the conventional ERCP technique. There were no significant differences between the two groups regarding the age, sex, indications, degree of ERCP difficulty, or interventions performed. The main study parameters in the VS group showed a nonsignificant trend towards a shorter interventional examination time (29 min, 5-50 min vs 31 min, 7-90 min, P = 0.28), shorter X-ray time (5.8 min, 0.6-14.1 min vs 6.1 min, 1.6-18.8 min, P = 0.48), and lower X-ray dose (1351 cGy/m(2), 159-5039 cGy/m(2) vs 1296 cGy/m(2), 202.2-6421 cGy/m(2), P = 0.34). A nonsignificant trend towards fewer adverse events occurred in the VS group as compared with the conventional ERCP group (cholangitis: 12% vs 16%, P = 0.12; pain: 4% vs 12.5%, P = 0.33; post-ERCP pancreatitis: 4% vs 12.5%, P = 0.14). In addition, there were no statistically significant differences in assessment by the physicians and endoscopy assistants using subjective questionnaires. CONCLUSION: ERCP using the short-guidewire V-system did not significantly improve ERCP performance or patient outcomes, but it may reduce and simplify the ERCP procedure in difficult settings.

Successful interventional treatment of postoperative bile duct leakage after Billroth II resection by unusual procedure using double balloon enteroscopy.

BACKGROUND: Endoscopic treatment of advanced biliary disorders and their complications following surgical procedures is often difficult especially after Billroth II gastric resection. In such cases, endoscopic access to the papilla and neopapilla is often low, and access to the choledocho- or hepaticojejunostomy is often difficult. Thus, percutaneous cholangiodrainage or re-operation is therefore indicated when endoscopic access to the papilla failed. But both of those methods are much more invasive and more likely to be followed by complications than use of a purely endoscopic approach. CASE REPORT: The present case report describes endoscopic access to the papilla with both push enteroscopy and double-balloon enteroscopy (DBE, push-and-pull enteroscopy) in a female patient after Billroth II resection with bile leakage following cholecystectomy. Successful closure of the bile duct fistula could be achieved via an unusual abdominal-biliary-jejunal cannulation way after several attempts of modern enteroscopy and in this way re-operation was avoided. CONCLUSIONS: Modern enteroscopy by experienced investigators using push-and-pull enteroscopes can provide access to the papilla even in complex postoperative anatomic rearrangements. Push-and-pull enteroscopes offer a further option for successful cannulation of the papilla and therapeutic interventions via additional stabilization with balloons and the modern enteroscopic approach by push-and-pull enteroscopy appears to provide more patient comfort, requires less analgo-sedation and examination time and in cases with intra-abdominal drainage this external access may be used as an additional aid for exploration and intervention in complex individual cases with extremely difficult treatable bile duct injuries.

[Pulsed radiofrequency ablation using perfused needle applicators in an in vitro trial on bovine liver]. / Getaktete Dreifachapplikation mit perfundierten Nadelapplikatoren bei Radiofrequenzablation: In-vitro-Versuch an der Rinderleber.

Intermittent energy application seems to have positive effects in achieving necrotic zones. We analyzed different pulse periods (PPs) to optimize this method. A radiofrequency alternating current was delivered via a triple-needle applicator (3 cm distance of each needle) introduced into freshly procured bovine liver. The open applicator system was constantly perfused with physiological NaCl solution (3×80 ml/h, power output was constant 90 W). Radiofrequency current was fed to the individual needle in turn of varying PPs (1, 2, 5, and 7 s) over 15 min. Each experimental run comprised a total of 30 applications and temperature was recorded over time. The largest necrotic diameters were found at PP 1 s (relevant: shortest axial diameter/D in the center of the lesion: 9.27 cm, SD±0.97 cm) (PP 2 s D=8.65 cm, SD±0.95 cm, p=0.021; PP 5 s D=8.35 cm, SD±0.95 cm, p=0.001; PP 7 s D=8.18 cm, SD±0.79 cm, p=0.0001). Neither doubling the perfusion rate nor raising the concentration of the perfusion liquid led at PP 1 s to increased necrotic diameters (p=0.82). Our study shows that reducing the PP to 1 s of an open perfused intermittent radiofrequency ablation system produces significantly larger coagulation volumes in explanted liver tissue reaching necrotic diameters over 9 cm. Neither doubling perfusion rates nor higher concentrated perfusion liquid increase necrotic diameters.

Mast cell tryptase in sera of patients with Crohn's disease and mastocytosis.

INTRODUCTION: The pathogenesis of Crohn's disease is unclear, but an abnormal immune response seems to play an important role. This study investigated whether serum tryptase could be shown in Crohn's disease as a marker of disease. MATERIALS AND METHODS: Mast cell tryptase was detected in sera of 48 patients with active Crohn's disease, 31 patients with inactive Crohn's disease, 17 patients with mastocytosis, and 50 controls. Tryptase detection was carried out by UniCap System. Tryptase levels are given as U/l x m2 body surface area to overcome variations of body weight, height, etc. between malnourished and normal persons. RESULTS: Serum tryptase levels (U/l x m2 body surface area) of controls were 2.4+/-1.0, of patients with Crohn's disease 2.5+/-2.0. In contrast, serum tryptase values were significantly increased in untreated patients with mastocytosis (21.19+/-18.55). DISCUSSION: Mast cell tryptase is not elevated in sera of Crohn's disease. It might thus be speculated that this highly mast cell associated mediator might only contribute to local symptoms of Crohn's disease such as diarrhea, abdominal pain, etc., but not to its systemic inflammatory effects (Th 1 cytokine pattern). Tryptase may be well used for the screening of patients with mastocytosis.

Alterations of taste perception in Crohn's disease and their dependency on disease activity and nutritional behavior.

BACKGROUND: The pathogenesis of Crohn's disease (CD) is unknown. Besides immunoregulatory, genetic and environmental aspects, a nutritional impact is also encountered. Whether taste perception exerts any influence on an increased consumption of carbohydrates is unknown. OBJECTIVE: To evaluate nutritional habits and taste perception in CD patients, either in active or inactive disease stages. DESIGN: A prospective study was performed with 31 active and 27 inactive CD patients, and 30 age and sex-matched healthy subjects. Nutritional behavior was determined using an extensive optical nutrition questionnaire and taste perception was assessed by a 3-drop method with exceeding dilution tests. RESULTS: Active and inactive CD patients exhibited a significant increased taste threshold for the detection of all solutions (bitter: P=0.0012; salty: P=0.0198; sour: P=0.0021; and sweet: P=0.0208). For recognition, the determination of bitter solution (P=0.0014) was significantly reduced in CD patients compared with healthy subjects. No impact of clinical or objective parameters of inflammation on taste perception could be established. The consumption of refined sugar in CD patients was higher than in healthy subjects, though not significant. CONCLUSIONS: An increased taste threshold for the detection of all 4 taste qualities in active and inactive CD patients suggests a systemic pathogenesis, such as an inflammation of the oral cavity, as a manifestation of CD. In this study, changes in taste threshold were not associated with altered sugar consumption.

Experiences with a long-term treatment of a massive gluteal acne inversa with infliximab in Crohn's disease.

BACKGROUND: In 40% of all cases of Crohn's disease fistulas emerge during the course of disease. Nevertheless, acne inversa has to be taken into account as an infrequent differential diagnosis. Infliximab as an antibody against the pro-inflammatory mediator TNF-alpha is active in cases of acute Crohn's disease, concomitant fistulas and cutaneous manifestations. CASE REPORT: We report on the case of a 54-year-old patient suffering for five years from a severe suppurative fistuling cutaneous disease concomitant to Crohn's disease. At the start of treatment the histological findings of a specimen presented chronically fibrosing lymphoplasmacellular dermatitis with both a very high number of plasma cells and a burrow-like fistula system. Due to superinfection the treatment was at first based on the administration of intravenous and oral doses of antibiotic agents, followed by a treatment course of 14 months with methotrexate and seven applications of infliximab. During the Crohn's disease, which was accompanied by persisting concomitant discomforts, an extensive surgical sanitation of the fistulous tracts was performed. Acne inversa was diagnosed in the subsequent histological analysis of the operative specimen. CONCLUSIONS: Acne inversa is a very rare cutaneous disease. Several case reports describe the successful treatment of acne inversa concomitant to Crohn's disease using anti-TNF-alpha-antibodies. The long-term course of the case presented here shows that the non-response to infliximab might be caused by both the long duration and the distinct grade of seriousness of the acne inversa.

Ghrelin and obestatin levels in type 2 diabetic patients with and without delayed gastric emptying.

Alterations in the neurohumoral regulation of the upper intestine may change rhythmicity and pattern of ghrelin and obestatin, the latter presumably antagonizing ghrelin effects. Five nongastroparetic diabetic patients and five with gastroparesis were investigated. Over 390 min including breakfast and lunch, ghrelin was significantly lower in patients with gastroparesis compared with in those without (P = 0.015). Ghrelin subsequent to lunch decreased significantly (P = 0.011) in patients without gastroparesis, but not in gastroparetic patients (P = 0.669). Obestatin was similar in both groups and unchanged. No significant differences in ghrelin-to-obestatin ratio were observed (P = 0.530). Loss of rhythmicity in the ghrelin levels of gastroparetic diabetics highlights the importance of integrity of the neurohumoral-intestinal axis. Stable diurnal obestatin levels do not support the concept of interaction between ghrelin and obestatin in terms of regulation of food intake and gastric emptying.

Helicobacter pylori as a protective factor against food allergy.

BACKGROUND: There is some evidence that Helicobacter pylori (Hp) infection may protect against asthma and allergy. The aim of the present study was to analyse the prevalence of Hp infection in adults with proven food allergy and to compare it with that in appropriate healthy controls. In addition, the effects of infection with Hp on urinary excretion of N-tele-methylhistamine and production of IgE and allergy mediators such as eosinophilic cationic protein (ECP) and mast cell tryptase, were assessed. MATERIAL/METHODS: Hp infection, the production of IgE and several allergy mediators and mucosal expression of interleukin-4 were measured in 42 patients with food allergy and compared with those in 20 healthy subjects. RESULTS: The prevalence of Hp infection among adult food allergy patients was 33.3% and it was significantly lower than that in the control group (40%). The excretion of urinary N-tele-methylhistamine was higher in food allergy patients than in healthy controls. In food allergy patients with Hp infection, the serum ECP was significantly lower than in food allergy patients without Hp infection. The serum IgE level was significantly higher in food allergy patients infected with Hp than in food allergy patients without Hp infection. CONCLUSIONS: We conclude that: 1) Hp infection is associated with a decreased risk for food allergy; 2) presence of Hp in food allergy patients has ameliorating effect on the production of allergy mediators such as ECP and mast cell tryptase and 3) Hp infection appears to be a protective factor against food allergy.

Bile acids induce overexpression of homeobox gene CDX-2 and vascular endothelial growth factor (VEGF) in human Barrett's esophageal mucosa and adenocarcinoma cell line.

OBJECTIVE: Barrett's esophagus (BE) is an acquired precancerous condition that develops from mucosal injury incurred after chronic gastroesophageal acid and bile reflux. The mechanism of progression of carcinogenesis in BE is still not fully understood. Recently, the role of bile acids and the homeobox gene transcription factor CDX-2 has been suggested in the pathogenesis of BE. The aims of the present study were 1) to compare the mRNA and protein expression of CDX-2 in biopsies obtained from patients with BE and normal squamous epithelium and 2) to study the effect of two different bile salts, ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA), on the mRNA expression of CDX-2 and vascular endothelial growth factor (VEGF) in Barrett's the adenocarcinoma cell line (OE-33). MATERIAL AND METHODS: CDX-2 expression was measured in Barrett's mucosa and normal esophageal mucosa obtained from 15 patients with BE histologically diagnosed by immunohistochemistry, Western blot, and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). In in vitro experiments, OE-33 cells were incubated with DCA (100 microM) and UDCA (100 microM) in neutral and shortly acidified media (pulse acidification). The expression of CDX-2 and VEGF was assessed by quantitative RT-PCR. RESULTS: Both mRNA and protein expression of CDX-2 were significantly up-regulated in Barrett's mucosa as compared to normal esophageal mucosa. In neutral medium, OE-33 cells showed an increase in CDX-2 expression after incubation with DCA or UDCA. After short acidification of the medium, expression of CDX-2 in OE-33 cells was significantly higher than that in cells incubated in neutral pH. The addition of DCA and UDCA did not cause any further alteration in CDX-2 expression. In neutral and acidified medium, VEGF mRNA expression was only significantly up-regulated by DCA, but not by UDCA. CONCLUSIONS: Bile acids, especially in acidic medium, increase expression of CDX-2. DCA appears to be a stronger stimulant of the expression of VEGF than UDCA in the Barrett's carcinoma cell line, indicating a stronger carcinogenic potential of this bile salt.

Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases.

AIM: To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation (RFA). METHODS: Six Patients with liver metastases of colorectal cancer and 6 with hepatocellular carcinoma (HCC) underwent RFA. Blood was sampled before, 4 and 8 wk after RFA. Test antigens were autologous liver and tumor lysate obtained from each patient by biopsy. Peripheral T cell activation was assessed by an interferon gamma (IFNgamma) secretion assay and flow cytometry. T cells were double-stained for CD4/CD8 and IFNgamma to detect cytotoxic T cells. The ratio of IFNgamma positive and IFNgamma negative T cells was determined as the stimulation index (SI). To assess cytolytic activity, T cells were co-incubated with human CaCo colorectal cancer and HepG2 HCC cells and release of cytosolic adenylate kinase was measured by a luciferase assay. RESULTS: Before RFA SI was 0.021 (+/- 0.006) for CD4(+) and 0.022 (+/- 0.004) for CD8(+) T cells against nonmalignant liver tissue and 0.018 (+/- 0.005) for CD4(+) and 0.021 (+/- 0.004) for CD8(+) cells against autologous tumor tissue. Four weeks after RFA SI against tumor tissue increased to 0.109 (+/- 0.005) for CD4(+) and 0.11 (+/- 0.012) for CD8(+) T cells against HCC, and to 0.115 (+/- 0.031) for CD4(+) and 0.15 (+/- 0.02) for CD8(+) cells for colorectal metastases (P < 0.0001). No increased SI was observed with nonmalignant tumor tissue at all time points. Before RFA cytolytic activity against the respective cancer cells was low with 2.62 (+/- 0.37) relative luminescence units (RLU), but rose more than 100 fold 4 and 8 wk after RFA. Spontaneous release was < 2% of maximum release in all experiments. CONCLUSION: Patients with primary and secondary tumors of the liver show a significant tumor-specific cytotoxic T-cell stimulation with a dramatically increased tumor specific cytolytic activity of CD8(+) T cells after RFA.

Insulin resistance and other metabolic aspects of the obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is usually associated with conditions known to increase insulin resistance and cardiovascular risk, such as hypertension, obesity, and diabetes. Thus, investigating whether obstructive sleep apnea itself is an independent risk factor for increased insulin resistance and whether continuous positive airway pressure treatment (CPAP) might improve insulin sensitivity brings up considerable methodological problems. Even if insulin sensitivity improves, it is hard to distinguish between an effect of CPAP treatment, e.g. in the reduction of nocturnal sympathetic activity caused by the sleep disturbance, and concomitant factors, such as weight loss. Two recent investigations were able to prove that OSAS is an independent risk factor for insulin resistance: one study in a statistical approach, the other by demonstrating a significant improvement of insulin sensitivity already two days after onset of CPAP therapy, thus clearly ruling out such confounding factors as changes in lifestyle or weight loss. However, it is still not clear if this improvement in insulin sensitivity is accompanied by an improvement in the usually elevated cardiovascular risk of patients with OSAS. Since a decrease in elevated markers of subclinical inflammation--nowadays regarded as the main culprit of cardiovascular complications and atherosclerosis--such as Interleukin-6 and C-reactive protein has been reported during CPAP therapy, and since an improvement in left ventricular function and a decrease in blood pressure were also reported under CPAP treatment, there are several good reasons to assume an improvement in metabolical function in OSAS patients due to CPAP treatment.

Activation of NFkappaB represents the central event in the neoplastic progression associated with Barrett's esophagus: a possible link to the inflammation and overexpression of COX-2, PPARgamma and growth factors.

The molecular mechanisms responsible for the progression of malignant transformation in Barrett's esophagus (BE) are still poorly understood. This study was undertaken (1) to investigate the gene and protein expression of cyclooxygenase-2 (COX-2), peroxisome proliferator-activated receptor-gamma (PPARgamma), interleukin-8 (IL-8), hepatocyte growth factor (HGF), gastrin, and its receptor (CCK-2) in the Barrett's epithelium; (2) to analyze the activity of NFkappaB in Barrett's esophagus with low-grade dysplasia; and (3) to assess the effects of PPARgamma ligand (ciglitazone) and gastrin on cell proliferation in the cell line derived from esophageal adenocarcinoma (OE-33). COX-2, PPARgamma, IL-8, HGF, gastrin, and CCK-2 expression levels relative to the control gene encoding GAPDH were analyzed by RT-PCR and Western blot in specimens of BE with low-grade dysplasia (n = 20) and compared with that in the normal squamous esophageal mucosa from the middle portion of the esophagus (n = 20). In vitro experiments included the incubation of cell line OE-33 with ciglitazone (1-15 microM) and gastrin (100 nM). NFkappaB activity in biopsies specimens was measured by highly sensitive ELISA. COX-2, PPARgamma, IL-8, HGF, gastrin, and CCK-2 expressions were significantly increased in BE compared with normal squamous esophageal mucosa. NFkappaB activity was significantly upregulated in BE. Ciglitazone inhibited cell proliferation of OE-33 cells as assessed by BrdU and this effect was attenuated partly by gastrin. (1) COX-2, PPARgamma, HGF, gastrin, and its receptor are significantly upregulated in BE, suggesting a possible role for these factors in Barrett's carcinogenesis; (2) the increased NFkappaB activity is probably linked to increased IL-8 and COX-2 expression; and (3) PPARgamma ligands might be useful as a new therapeutic option in the prevention and treatment of Barrett's carcinoma.

Resistin levels in patients with obstructive sleep apnoea syndrome--the link to subclinical inflammation?

BACKGROUND: The role of resistin, a "new" white adipose tissue hormone, still needs to be established. Its linkage to insulin sensitivity and body mass was controversial in previous studies. MATERIAL/METHODS: Twenty obese patients (BMI: 32.1+/-6.9 kg/m2 ) with obstructive sleep apnoea syndrome (OSAS) (Apnoea-Hypopnoea Index: 48.6+/-19.1, underwent measurements of resistin, interleukin-6 (IL-6), intracellular adhesion molecule-1 (ICAM-1), CRP and the insulin sensitivity index (ISI) by hyperinsulinaemic euglycaemic clamp before, 2 days and 2 months after onset of CPAP treatment. RESULTS: Resistin remained unchanged during CPAP-therapy and was negatively correlated to ISI (r=-0.359; p=0.006), the latter was significantly improved by CPAP (p<0.001). In a correlation matrix, IL-6 and ICAM-1 were significantly (p=0.001) correlated to resistin (p=0.614 and 0.427). Changes of inflammatory markers under CPAP treatment were related to AHI, as well as resistin changes. CONCLUSIONS: In agreement with previous investigations, we could only demonstrate a weak linkage between ISI and resistin. However, at least in obese patients with OSAS, there is a close relation to subclinical inflammation (IL-6) and endothelial activation (ICAM-1).

Hepatic transit time of an echo enhancer: an indicator of metastatic spread to the liver.

OBJECTIVE: Can sonographic measurements of the transit time of an echo enhancer from the hepatic artery to the hepatic vein discriminate between patients with and without liver metastases? METHOD: The hepatic transit time (hepatic artery to hepatic vein delay) of an echo enhancer (Optison) was measured in pulse inversion mode on the basis of time intensity curves (TIC) in patients with gastrointestinal tumours with proven liver metastases and in patients without liver metastases. RESULTS: Sixty-four patients (46 males, 18 females, mean age 61 +/- 13 years) were admitted to the study. Fourteen patients had metastatic growth in the liver with a primary tumour in situ (group A). Fourteen patients had liver metastases following primary tumour resection (group B). Twenty-eight patients had a known primary tumour but no liver metastases (group C), and eight patients had neither liver symptoms nor a primary tumour (group D). The mean hepatic transit time in patients with liver metastases was 6.6 +/- 1.8 s in group A and 6.7 +/- 1.7 s in group B, whereas in patients without liver metastases it was significantly longer; namely, 15.7 +/- 4.4 s in group C and 15.0 +/- 2.0 s in group D (P < 0.001). The transit times in all patients with liver metastases were < or = 10 s, while in all patients without metastases except for four the times were > or = 12 s and one of the four had already developed liver metastases on early follow-up. CONCLUSIONS: Measurement of the hepatic transit time permits discrimination of patients with and without liver metastases.