Presence Of Active Inflammation Research Articles

P261 Determination of faecal haemoglobin is equally effective as faecal calprotectin in identifying inflammatory bowel disease patients with active endoscopic inflammation

Background: Faecal calprotectin is a non-invasive tool to asses colonic inflammation in patients with inflammatory bowel disease (IBD). However, the diagnostic accuracy of calprotectin is modest and analysis is relatively costly and therefore additional markers are needed. We compared the efficacy of faecal haemoglobin and calprotectin in the prediction of active endoscopic inflammation in IBD patients. Methods: Consecutive patients with either Crohn’s colitis (CD) or ulcerative colitis (UC) scheduled for surveillance colonoscopy collected a stool sample prior to the start of bowel preparation. Three experienced endoscopists assessed the presence of active inflammation in each colonic segment. Stool samples were analyzed for calprotectin and haemoglobin, both with a Ridascreen® enzyme-linked immunosorbent assay (R-Biopharm, Germany) and were analyzed without reference to colonoscopy findings and vice versa. ROC statistics were used to determine cutoff values for calprotectin and haemoglobin. Results: A total of 119 patients were included, of which 54 patients had CD, 59 had UC and 6 indeterminate colitis. Median (interquartile range [IQR]) calprotectin and haemoglobin concentrations were 118 mg/g (IQR 31 367) and 0.48 mg/g (IQR 0.27 5.73) respectively. Active inflammation was encountered in 43 patients (36%) (5 severe, 9 moderate and 29 mild). Calprotectin and haemoglobin levels were significantly higher in patients with active inflammation compared to patients with no inflammation [451mg/g vs 52mg/g, p < 0.01 and 10.34mg/g vs 0.34mg/g, p < 0.01 respectively (Mann Whitney U test)]. A cutoff value of 172mg/g for calprotectin predicted endoscopic inflammation with 79% sensitivity, 80% specificity, 69% positive predictive value and 87% negative predictive value. The predictive accuracy of calprotectin (area under the curve [AUC]) was 0.88 which was similar for patients with CD and UC (AUC 0.86 and 0.86 respectively). For haemoglobin, a cutoff value of 1.45mg/g indicated endoscopic inflammation with 77% sensitivity, 88% specificity, 79% positive predictive value and 87% negative predictive value. The predictive accuracy of haemoglobin was 0.88 (AUC) which was similar for patients with CD and UC (AUC 0.87 and 0.81 respectively). A combination of both tests did not increase the predictive accuracy compared to each test alone (AUC 0.88). Conclusions: Faecal haemoglobin can identify IBD patients with active inflammation with a predictive accuracy similar to faecal calprotectin. P262 Demographic characteristic of children with early clinical manifestation of the inflammatory bowel disease S. Szymanska1 *, M. Szczepanski1, P. Landowski2, G. CzajaBulsa3, E. Jarocka-Cyrta4, B. Korczowski5, E. Krzesiek6, E. Szymanska1, J. Kierkus1. 1The Children Memorial Health Institute, Hepatology and Feeding Disorders, Warsaw, Poland, 2Medical University of Gdansk, Poland, 3Pomeranian Medical University, Poland, 4Medical University of Bialystok, Poland, 5Medical College. University of Rzeszow, Poland, 6Medical University of Wroclaw, Poland

Opposing Roles for EGFR in Colitis-Associated Cancer: The Presence of Active Inflammation Determines a Protective Versus Tumorigenic Role for EGFR

Opposing Roles for EGFR in Colitis-Associated Cancer: The Presence of Active Inflammation Determines a Protective Versus Tumorigenic Role for EGFR

Surgical treatment of globe subluxation in the active phase of the myogenic type of Graves orbitopathy: case reports

The purpose of the present article is to present and discuss two cases of globe subluxation in the active phase of myogenic Graves' orbitopathy and to evaluate the prevalence of this phenomenon. Two patients with the myogenic variant of Graves' orbitopathy that had being treated with oral and intravenous steroid pulses developed globe subluxation. Both had to have urgent eyelid and orbital decompression. After these observations, we reviewed the medical records of a sample of 284 patients (482 orbits) who had had orbital decompression at our Institution from 1992 to 2010, with a search for cases presenting severe proptosis or globe subluxation in the active phase of myogenic Graves' orbitopathy. No patient had to have decompression for globe subluxation in the active phase of Graves' orbitopathy. The prevalence of this event as an indication for surgery in the myogenic variant of Graves' orbitopathy was therefore 0.7% (2/284) or even less. The combination of lowering the upper eyelid and orbital decompression had a dramatic therapeutic effect on these patients despite the presence of intense inflammatory signs in the orbits. In conclusion, patients affected with the myogenic variant of Graves' orbitopathy may develop globe subluxation. Urgent surgical treatments should not be postponed despite the presence of active inflammation.

The role of RANK ligand/osteoprotegerin in rheumatoid arthritis

In the complex system of bone remodeling, the receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG) pathway is the coupling factor between bone formation and bone resorption. RANKL binds to the RANK receptor of pre-osteoclasts and mature osteoclasts and stimulates their activation and differentiation. The production of RANKL/OPG by osteoblasts is influenced by hormones, growth factors and cytokines, which each have a different effect on the production of RANKL and OPG. Ultimately, the balance between RANKL and OPG determines the degree of proliferation and activity of the osteoclasts. In rheumatoid arthritis (RA), bone erosions are the result of osteoclastic bone resorption at the sites of synovitis, where RANKL expression is also found. Furthermore, magnetic resonance imaging (MRI) bone edema in RA indicates the presence of active inflammation within bone and the presence of osteitis, which is also associated with the expression of RANKL. Bone loss has been documented in the cortical and trabecular bone in the joints of the hand of RA patients. Both synovitis and periarticular bone involvement (osteitis and bone loss) are essential components of RA: they occur early in the disease and both are predictive for the occurrence and progression of bone damage. RANKL knockout mice and mice treated with OPG did not develop focal bone loss, in spite of persistent joint inflammation. Inhibition of osteoclasts by denosumab, a humanized antibody that selectively binds RANKL, has revealed in patients with RA that the occurrence of erosions and periarticular bone loss can be halted, however without affecting synovial inflammation. This disconnect between inflammation and bone destruction opens new ways to separately focus treatment on inflammation and osteoclastogenesis for preventing and/or minimizing the connection between joints and subchondral bone and bone marrow.

The Fall of the Erythrocyte Sedimentation Rate

Abstract 4774The Fall of the Erythrocyte Sedimentation Rate, Ashley J. Archambault, MLS(ASCP), Gyorgy Abel, MD, PhD, John Gawoski, MD, Tim Skelton, MD, PhD, Charles Arkin, MD, Department of Laboratory Medicine, Lahey Clinic Medical Center, Burlington MAThe Erythrocyte Sedimentation Rate (ESR) is widely used to indicate the presence of active inflammation, particularly in rheumatic and infectious disorders. It has long been a mainstay in diagnostic protocols, as well as being a standard in the work-up of temporal arteritis. However, despite its entrenchment in the minds of many physicians, an increasing number of medical professionals believe that the ESR should be eliminated since its results are often misleading and too nonspecific. Moreover other indicators of inflammation such as the C-reactive protein (CRP) and fibrinogen are now readily available to provide more reliable information. The ESR is also costly, labor intensive, and hazardous to laboratory personnel.Based on the above, Lahey Clinic Medical Center eliminated ESR testing in April of 2010. To accomplish this, an initial informational campaign was launched among the Lahey Clinic medical staff. Literature was distributed and face-to-face meetings were conducted with the most frequent users of the test. Details of the ESR's limitations and the suitability of its replacement by the CRP were emphasized. To strengthen the contention that ESRs are not essential to our institution, two in-house studies were performed: Study 1 reviewed 6 months of patient data from 2008 in order to evaluate cases where the CRP was negative and the ESR was positive. Study 2 used multiple regression analysis to show that ESR values could be calculated from, and presumably replaced by, other clinical data.Study 1: The table below shows that among 4,858 paired ESR/CRP results collected over 6 months there were 17 cases with markedly elevated ESRs (> 50) and normal CRPs (≤5). There were 5,944 unpaired ESRs for this period. Chart reviews of the 17 cases showed that the ESR provided no additional clinical value and, of note, 4 of the 17 patients did have elevated CRPs in the course of their illness. In Study 2, multiple regression analysis of 155 specimens identified 4 independent correlates of the ESR among 8 variables studied: Fibrinogen, Globulin, Hematocrit and Age (collective r2 = 0.85). The scatter plot in the figure displays the relation of the observed to the calculated ESRs.Table:Results of 4858 Paired CRP/ESR Tests over 6 Months in 2008ESRCRP≤20>20 ≤50>50TOTAL≤51830304172151>5 ≤10818326561200>104466144471507TOTAL309412445204858 [Display omitted] In late 2009 a memo went out to our physicians giving three months notice of the ESR's discontinuation and recommending use of the CRP in its place. During this period, reminders of the approaching deadline were appended to all ESR results. For the Departments of Rheumatology and Infectious Diseases, an additional three months were granted during which time calculated ESR, fibrinogen, globulin, and hematocrit values were reported for every ESR ordered.In comparison to Study 1, the same six month period in 2011 shows a fall of 10,802 ESRs, a gain of 5,669 CRPs, and a drop in utilization of about 5,000 tests or 10,000 per year. These numbers suggest that CRPs replaced the unpaired ESRs and the utilization drop was due primarily to deletion of ESRs from paired orders.Over sixteen months of post ESR testing, the laboratory received only four inquiries from the medical staff: a complaint that a CRP did not automatically replace an ESR order; a request for supportive literature; and two requests for ESR values that were needed to satisfy standard treatment protocols. The latter were provided with calculated ESRs.In summary, ESR elimination occurred smoothly and with minimal incident. Sixteen months of experience have yielded no negative clinical effects but have produced the perceived benefits of utilization reduction, more available technologist time, less bio-hazard exposure, and elimination of an obsolete test. Disclosures:No relevant conflicts of interest to declare.

The time has come for clinical cardiovascular trials with plaque characterization as an endpoint

This editorial refers to ‘Determinants of magnetic resonance imaging detected carotid plaque components: the Rotterdam Study’, by Q. van den Bouwhuijsen et al. doi:10.1093/eurheartj/ehr227 . Atherosclerosis and its clinical sequelae are responsible for coronary artery disease, cerebrovascular complications, and peripheral arterial disease, a leading cause of mortality and morbidity in society.1 At the heart of the atherosclerotic disease cascade is the atherosclerotic plaque. For many years, pathology and post-mortem studies were the only method to evaluate the manifestation of atherosclerosis. The vulnerability of atherosclerotic plaques to rupture and cause cardiovascular and cerebrovascular events has long been associated with the presence of a thin fibrous cap with a large lipid core, endothelial denudation with platelet aggregation, presence of active inflammation, calcification, intraplaque haemorrhage, endothelial dysfunction, outward remodelling, and the …

IRF4 regulates IL-17A promoter activity and controls RORγt-dependent Th17 colitis in vivo

The transcription factor IRF4 is involved in several T-cell-dependent chronic inflammatory diseases. To elucidate the mechanisms for pathological cytokine production in colitis, we addressed the role of the IRF transcription factors in human inflammatory bowel disease (IBD) and experimental colitis. IRF levels and cytokine production in IBD patients were studied as well as the effects of IRF4 deficiency in experimental colitis. In contrast to IRF1, IRF5, and IRF8, IRF4 expression in IBD was augmented in the presence of active inflammation. Furthermore, IRF4 levels significantly correlated with IL-6 and IL-17 mRNA expression and to a lesser extent with IL-22 mRNA expression in IBD. To further explore the role of IRF4 under in vivo conditions, we studied IRF4-deficient and wildtype mice in experimental colitis. In contrast to DSS colitis, IRF4 deficiency was protective in T-cell-dependent transfer colitis associated with reduced RORα/γt levels and impaired IL-6, IL-17a, and IL-22 production, suggesting that IRF4 acts as a master regulator of mucosal Th17 cell differentiation. Subsequent mechanistic studies using database analysis, chromatin immunoprecipitation, and electrophoretic mobility shift assays identified a novel IRF4 binding site in the IL-17 gene promoter. Overexpression of IRF4 using retroviral infection induced IL-17 production and IL-17 together with IL-6 induced RORγt expression. IRF4 can directly bind to the IL-17 promotor and induces mucosal RORγt levels and IL-17 gene expression thereby controlling Th17-dependent colitis. Targeting of this molecular mechanism may lead to novel therapeutic approaches in human IBD.

CD10 immunohistochemistry stains enteric mucosa, but negative staining is unreliable in the setting of active enteritis

Ileal pouch–anal anastomosis is the definitive therapy for ulcerative colitis that is refractory to medical treatment or that has developed neoplasia. Patients with this procedure are routinely followed using directed endoscopic biopsies to monitor for dysplasia in the rectal cuff, residual/recurrent ulcerative colitis, and nonspecific acute inflammation of the ileal pouch (pouchitis), which have different clinical management and outcomes. Thus, accurate localization of mucosal biopsies is crucial to a definitive histological diagnosis, but is complicated by overlapping clinical presentations of pouchitis and ulcerative colitis, post-surgical and inflammatory changes to the mucosa, and altered endoscopic anatomy, resulting in difficulty determining whether a mucosal biopsy is ileal or rectal in origin for both the endoscopist and the pathologist. We explored the utility of CD10 immunohistochemistry to aid diagnosis in this clinical setting by highlighting the enteric mucosa, based on previous studies showing its utility in brush border staining and in the diagnosis of microvillous inclusion disease. We found uniformly positive CD10 immunostaining in normal enteric mucosa, but variable loss of expression in the setting of active enteritis. Specifically, CD10 staining was lost in up to 10% of the mucosa in 1/12 ileostomies and 4/13 enteric anastomoses, in 10–80% of the mucosa in 9/10 cases of Crohn's ileitis, in 10–60% of the mucosa in 7/16 ileal pouches, and in 20–90% of the mucosa in 6/8 cases of backwash ileitis, usually in the presence of active inflammation. There was no CD10 expression by normal or diseased colonic mucosa. Therefore, while CD10 immunostaining identifies normal enteric mucosa with 100% specificity, negative staining does not definitively exclude small intestinal mucosa in the setting of active enteritis, a common condition in ileal pouch mucosa.

P306 - Targeting angiogenesis in colitis-associated cancer

P306 - Targeting angiogenesis in colitis-associated cancer

Deep Corneal Calcification Associated With Preservative-free Eyedrops and Persistent Epithelial Defects

To describe the formation of deep calcareous degeneration of the cornea associated with the use of preservative-free eyedrops in patients with a persistent epithelial defect and active ocular surface inflammation. A case series of 6 patients with persistent epithelial defects (1 with diabetes, 3 with penetrating keratoplasty, and 2 with herpes zoster) treated with preservative-free medications was reviewed over 18 months. Each patient subsequently developed deep calcareous corneal degeneration. Data regarding underlying etiology, diagnosis, clinical findings, and medications used were recorded. Each medication used was analyzed for phosphate levels by using a Roche 917 analyzer. All 6 cases of calcareous degeneration of the cornea had persistent epithelial defects, treated with preservative-free medications (timolol, dexamethasone, and prednisolone), in the presence of active inflammation on the ocular surface. The mean levels of phosphate were 130, 42.9, and 22.9 mM in timolol, dexamethasone, and prednisolone, respectively. All 6 patients had some degree of corneal opacification and reduced visual acuity. A contributory factor in our case series seems to be the use of preservative-free medications in persistent epithelial defects. The preservative-free medications we measured had high levels of phosphate, which may not be common knowledge.

Compelling nature of arterial manifestations in Behçet disease

We present our experience with surgical treatment of arterial complications in Behcet disease (vasculo-Behcet disease), and the long-term results and pitfalls of surgical treatment. Between January 1990 and January 2003, 20 consecutive patients underwent surgery to treat vasculo-Behcet disease. Most patients (17 of 20) were men, with mean age of 38.4 years. Thirty-four operations were performed in 20 patients. The operative mortality rate was 5.8% (2 patients). There were 17 emergency operations, 6 because of ruptured primary abdominal aneurysms. There were five others with critical limb ischemia, resulting in 3 amputations. All patients were followed up postoperatively on average for 44 months (range, 6 months-14 years). Two additional patients were lost to follow-up. After the initial operation 10-year survival rate was 30%, 10-year complication-free survival rate was 13%, and 5-year repeat operation-free survival rate was 26%. Although surgical intervention should be postponed until active inflammation has subsided, often this is not possible, because of the emergent nature of these problems. Most arterial complications of vasculo-Behcet disease present with a pseudoaneurysm rupture or with impending rupture. An aggressive surgical approach can be life-saving in such instances, and should be undertaken regardless of long-term complications, which are more common when the operation is performed in the presence of active inflammation. Early and late results can be improved by individualizing, selecting a disease-free area for reconstruction, and eliminating use of autologous graft material.

Clinical and MRI assessment of brain damage in MS.

Cognitive impairment in multiple sclerosis (MS), generally in the form of the so-called subcortical dementia, results predominantly by the disruption of communication among cortical and subcortical areas, consequent to white matter damage. Studies with conventional magnetic resonance imaging (MRI) demonstrated that cognitive impairment in MS patients is related to lesion burden, although the strength of this correlation is weak. This can be partially explained by the poor pathological specificity of conventional MRI techniques and by damage in the normal-appearing white matter (NAWM). This interpretation is supported by studies using non-conventional MRI techniques, more specific to the heterogeneous substrates of MS pathology, such as the assessment of hypointense lesion load on T1-weighted scans and the measurement of the magnetization transfer ratio (MTR) of whole brain, MS lesions and NAWM. Other factors, such as the site of MS lesions and the presence of active inflammation, also seem to play an important role.

Inflammation and atrophy in multiple sclerosis: MRI associations with disease course

Brain atrophy may be a useful surrogate marker of axonal loss and disease progression in multiple sclerosis (MS). Several studies have suggested that inflammatory disease activity is a risk factor for atrophy in the early stages of the disease, but may become less important later in the disease course. We aimed to investigate the relationships between atrophy and active inflammation at different stages of the disease course using brain volume measurements from magnetic resonance imaging (MRI) in patients with both relapsing–remitting (RR) ( n=95) and secondary progressive (SP) ( n=76) MS. Conventional dual echo and three-dimensional magnetization-prepared rapid-acquisition gradient echo imaging were performed in all patients and in 31 healthy controls. Supratentorial and infratentorial brain, and lateral ventricular volumes were determined using modern design stereology. Patients with SP MS had smaller supratentorial ( p=0.003) and infratentorial brain volumes ( p=0.0003), and larger lateral ventricles ( p=0.02) than patients with RR MS. RR MS patients with T 1-enhancing lesions had smaller supratentorial ( p=0.02) and infratentorial ( p=0.002) brain volumes and larger ventricles ( p=0.002) than those without enhancing lesions. SP MS patients with enhancing lesions also had significantly larger lateral ventricles ( p=0.03). Categorical analysis showed that more RR MS patients with enhancing lesions had smaller supratentorial brain ( p=0.005), or larger lateral ventricular ( p=0.028) volumes, and more SP MS patients with enhancing lesions had increased lateral ventricle volumes ( p=0.013), than patients without enhancements. The number of enhancing lesions was significantly correlated with lateral ventricular volumes in both RR MS ( r=0.39, p=0.0001) and SP MS ( r=0.46, p<0.0001). Our data shows that the presence of active inflammation on a single MRI in the course of RR and SP MS, is associated with a higher risk and higher level of brain atrophy. These findings emphasise the important long-term relationship between inflammation and atrophy in MS and provide additional support for the strategy of early anti-inflammatory treatment to protect tissue integrity.

Pathology of inflammatory bowel diseases (IBD): variability with time and treatment.

The diagnosis of chronic idiopathic IBD and the differential diagnosis between Crohn's disease and ulcerative colitis can be made in most cases on cumulative clinical, radiological, endoscopical, biochemical and pathological evidence. Diagnostic difficulties can however, occur in fulminant colitis, in early onset disease and in long-standing disease. The microscopic evaluation of disease activity is based on the presence of active inflammation. Effective medical treatment has however, an influence upon the morphology and the evolution of the lesions and hence can affect the diagnostic features and the microscopic features used for the assessment of disease activity. A literature review was performed on clinical drug trials in IBD and the effect of the drugs upon the microscopic features. Several studies have shown that the diagnostic microscopic features and the features characteristic for disease activity vary with time and treatment. For an adequate analysis of biopsy samples of patients with IBD the pathologist should be aware of the duration of the symptoms and the type of treatment given to the patient.

Assessment of the damage of the cerebral hemispheres in MS using neuroimaging techniques.

The pattern of mental dysfunction in multiple sclerosis (MS) is characteristic of the so-called subcortical dementia. Cognitive dysfunction results predominantly by the disruption of communication among cortical and subcortical areas, as a consequence of the white matter damage. As expected, studies with conventional magnetic resonance imaging (MRI) demonstrated that cognitive impairment in MS patients is related to the lesion burden, although the strength of this correlation is weak. This can be partially explained by the poor pathological specificity of conventional MRI techniques and by the invisible damage in the normal-appearing white matter (NAWM). Recent studies using non-conventional MRI techniques with a higher specificity for the heterogeneous substrates of MS pathology, such as the assessment of hypointense lesion load on T1-weighted scans and the measurement of the magnetization transfer ratio (MTR) of whole brain, MS lesions and NAWM, support this interpretation. Other factors, such as the site of MS lesions and the presence of active inflammation, also seem to play an important role.

The Treatment of Inclusion Body Myositis

We have sought to examine the response to immunosuppressive therapeutic intervention in inclusion body myositis (IBM) in a retrospective review of prior responses to therapy and in an open, randomized crossover trial. We collected information on the response to prior therapy on 25 patients, and for prospective therapy on 11 of these patients. All met criteria for a definite idiopathic inflammatory myopathy and had biopsy-proven IBM. Clinical and laboratory results were assessed by interviews of patients and by chart review in the retrospective trial. Manual muscle strength was assessed by a single trained observer; the patients' activities of daily living were assessed by questionnaire; and serum tests of muscle-associated enzymes were measured in the prospective trial. In the retrospective review, prednisone appeared to have been of some, albeit modest, clinical benefit in 10 of 25 (40%) patients. Other therapies, primarily azathioprine and methotrexate, also appeared to have halted the progression of weakness in 8 of 35 trials (23%). In the prospective study, combination therapy of oral azathioprine and methotrexate and a biweekly infusion of high-dose intravenous methotrexate with leucovorin rescue were given for 3 to 6 months in an open, crossover design. Both the oral and the intravenous regimens were clinically effective in some patients. There was clinical improvement in 3 trials, stabilization in 11 trials, and worsening in 5 trials, out of a total of 19 completed (22 intended) trials. The presence of active inflammation at entry into the prospective therapeutic protocol, either directly observed on muscle biopsy or indirectly indicated by serum creatine kinase level, may have been associated with clinical improvement. A complete laboratory response with normalization of creatine kinase and other muscle-associated enzymes did not, however, significantly predict clinical responsiveness in the prospective trial. In this first report, to our knowledge, of a prospective trial of immunosuppressive therapy for this disease, stabilization and even slight improvement of strength and functional abilities appeared to be achieved in some patients. We believe that prednisone and other immunosuppressive therapies were of modest benefit in about half of patients with inclusion body myositis, especially those with some evidence of active inflammation. Stabilization of an otherwise inexorably deteriorating course appears, therefore, to be an attainable goal in some patients with IBM.

Increased absorption of polyethylene glycol 600 deposited in the colon in active ulcerative colitis.

A defect in the barrier function of the intestinal mucosa has been proposed as important in both the pathogenesis and systemic manifestations of inflammatory bowel disease. After colonoscopy, polymers of polyethylene glycol (PEG) with molecular weights of 414-810 (mean 600), were instilled in the descending colon of patients with ulcerative colitis (n = 17) and in controls without intestinal inflammation (n = 8). The patients with active ulcerative colitis (n = 6) had a significantly increased uptake of PEGs in the molecular weight range 458-810, measured as urinary excretion over the first 6 hours after instillation. The median values for their excretion were 2.85-3.80% of PEGs instilled compared with 0.32-0.94% for patients in remission (n = 11) (p < 0.05-0.01) and 0.17-0.60% for the controls (p < 0.05-0.01). The differences in absorption of PEG 414 did not reach the present level of statistical significance. There was a positive correlation between PEG absorption and the endoscopic and histological grading of inflammatory activity in the sigmoid colon (p < 0.01-0.001). These findings support a correlation between the presence of active inflammation and PEG absorption. There was little evidence to support the presence of a primary defect in the colonic barrier in patients with ulcerative colitis.

Helicobacter pyloriand Chronic Active Inflammation of the Duodenum and Stomach in Duodenal Ulcer Patients Treated with Ranitidine, Misoprostol, or an Acid-Neutralizing Agent

Biopsy specimens from the stomach and duodenum of 45 duodenal ulcer patients treated with ranitidine, misoprostol, or an antacid were examined. During 4 weeks of treatment the duodenal ulcer healed in 31 patients. The treatment regimens showed no significant effect on the amount of Helicobacter-like structures (HLS) or the presence of active inflammation, either in the stomach or in the duodenum. All patients had chronic active antral gastritis before and after treatment. HLS were found histologically in 91.7% of all antral specimens, in 94.2% of the gastric corpus specimens, in 15.9% of the duodenal bulb specimens, and in 0.9% from the lower duodenal knee. The frequency of chronic active gastritis was clearly lower in the gastric corpus than in the antrum, whereas the occurrence of HLS was about the same. This may indicate a higher resistance of the gastric corpus mucosa to H. pylori.

Search for a specific marker of mucosal dysplasia in chronic ulcerative colitis

We have tried to identify a histochemical or immunohistochemical marker that would reliably detect mucosal dysplasia in chronic ulcerative colitis. Colonic biopsy specimens were taken from patients with long-standing ulcerative colitis undergoing surveillance colonoscopy. Control tissue was obtained from the margins of colonic resections performed for neoplastic or nonneoplastic diseases. Sections of the specimens were examined by periodic acid-Schiff staining, high iron diamine Alcian blue staining for sialomucins and sulfomucins, and binding of the lectins peanut agglutinin, Ulex europeus agglutinin I, and Ricinis communis I agglutinin. Sections were reacted also with anticarcinoembryonic antigen antibodies to determine whether a nonpolar surface distribution of the antigen was a feature of dysplasia. We found that changes in colonic mucin, characterized by periodic acid—Schiff-positive mucin outside of goblet cells, an increase in binding of peanut agglutinin, and an increase in the relative amount of sialylated mucin, were associated with morphologic dysplasia. However, identical alterations were observed, albeit less commonly, in colitis without dysplasia, particularly in the presence of active inflammation. No abnormality in the surface distribution of carcinoembryonic antigen or Ricinis communis I agglutinin was observed. Thus, we did not identify a reliable corollary test to the histologic diagnosis of mucosal dysplasia in ulcerative colitis. With regard to these histochemical markers, the colonic mucosa appears to respond similarly to inflammation and neoplasia.

Wound Necrosis Following Dacryocystorhinostomy in Patients With Wegener's Granulomatosis

Two patients with Wegener's granulomatosis underwent dacryocystorhinostomy (DCR) for nasolacrimal duct obstruction and epiphora. Wound necrosis occurred in each individual with the formation of a nasal-cutaneous fistula. A pedicle flap was the treatment of choice in one case, while direct closure of the necrotic incision site and high-dose steroid therapy was used in the other. Both did well with complete wound healing. The tearing persisted in one and resolved in the other. Dacryocystorhinostomy should be avoided whenever possible in patients with Wegener's granulomatosis, and steroid dosage should be increased if surgery is necessary in the presence of active inflammation.