Virginia Donovan

In vitro changes in the properties of rabbit colonie muscularis mucosae in colitis

BACKGROUND The muscularis mucosae is the muscle layer closet to the site of elevated inflammatory mediator production in inflammatory bowel disease. Thus, it is the first muscle layer subject to their influence. METHODS Using a rabbit trinitrobenzene sulfonic acid model of colitis, changes in the properties of the muscularis mucosae resulting from the inflammatory process were studied in vitro. RESULTS Animals developed a mild colitis-like inflammation that was confined to the epithelium, lamina propria, and submucosa. Colitic muscularis mucosae contractile responses to leukotriene D4 and prostaglandins E2 and F2 alpha were significantly attenuated relative to the maximum tissue response to acetylcholine, whereas responses to histamine, substance P, and vasoactive intestinal polypeptide were unchanged. In addition, the stress-generating capacity of the colitic muscularis mucosae was compromised in a stimulus-independent manner and passive tension increased relative to active tension. CONCLUSIONS The muscularis mucosae undergoes two significant alterations in colitis: (a) a selective desensitization to the effects of arachidonic acid metabolites and (b) an impairment of its excitation-contraction coupling mechanism. A loss of the ability of the muscularis mucosae to cause mucosal movement and alter luminal surface area may be an important early stage in the pathophysiology of inflammatory bowel disease.

Radiology–Pathology Conference: Juvenile granulosa cell tumor☆

Juvenile granulosa cell tumor (GCT) of the ovary is a rare neoplasm occurring in premenarchal girls and young women. Juvenile GCT that occurs in premenarchal girls usually produces sexual precocity as a consequence of estrogen secretion. Juvenile GCTs are more likely to grow to a relatively large size with a much smaller likelihood of peritoneal spread, unlike their counterpart, epithelial ovarian neoplasms. We report the radiology and pathology of a patient with juvenile GCT and review the literature of this rare tumor.

Endometriosis of Abdominal and Pelvic Wall Scars: Multimodality Imaging Findings, Pathologic Correlation, and Radiologic Mimics

Implantation of an endometriotic lesion within a pelvic or abdominal wall scar is an uncommon but well-described condition that may be the underlying cause of acute or chronic recurrent abdominal or pelvic pain, especially after cesarean section. Radiologists may not consider scar endometriosis when it is encountered at cross-sectional imaging. Cesarean section scars are the most common site of extraovarian or extrauterine endometriosis. The condition also has been identified in other uterine surgery-related scars and in the skin, subcutaneous tissues, and abdominal and pelvic wall musculature adjacent to these scars. The most plausible cause of scar endometriosis is implantation of endometrial stem cells at the surgical site at the time of uterine surgery. Patients with scar endometriosis may be asymptomatic or present with cyclical pain corresponding to the menstrual cycle. Cross-sectional imaging findings vary from the nonspecific to those suggestive of the diagnosis when combined with clinical history. In particular, the presence of blood products in an anterior abdominal wall mass at magnetic resonance (MR) imaging with no other explanation is strongly suggestive of scar endometriosis. Ultrasonography, computed tomography, and MR imaging may be used to depict an endometriotic lesion, exclude endometriosis, or provide evidence for an alternative diagnosis.

Calcification in untreated mediastinal Hodgkin's lymphoma.

Calcification is very rarely reported in untreated thoracic lymphoma. However, calcification can occur (although uncommonly) in lymphoma following chemotherapy or radiation, and in areas of scaring or fibrous healing. The authors describe the case of a pregnant woman with a large mediastinal mass that contained calcifications visible on both chest radiography and thoracic computed tomography, which proved to be Hodgkins lymphoma.

Morphological factors influencing transepithelial conductance in a rabbit model of ileitis

BACKGROUND & AIMS Infection of rabbits with coccidia (Eimeria magna) causes chronic ileal inflammation and diarrhea. Inflamed ileum also shows decreased transmural conductance. The aim of this study was to characterize morphological factors known to affect paracellular permeability that may alter transmural conductance in inflamed ileum. METHODS Ileal mucosa was mounted in Ussing chambers for study of [3H]mannitol and [3H]inulin fluxes. Light and electron microscopy were used for morphometric studies. Alterations in the zonula occludens of epithelial cells were evaluated in freeze-fracture replicas. RESULTS Inflamed ileum showed diminished paracellular fluxes. Inoculated rabbits showed marked lymphoplasmocytic infiltration and villus blunting in ileum. Villus linear junctional density was unaffected. However, total villus apical surface area per square centimeter of tissue was reduced in inflamed ileum, causing a diminished total villus linear junctional pathway per square centimeter of apical surface. Villus zonula occludens strand number was reduced in inflamed ileum, whereas the frequency of both villus and crypt lateral surface extrajunctional strands increased. CONCLUSIONS Chronic inflammation exerts a profound effect on ileal paracellular permeability. Morphological data suggest that this effect may be caused in part by alterations in inflamed ileal mucosal structure and tight junctional organization and density, particularly on villi.

Primary CNS T-Cell Lymphoma of the Spinal Cord: Case Report and Literature Review

Primary central nervous system lymphoma (PCNSL) accounts for 1% of all lymphoma diagnoses and as many as 6% of all central nervous system (CNS) tumors. Most cases of PCNSL are of B-cell type; few are of T-cell lineage. PCNSL mainly occurs intracranially; primary spinal-cord lymphoma only occurs rarely. Moreover, intramedullary presentation without intracranial lesions is virtually unknown. Herein, we present a case of primary T-cell CNS lymphoma limited to the intramedullary spinal cord in an 82-year-old white man, along with a review of the literature on this condition and similar conditions.

Effects of rotavirus on epithelial transport in rabbit small intestine.

The present study investigated changes in small intestinal epithelial transport in rabbits infected with rotavirus. The crypt depth-villus height ratio was increased in infected ileal tissue as a result of a significant increase in crypt depth and patchy shortening of the villi. Similar villus damage was seen in the jejunum. Despite these histological changes, basal fluid absorption by both the ileum and jejunum of infected animals was unaltered. Values for basal short-circuit current and resistance were similar; however, the increase in short-circuit current evoked by prostaglandin E2 was significantly smaller in rotavirus-infected tissues than in controls. The apparentVmax for electrogenic glucose and alanine uptake by the jejunum was significantly increased following inoculation with rotavirus. Reduced responsiveness to the secretory effect of prostaglandin E2 and increased nutrient uptake may limit diarrhea that would otherwise be expected to occur as a result of the changes in mucosal architecture. This has important implications on the clinical treatment of rotavirus diarrhea, suggesting that oral rehydration therapy, which depends on the active transport of nutrients, may provide a more effective treatment than the use of cyclooxygenase inhibitors.

Diagnosis of gastric glomus tumour by endoscopic ultrasound-guided fine needle aspiration cytology: a case report.

Dear Editor, Glomus tumour (GT) is a distinct, benign, solitary cellular proliferation that arises from modified smooth muscle cells of the glomus body, a type of neuromyoarterial receptor which plays an important role in the regulation of arterial blood flow. The majority of GTs occur in the deep dermis or subcutis of the upper or lower extremity, where arteriovenous anastomoses are numerous. However, they may also develop at sites at which the glomus body may be sparse or even absent, such as bone and joints, skeletal muscle, soft tissue, mediastinum, trachea, kidney, uterus, vagina and stomach. Although the histopathological features of gastric GT have been well described in the literature, its cytological features, which may help in a definitive preoperative diagnosis, have rarely been described. We report a case of gastric GT diagnosed by endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) cytology supported by cell block immunohistochemistry (IHC), and later confirmed on endoscopic submucosal resection (ESMR). Because they are derived from modified smooth muscle cells, GTs exhibit a similar immunoprofile. Conservative local resection is usually the optimal therapy for gastric GT. However, because of the intramural location, which precludes an endoscopic biopsy diagnosis, and the lack of specific clinical or radiological features to distinguish them from other intramural masses, GTs are commonly diagnosed histologically after either an endoscopic submucosal or radical resection. FNA cytology obtained by EUS can be used for preoperative diagnosis to distinguish GTs from more aggressive gastric tumours, sparing the patient an extensive surgical resection. We came across a 51-year-old man who presented with dyspepsia. An upper gastrointestinal endoscopy (Figure 1) showed a 2.4 9 2-cm, round, hypoechoic and enhancing submucosal lesion in the gastric antrum causing mass effect. The EUS-FNA smears showed cohesive clusters of uniform round cells with ill-defined cytoplasmic borders and scanty amphophilic cytoplasm, admixed with spindleshaped endothelial cells (Figure 2). The nuclei were round with smooth nuclear membranes and evenly distributed dusty chromatin. The cell block showed monomorphic cellular clusters arranged around sinusoidal spaces (Figure 3). The differential diagnoses considered were low-grade neuroendocrine tumour (LGNET), epithelioid gastrointestinal stromal tumour (GIST)/leiomyoma, poorly differentiated carcinoma (PDCA), haemangiopericytoma (HPC), perivascular epithelioid cell tumour (PEComa) and paraganglioma. The cells showed strong immunoreactivity for smooth muscle antigen (SMA; Figure 3, inset) and vimentin, and were negative for desmin, CD34, c-kit (CD117), chromogranin, synaptophysin and pancytokeratin (panCK). The negative neuroendocrine markers and cytokeratin excluded a neuroendocrine neoplasm and PDCA. CD117 and CD34 negativity ruled out GIST and HPC. The desmin ( )/actin (+) immunophenotype was unusual for a leiomyoma, but fitted that of GT, as did the morphology. Subsequently, the diagnosis was confirmed on ESMR. Neither the cytological preparation nor histological sections revealed any features of malignancy, such as mitotic figures, necrosis, high nuclear grade or infiltrative growth pattern. The patient is on follow-up and has been doing well for the last 23 months. DeBusscher demonstrated the presence of glomus bodies in the submucosa and subserosa of the stomach, mainly along the lesser curvature and the posterior wall near the cardia, explaining the selective occurrence of GT in the stomach. Vinette-Leduc and Correspondence Sambit Kumar Mohanty, Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Room 8709, South Towers, 8th Floor, Los Angeles, CA 90048, USA Tel: +516-444-2931; Fax: +310-423-1571; E-mail: sambit.mohanty@cshs.org

Ion transport across the cecum in normal and colitic mice.

This study was conducted to determine the iontransport mechanisms in the normal mouse cecum andcompare them to an inbred mouse model of colitis. TheUssing chamber-voltage clamp technique was used to monitor the short circuit current(Isc). The basal Isc in the normalcecum was 82.6 ± 5.8 μA/cm2. It wasnot affected by bumetanide, 9-anthracene carboxylate,amiloride, and phenamil or by removal of Cl- ions; but was abolished by theremoval of Na+ ions. Flux measurementsrevealed the presence of neutral NaCl transport. In thecolitic cecum, the basal current was significantlyhigher than the normal cecum. Basal current in the normal cecum wasdue primarily to Na+ absorption through aNa+ channel, while in the colitic cecum itwas due to Cl- ion secretion. cAMP additionin colitic cecum did not increase Cl- secretion, further suggestingthat the tissue is already secreting at a maximalrate.

Automated Real-Time Collection of Pathogen-Specific Diagnostic Data: Syndromic Infectious Disease Epidemiology

Background Health care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are comprehensive and specific with respect to the pathogen but are rapid in reporting the data. It has proven difficult to implement these requirements on a large scale while maintaining patient privacy. Objective The aim of this study was to demonstrate the automated export, aggregation, and analysis of infectious disease diagnostic test results from clinical laboratories across the United States in a manner that protects patient confidentiality. We hypothesized that such a system could aid in monitoring the seasonal occurrence of respiratory pathogens and may have advantages with regard to scope and ease of reporting compared with existing surveillance systems. Methods We describe a system, BioFire Syndromic Trends, for rapid disease reporting that is syndrome-based but pathogen-specific. Deidentified patient test results from the BioFire FilmArray multiplex molecular diagnostic system are sent directly to a cloud database. Summaries of these data are displayed in near real time on the Syndromic Trends public website. We studied this dataset for the prevalence, seasonality, and coinfections of the 20 respiratory pathogens detected in over 362,000 patient samples acquired as a standard-of-care testing over the last 4 years from 20 clinical laboratories in the United States. Results The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks, and adenovirus and the bacterial pathogens show constant detection over the year. The dataset can also be considered in an ecological framework; the viruses and bacteria detected by this test are parasites of a host (the human patient). Interestingly, the rate of pathogen codetections, on average 7.94% (28,741/362,101), matches predictions based on the relative abundance of organisms present. Conclusions Syndromic Trends preserves patient privacy by removing or obfuscating patient identifiers while still collecting much useful information about the bacterial and viral pathogens that they harbor. Test results are uploaded to the database within a few hours of completion compared with delays of up to 10 days for other diagnostic-based reporting systems. This work shows that the barriers to establishing epidemiology systems are no longer scientific and technical but rather administrative, involving questions of patient privacy and data ownership. We have demonstrated here that these barriers can be overcome. This first look at the resulting data stream suggests that Syndromic Trends will be able to provide high-resolution analysis of circulating respiratory pathogens and may aid in the detection of new outbreaks.