High circulating serum immunoglobulin G4 (IgG4) levels have been proposed as a marker of autoimmune pancreatitis (AIP). The aim of the present study was to review the data existing in the English ...literature on the usefulness of the IgG4 serum levels in the diagnosis and follow up of patients with AIP. A total of 159 patients with AIP and 1099 controls were described in seven selected papers reporting the usefulness of serum IgG4 in diagnosing AIP. In total, 304 controls had pancreatic cancer, 96 had autoimmune diseases, and the remaining 699 had other conditions. The summary receiver–operating characteristic curve analysis was carried out by means of Meta‐DiSc open‐access software. Serum IgG4 showed good accuracy in distinguishing between AIP and the overall controls, pancreatic cancer and other autoimmune diseases (area under the curve ± SE: 0.920 ± 0.073, 0.914 ± 0.191, and 0.949 ± 0.024, respectively). The studies analyzed showed significantly heterogeneous specificity values in each of the three analyses performed. The analysis of the four studies comparing AIP and pancreatic cancers also showed significantly heterogeneous values of sensitivities and odds ratios. Regarding the usefulness of IgG4 as a marker of efficacy of steroid treatment, a decrease in the serum concentrations of IgG4 was found in the four available studies. The serum IgG4 subclass is a good marker of AIP, and its determination should be included in the diagnostic workup of this disease. However, the heterogeneity of the studies published until now means that more studies are necessary in order to better evaluate the true accuracy of IgG4 in discriminating AIP versus other autoimmune diseases.
Acute pancreatitis, chronic pancreatitis and pancreatic cancer are responsible for most of the burden of exocrine pancreatic disease. Glandular damage from recurrent bouts of acute pancreatitis can ...lead to irreversible changes characteristic of chronic pancreatitis. In recent decades accumulating evidence has defined longstanding pre-existing chronic pancreatitis as a strong risk factor for pancreatic cancer. The lag period between diagnosis of chronic pancreatitis and pancreatic cancer is usually one or two decades: pancreatitis appearing a year or two before the diagnosis of pancreatic cancer is often the result of tumour-related ductal obstruction. The risk of developing pancreatic cancer appears to be highest in rare types of pancreatitis with an early onset, such as hereditary pancreatitis and tropical pancreatitis. Even though there is a strong link between chronic pancreatitis and pancreatic cancer, over a 20 year period only around five percent of patients with chronic pancreatitis will develop pancreatic cancer. Until the development of more sophisticated screening procedures, screening is not recommended for patients with chronic pancreatitis.
Background & Aims
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The mechanisms underlying abdominal pain perception in irritable bowel syndrome (IBS) are poorly understood. Intestinal mast cell infiltration may perturb nerve function leading ...to symptom perception. We assessed colonic mast cell infiltration, mediator release, and spatial interactions with mucosal innervation and their correlation with abdominal pain in IBS patients.
Methods
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IBS patients were diagnosed according to Rome II criteria and abdominal pain quantified according to a validated questionnaire. Colonic mucosal mast cells were identified immunohistochemically and quantified with a computer-assisted counting method. Mast cell tryptase and histamine release were analyzed immunoenzymatically. Intestinal nerve to mast cell distance was assessed with electron microscopy.
Results
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Thirty-four out of 44 IBS patients (77%) showed an increased area of mucosa occupied by mast cells as compared with controls (9.2% ± 2.5% vs. 3.3 ± 0.8%, respectively;
P < 0.001). There was a 150% increase in the number of degranulating mast cells (4.76 ± 3.18/field vs. 2.42 ± 2.26/field, respectively;
P = 0.026). Mucosal content of tryptase was increased in IBS and mast cells spontaneously released more tryptase (3.22 ± 3.48 pmol/min/mg vs. 0.87 ± 0.65 pmol/min/mg, respectively;
P = 0.015) and histamine (339.7 ± 59.0 ng/g vs. 169.3 ± 130.6 ng/g, respectively;
P = 0.015). Mast cells located within 5 μm of nerve fibers were 7.14 ± 3.87/field vs. 2.27 ± 1.63/field in IBS vs. controls (
P < 0.001). Only mast cells in close proximity to nerves were significantly correlated with severity and frequency of abdominal pain/discomfort (
P < 0.001 and
P = 0.003, respectively).
Conclusions
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Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.
BACKGROUND AND PURPOSE: Nonalcoholic fatty liver disease is frequently associated with type 2 diabetes mellitus, obesity, and dyslipidemia, but some patients have normal glucose tolerance or normal ...weight. We tested the hypothesis that there is an association between nonalcoholic fatty liver disease and insulin resistance that is independent of diabetes and obesity.
SUBJECTS AND METHODS: We measured anthropometric and metabolic variables in 46 patients with chronically elevated serum aminotransferase levels, “bright liver” on ultrasound scan, and normal glucose tolerance. Indexes of insulin resistance and secretion were determined using the homeostasis model assessment method. They were compared with 92 normal subjects who were matched for age and sex.
RESULTS: Patients with nonalcoholic fatty liver disease were characterized by fasting and glucose-induced hyperinsulinemia, insulin resistance, postload hypoglycemia, and hypertriglyceridemia. Insulin resistance odds ratio (OR) = 15 per percent increase, 95% confidence interval (CI): 3.0 to 70, fasting triglyceride level (OR = 3.1 per mmol/liter increase, 95% CI: 1.1 to 8.9), 180-minute blood glucose level (OR = 4.3 per mmol/liter decrease, 95% CI: 1.6 to 12), and average insulin concentration in response to oral glucose (OR = 3.0 per 100 pmol/liter increase, 95% CI: 1.5 to 6.2) were independently associated with nonalcoholic fatty liver disease. The exclusion of overweight and obese subjects did not change the results.
CONCLUSION: Nonalcoholic fatty liver disease is associated with insulin resistance and hyperinsulinemia even in lean subjects with normal glucose tolerance. Genetic factors that reduce insulin sensitivity and increase serum triglyceride levels may be responsible for its development.
Background & Aims Acute infectious gastroenteritis increases the risk for irritable bowel syndrome (IBS) and functional dyspepsia (FD). Children are particularly vulnerable to gastroenteritis because ...of the immaturity of their intestinal barrier, enteric nervous system, and immune response to pathogens. We investigated whether acute gastroenteritis in early life increases the risk of IBS and FD throughout adulthood. Methods In 1994, we identified and monitored a single culture-proven foodborne Salmonella enteritidis outbreak that involved 1811 patients (mostly pediatric) in Bologna, Italy. Clinical data were collected and a prospective, controlled, cohort study was designed. Long-term effects were assessed by mailing a questionnaire to 757 subjects 16 years after the outbreak (when all of the children were adults). We randomly selected a cohort of 250 adults exposed to Salmonella as children, all 127 individuals exposed as adults, and a cohort of nonexposed participants matched for number, age, sex, and area of residence (controls). Results Among 198 exposed participants, 64 reported FD (32.3%), compared with 51 of 188 controls (27.1%; P = .268). Among 204 exposed participants, 75 reported having IBS (36.8%) compared with 44 of 189 controls (23.3%; P = .004). The odds ratio for IBS among people exposed to the Salmonella was 1.92 (95% confidence interval: 1.23–2.98). The prevalence of IBS was higher in individuals exposed Salmonella as children than in controls (35.3% vs 20.5%; P = .008), but not in individuals exposed as adults, compared with controls. After multivariate logistic regression, post-infectious IBS was independently associated with anxiety and FD. Conclusions Based on data collected from a single culture-proven foodborne Salmonella enteritidis outbreak in 1994, Salmonella -induced gastroenteritis during childhood (but not adulthood) is a risk factor for IBS.
An increase in enzyme lactate dehydrogenase (LDH) in serum is a negative prognostic factor for survival in cats affected by lymphoma. Measuring LDH at the time of diagnosis has been studied for ...differentiating neoplastic disease from non-neoplastic disease in dogs. Inflammatory bowel disease (IBD) and alimentary lymphoma are common diseases in cats.
The aim of this study was to determine whether elevation of total LDH occurred in cats with alimentary lymphoma and non-neoplastic gastrointestinal disease, such as IBD, and to evaluate whether this enzyme is useful in supporting the differential diagnosis of these specific diseases.
A prospective non-randomized controlled study was carried-out in a real world setting of three Italian private veterinary clinics. Seventy-one client-owned cats with a history of chronic gastrointestinal symptoms were enrolled; 33 cats were histologically diagnosed as having alimentary lymphoma and 38 cats as having IBD. Serum samples of total LDH analysis were measured.
Gender (P = 0.016) and age (P = 0.046) were found to be significant factors influencing the differentiation of serum total LDH between cats with alimentary lymphoma and those with IBD. Despite low diagnostic accuracy in the overall population (63%), a cut-off value of serum total LDH ranging from 0.85- to 1.04-times the upper reference limit showed good capability (accuracy >80%) of differentiating these two conditions in neutered males and cats younger than 8 years of age (AUC: 0.805, 0.833; sensitivities: 76.9%, 83.3%; specificities: 80.0%, 76.5%; PPV: 76.9%, 55.6%; NPV: 80.0%, 92.9%; respectively).
Although our study showed that gender and age are significant factors in differentiating serum total LDH between cats with alimentary lymphoma and those with IBD, this test had poor diagnostic accuracy in differentiating between these two conditions in the overall population.
Immune activation may be involved in the pathogenesis of irritable bowel syndrome (IBS). However, the relative magnitude of this immune component and its correlation with gender and gastrointestinal ...complaints in IBS patients remains poorly elucidated.
We enrolled 48 IBS patients, with either diarrhea or constipation, 12 patients with microscopic colitis, 20 patients with ulcerative colitis, and 24 healthy controls. Colonic immunocytes were identified with quantitative immunohistochemistry on mucosal biopsies. Gastrointestinal symptoms were assessed using a validated questionnaire.
IBS patients showed a significant 72% increase in mucosal immune cells compared to controls (P<0.001). Further analyses showed that increased immune cells were present in 50% of the IBS patients. The magnitude of the immune infiltrate in IBS was significantly lower than that of microscopic colitis or ulcerative colitis (42% and 124% increases vs. IBS, respectively; P<0.001). Compared with controls, IBS patients had increased numbers of CD3+, CD4+, and CD8+ T cells and mast cells (P<0.001). Compared to male IBS patients, female IBS patients had greater numbers of mast cells (P=0.066), but lower numbers of CD3+ and CD8+ T cells (P=0.002 and <0.001, respectively). Mucosal mast cell infiltration of IBS patients was significantly associated with abdominal bloating frequency (P=0.022) and with symptoms of dysmotility-like dyspepsia (P=0.001), but not ulcer-like dyspepsia.
A large subset of IBS patients shows gender-dependent mucosal infiltration of immunocytes that correlates with abdominal bloating and dysmotility-like dyspepsia. These results provide the rationale for considering immune mechanisms as a pathophysiological component in a subset of IBS patients.
Background: Mandibular second molar (M2) periodontal defects after third molar (M3) removal in high‐risk patients are a clinical dilemma for clinicians. This study compares the healing of periodontal ...intrabony defects at distal surfaces of mandibular M2s using bioabsorbable and non‐resorbable membranes.
Methods: Eleven patients with bilateral probing depths (PDs) ≥6 mm distal to mandibular M2s and intrabony defects ≥3 mm, related to the total impaction of M3s, were treated with M3 extraction and covering of the surgical bone defect with a bioabsorbable collagen barrier on one side and a non‐resorbable expanded polytetrafluoroethylene (ePTFE) barrier contralaterally. The PD, clinical attachment level (CAL), M2 mobility, and furcation class probing were evaluated preoperatively and 3, 6, and 9 months postoperatively. Intraoral periapical radiographs were taken immediately preoperatively and 3 and 9 months postoperatively.
Results: Both treatment modalities were successful. At 9 months, the mean PD reduction was 5.2 ± 3.9 mm for bioabsorbable sites and 5.5 ± 3.0 mm for non‐resorbable sites; the CAL gain was 5.9 ± 3.3 mm and 5.5 ± 3.4 mm, respectively. The outcome difference between the two sites for PD and CAL did not differ statistically (P >0.05) at any assessment time.
Conclusion: Bioabsorbable collagen membranes in guided tissue regeneration treatment of intrabony defects distal to the mandibular M2 obtained the same marked PD reductions and CAL gains as non‐resorbable ePTFE membranes after M3 extraction.
The aim of this study is to determine whether any correlation between CT findings and functional parameters exists to predict subclinical glucocorticoid secretion.
This is a retrospective database ...study of 55 patients with incidentally discovered adenomas, investigated through CT with an adrenal protocol, assessing diameters and attenuation values on the unenhanced and contrast-enhanced phases. Patients underwent blood cortisol and corticotropin evaluation and overnight dexamethasone suppression test (DST), in accordance with clinical recommendations. Cortisol levels higher than 50 nmol/L after DST identified subclinical cortisol secretion. We identified 28 subjects with lipid-rich nonsecreting adenomas, nine with lipid-rich secreting adenomas, 11 with lipid-poor nonsecreting adenomas, and seven with lipid-poor secreting adenoma.
Cortisol levels after DST were significantly and positively related to mass diameters. At univariate analysis, maximum and minimum diameters and attenuation in the delayed phase were significantly related to the presence of secreting or nonsecreting adenoma; at multivariate analysis, only the minimum diameter and the attenuation in the venous phase entered the stepwise logistic regression. Similarly, minimum diameter and attenuation in the venous phase emerged also at the multivariate stepwise regression between radiologic parameters and cortisol levels after DST. The formula of the radiologic score computed by using the coefficients of the multivariate regression was as follows: (0.1914 × minimum diameter) + (0.0308 × enhanced attenuation). The diagnostic accuracy of this discriminatory score in differentiating secreting from nonsecreting adenomas was 84.9%, the sensitivity was 81.3%, and the specificity was 87.2%. Adenomas with scores greater than 7.59 were considered as secreting adenomas, and adenomas with scores less than 7.36 were considered as nonsecreting adenomas.
This study shows that imaging parameters can predict subclinical cortisol hypersecretion in patients with adrenal adenomas.
Chronic idiopathic intestinal pseudo-obstruction (CIIP) is a rare disease characterized by episodes resembling mechanical obstruction in the absence of organic, systemic, or metabolic disorders. ...Intestinal motor abnormalities have long been identified in CIIP patients. Little is known of the natural history of the disease in adults. This study evaluated the clinical course of CIIP over time.
Fifty-nine consecutive CIIP patients without underlying collagen, vascular diseases, or mitochondrial cytopathies were evaluated between 1985 and 2001. Family history, onset of digestive symptoms, previous surgeries, episodes suggestive of subacute intestinal obstruction, digestive symptoms, body mass index, and feeding habits were recorded. Small bowel manometry was performed by a perfusion technique, and abnormal motor patterns were visually identified. Full-thickness biopsies were available in 11 cases and were processed for immunohistochemical analysis of myogenic and neurogenic components of the gut wall.
Patients were prospectively followed up for a median of 4.6 years (range, 1-13 years). Diagnosis was often made several years after symptom onset (median, 8 years). Thus, the majority of patients (88%) underwent useless and potentially dangerous surgeries (mean, 2.96 per patient). Manometry invariably showed abnormal motor patterns. Pathologic findings included neuropathies in all investigated cases and abnormalities of interstitial cells of Cajal in 5 of 11 cases. Long-term outcome was generally poor despite surgical and medical therapies; 4 patients died of disease-related complications, 4 underwent small bowel transplantation, almost one third required long-term home parenteral nutrition, and two thirds had some sort of nutritional limitations.
CIIP is a severe, often unrecognized disease characterized by disabling and potentially life-threatening complications over time.
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