Second-generation distal attachment cuff for adenoma detection in screening colonoscopy: a randomized multicenter study.

BACKGROUND AND AIMS: Randomized studies have demonstrated that a distal attachment cap with rubber side arms, the Endocuff Vision (ECV; Olympus America, Center Valley, Pa, USA), increased colonoscopic adenoma detection rate (ADR) in various mixed patient collectives. This is the first study to evaluate its use in a primary colonoscopic screening program. METHODS: Patients over age 55 years undergoing screening colonoscopy in 9 German private offices in Berlin and Hamburg were randomized to either the study group using ECV or the control group using high-definition colonoscopies (standard of care). The main outcome parameter was ADR, whereas secondary outcomes were detection rates of all adenomas per colonoscopy (APCs), of adenoma subgroups, and of hyperplastic polyps. RESULTS: Of 1416 patients (mean age, 61.1 years; 51.8% women), with a median of 41 examinations per examiner (n = 23; interquartile range, 12-81), 700 were examined with ECV and 716 without. Adjusting for the effects of the colonoscopies, ADR was 39.5% (95% confidence interval [CI], 32.6%-46.3%) in the ECV group versus 32.2% (95% CI, 25.9%-38.6%) in the control group, which resulted in an increase of 7.2% (95% CI, 2.3%-12.2%; P = .004). The increase in ADR was mainly because of small polyps, with adjusted ADRs for adenomas <10 mm of 33.3% (95% CI, 26.5%-40.2%) for study patients versus 24.0% (95% CI, 18.2%-29.8%) for control patients (P < .001). APC was also significantly increased (.57 ECV vs .51 control subjects, P = .045). CONCLUSIONS: A distal attachment cap with side arms significantly increased the ADR in patients undergoing primary colonoscopic screening. Because of the correlation of ADR and interval cancer, its use should be encouraged, especially in this setting. (Clinical trial registration number: NCT03442738.).

Age-dependent interactions of maxillary sutures during RME and their effects on palatal morphology : CBCT and dental cast analysis.

PURPOSE: The effects of rapid maxillary expansion (RME) on the transverse palatine and midfacial sutures have been extensively scrutinized. Unlike the dentition stage, age-dependency was not yet regarded when investigating morphological changes of the tooth-bearing palate. Therefore, the first aim of the present study was to analyse age-dependent sutural and morphological changes of the palate in selected patients by cone-beam computed tomography (CBCT) and dental cast analysis. Secondly, age-dependent effects of RME on width, height, and depth of the palate in the region of the maxillary palatine processes were investigated by a comprehensive dental cast study, so that the combination of results could be used to provide a biomechanical explanation of the occurring changes. METHODS: CBCT datasets of 9 patients (between 7.3 and 13.8 years) were measured around the median palatal suture and compared with the results of an individualised dental cast analysis. In addition, possible effects on other maxillary sutures were investigated. In the dental cast study, changes after RME in the tooth-bearing palate were analysed three-dimensionally in 60 children and adolescents. It was possible to divide those into three equally sized, age-dependant groups (PG1: < 10 years, n = 20; PG2: ≥ 10 < 12 years, n = 20; PG3: ≥ 12 years, n = 20). RESULTS: The CBCT analysis reveals age-related differences in sutural responses. The opening width of the median palatine suture decreases cranially (frontal) and dorsally (horizontal). The opening mode thus changes from parallel to triangular in both planes. The transverse palatine suture completely opens in younger patients only (PG1 and PG2). The width increases are always significant in all patients. While in PG1 the width increase is greater posteriorly than anteriorly, this is always reversed in PG2 and PG3. The palatal height always increases significantly anteriorly, but posteriorly only in the youngest patients (PG 1) median and paramedian. In PG 2 and PG 3, the posterior height change is very small. That is the reason why the anteroposterior comparison reveals a much more pronounced height increase anteriorly than posteriorly. CONCLUSION: The comparison of selected CBCT data with a dental cast analysis allows the conclusion that the maxillary expansion after RME in children up to 10 years is rather parallel, whereas it occurs V­shaped (anterior > posterior transversal, inferior > superior vertical) with increasing age, especially in adolescents from the age of 12. In addition to an age-progressive rigidity of the pterygopalatomaxillary junction, morphological changes of the transverse palatine suture during growth seem to be causal. Thus, age-dependent effects of palatal expansion occur due to a positional change of maxillary centres of rotation and resistance. From dental cast measurements, especially at the skeletal-basal level, conclusions can be drawn about the median palatal suture opening mode.

Low Sensitivity of Simtomax Point of Care Test in Detection of Celiac Disease in a Prospective Multicenter Study.

BACKGROUND & AIMS: Point of care tests (POCTs) might be used to identify patients with undiagnosed celiac disease who require further evaluation. We performed a large multicenter study to determine the performance of a POCT for celiac disease and assessed celiac disease prevalence in endoscopy centers. METHODS: We performed a prospective study of 1055 patients (888 adults; median age, 48 yrs and 167 children; median age, 10 yrs) referred to 8 endoscopy centers in Germany, for various indications, from January 2016 through June 2017. Patients were tested for celiac disease using Simtomax, which detects immunoglobulin (Ig)A and IgG antibodies against deamidated gliadin peptides (DGP). Results were compared with findings from histologic analyses of duodenal biopsies (reference standard). The primary aim was to determine the accuracy of this POCT for the detection of celiac disease, to identify candidates for duodenal biopsy. A secondary aim was to determine the prevalence of celiac disease in adult and pediatric populations referred for outpatient endoscopic evaluation. RESULTS: The overall prevalence of celiac disease was 4.1%. The POCT identified individuals with celiac disease with 79% sensitivity (95% CI, 64%-89%) and 94% specificity (95% CI, 93%-96%). Positive and negative predictive values were 37% and 99%. When we analyzed the adult and pediatric populations separately, we found the test to identify adults with celiac disease (prevalence 1.2%) with 100% sensitivity and 95% specificity. In the pediatric population (celiac disease prevalence 19.6%), the test produced false-negative results for 9 cases; the test therefore identified children with celiac disease with 72% sensitivity (95% CI 53%-86%). Analyses of serologic data revealed significantly lower DGP titers in the false-negative vs the true-positive group. CONCLUSIONS: In a study of more than 1000 adults and children, we found the Simtomax POCT to detect celiac disease with lower overall levels of sensitivity than expected. Although the test identifies adults with celiac disease with high levels of sensitivity and specificity, the prevalence of celiac disease was as low as 1.2% among adults. The test's lack of sensitivity might be due to the low intensity of the POCT bands and was associated with low serum DGP titers. Study ID no: DRKS00012499.

Mucosal Inducible NO Synthase-Producing IgA+ Plasma Cells in Helicobacter pylori-Infected Patients.

The mucosal immune system is relevant for homeostasis, immunity, and also pathological conditions in the gastrointestinal tract. Inducible NO synthase (iNOS)-dependent production of NO is one of the factors linked to both antimicrobial immunity and pathological conditions. Upregulation of iNOS has been observed in human Helicobacter pylori infection, but the cellular sources of iNOS are ill defined. Key differences in regulation of iNOS expression impair the translation from mouse models to human medicine. To characterize mucosal iNOS-producing leukocytes, biopsy specimens from H. pylori-infected patients, controls, and participants of a vaccination trial were analyzed by immunohistochemistry, along with flow cytometric analyses of lymphocytes for iNOS expression and activity. We newly identified mucosal IgA-producing plasma cells (PCs) as one major iNOS(+) cell population in H. pylori-infected patients and confirmed intracellular NO production. Because we did not detect iNOS(+) PCs in three distinct infectious diseases, this is not a general feature of mucosal PCs under conditions of infection. Furthermore, numbers of mucosal iNOS(+) PCs were elevated in individuals who had cleared experimental H. pylori infection compared with those who had not. Thus, IgA(+) PCs expressing iNOS are described for the first time, to our knowledge, in humans. iNOS(+) PCs are induced in the course of human H. pylori infection, and their abundance seems to correlate with the clinical course of the infection.

Urinary calprotectin and the distinction between prerenal and intrinsic acute kidney injury.

BACKGROUND AND OBJECTIVES: To date there is no reliable marker for the differentiation of prerenal and intrinsic acute kidney injury (AKI). We investigated whether urinary calprotectin, a mediator protein of the innate immune system, may serve as a diagnostic marker in AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a cross-sectional study with 101 subjects including 86 patients with AKI (34 prerenal, 52 intrinsic including 23 patients with urinary tract infection) and 15 healthy controls. Assessment of urinary calprotectin concentration was by ELISA and immunohistochemistry of kidney biopsy specimens using a calprotectin antibody. Inclusion criteria were: admission to hospital for AKI stage 1 to 3 (Acute Kidney Injury Network); exclusion criteria were: prior renal transplantation and obstructive uropathy. RESULTS: Median urinary calprotectin was 60.7 times higher in intrinsic AKI (1692 ng/ml) than in prerenal AKI (28 ng/ml, p <0.01). Urinary calprotectin in prerenal disease was not significantly different from healthy controls (45 ng/ml, p = 0.25). Receiver operating curve curve analysis revealed a high accuracy of calprotectin (area under the curve, 0.97) in predicting intrinsic AKI. A cutoff level of 300 ng/ml provided a sensitivity of 92.3% and a specificity of 97.1%. Calculating urinary calprotectin/creatinine ratios did not lead to a further increase of accuracy. Immunostainings of kidney biopsies were positive for calprotectin in intrinsic AKI and negative in prerenal AKI. CONCLUSIONS: Accuracy of urinary calprotectin in the differential diagnosis of AKI is high. Whereas calprotectin levels in prerenal disease are comparable with healthy controls, intrinsic AKI leads to highly increased calprotectin concentrations.

Surveillance colonoscopy in patients with inflammatory bowel disease: comparison of random biopsy vs. targeted biopsy protocols.

BACKGROUND: Endoscopic surveillance in patients with long-standing inflammatory bowel disease (IBD) improves early detection of intraepithelial neoplasia (IEN). We aimed to compare three different endoscopic surveillance strategies in the detection of IEN. METHODS: One hundred fifty surveillance colonoscopies (ulcerative colitis, UC n = 141; Crohn's disease, CD n = 9) were carried out. Random quadrant biopsies were taken (group I, n = 50). Chromoendoscopy with indigo carmine was performed and subsequently quadrant biopsies were collected (group II, n = 50). Patients in group III (n = 50) underwent confocal endomicroscopy (CEM), and CEM-guided as well as random quadrant biopsies were taken (group III, n = 50). The findings of CEM were correlated to conventional histology. Patients with high-grade IEN underwent surgery or strict follow-up by patients' request. RESULTS: In group I (1531 biopsies), no IEN was detected by histology. In group II (1,811 biopsies), chromoendoscopy-guided biopsies revealed high-grade IEN in two patients (4% detection rate). In four patients of group III (1477 biopsies), areas with high-grade IEN were clearly visible by CEM and confirmed by histology (8% detection rate, p < 0.05). Of six patients with high-grade IEN, five patients underwent proctocolectomy. Colorectal cancer was detected in one out of five patients. CONCLUSION: Targeted biopsy protocols guided by either chromoendoscopy or CEM led to higher detection rates of IEN and are thus mandatory for surveillance colonoscopies in patients with long-standing UC. Random biopsy protocols should be replaced by chromoendoscopy-guided protocols.

Capsule endoscopy in small-bowel surveillance of patients with hereditary polyposis syndromes.

PURPOSE: Familial adenomatous polyposis (FAP) and Peutz-Jeghers syndrome (PJS) are hereditary polyposis syndromes with a high risk for benign small-bowel polyps and cancer. The aim of this study was to assess the prevalence of small-bowel polyps beyond the duodenum in patients with FAP and PJS and to examine the clinical value and the optimal interval of capsule endoscopy (CE) for the surveillance of small-bowel polyps in patients with FAP. METHODS: Between 2002 and 2009, standard gastroscopy, duodenoscopy, and CE were performed on 19 consecutive patients with hereditary polyposis syndromes (FAP n=15; PJS n=4). The number, size, and location of polyps detected by CE were assessed. Five FAP patients had repeated CEs in intervals of 2-7 years. RESULTS: In 13 of the 15 (87%) FAP patients, small-bowel polyps were detected by CE ranging from estimated <5 mm to >10 mm in size. Thereof, in four patients, medium-sized (5-10 mm) or large-sized (>10 mm) polyps were seen-all of them located in the proximal jejunum. In three FAP patients with repeated CEs, the latest CE displayed medium- and large-sized polyps in the proximal jejunum, whereas previous CEs had detected only small-sized (<5 mm) polyps. In three of the four PJS patients, large-sized small-bowel polyps were visualized by CE which could then be removed by double-balloon enteroscopy (DBE) or surgical resection. CONCLUSION: CE is an effective and safe method for small-bowel surveillance in FAP and PJS.

[A young man with chronic diarrhea and epigastric pain]. / Junger Mann mit chronischer Diarrhö und Oberbauchschmerzen.

CASE REPORT: A 26-year-old man was admitted to hospital with a 6-month history of diarrhea and abdominal pain. Before admission, upper and lower gastrointestinal endoscopy had shown a mild erosive duodenitis and the patient was started on a proton pump inhibitor. Physical examination and laboratory tests on admission were not constructive. In addition, repeated gastrointestinal endoscopy, cross-sectional imaging and neuroendocrine markers did not point to a specific etiology. Therefore, as a provocation test, the proton pump inhibitor therapy was discontinued. Discontinuation resulted in a progression of the patient's symptoms and an endoscopic detection of duodenal ulcers. Except for the normal serum gastrin levels, this constellation was suggestive of a gastrinoma, so that further investigations were initiated. Subsequently, the diagnosis could be confirmed and the gastrinoma located. After successful pancreaticoduodenectomy, the patient was symptom-free. CONCLUSION: As part of a systematic investigation on chronic diarrhea, the work-up for neuroendocrine causes can play an important role. In this context, it should be kept in mind that some gastrinoma patients present without an elevation of serum gastrin levels. Regardless of a negative gastrin test, a typical symptom constellation should therefore prompt further investigations.

Altered ENaC expression leads to impaired sodium absorption in the noninflamed intestine in Crohn's disease.

BACKGROUND & AIMS: Crohn's disease (CD) is a chronic inflammatory bowel disease. In this study, we have investigated sodium absorption via epithelial sodium channels (ENaC) in the macroscopically noninflamed colon in active CD. METHODS: Sodium transport via ENaC was investigated in Ussing chambers using biopsy specimens of sigmoid colon from controls and active CD limited to the small intestine. ENaC messenger RNA expression and subcellular localization were studied by real-time polymerase chain reaction and confocal microscopy. Effects of proinflammatory cytokines on ENaC and signaling via mitogen-activated protein kinases were investigated in rat distal colon. Therapeutic inhibition of mitogen-activated protein kinases was studied in CD biopsy specimens. RESULTS: Electrogenic sodium absorption via ENaC was strongly impaired in the macroscopically noninflamed CD colon because of reduced gamma-ENaC transcription, whereas subcellular localization of ENaC was not changed. In contrast to impaired epithelial sodium transport, epithelial barrier function was not altered in noninflamed CD colon, indicating that paracellular leak flux of ions did not contribute to decreased sodium absorption. Exposure of rat distal colon to tumor necrosis factor alpha led to reduced electrogenic sodium absorption because of impaired transcriptional gamma-ENaC induction, which resembled the changes found in CD. Tumor necrosis factor alpha effects were dependent on extracellular signal-regulated kinase 1/2 but not p38 or c-Jun-N-terminal kinase because inhibition of mitogen-activated protein kinase/extracellular regulated kinase (MEK)1/2 but not inhibition of p38 or c-Jun-N-terminal kinase prevented suppression of ENaC. Finally, therapeutic inhibition of MEK1/2 restored electrogenic sodium absorption in CD. CONCLUSIONS: In CD, macroscopically noninflamed colon contributes to diarrhea via impaired ENaC-mediated sodium absorption. Inhibition of extracellular signal-regulated kinase might serve as a potential therapeutic strategy for CD diarrhea.

Through the endoscope balloon dilation of ileocolonic strictures: prognostic factors, complications, and effectiveness.

BACKGROUND/AIMS: About half of all Crohn's disease (CD) patients undergo surgery at some point, many because of strictures. An alternative possibility is to dilate strictures endoscopically. However, little is known about prognostic factors. PATIENTS AND METHODS: Thirty-two patients with primary CD (n=2), radiogenic strictures (n=1), or postoperative strictures (27 because of CD; 2 after resection because of cancer), were planned to undergo colonoscopic dilatation of which 25 patients were dilated (10 men; 15 women; median age 48). Length of stenosis, diameter of stricture, balloon size, smoking status, ulcer in the stricture, passage postdilatation, hemoglobin level, complications, redilatation, and subsequent surgery were recorded. Only patients with at least 6 months follow up were included. RESULTS: Five out of 32 patients had no stenosis, marked inflammation, or fistulas adjacent to the stricture. One patient each had a long stricture (8 cm) or a filiform stenosis ruling out dilatation [technical success, 25/27 (92.6%)]. Among these 25 patients, 39 colonoscopies with 51 dilatations were performed. After a single dilatation, 52% were asymptomatic while 48% needed another intervention, half of them surgery. Bleeding without need for transfusion occurred in 3 out of 39 colonoscopies and one perforation required surgery. Significant prognostic factors were smoking and ulcers in the stricture (P<0.05 each). Some ulcers led to intussusception requiring surgery in spite of good dilatation results. CONCLUSION: Through the endoscope balloon stricture dilatation is a relatively safe and often effective treatment modality in ileocolonic strictures. The presence of ulcers in the stricture have a worse outcome as do smokers.

Disrupted barrier function through epithelial cell apoptosis.

Epithelial barrier function is determined by trans- and paracellular permeabilities, the latter of which is mainly influenced by tight junctions (TJs) and apoptotic leaks within the epithelium. The present article aims to present experimental evidence for a functional role of epithelial apoptoses by means of cell culture models as well as in tissues from patients with inflammatory bowel disease. It is shown that epithelial apoptoses are sites of elevated conductance within the intestinal epithelium and that proinflammatory cytokines like TNF-alpha upregulate both the apoptotic rate and single apoptotic conductivity, making cytokine-induced apoptosis functionally far more relevant than is spontaneous apoptosis. In ulcerative colitis and Crohn's disease (CD), but not in collagenous colitis, apoptotic rates are increased to about 5%, in mild-to-moderately inflamed colon specimens, where as the control apoptotic rate is about 2%. Thus, epithelial apoptoses lead to a loss of ions and water into the intestinal lumen, causing leak flux diarrhea and enabling small antigens of <4,000 Da in the intestinal lumen to enter the intestinal mucosa, thereby perpetuating inflammatory responses. In addition to TNF-alpha, interleukin (IL)-13 is an important inductor of epithelial apoptosis in Th2 immune responses. Therapeutically,TNF-alpha-antibodies (infliximab) can restore barrier function in Crohn's disease by downregulating epithelial apoptoses, while epithelial TJs are unaffected.

Distraction osteogenesis in adolescents with maxillary arch deficiency and dental crowding: a 3-year follow-up.

BACKGROUND: In this study, the authors evaluated the long-term results after using anterior segmental osteotomy and distraction osteogenesis for the correction of sagittal maxillary deficiency associated with dental crowding. METHODS: Six young adolescents (four boys and two girls) underwent surgery and distraction at a mean age of 11.2 years (range, 10 to 12 years) and were followed up for 3 years. A tooth-borne distraction device was used for interdental distraction. The evaluation consisted of hard- and soft-tissue profile analysis and dental arch measurements before, immediately after, and 3 years after distraction. RESULTS: The results showed that the facial profile, the occlusion, and the dental crowding could be successfully corrected and that the results were stable after 3 years' follow-up. The mean facial convexity angle was changed from 1 to 8 degrees. The average advancement at point A was 4 mm and the SNA increased by an average of 4 degrees. Lengthening of the dental arch by an average of 4 mm created approximately 8 mm of new space, sufficient to resolve the dental crowding in all patients, thus avoiding an extraction of healthy teeth. CONCLUSION: The results of this study demonstrated that anterior segmental maxillary osteotomy combined with distraction osteogenesis offers an alternative for the treatment of adolescents suffering from sagittal maxillary deficiency with dental crowding.

Both IL-12p70 and IL-23 are synthesized during active Crohn's disease and are down-regulated by treatment with anti-IL-12 p40 monoclonal antibody.

BACKGROUND: Interleukin (IL)-12p70 and IL-23 are key T helper-1 (TH1) cytokines that drive the inflammation seen in numerous models of intestinal inflammation. These molecules contain an identical p40 chain that is bound to a p35 chain in IL-12 and a p19 chain in IL-23, making both potentially susceptible to modulation by an anti-IL-12p40 monoclonal antibody (mAb). METHODS: In the present study, we sought to determine whether active inflammation in Crohn's disease (CD) is associated with the increased synthesis of both of these cytokines and whether patients treated with an anti-IL-12p40 mAb down-regulate IL-23 as well as IL-12p70 as previous reported. RESULTS: To this end we initially determined that IL-12p70 secretion by control and CD antigen-presenting cells (macrophages) in lamina propria mononuclear populations is optimized by stimulation with CD40L and interferon-gamma. In subsequent studies using these stimulation conditions we found that patients with CD manifested both increased IL-12p70 and IL-23 secretion before anti-IL-12p40 mAb treatment and normal levels of secretion of these cytokines following cessation of treatment. Antigen-presenting cells in lamina propria mononuclear cells from ulcerative colitis patients, in contrast, produced only baseline levels of IL-23. Finally, we found that IL-23-induced T cell production of IL-17 and IL-6 are also greatly reduced after antibody treatment. The latter data are parallel to those from previous studies showing that anti-IL-12p40 down-regulates IFN-gamma and tumor necrosis factor-alpha secretion. CONCLUSIONS: We conclude that CD but not ulcerative colitis is associated with high levels of both IL-12p70 and IL-23 secretion as well as the secretion of downstream effector cytokines, and that this cytokine production is down-regulated following administration of IL-12p40 mAb.

A non-tooth-borne mouth-opening device for postoperative rehabilitation after surgical release of trismus.

BACKGROUND: The treatment of severe trismus requires a combination of surgical release and postoperative rehabilitation; the latter is essential for preventing a relapse due to postoperative inactivity and scarring. Mouth-opening devices for this purpose are placed between or fixed to the teeth to keep the dental arches apart; but patients suffering from severe trismus often present with partially or totally edentulous arches, decayed teeth, or periodontitis, which do not allow for the use of such devices. METHODS: In this article, a new mouth-opening device is described. It applies force to two intraoral screws placed in the vestibulum of the maxillary and mandibular bones. It can be used in patients with poor dental conditions and allows rehabilitation to start immediately after trismus release. RESULT: A case is presented. The interalveolar distance was improved from 5 mm to 45 mm and maintained at 6-month follow-up. CONCLUSION: Our non-tooth-borne mouth opening device is useful for postoperative rehabilitation after surgical release of trismus.

Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution.

BACKGROUND & AIMS: Ulcerative colitis (UC) is characterized by a Th2 immune response with inflammation and epithelial barrier dysfunction. So far, Th2 cytokines have not been shown to directly influence epithelial barrier function. METHODS: Lamina propria mononuclear cells (LPMCs) were stimulated and interleukin (IL)-13 was measured by enzyme-linked immunosorbent assay. Functional IL-13 and IL-4 effects were studied on HT-29/B6 colonic epithelial cells in Ussing chambers and by conductance scanning. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assays. IL-13/IL-4 receptors were analyzed by reverse-transcription polymerase chain reaction and immunofluorescence. Western blotting combined with immunofluorescence was used to detect tight junction proteins. Furthermore, restitution velocity was measured. Finally, mucosal biopsy specimens from patients with UC were compared with cultured cells for these features. RESULTS: LPMCs from patients with UC produced large amounts of IL-13 (985 +/- 73 pg/mL), much more than from controls or patients with Crohn's disease. IL-13Ralpha1 and IL-4Ralpha receptors were present in HT-29/B6 cells and colonic epithelial cells of control patients and patients with UC. IL-13 had a dose-dependent effect on transepithelial resistance of HT-29/B6 monolayers (reduction to 60% +/- 4%), whereas IL-4 had no effect. This was due to an increased number of apoptotic cells (5.6-fold +/- 0.9-fold) and an increased expression of the pore-forming tight junction protein claudin-2 to 295% +/- 37%, both of which contributed equally. Finally, epithelial restitution velocity decreased from 15.1 +/- 0.6 to 10.6 +/- 0.5 microm/h after treatment with IL-13. Parallel changes were observed in human samples, with an increase in claudin-2 expression to 956% +/- 252%. CONCLUSIONS: IL-13 was identified as an important effector cytokine in UC that impairs epithelial barrier function by affecting epithelial apoptosis, tight junctions, and restitution velocity.

The medial surface of the mandible as an alternative source of bone grafts in orthognathic surgery.

A technique of harvesting bone grafts from the medial surface of the angle of the mandible during a bilateral sagittal split osteotomy procedure is described. In 20 patients who underwent mandibular setback for the correction of class III dentofacial deformities, bone grafts were harvested from the medial mandibular angle and used for simultaneous augmentation of the midface or for interpositioning and stabilization of the maxilla after LeFort I maxillary anterior or inferior repositioning. The mean postoperative follow-up was 6 months (range, 3-12 months). No complications occurred, and postoperative morbidity was similar to that encountered by patients who undergo sagittal split osteotomy without bone harvest. The technique described shows that the medial mandibular angle is a suitable donor site for membranous bone grafts in patients who undergo sagittal split osteotomy.

Anterolateral thigh fasciocutaneous flap for simultaneous reconstruction of refractory scalp and dural defects. Report of two cases.

Infected full-thickness defects of the calvaria including the scalp, cranial bone, and dura mater, are often refractory to treatment and pose a difficult and urgent therapeutic problem for reconstructive surgeons. The authors report two cases in which successful reconstruction was achieved in one stage by using an anterolateral thigh fasciocutaneous flap. The well-vascularized fascia components were used to repair the infected dural defects. The skin flaps were used for coverage reconstruction.

Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis.

While Crohn disease (CD) has been clearly identified as a Th1 inflammation, the immunopathogenesis of its counterpart inflammatory bowel disease, ulcerative colitis (UC), remains enigmatic. Here we show that lamina propria T (LPT) cells from UC patients produce significantly greater amounts of IL-13 (and IL-5) than control cells and little IFN-gamma, whereas comparable cells from CD patients produce large amounts of IFN-gamma and small amounts of IL-13. We then show that stimulation of UC LPT cells bearing an NK marker (CD161) with anti-CD2/anti-CD28 or with B cells expressing transfected CD1d induces substantial IL-13 production. While this provided firm evidence that the IL-13-producing cell is an NK T (NKT) cell, it became clear that this cell does not express invariant NKT cell receptors characteristic of most NKT cells since there was no increase in cells binding alpha-galactosylceramide-loaded tetramers, and alpha-galactosylceramide did not induce IL-13 secretion. Finally, we show that both human NKT cell lines as well as UC CD161(+) LPT cells are cytotoxic for HT-29 epithelial cells and that this cytotoxicity is augmented by IL-13. These studies show that UC is associated with an atypical Th2 response mediated by nonclassical NKT cells producing IL-13 and having cytotoxic potential for epithelial cells.

Intestinal flora and mucosal immune responses.

The normal intestinal flora and the mucosal immune system exist in close spatial proximity. A normal structure and function of both very complex systems is required for health and develops in a constant and interactive process. An abnormal host response to the normal intestinal flora leads to chronic intestinal inflammation. Probiotic bacteria may modulate the intestinal flora and the mucosal immune response and are an effective therapy for remission maintenance of ulcerative colitis and pouchitis.