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Das Ziel von HyAdd3D ist es, mit neuer Anlagentechnik komplexe Bauteile additiv zu fertigen und gleichzeitig den Anforderungen einer Multimaterialfertigung gerecht zu werden. Das Projekt umfasst die Entwicklung einer hybriden Verfahrenslösung, welche in der Lage ist, neue Materialien mit funktionalen Zusatzstoffen zu verarbeiten. Der Beitrag beschreibt den HyAdd3D-Ansatz und beleuchtet den aktuellen Projektstand. Abschließend werden die aktuellen Ergebnisse zusammengefasst und ein Ausblick auf die folgenden Entwicklungsschritte gegeben. The aim of HyAdd3D is to create complex additive manufactured components with novel equipment technology whilst simultaneously fulfilling the requirements of the multi-material manufacturing process. The project engages in developing a hybrid procedure solution that is able to process new materials with functional additives. This article describes the HyAdd3D approach and examines the current project status. All relevant findings are summarized to conclude and further developing measures are explained.

Purpose Surgical site infection (SSI) occurs in up to 25% of patients after elective laparotomy. We aimed to determine the effect of SSI on healthcare costs and patients’ quality of life. Methods In this post hoc analysis based on the RECIPE trial, we studied a 30-day postoperative outcome of SSI in a single-center, prospective randomized controlled trial comparing subcutaneous wound irrigation with 0.04% polyhexanide to 0.9% saline after elective laparotomy. Total medical costs were analyzed accurately per patient with the tool of our corporate controlling team which is based on diagnosis-related groups in Germany. Results Between November 2015 and May 2018, 456 patients were recruited. The overall rate of SSI was 28.2%. Overall costs of inpatient treatment were higher in the group with SSI: median 16.685 €; 19.703 USD (IQR 21.638 €; 25.552 USD) vs. median 11.235 €; 13.276 USD (IQR 11.564 €; 13.656 USD); p p = 0.001) and costs on the surgical ward (median 8.404 €; 9.924 USD with SSI vs. median 4.690 €; 5.538 USD without SSI; p p p = 0.52). Conclusion SSI after elective laparotomy increased hospital costs substantially. This is an additional reason why the prevention of SSI is important. Overall costs for intraoperative wound irrigation with saline were comparable with polyhexanide.

Das Projekt „NextFactory“ kombiniert verschiedene Technologien mit dem Ziel, ein neuartiges Produktionsmittel zur Herstellung mikromechatronischer Systeme als funktionale Prototypen oder in kleinsten Stückzahlen zur Verfügung zu stellen. Der Fachartikel gibt einen Überblick zu dem produktionstechnischen Ansatz sowie zur Vision des Projekts und beleuchtet anschließend den aktuellen Projektstand. Zuletzt werden die aktuellen Ergebnisse zusammengefasst und ein Ausblick auf die kommenden Entwicklungsschritte gegeben. The NextFactory project is based on different technological pillars to innovate the production technology for functional prototypes and small lot sizes of micro-mechatronic systems. This paper presents the vision of the project, followed by a closer look on the current status of the technological developments and concludes with the presentation of preliminary results and an outlook on the next development steps.

There is no general consensus regarding the ideal timing of surgery in patients with refractory ulcerative colitis (UC). Decision-making and timing of restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is influenced by treating physicians and patients themselves. The aim of this study was to determine whether or not patients would have preferred the operation to be performed earlier, at the same time, or at a later point of time and to determine the reasons for their preference. Clinical data of 193 patients with UC who have undergone IPAA were documented in a prospective database at our institution between 2004 and 2015. From this database, 190 patients were identified and a standardized custom-made questionnaire was mailed for follow-up survey. Patients who did not respond were called by telephone and encouraged to complete the questionnaire. One hundred nine questionnaires were eligible for analysis (57.4%). Average time between diagnosis and surgery was 11.2 ± 10.8 years (mean ± SD). Indications for surgery were refractory disease (70.6%), colitis-associated colorectal cancer (11.0%), high-grade dysplasia or stenosis (11.9%), and septic complications of UC (6.4%); 39 of 77 patients (50.6%) with refractory UC reported to have preferred their operation to be carried out earlier as it was actually performed (16.8 ± 11.9 months). Refractory course of the disease was identified as a predictor for a retrospectively desired earlier surgical approach (p = 0.014). A substantial proportion of patients felt that they should have undergone surgery earlier than actually performed. It appears that timing of the decision to undergo surgery is suboptimal. This situation may be improved by earlier surgical consultation in the course of the disease.

Background: Crohn's disease (CD) as one of the major entities of chronic inflammatory bowel diseases can affect all segments of the gastrointestinal tract but occurs most often in the small bowel, the terminal ileum, the colon, and the rectum. Typical symptoms include tiredness, lower abdominal pain, fever, and diarrhea, which are initially treated by conservative measures. Most patients will eventually develop complications such as fistulas, abscesses, or strictures. Surgery is often unavoidable in these cases. Methods: This review considers studies on the treatment of CD, published from 1979 up to now. The literature regarding the course, complications, and surgical therapy of CD was reviewed. Searches were performed in PubMed, using the following key words: CD, surgery, immunosuppression, guidelines, malnutrition as well as appropriate sub-items. In most cases the literature is limited to detailed information on specific therapeutic or diagnostic topics. Moreover, many studies are designed retrospectively and with a small number of patients. Additionally, our long-standing experience with patients suffering from CD is taken into consideration in this review. Results: There is a wide variety of indications for surgery in CD which includes complications like strictures, fistulas and abscess formation, neoplasia, or refractoriness to medical therapy. The risk of developing complications is about 33% after 5 years, and 50% after 20 years. Furthermore, one-third of CD patients need surgical therapy within the first 5 years of diagnosis. The treatment requires close cooperation between gastroenterologists and surgeons. When indicated, surgery should be performed in a ‘conservative' fashion, i.e. as limited as possible, in order to achieve the required result and to avoid small bowel syndrome. Conclusion: This article provides a complete overview of indications and specific surgical treatment in patients with CD. Surgery is typically indicated when complications of CD occur. An interdisciplinary collaboration is necessary in order to ensure optimal indications and timing of surgery. This is of paramount importance to achieve the ultimate goal, i.e. a good quality of life of the patients.

Die Koloproktomukosektomie (CPM) gilt als Verfahren der Wahl fur die chirurgische Therapie der Colitis ulcerosa (CU). Bei ausgepragter Immunsuppression (IS) wird dabei haufig ein dreizeitiges (3Z) Vorgehen gewahlt, bei dem eine subtotale Kolektomie der ileoanalen Pouchanlage (IPAA) und abschliesenden Ileostomaruckverlagerung vorangestellt wird. Im Vergleich zum zweizeitigen (2Z) Vorgehen wird dadurch eine Reduktion der perioperativen Komplikationen erwartet, allerdings ist ein zusatzlicher stationarer Aufenthalt und operativer Eingriff erforderlich. Ziel der hier vorliegenden Studie war es, die beiden Vorgehensweisen im Hinblick auf das klinische Outcome nach IPAA zu vergleichen, um die tatsachliche Effektivitat dieser beiden Konzepte uberprufen zu konnen. Zwischen 1997 und 2010 wurden insgesamt 225 Patienten mit IPAA operiert und einem 2Z oder 3Z Verfahren unterzogen. Zur Erfassung des klinischen Outcomes wurde der operative Schritt der Pouchanlage und IPAA gewertet. Die Datenerhebung erfolgte im Rahmen einer prospektiven Studiendokumentation. Von 225 Patienten mit CPM mussten 66 aufgrund einer anderen Diagnose als CU (FAP, Colitis indeterminata, Morbus Crohn) sowie Patienten mit definitiver ILS-Anlage ohne Moglichkeit oder Wunsch einer IPAA (n = 54) ausgeschlossen werden. Untersucht wurden 71 Patienten mit einem 2Z (w = 30, m = 41) und 34 Patienten mit einem 3Z Vorgehen (w = 21, m = 13). Das 3Z Vorgehen wies im Vergleich zum 2Z eine kurzere Operationszeit (246 vs. 296 min; p

Coloproctomucosectomy (CPM) with ileopouchanal anastomosis (IPAA), as the procedure of choice for surgical management of ulcerative colitis (UC), is commonly performed either as a 2- or 3-staged procedure. For patients with considerable immunosuppression, reduced nutritional or general health status, and as part of emergency treatment, a 3-staged (3S) procedure is recommended by guidelines to minimize perioperative complication rates compared to 2-staged (2S) procedure. However, the necessity of additional hospitalization and surgery is suspect to affect quality of life (QoL). In this prospective, observational study, we evaluate the long-term QoL after 2- and 3-staged interventions of CPM with IPAA for patients with UC.Between 1997 and 2011, a total of 233 patients underwent CPM and had a 2- or 3-staged procedure. In 108 patients, surgical procedure was completed, and evaluation of QoL was performed by specific questionnaires (IBDQ, FIQoL, SF-12, CCS) up to 20 years after ileostomy closure. Data were collected within the framework of a prospective study.Observing a total of 84 patients (2S: n = 59; 3S: n = 25), QoL measured by IBDQ was higher after CPM, compared to preoperative (2S: 15 → 31; 3S: 17 → 28; p 0.01), with no differences between 2S or 3S procedures (p 0.05). Specific QoL assessment concerning incontinence and stool frequency (CCS, FIQoL) did not differ either (CCS: 2S:3S = 12:15; p 0.05). General health-related QoL, determined by SF-12 score, did not differ between 2S or 3S procedures.The indication for a 2-staged or 3-staged procedure should be adjusted to the severity of the underlying disease, nutritional status of the patient, and the extent of immunosuppression at the time of surgery. It should not be affected by the fear of complications or a reduced quality of life by additional surgery in 3-staged versus 2-staged procedures.

Objectives Polycystic ovary syndrome (PCOS) and/or insulin resistance (IR) are frequent conditions in women choosing assisted reproduction techniques (ART). However, infertility work-up has to include testing of insulin sensitivity to diagnose IR. It was the aim of the study to analyze the frequency of impaired glucose tolerance (IGT) or gestational diabetes (GD) in the first weeks of gestation after ART in women receiving metformin. Design and methods This study included 107 women who were seeking ART under the pretreatment of metformin for PCOS, confirmed IR, recurrent spontaneous miscarriages (RSA) or other fertility disorders. They were examined for prepregnancy health parameters (weight, glucose tolerance). When pregnancy was confirmed a 75 g oral glucose tolerance test (OGTT) was conducted between the 5(th) and 7(th) week of gestation. Results A high rate of GD or IGT already was observed in the first weeks of pregnancy in our cohort under metformin treatment. The predominant risk factor for diagnosed early onset of IGT or GD (58 cases) was PCOS (p=0.014). The frequency of GD was the highest in the subgroup with prepregnancy confirmed IR not fulfilling the criteria of PCOS (55%); it was 40.6% in PCOS women and 26.1% in women neither exhibiting IR nor PCOS. Conclusions Women seeking ART and being treated with metformin still show a very high rate of GD or IGT after achieving pregnancy by ART. Therefore in women undergoing ART screening for GD should be performed as soon as pregnancy is confirmed to avoid miscarriages due to overlooked uncontrolled glucose metabolism.

Knowledge about the changes in the electric conductivity during the coagulation process of radiofrequency ablation of the liver is a prerequisite for the predictability of produceable thermonecrosis in the liver.Continuous measurements of the electric conductivity sigma in ex vivo porcine liver (n = 25) were done during the coagulation and cooling process at the temperature range of the radiofrequency ablation at a frequency of 470 kHz relevant for the radiofrequency ablation. Measurements of the electric conductivity were performed in both perfused porcine liver (n = 3) and a human surgical specimen from a colorectal liver metastasis.At a body temperature of 37 degrees C, conductance sigma was 0.41 siemens per metre (0.32 S/m; 0.52 S/m). Conductance sigma increased continuously and uniformly at a temperature of 77 degrees C. Maximum conductance sigma with 0.79 S/m (0.7 S/m; 0.87 S/m) was reached at 80 degrees C. A continuous reduction of conductance was observed during the cooling phase. At 37 degrees C, the specific conductance sigma in the healthy perfused porcine liver was 0.52 S/m, 0.55 S/m and 0.57 S/m (mean 0.55 S/m). The electric conductivity of the human colorectal liver metastasis was clearly higher.Changes in the specific conductivity during the coagulation and the cooling phase play an important role for the produceable size of a coagulation necrosis and necessitates an adaptation of the therapy parameters during radiofrequency ablation.

OBJECTIVE: It is a common clinical experience that type 2 diabetic patients are susceptible to opportunistic infections. The underlying reasons for this immune deficiency are not yet understood. Dendritic cells (DC) play a key role in initiating innate and adapted immune responses. DESIGN: In order to investigate changes in the DC compartment in the peripheral blood in type 2 diabetes, we analyzed blood from patients under poor and good metabolic control and compared them to healthy controls. PATIENTS: 5 mls of blood were collected from 15 healthy controls, 15 diabetic patients with an HbA1c >7.0 and 15 patients with an HbA1c

Summary objective Antihypertensive drugs influence the neurohumoral cardiovascular system and the concentration of hormones involved in blood pressure regulation. Little is known, however, about the extent to which various antihypertensive drugs influence cardiovascular hormone concentrations and thus disturb the differential diagnosis of hypertension in clinical practice. In this study we compare the impact of different antihypertensive medicaments on the renin–angiotensin–aldosterone system in patients with essential hypertension who are screened for primary aldosteronism. design and subjects We analysed serum aldoster-one (SAC) and plasma renin concentration (PRC) in 37 normotensive controls, 144 hypertensive patients with essential hypertension, and 19 patients with primary aldosteronism. Patients were on different treatment regimens such as single drug or combination therapy with β-blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II subtype 1 (AT1) receptor antagonists, calcium channel blockers, spironolactone and no treatment. results In patients with essential hypertension, β-blocker therapy (n = 47) led to a highly significant suppression of renin, whereas serum levels of aldosterone were not significantly altered. ACE inhibitors and AT1 receptor antagonists (n = 55) decreased aldosterone levels only to a minor extent. Calcium channel blockers (n = 23) had no significant influence on SAC or PRC. In patients with primary aldosteronism treated with spironolactone (n = 8), renin escaped suppression and reached very high levels. conclusion β-blockers and aldosterone antagonists have the strongest impact on the renin–angiotensin system. The decrease in renin concentration by β-blockers leads to an increase in the ratio of aldosterone to renin, and thus to false-positive results in patients with essential hypertension. Calcium channel blockers, and probably also ACE inhibitors and AT1 receptor antagonists alone or in combination, may be continued during screening for primary aldosteronism by determination of renin and aldosterone concentration.

The ratio of serum aldosterone to plasma renin activity (PRA) has been proposed as sensitive screening method in the diagnosis of primary aldosteronism under random conditions. However, the method for determination of renin activity is hampered by the necessity of ice cooling during storage and transport. The present study was therefore conducted to examine the ratio of serum aldosterone to plasma renin concentration (ARR) and its usefulness in diagnosis of primary aldosteronism under ambulatory conditions and given antihypertensive medication. 146 patients with arterial hypertension who consecutively attended the outpatient clinic were studied prospectively. Patients with secondary hypertension besides primary aldosteronism were not included in the series. 37 normotensive patients served as control. Also, 17 patients with known primary aldosteronism were retrospectively examined. Among the hypertensive group 2 patients with Conn's syndrome were newly detected (1.4%). ARR was 7.92 +/- 6.04 [pg/ml]/[pg/ml] in normotensive controls (range from 2.03 to 26.98), 14.61 +/- 18.50 [pg/ml]/[pg/ml] in patients with essential hypertension (n = 144, range from 0.41 to 115.45) and 155.92 +/- 127.84 [pg/ml]/[pg/ml] in patients with primary aldosteronism (n = 19, range from 6.75 to 515). 17 of the 19 patients with Conn's syndrome had an ARR of more than 50. Under ongoing drug treatment this represents a sensitivity of 89% and a specificity of 96%. Sensitivity decreased to 84% and specificity increased to 100% when a second criteria (aldosterone > or = 200 pg/ml) was included. In summary, ARR using renin concentration is a useful screening parameter for primary aldosteronism.

Severe courses of Crohn’s disease (CD) during pregnancy are rare. However, if occurring, the risk of miscarriage and low birth weight is increased. At present, only limited data is available on the treatment of CD during pregnancy. In particular, there are no standard guidelines for surgical therapy. Nevertheless, surgery is often unavoidable if complications during the course of the disease arise. This study provides a critical overview of conventional and interventional treatment options for CD complications during pregnancy and analyses the surgical experience gained thus far. For illustrative purposes, clinical cases of three young women with a severe clinical course during pregnancy are presented. After treatment-refractory for conservative and interventional measures, surgery remained as the only treatment option. In all cases, a split stoma was created after resection to avoid anastomotic leaks that would endanger the lives of mother and child. The postoperative course of all three patients was uneventful, and pregnancy remained intact until delivery. No further CD specific medication was required before birth. The management of CD patients during pregnancy requires close interdisciplinary co-operation between gastroenterologists, obstetricians, anaesthetists and visceral surgeons. For the protection of mother and child treatment should thus be delivered in a specialised centre. This article demonstrates the advantages of surgical therapy by focusing on alleviating CD complaints and preventing postoperative complications.

Laparoscopic interventions to minimize access trauma are increasingly gaining importance for both cosmetic reasons and lower postoperative morbidity. The aim of this study was to compare the clinical outcomes for different laparoscopic colectomy and proctocolectomy accesses considering IBD. A comparison was made between total laparoscopic (LR)-without an extra incision for sample--and laparoscopic-assisted resection using a small incision for retrieval of the specimen (LAR) PATIENTS AND METHODS: From 2006 to 2012, 109 IBD patients underwent minimal invasive total colectomy or proctocolectomy. Patients were subdivided according to access into LR and LAR. Perioperative outcomes were evaluated.86 patients with Ulcerative Colitis (UC) and 23 with Crohn's disease (CD) were included (LR: 64 UC/13 CD, LAR: 22 UC/10 CD). Among them, there were no differences in age, BMI, sex, ASA score or pre-existing immunosuppression. Patients with LR and UC had a higher disease activity score (Truelove III LR: 42 %, LAR: 5 %; p = 0.005). The Crohn's Disease Activity Index did not differ. Patients with LR had a shorter operating time (LR: 211.5, LAR: 240 min; p = 0.002). There was no significant difference in hospital stay (LR: 11, LAR: 12.5 days; p ≥ 0.05), length of stay at the ICU (both 1 days; p ≥ 0.05), duration of required analgesia (LR: 7 days, LAR: 8 days; p ≥ 0.05), and nutritional build-up (both 5 days; p ≥ 0.05). Groups had the same overall complication rate, but surgical site infection rates tended to be higher in patients with LAR (LR: 9.1 %, LAR: 21.9 %, p = 0.07).Laparoscopic procedures for colectomy and proctocolectomy are safe and effective techniques for patients with colon involvement and IBD. Minimizing the access trauma in laparoscopic colectomy offers a potential advantage of reduced surgical site infections, especially for frequently immunosuppressed IBD patients.

GLP-1, an incretin hormone of the enteroinsular axis with insulinotropic and glucagonostatic activity, is secreted after nutrient ingestion. GLP-1 is mainly produced by intestinal L-cells in the lower gastrointestinal tract (GIT); simple carbohydrates are absorbed in the upper GIT and α-glucosidase inhibition leads to augmented and prolonged GLP-1 release in normal subjects. In a cross-over study, 100 mg acarbose or placebo was administered simultaneously with 100 g sucrose to 11 hyperglycaemic Type 2 diabetic patients poorly controlled with diet and sulphonylureas. Plasma levels of GLP-1, insulin, C-peptide, glugacon, GIP, glucose and H2-exhalation were measured over 6 h. Differences in the integrated responses over the observation period were evaluated by repeated measurement analysis of variance with fasting values used as covariates. With acarbose, sucrose reached the colon 60–90 min after ingestion as indicated by a significant increment in breath hydrogen exhalation (p = 0.005). After an early GLP-1 increment 15 min after sucrose under both conditions, GLP-1 release was prolonged in the acarbose group (p = 0.001; significant from 210 to 360 min). Initially (0–150 min), glucose (p = 0.001), insulin (p = 0.001), and GIP (p

The coloproctomucosectomy (CPM) is the procedure of the choice for the surgical treatment of ulcerative colitis (UC). In cases with pronounced immunosuppression (IS), a 3-step (3S) procedure [i.e., subtotal colectomy and ileal pouch-anal anastomosis (IPAA) and finally ileostomy reconstruction] is often selected. Fewer perioperative complications can be expected compared to the 2-step (2S) procedure; however, an additional in-hospital stay and surgical intervention are necessary. The aim of the present study was to compare both approaches using the clinical outcome of our patients undergoing IPAA to determine efficacy of these two concepts.From 1997-2010, a total of 225 patients were operated using a 2S or 3S IPAA procedure. Clinical outcomes were evaluated based on the number of surgical steps for the ileoanal pouch procedure and IPAA. The survey was performed within the scope of prospective study.Of the 225 patients with CPM, 66 were excluded due to a diagnosis other than UC (familial adenomatous polyposis, indeterminate colitis, Crohn's disease) and patients with permanent ILS procedures without the possibility or wish for an IPAA (n = 54). Included were 71 patients with 2S (w = 30, m = 41) and 34 patients with 3S procedures (w = 21, m = 13). Compared to the 2S procedure, the 3S procedure was shown to have shorter operation times (246 versus 296 min; p = 0.05), shorter hospital stays (15.5 versus 24.6 days; p = 0.05), shorter intensive care unit stays (3.3 versus 7.2 days; p = 0.05), and fewer major complications (5.9 % versus 22.5 %; p = 0.035). Patients with 3S procedures had a higher BMI (26.2 versus 23.1 kg/m²; p = 0.05) and fewer required IS (10 % vs. 62 %; p 0.05).The decision for a 3S procedure in UC and pronounced IS is advisable and justified. Using a 3S procedure, immunosuppression and its influence on perioperative morbidity are thus reduced. The IPAA can be performed with shorter operation times, shorter hospital stays and fewer major complications.

The efficacy of metformin for the treatment of obesity has been evaluated in few clinical trials with inconclusive results. Moreover, the effectiveness in a real-life outpatient setting has not been tested until today. In this study we aimed to examine the effectiveness of metformin as a weight reducing drug in obese and overweight patients with regard to their degree of insulin resistance. We treated 154 consecutive patients with a body mass index ≥27 kg/m2 in an outpatient setting over 6 months with metformin up to a dosage of 2 500 mg per day. Additionally, we included 45 untreated patients as controls. Patients were monitored for weight changes over 6 months. Before metformin treatment was started insulin sensitivity was determined in all patients by calculating HOMA index and Matsuda index after a 75 g oral glucose tolerance test. The mean weight loss in the metformin treated group was 5.8±7.0 kg (5.6±6.5%). Untreated controls gained 0.8±3.5 kg (0.8±3.7%) on average. Patients with severe insulin resistance lost significantly more weight as compared to insulin sensitive patients. The percentage of weight loss was independent of age, sex or BMI. Metformin is an effective drug to reduce weight in a naturalistic outpatient setting in insulin sensitive and insulin resistant overweight and obese patients.

Radiofrequency ablation (RFA) is an established procedure for therapy of tumors of parenchymatous organs like the liver. RFA could also be suitable for the minimally invasive therapy of singular thyroid nodules. The aim of this study was to establish a dose-response relationship for RFA of thyroid nodules. Thermal lesions were induced in healthy porcine thyroid glands ex vivo (n = 110) and in vivo (n = 10) using a bipolar radiofrequency system. RF was applied in a power range of 10–20 watts. During the ablation, continuous temperature measurement at a distance of 5 and 10 mm from the applicator was performed. The transversal and axial lesion diameters were measured, and the volume was calculated. Furthermore, enzyme histochemical analysis of the thyroid tissue was performed. The inducible lesion volumes were between 2.43 ± 0.68 cm3 at 10 W and 0.91 ± 0.21 cm3 at 20 W. The maximum temperatures after RF ablation were between 30.0 ± 8.6 °C and 53.5 ± 8.6 °C at a distance of 5 mm and between 44.0 ± 9.7 °C and 61.6 ± 13.9 °C at a distance of 10 mm from the applicator. The histochemical analysis demonstrates a complete loss of NADPH dehydrogenase activity in thermal lesions as a sign of irreversible cell damage. RFA induces reproducible clinically relevant lesions with irreversible cell damage and seems to be suitable for therapy of singular thyroid nodules.

Background The precise measurement of osmolality is crucial in the differential diagnosis of disorders of water balance. Storage conditions, and freezing and thawing of serum or plasma samples before osmometry may influence the accuracy of measured values. Methods A series of serum and plasma samples of 25 healthy young individuals were stored under different conditions at different temperatures (room temperature (22 degrees C), 7 degrees C, -21 degrees C, -78 degrees C) for up to 56 days. Before freezing a protein-stabilizing agent (bacitracin) was added to one part of the samples. Osmolality was examined using the freezing point method. Results At room temperature osmolality was stable for up to 3 days but showed a tendency toward an increase that was significant on day 14. In contrast, at 7 degrees C an initial significant decrease in serum osmolality occurred (day 1), which was followed by a slow increase. Serum samples stored at -21 degrees C showed a significantly lower osmolality on the 14th day compared to baseline. Adding bacitracin before freezing reduced this decrease by more than half, but the deviation was still significant. In samples stored at -78 degrees C no significant alteration of osmolality from baseline was observed over the observation period of 56 days if samples were thawed in a 37 degrees C water bath. Conclusion Immediate measurement of osmolality is most reliable in order to obtain accurate values, although storing at room temperature does not influence osmolality significantly during the first 3 days. If storage is necessary for longer, samples should be stored at -78 degrees C and must be thawed quickly (at 37 degrees C). Under these conditions reliable values can be obtained from frozen serum or plasma. Storage at 7 degrees C is not recommended. If samples are stored at -21 degrees C the addition of a protein-stabilizing agent may be useful.

We report on a 36-year-old patient suffering from chronic hepatitis C. Because of elevated liver enzymes and histology showing chronic inflammation and periportal fibrosis, interferon-alpha (IFN) therapy was started with a dosage of 5 Mio units three times a week. Four months later the patient hat to be hospitalized due to the typical clinical features of a recent onset type 1 diabetes (BG300 mg/dl, HbA1c 9.6%, ketonuria). In serum samples prior to and following interferon therapy, we analyzed titers of diabetes-related autoantibodies responding to GAD65 (glutamic acid decarboxylase), IA2c (tyrosine phosphatase) and ICA (islet cell autoantibodies). While ICA were negative before starting therapy, IA2c-antibodies were highly elevated. In contrast. GAD65-antibodies were elevated only slightly over the cut-off of the assay before therapy (controlled by a second different RIA assay) and increased 100 fold during IFN-alpha treatment. Additionally thyroid antibodies appeared. After the end of the IFN therapy, GAD65- and IA2c antibodies remained on high levels and also ICA could now be found. The patient was positive for HLA-DR4. This case supports the hypothesis that IFN-alpha therapy may lead to an augmented autoimmune reaction against islet cell antigens resulting in the development of diabetes mellitus type 1, especially if there are other predisposing factors before IFN treatment. We further discuss the possible involvement of interferon-alpha in the pathogenesis of autoimmune diabetes with reference to recent studies.

GLP-1, an incretin hormone of the enteroinsular axis with insulinotropic and glucagonostatic activity, is secreted after nutrient ingestion. GLP-1 is mainly produced by intestinal L-cells in the lower gastrointestinal tract (GIT); simple carbohydrates are absorbed in the upper GIT and alpha-glucosidase inhibition leads to augmented and prolonged GLP-1 release in normal subjects. In a cross-over study, 100 mg acarbose or placebo was administered simultaneously with 100 g sucrose to 11 hyperglycaemic Type 2 diabetic patients poorly controlled with diet and sulphonylureas. Plasma levels of GLP-1, insulin, C-peptide, glugacon, GIP, glucose and H2-exhalation were measured over 6 h. Differences in the integrated responses over the observation period were evaluated by repeated measurement analysis of variance with fasting values used as covariates. With acarbose, sucrose reached the colon 60-90 min after ingestion as indicated by a significant increment in breath hydrogen exhalation (p = 0.005). After an early GLP-1 increment 15 min after sucrose under both conditions, GLP-1 release was prolonged in the acarbose group (p = 0.001; significant from 210 to 360 min.). Initially (0-150 min), glucose (p = 0.001), insulin (p = 0.001), and GIP (p0.001) were suppressed by acarbose, whereas later there were no significant differences. Glucagon levels were higher with acarbose in the last 3 h of the 6 h observation period (p = 0.02). We conclude that in hyperglycaemic Type 2 diabetic patients, ingestion of acarbose with a sucrose load leads to elevated and prolonged GLP-1 release.

During recent years the infectious etiology of the majority of cases of chronic active type B gastritis and peptic ulcers has become increasingly evident. The chronicity of clinical symptoms and histopathological features such as numerous mucosal lymphocytic aggregates have implied a role of the specific cellular immune system. Whereas in Type A chronic active gastritis a pathogenetic role of lymphocytes and their target structures have been amply documented, in chronic active type B gastritis particularly that associated with Helicobacter pylori infection the nature of a specific immune response and its role in the pathogenesis of the epithelial and mucosal lesion has remained obscure. Here we report that CD4+ mucosal lymphocytes appear to selectively accumulate in Helicobacter pylori associated chronically active antral gastritis. Moreover, lamina propria gamma delta T lymphocytes were found to be more frequent in chronic active type B gastritis irrespective of the presence of absence of Helicobacter pylori.

The pathogenesis of chronic gastritis and the presumed causative role of Helicobacter pylori has led to considerable dispute in this field of research. However, a large number of studies involving self-inoculations1,2, epidemiological assessments3,4, histopathological evaluations5–7 and the fact that after eradication of H. pylori the marked inflammatory lesions in the gastric mucosa disappear8,9 have provided compelling evidence suggesting H. pylori as a principal causative agent in this form of gastritis. Furthermore, therapeutic trials showed that combined antibiotic and antacid therapy was more effective in preventing disease relapse than antacid therapy alone10. Mechanisms involved in the development of mucosal lesions include a variety of toxins11–14 and enzymes secreted by H. pylori that destroy epithelial cells and digest the protective gastric mucus14,15. Moreover, mucosal lesions are characterized by a marked lymphocytic infiltrate, suggesting a specific immune reaction that may lead to considerable mucosal pathology5,6,9. Specifically, it has been claimed that CD4+ T cells and γδ T cells play a critical role in H. pylori-associated gastritis16. The presence of γδ T cells in the mucosal lesions has implicated endogenous and bacterial heat-shock proteins as potential target antigens for the specific local immune reaction, as some investigators have reported that heat-shock proteins selectively stimulate γδ T cells in vitro 17. Heat-shock proteins are a group of proteins believed to function as chaperones in all prokaryotic and eukaryotic cells that are expressed at enhanced levels under conditions such as physical, thermal or chemical stress in order to prevent denaturation of proteins that are vital for cell function18–20. Importantly, enhanced heat-shock protein expression was observed in tissues stressed by chronic bacterial infection19 in rheumatoid arthritis lesions in conjunction with local accumulation of γδ T cells17. However, whether the accumulation of γδ T cells in H. pylori-affected mucosal lesions represents a specific phenomenon is unclear at present, since to date the presence of γδ T cells has not been evaluated in other forms of gastritis that are not associated with H. pylori. In addition to the marked lymphocytic infiltration epithelial cells within the mucosal lesions exhibit an increased expression of MHC class II molecules21–23. Therefore, in our study we comparatively analysed the T cell receptor usage of infiltrating lymphocytes in chronic gastritis with regard to the presence or absence of H. pylori. In addition, the functional status of the infiltrating inflammatory cells was assessed by determining the expression of IL-2 receptors and MHC class II molecules.

SummaryRORγt+ innate lymphoid cells (ILCs) are crucial players of innate immune responses and represent a major source of interleukin-22 (IL-22), which has an important role in mucosal homeostasis. The signals required by RORγt+ ILCs to express IL-22 and other cytokines have been elucidated only partially. Here we showed that RORγt+ ILCs can directly sense the environment by the engagement of the activating receptor NKp44. NKp44 triggering in RORγt+ ILCs selectively activated a coordinated proinflammatory program, including tumor necrosis factor (TNF), whereas cytokine stimulation preferentially induced IL-22 expression. However, combined engagement of NKp44 and cytokine receptors resulted in a strong synergistic effect. These data support the concept that NKp44+ RORγt+ ILCs can be activated without cytokines and are able to switch between IL-22 or TNF production, depending on the triggering stimulus.