Secretory Meningioma of the Right Frontal Lobe: Clinical Presentation and Pathological Insights.

This article presents a case study of a rare convexity meningioma located in the frontal lobe of the right cerebellar hemisphere. Meningiomas comprise a substantial part of central nervous system neoplasms and are classified into benign, atypical, or anaplastic categories, each encompassing a variety of histological subtypes, among which the secretory meningioma is notably rare. A 77-year-old male presented with a clinical history of headache, impaired memory functions, an initial form of apathetic-abulic syndrome, and a single seizure, which were considered to be indicative of epileptic symptoms that had been present for several weeks. The imaging studies conducted showed a convexity tumor characterized by a rounded morphology and homogeneous contrast enhancement, positioned adjacent to the frontal lobe's cortical surface. This clinical report details the pathology of a secretory type of meningioma, which is distinguished by the atypical epithelial differentiation of meningothelial cells, resulting in hyaline fiber production. The neoplasm's anatomical accessibility permitted successful surgical resection. The tumor's position was appropriate for surgical removal, and the histological variant, along with the patient's favorable clinical course, is of particular scientific interest.

Glycan-Tailored Glycoproteomic Analysis Reveals Serine is the Sole Residue Subjected to O-Linked Glycosylation in Acinetobacter baumannii.

Protein glycosylation is a ubiquitous process observed across all domains of life. Within the human pathogen Acinetobacter baumannii, O-linked glycosylation is required for virulence; however, the targets and conservation of glycosylation events remain poorly defined. In this work, we expand our understanding of the breadth and site specificity of glycosylation within A. baumannii by demonstrating the value of strain specific glycan electron-transfer/higher-energy collision dissociation (EThcD) triggering for bacterial glycoproteomics. By coupling tailored EThcD-triggering regimes to complementary glycopeptide enrichment approaches, we assessed the observable glycoproteome of three A. baumannii strains (ATCC19606, BAL062, and D1279779). Combining glycopeptide enrichment techniques including ion mobility (FAIMS), metal oxide affinity chromatography (titanium dioxide), and hydrophilic interaction liquid chromatography (ZIC-HILIC), as well as the use of multiple proteases (trypsin, GluC, pepsin, and thermolysis), we expand the known A. baumannii glycoproteome to 33 unique glycoproteins containing 42 glycosylation sites. We demonstrate that serine is the sole residue subjected to glycosylation with the substitution of serine for threonine abolishing glycosylation in model glycoproteins. An A. baumannii pan-genome built from 576 reference genomes identified that serine glycosylation sites are highly conserved. Combined this work expands our knowledge of the conservation and site specificity of A. baumannii O-linked glycosylation.

Development and validation of an algorithm of diagnostic and procedural codes for the identification of children hospitalized with a tracheostomy in Ontario, Canada.

BACKGROUND: The requirement for a tracheostomy in children is associated with significant morbidity, mortality, and healthcare utilization. Easy identification of children with tracheostomies would facilitate important research on this population and provide quality improvement initiatives. AIM: The purpose of this study is to determine whether an algorithm of diagnostic and procedural codes can accurately identify children hospitalized with a tracheostomy using routinely collected health data. METHODS: Chart reviews were performed at the Children's Hospital of Eastern Ontario (CHEO) and the London Health Sciences Center (LHSC) to establish a true positive cohort of pediatric patients with tracheostomies admitted between 2008 and 2016. A multidisciplinary team developed algorithms of diagnostic and procedural codes contained within the Canadian Institute for Health Information Discharge Abstract Database. Algorithms were tested and refined against the true-positive and true-negative cohort. The accuracy of the diagnostic codes related to tracheostomy complications was also evaluated. RESULTS: A chart review identified 158 unique children with tracheostomies (77 at CHEO, 81 at LHSC) with 901 individual admissions (401 at CHEO, 507 at LHSC). The best algorithms for identifying children with a tracheostomy had a sensitivity and specificity of more than 99%, a positive predictive value (PPV) of 94.0% and negative predictive value (NPV) of 100%. The algorithm for the identification of tracheostomy-related complications had a sensitivity of 76.7%, a specificity of 65%, PPV of 52.3%, and an NPV of 84.7%. CONCLUSIONS: This study provides an algorithm for the accurate identification of children hospitalized in Canada with a tracheostomy, facilitating population-level epidemiological research and quality improvement initiatives.

Quality Indicators for the Diagnosis and Management of Acute Bacterial Rhinosinusitis.

BACKGROUND: Acute bacterial rhinosinusitis (ABRS) is a highly prevalent disease that is treated by a variety of specialties, including but not limited to, family physicians, emergency physicians, otolaryngology-head and neck surgeons, infectious disease specialists, and allergy and immunologists. Unfortunately, despite high-quality guidelines, variable and substandard care continues to be demonstrated in the treatment of ABRS. OBJECTIVE: This study aimed to develop ABRS-specific quality indicators (QIs) to evaluate the diagnosis and management that reduces symptoms, improves quality of life, and prevents complications. METHODS: A guideline-based approach, proposed by Kötter et al., was used to develop QIs for ABRS. Candidate indicators (CIs) were extracted from 4 guiding documents and evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Each CI and its supporting evidence was summarized and reviewed by an expert panel based on validity, reliability, and feasibility of measurement. Final QIs were selected from CIs utilizing the modified RAND/University of California at Los Angeles appropriateness methodology. RESULTS: Twenty-nine CIs were identified after literature review and evaluated by our panel. Of these, 5 CIs reached consensus as being appropriate QIs, with 1 requiring additional discussion. After a second round of evaluations, the panel selected 7 QIs as appropriate measures of high-quality care. CONCLUSION: This study proposes 7 QIs for the diagnosis and management of patients with ABRS. These QIs can serve multiple purposes, including documenting the quality of care; comparing institutions and providers; prioritizing quality improvement initiatives; supporting accountability, regulation, and accreditation; and determining pay for performance initiatives.

Quality indicators for the diagnosis and management of chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) has been identified as a high-priority disease category for quality improvement. To this end, this study aimed to develop CRS-specific quality indicators (QIs) to evaluate diagnosis and management that relieves patient discomfort, improves quality of life, and prevents complications. METHODS: A guideline-based approach, proposed in 2012 by Kötter et al. was used to develop QIs for CRS. Candidate indicators (CIs) were extracted from 3 practice guidelines and 1 international consensus statement on the diagnosis and management of CRS. Guidelines were evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Each CI and its supporting evidence was summarized and reviewed by an expert panel based on validity, reliability, and feasibility of measurement. Final QIs were selected from CIs utilizing the modified RAND Corporation-University of California, Los Angeles (RAND/UCLA) appropriateness methodology. RESULTS: Thirty-nine CIs were identified after literature review and evaluated by our panel. Of these, 9 CIs reached consensus as being appropriate QIs, with 4 requiring additional discussion. After a second round of evaluations, the panel selected 9 QIs as appropriate measures of high-quality care. CONCLUSION: This study proposes 9 QIs for the diagnosis and management of patients with CRS. These QIs can serve multiple purposes, including documenting the quality of care; comparing institutions and providers; prioritizing quality improvement initiatives; supporting accountability, regulation, and accreditation; and determining pay-for-performance initiatives.

Temporary Frontal Paralysis Secondary to Blunt Trauma Frontal Sinus Fracture.

Frontal sinus fractures (FSF) are relatively uncommon and can be challenging for trauma surgeons to manage. Patients with FSF typically present with facial swelling, pain, and nasofrontal ecchymosis. Here we present a rare case of a patient with FSF and anterior table fracture where the main presenting symptom was bilateral frontal paralysis. We outline our management strategy and review the current literature in regard to management of FSF.

Development and validation of an administrative data algorithm to identify adults who have endoscopic sinus surgery for chronic rhinosinusitis.

BACKGROUND: This was a diagnostic accuracy study to develop an algorithm based on administrative database codes that identifies patients with Chronic Rhinosinusitis (CRS) who have endoscopic sinus surgery (ESS). METHODS: From January 1st, 2011 to December 31st, 2012, a chart review was performed for all hospital-identified ESS surgical encounters. The reference standard was developed as follows: cases were assigned to encounters in which ESS was performed for Otolaryngologist-diagnosed CRS; all other chart review encounters, and all other hospital surgical encounters during the timeframe were controls. Algorithm development was based on International Classification of Diseases, version 10 (ICD-10) diagnostic codes and Canadian Classification of Health Interventions (CCI) procedural codes. Internal model validation was performed with a similar chart review for all model-identified cases and 200 randomly selected controls during the following year. RESULTS: During the study period, 347 cases and 185,007 controls were identified. The predictive model assigned cases to all encounters that contained at least one CRS ICD-10 diagnostic code and at least one ESS CCI procedural code. Compared to the reference standard, the algorithm was very accurate: sensitivity 96.0% (95%CI 93.2-97.7), specificity 100% (95% CI 99.9-100), and positive predictive value 95.4% (95%CI 92.5-97.3). Internal validation using chart review for the following year revealed similar accuracy: sensitivity 98.9% (95%CI 95.8-99.8), specificity 97.1% (95%CI 93.4-98.8), and positive predictive value 96.9% (95%CI 93.0-99.8). CONCLUSION: A simple model based on administrative database codes accurately identified ESS-CRS encounters. This model can be used in population-based cohorts to study longitudinal outcomes for the ESS-CRS population.

Glomangiopericytoma simulating an intracavernous meningioma.

BACKGROUND: Glomangiopericytoma is an uncommonly encountered tumor of the nose and paranasal sinuses, accounting for <0.5% of all sinonasal tumors. Extension of these lesions to the anterior or middle cranial fossa is rare. When this occurs, diagnosing glomangiopericytoma is extremely challenging, as it is often confused with other anterior skull base tumors. CASE DESCRIPTION: We report a case of a giant glomangiopericytoma localizing into the cavernous sinus in a 48-year-old female who presented with mild left-sided ptosis for 48 months. The lesion simulated an intracavernous meningioma on preoperative imaging. An expanded endoscopic endonasal approach was used to debulk the portion of the lesion in the medial compartment of the cavernous sinus. Postoperatively, the patient's ptosis resolved completely, and no new deficits were sustained. CONCLUSION: This is the only case of glomangiopericytoma localizing solely to the cavernous sinus reported to date.

Chronic rhinosinusitis identification in administrative databases and health surveys: A systematic review.

OBJECTIVES/HYPOTHESIS: Much of the epidemiological data on chronic rhinosinusitis (CRS) are based on large administrative databases and health surveys. The accuracy of CRS identification with these methods is unknown. METHODS: A systematic review was performed to identify studies that measured the accuracy of CRS diagnoses in large administrative databases or within health surveys. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess study quality. RESULTS: Of 512 abstracts initially identified, 122 were selected for full-text review; only three studies (2.5%) measured the accuracy of CRS patient identification. In a single, large administrative database study with a CRS prevalence of 54.8%, a single International Classification of Diseases-9th Revision diagnostic code for CRS had a positive predictive value (PPV) of only 34%. A diagnostic code algorithm identified CRS patients with a PPV of 91.3% (95% confidence interval [CI], 85.3-95.1); in a population with a CRS prevalence of 5%, this algorithm had a PPV of 31%. In health survey studies having an estimated CRS prevalence of 25% to 46%, self-reported symptom-based CRS diagnosis had a PPV of 62% (95% CI, 50.2-72.1) when nasal endoscopy was the gold standard for CRS diagnosis, and 70% (95% CI, 57.4-80.8) when otolaryngologist-based CRS diagnosis (after interview and nasal endoscopy) was the gold standard. CONCLUSION: Most health administrative data and health surveys examining CRS did not consider the accuracy of case identification. For unselected populations, administrative data and health surveys using self-reported diagnoses inaccurately identify patients with CRS. Epidemiological results based on such data should be interpreted with these results in mind. Laryngoscope, 126:1303-1310, 2016.

Primary Osteosarcoma of the Skull Base Treated with Endoscopic Endonasal Approach: A Case Report and Literature Review.

Introduction Giant cell-rich osteosarcoma (GCRO) is a rare pathologic diagnosis, and most cases have involved the appendicular skeleton. We present a challenging diagnosis of GCRO of the skull base treated with an endoscopic endonasal approach. Case Presentation An 18-year-old female patient presented with acute monocular visual loss. Imaging revealed a large clival mass encasing the internal carotid arteries bilaterally with pituitary and optic nerve compression. The lesion was resected via a staged endoscopic endonasal approach and the patient's vision normalized postoperatively. The final pathological diagnosis was challenging and, after consultation with multiple North American centers, was concluded as GCRO. The tumor recurred and further surgery was performed, followed by adjuvant chemoradiation. Conclusion We highlight diagnostic challenges of GCRO of the skull base, and describe, with intraoperative pictures, successful surgical resection via an endoscopic endonasal approach. Based on our literature review, this is the first published case report of GCRO of the skull base.

Eyelid and brow asymmetry in patients evaluated for upper lid blepharoplasty.

INTRODUCTION: In evaluation for blepharoplasty, patients often desire improved cosmesis and/or correction of visual field deficits. However, patients are usually unaware of eyelid or brow asymmetry. Furthermore, the prevalence of eyelid and brow asymmetry is infrequently reported in the medical literature. PURPOSE: To determine the prevalence of brow and eyelid asymmetry in patients evaluated for upper lid blepharoplasty. METHODS: One hundred consecutive patients evaluated for upper lid blepharoplasty were included in the study. Standard pre-operative photographs were taken of all patients using consistent background and photographic equipment. Two of the authors (KM & AM) independently recorded the margin pupil (MPD), central eyebrow (CED), nasal eyebrow (NED) and temporal eyebrow (TED) distances. To test the inter-observer reliability, the senior author (SMT) recorded the same measurements for 10% of randomly selected patients. We calculated 95% confidence intervals to compare symmetry between the right and left sides. RESULTS: One hundred patients (94 female, mean age 57.7) were included in the study. The average MPD, CED, NED and TED distances were 0.55 mm (95% CI 0.45-0.65), 1.77 mm (95% CI 1.47-2.07), 1.34 mm (95% CI 1.14-1.54), and 1.78 mm (95% CI 1.50-2.06), respectively. Ninety-three percent of patients had at least one asymmetric measurement of greater than 1 mm. Seventy-five percent of patients studied had at least one measurement greater than 2 mm while 37 percent had at least one greater than 3 mm. CONCLUSION: Brow and eyelid asymmetry is common in patients being evaluated for upper lid blepharoplasty. The facial plastic surgeon should identify and document facial asymmetry pre-operatively, and discuss it with prospective blepharoplasty patients. This will improve informed consent and patient expectations.

The use of postoperative topical corticosteroids in chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis.

BACKGROUND: Topical intranasal corticosteroids (INCSs) are used to control disease symptoms in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). The evidence to recommend INCSs as part of the postoperative care is limited. This study was designed to assess the efficacy of INCSs in the postoperative care of patients undergoing functional endoscopic sinus surgery (FESS) during the 1st year postoperatively. METHODS: We searched the Cochrane Central Register of Controlled Trials (1995 to May 2012), MEDLINE (January 1948 to May 2012), EMBASE (January 1980 to May 2012), and the reference lists of articles. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Randomized controlled trials (RCT) and cohort studies comparing INCSs with placebo or comparing different types of INCSs were included. RESULTS: Eleven studies (n = 945 patients) were RCTs and one prospective cohort study (n = 32 patients). As measured by the standardized mean difference (SMD) INCSs had a beneficial effect on symptom scores (SMD, -1.35; 95% CI, -2.05 to -0.64; p = 0.0002; 3 trials; 137 patients) and polyp score (SMD, 0.53; 95% CI, -0.91 to -0.14; p = 0.007; 5 trials; 223 patients). Compared with placebo, the use of INCSs decreased the odds of polyp recurrence (odds ratio, 0.17; 95% CI, 0.06-0.51; p = 0.002; 2 trials; 74 patients). Two RCTs (n = 105) and one cohort study (n = 32) reported normal adrenocorticotropic hormone levels postintervention. CONCLUSION: INCS use is a safe therapy in postoperative management of CRSwNP patients. INCS showed significant improvement in polyp score, patients' symptoms and significant decrease in polyp recurrence in the first year postoperatively.

The inferior turbinate flap in skull base reconstruction.

BACKGROUND: As the indications for expanded endonasal approaches continue to evolve, alternative reconstructive techniques are needed to address increasingly complex surgical skull base defects. In the absence of the nasoseptal flap, we describe our experience with the posterior pedicle inferior turbinate flap (PPITF) in skull base reconstruction. DESIGN: Case series. SETTING: Academic tertiary care centre. METHODS: Patients who underwent reconstruction of the skull base with the PPITF were identified. Medical records were reviewed for demographic, presentation, treatment, follow-up, surgical and outcomes data. MAIN OUTCOME MEASURES: Flap survival, adequacy of seal, and complications. RESULTS: Two patients with residual/recurrent pituitary adenomas met the inclusion criteria. The nasoseptal flap was unavailable in each case due to a prior septectomy. Salvage of the original nasoseptal flap was not possible, as it did not provide adequate coverage of the resultant defect due to contraction from healing. All PPITFs healed uneventfully and covered the entire defect. No complications were observed in the early post-operative period. Endoscopic techniques and limitations of the PPITF are also discussed. CONCLUSIONS: Our clinical experience supports the PPITF to be a viable alternative for reconstruction of the skull base in the absence of the nasoseptal flap.

Effect of fibula free flap harvest on the gait of head and neck cancer patients: preliminary results.

OBJECTIVE: To determine the impact of fibula free flaps (FFFs) on gait. DESIGN: Prospective trial. SETTING: FFF patients who gave consent were enrolled. METHODS: At preoperative and 3-month postoperative visits, patients walked 30 m with the Walkabout Portable Gait Monitor (WPGM), a portable device developed at Dalhousie University that records acceleration of the centre of mass. Gaitview software provided several outputs for analysis: vertical (VA) and forward (FA) asymmetry, horizontal to vertical power ratio (HVP), vertical to forward power ratio (VFP), velocity, and step length. Patients were compared pre- and postoperatively and to age-matched control data with a Student paired t-test. Patients completed a self-comorbidity questionnaire and a point evaluation system (PES) with subjective questions on gait. PES data were compared to a Mann-Whitney U test using SPSS, version 15.0.1. MAIN OUTCOME MEASURES: Gaitview output and PES questionnaire. RESULTS: From September 2008 to January 2010, 12 patients enrolled in the study. Eight provided 3-month postoperative data. The Gaitview analysis showed that none of the six parameters changed postoperatively. The VA and FA preoperatively and at 3 months postoperatively were 21.3 versus 24.2, p > .50, and 65.4 versus 74.9, p > .50, respectively. The HVP and VFP preoperatively and postoperatively were 133.4 versus 138.9, p > .50, and 129.6 versus 122.8, p > .50, respectively. The velocity and step length preoperatively and postoperatively were 125.9 versus 119.5 cm/s, p > .50, and 76.0 versus 74.9 cm, p > .50, respectively. The subjective PES questionnaire did not change significantly (p  =  .26). CONCLUSION: Preliminary findings confirm that the FFF is associated with little subjective or objective gait impairment.

Hand-assisted laparoscopic abdomino-perineal resection utilizing the planned end colostomy site.

BACKGROUND: Aim of the study was to determine the feasibility and outcomes of utilizing the planned end colostomy site for placing the hand-assist device in performing hand-assisted laparoscopic abdominoperineal resections (HAL APR) in patients with low rectal cancer. METHODS: Patients with low rectal cancers not suitable for a sphincter salvage proctectomy were recruited. HAL APR was performed by placing the hand-assist device over the planned colostomy site. Standard total mesorectal excision (TME) was performed, and the specimen was delivered via the perineal incision. Patient data and perioperative variables were obtained from the institution colorectal cancer database and analyzed. RESULTS: Six patients underwent HAL APR from November 2004 to January 2006. Mean operative time was 213 min with no conversions or intraoperative complications. One patient developed post-operative ileus which resolved spontaneously. There were no other morbidities or mortalities. Mean hospitalization was 6.8 days. After a mean follow-up of 13.3 months, one patient developed a parastomal hernia which was subsequently repaired during liver resection for liver metastases. No other long-term complications occurred. CONCLUSION: HAL APR with the hand device placed at the planned stoma site is technically feasible. Without creating an additional incision, the operation is oncologically comparable and renders similar short-term outcomes as SL methods, maintaining the benefits of a minimally invasive approach.

Level VI node size as a predictor of malignancy in papillary thyroid cancer.

OBJECTIVE: To determine the incidence of metastatic lymph nodes < 1 cm in routine level VI neck dissections in papillary thyroid cancer (PTC). DESIGN: Retrospective chart review. SETTING: Tertiary referral hospital. METHODS: A retrospective review was conducted of all patients who had thyroid surgery and routine level VI neck dissection for PTC from June 2005 to February 2009. The number of lymph nodes present, node size, and malignancy status were recorded. Patients with level VI micrometastases (positive nodes < 1 cm) were compared with those with no positive nodes. RESULTS: Forty-six patients had level VI neck dissection for PTC, with a total of 379 lymph nodes. No patient had permanent hypocalcemia or recurrent laryngeal nerve injury. Nodes > or = 1 cm had a 77% likelihood of being positive (95% confidence interval [CI] 0.58-1.00), whereas nodes < 1 cm had a 24% (95% CI 0.20-1.00) likelihood of being positive. Seventeen (37%) patients had micrometastases only. Older age, male sex, and primary tumour > 5 cm were not predictive of an increased risk of micrometastases. Patients with extrathyroidal extension were significantly more likely to have micrometastases (p < .05). CONCLUSIONS: With a significant percentage of metastatic level VI neck nodes < 1 cm in PTC, the decision to perform a level VI neck dissection cannot be based on preoperative ultrasound size criteria alone. Routine level VI neck dissection is a safe addition to thyroid surgery for PTC. We could identify no preoperative risk factors to predict the likelihood of micrometastases.

Quality of life and impact of surgery on patients with chronic rhinosinusitis.

OBJECTIVE: To measure the impact of chronic rhinosinusitis (CRS) on the health of Nova Scotians and evaluate the role of surgery in modifying this impact. METHODS: Nova Scotia residents with CRS referred to one otolaryngologist were enrolled. The Chronic Sinusitis Survey (CSS) and Short Form 36-Item Health Survey (SF-36) were administered preoperatively and at two postoperative visits. The SF-36 data were compared with Canadian published norms. Also, the postoperative survey results were compared with preoperative data to evaluate the role of surgery in improving health. RESULTS: Thirty-eight patients completed preoperative and 3-month forms, and 26 patients completed preoperative and 3- and 12-month postoperative forms. Patients with CRS showed a significant decrease in five of eight SF-36 subscales. Surgery significantly improved preoperative scores for six of eight subscales and both the physical (PCS) and mental (MCS) component summary scores (p < .05). Males were more likely than females to report postoperative improvements (p = .02). Males under 50 years were more likely to show improvement in the PCS score (p = .02), with no significant change in the MCS score. Females under 50 years were more likely to show improvement in the MCS score (p = .02), with age having no effect on PCS score. CONCLUSION: This study confirms that Canadians with CRS have lower quality of life and for the first time in Canada demonstrates that functional endoscopic sinus surgery can restore health. Males showed a greater response than females, and patients under 50 years were more likely to improve after surgery. This information on patient factors influencing outcomes may help physicians when counseling patients regarding surgery for CRS.

The health and resource utilization of Canadians with chronic rhinosinusitis.

OBJECTIVES: To determine the impact of chronic rhinosinusitis (CRS) on the physical and mental health and health-resource utilization of Canadians. STUDY DESIGN: Cross-sectional. METHODS: Data from the detailed health portion of cycle 3 (1998-1999) of the National Population Health Survey (NPHS), which involved 17,000 Canadians, were used to evaluate Canadians with self-reported CRS. RESULTS: NPHS data confirmed lower mental and physical health, with CRS sufferers being almost three times more likely to report their health as poor (4.6% vs. 1.7%). Health Utility Index data identified a significant decline in the mental health of patients with CRS, which was associated with more depression (8.4% vs. 4.1%), more antidepressant use (9.1% vs. 4.6%), and more visits to mental-health professionals (11.8% vs. 7.0%). CONCLUSIONS: CRS significantly affects both physical and mental health. The mental impact of CRS remains largely unrecognized and should be of greater focus during patient care and in further research.

Loss of the tight junction protein ZO-1 in dextran sulfate sodium induced colitis.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with increased intestinal permeability and decreased expression of tight junction (TJ) proteins in the inflamed mucosa. Whether this alteration in TJ expression is a prerequisite for the development of intestinal inflammation or a secondary result of that inflammation is unknown. This study looked at the expression of the TJ protein ZO-1 and the corresponding permeability changes in dextran sulfate sodium (DSS) induced colitis in a mouse model. MATERIALS AND METHODS: BALB/c mice were fed 3% DSS or water for 1, 3, 5, or 7 days. The animals were weighed, stool was checked for blood, and the colon length measured. Segments of the colon were used for histology, immunohistochemistry for ZO-1, or Western blot for TJ proteins. Colonic permeability was measured using Evan's Blue dye. RESULTS: DSS treated animals had heme positive stools, colitis by histology, significant weight loss, and colon shortening. There was an absence of ZO-1 by Western blot in the 7-day DSS treated animals, double the amount of claudin-1 and normal cytokeratin. The loss of ZO-1 started after 1 d of DSS treatment and was followed by a significant increase in permeability to Evan's blue by day 3. CONCLUSIONS: The loss of ZO-1 and increased permeability preceded the development of significant intestinal inflammation suggesting that in DSS colitis alterations in the TJ complex occur before the intestinal inflammation and not as a consequence of it. These changes in the TJ complex may facilitate the development of the inflammatory infiltrate seen in colitis.

Tumor necrosis factor alpha disrupts tight junction assembly.

BACKGROUND: We have previously shown an increase in intestinal permeability and a corresponding decrease in the expression of tight junction (TJ) proteins in the in testines of patients with Crohn's disease (CD). Tumor necrosis factor-alpha (TNFalpha) has been implicated in the inflammatory process of CD and its suppression has therapeutic benefit. ZO-1, occludin, and the claudins are key proteins in the TJ. HYPOTHESIS: TNFalpha disrupts the TJ. METHODS: MDCK cells were incubated with TNFalpha (0-100 ng/ml) for 5 days. Qualitative evaluation of the TJ was done with monoclonal antibody to ZO-1 detected by an immunofluorescence. Duplicate cells were lysed and ZO-1, occludin, and claudin-1 amount determined by western blot. RESULTS: Immunofluorescent staining of MDCK cells for ZO-1 showed TJ structural disruption with increasing amount of TNFalpha characterized by fragmented staining of ZO-1. There were no significant differences in quantitation of ZO-1 or occludin in the MDCK cells for all TNFalpha concentrations. There was a significant decrease in the amount of claudin-1 with increasing concentration of TNFalpha. CONCLUSIONS: (1) MDCK TJs are qualitatively disrupted by TNFalpha. (2) This disruption is not because of a decrease in cell number, lack of cell layer confluency, or a decrease in the amount of ZO-1 or occludin. (3) The amount of claudin-1 present in the cell is decreased with increasing amounts of TNFalpha suggesting that the lack of claudin-1 may cause a relocation of ZO-1 away from the TJ. (4) This rearrangement may play a role in the increased intestinal permeability seen in CD and other diseases.