Primary epiploic appendagitis: CT diagnosis

The purpose of this study was to analyze the CT signs of primary epiploic appendagitis. A retrospective search of the CT database over 12 months for this diagnosis revealed 11 cases. The clinical findings were recorded. Softcopy CT images were reviewed by two experienced abdominal radiologists (KS, DM) for location of lesion, size, shape, presence of central hyperdense focus, degree of bowel wall thickening, mass effect, and ancillary signs. Abdominal pain was the primary symptom in all patients. Preliminary diagnoses were appendicitis (n=2), diverticulitis (n=5), pancreatitis (n=1), ovarian lesion (n=1), or unknown (n=2). Abdominal examination and white blood cell count were uninformative. CT examination revealed a solitary (n=11), ovoid (n=9) fatty lesion with some soft tissue stranding adjacent to the left colon (n=6), transverse colon (n=3), or right colon (n=2). Central hyperdensity (n=5), mild bowel wall thickening (n=2), and parietal peritoneal thickening (n=4) were also seen. In 4 patients the lesions were not visible on follow-up CT examination performed 23–184 days later. Primary epiploic appendagitis can clinically mimic other, more serious inflammatory conditions. Knowledge of its findings on CT would help the radiologist make the diagnosis and allow a more conservative approach to patient care.     

Conscious sedation for patients undergoing enteroclysis: comparing the safety and patient-reported effectiveness of two protocols

Objective

To compare the safety and patient-reported effectiveness of two regimens for conscious sedation during enteroclysis.

Materials and methods

We surveyed two groups of outpatients and retrospectively reviewed procedure records for conscious sedation and complications. Patients were divided into Group One (received sedative/amnesic diazepam), and Group Two, (received amnesic/sedative, midazolam and analgesic fentanyl).

Results

All enteroclyses were successfully completed; there were no hospital admissions due to complications. In Group One (n = 106), mean dose of diazepam was 12.7 mg. 25% had oxygen desaturation (n = 25), and post-procedure vomiting without aspiration (n = 1). 56% of outpatients completed phone surveys, and 68% recalled procedural discomfort. In Group Two (n = 45), mean doses were 3.9 mg midazolam and 108 mcg fentanyl. 31% had desaturation (n = 13), and post-procedure vomiting without aspiration (n = 1). 87% had only a vague recall of the procedure or of any discomfort.

Conclusion

A combination of amnesic and fentanyl prevented the recall of discomfort of nasoenteric intubation and infusion in most patients who had enteroclysis compared to diazepam. Most of the patients would undergo the procedure again, if needed.     

Ezrin Expression Is an Independent Prognostic Factor in Gastro-intestinal Cancers

Background

Ezrin, a member of the ezrin–radixin–moesin (ERM) family of plasma membrane–cytoskeleton linker proteins, has been associated with metastatic behavior.

Methodology

Microarrayed pathological tissues of surgically resected colorectal cancer liver metastasis (CRLM) and whole tissue sections of cancer of the ampulla of Vater (CAV) were analyzed to determine ezrin expression levels and correlation with survival. The requirement of ezrin in invasive capability was assessed using in vitro assays.

Results

Surgically resected CAV showing a low ezrin score have a better 5-year disease-specific survival than those showing a high ezrin score (P?<?0.0001). Similarly, high ezrin expression at the invasive front of CRLM resulted in poor disease-free survival (P?=?0.05). Multivariate analysis demonstrated high ezrin expression to be an independent adverse prognostic factor for CAV (hazard ratio (HR) 15.22 (95 % confidence interval (CI) 1.98–117.03), P?<?0.01) and CRLM (HR 6.42 (95 % CI 1.01–52.43), P?=?0.05), among other clinically relevant variables such as lymph node metastasis (for CAV) and the presence of extrahepatic disease, large hepatic metastases (>5 cm), and close surgical resection margins (<5 mm) (all for CRLM). In vitro experiments indicated that ezrin expression was vital for cellular processes such as adhesive and invasive activity.

Significance

High ezrin expression indicates an adverse prognosis in primary CAV and CRLM.     

A small molecule C5a receptor antagonist protects kidneys from ischemia/reperfusion injury in rats

BACKGROUND: C5a has been implicated in numerous pathophysiological conditions, including ischemia/reperfusion (I/R) injury of the kidney. We examined whether a novel and specific C5a receptor antagonist, the cyclic compound AcF-[OPdChaWR] could moderate I/R-induced renal injury in rats. METHODS: Female Wistar rats were subjected to renal ischemia (60 min) and reperfusion (5 h). Rats were treated with either 1 mg/kg IV in 5% ethanol/saline or 10 mg/kg PO in 25% ethanol/saline prior to ischemia. I/R injury was characterized by significant tissue hemorrhage with increased microvascular permeability, elevated renal tissue levels of tumor necrosis factor-alpha (TNF-alpha) and myeloperoxidase (MPO), increased serum levels of creatinine and aspartate aminotransferase (AST) and hematuria. RESULTS: Pre-ischemic treatment with the C5a receptor (C5aR) antagonist (1 mg/kg IV or 10 mg/kg PO) substantially inhibited or prevented I/R-induced hematuria, vascular leakage, tissue levels of TNF-alpha and MPO, and serum levels of AST and creatinine. Histological examination of kidneys from antagonist pretreated I/R animals showed a marked reduction in tissue damage compared to drug-free I/R rats. This antagonist, however, did not inhibit complement-mediated lysis of red blood cells, suggesting unimpaired formation of the membrane attack complex (MAC). CONCLUSIONS: The results demonstrate for the first time that a selective antagonist of both human and rat C5a receptors, given either intravenously or orally, significantly protects the kidney from I/R injury in the rat. We conclude that C5a is an important pathogenic agent in renal I/R injury, and that C5a receptor antagonists may be useful therapeutic agents for the pretreatment of anticipated renal reperfusion injury in humans.     

Glutamine-induced free radical production in cultured astrocytes

Ammonia is a neurotoxin implicated in the pathogenesis of hepatic encephalopathy, Reye's syndrome, inborn errors of the urea cycle, glutaric aciduria, and other metabolic encephalopathies. Brain ammonia is predominantly metabolized to glutamine in astrocytes by glutamine synthetase. While the synthesis of glutamine has generally been viewed as the principal means of ammonia detoxification, this presumed beneficial effect has been questioned as growing evidence suggest that some of the deleterious effects of ammonia may be mediated by glutamine rather than ammonia per se. Since ammonia is known to induce the production of free radicals in cultured astrocytes, we investigated whether such production might be mediated by glutamine. Treatment of astrocytes with glutamine (4.5 mM) increased free radical production at 2-3 min (95%; P < 0.05), as well as at 1 and 3 h (42% and 49%, respectively; P < 0.05). Similarly treated cultured neurons failed to generate free radicals. Free radical production by glutamine was blocked by the antioxidants deferoxamine (40 microM) and alpha-phenyl-N-tert-butyl-nitrone (250 microM), as well as by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (500 microM). Free radical production was also blocked by 6-diazo-5-oxo-L-norleucine (1 mM), an inhibitor of glutaminase, suggesting that ammonia released by glutamine hydrolysis may be responsible for the generation of free radicals. Additionally, the mitochondrial permeability transition inhibitor, cyclosporin A, blocked free radical production by glutamine. The results indicate that astrocytes, but not neurons, generate free radicals following glutamine exposure. Glutamine-induced oxidative and/or nitrosative stress may represent a key mechanism in ammonia neurotoxicity.     

Non-cholinergic excitation in neurons after a chronic glutamate receptor blockade

Previous experiments revealed a dramatic increase in excitatory acetylcholine transmission in hypothalamic cultures during a chronic decrease in glutamate activity. Data suggested that in the absence of glutamate excitation, acetylcholine becomes the major excitatory neurotransmitter. However, non-cholinergic excitatory activity was also detected in some neurons. Here, using calcium imaging in hypothalamic cultures chronically subjected to the glutamate receptor blockade, we demonstrate the contribution of metabotropic glutamate receptors, P2-purinoreceptors, histamine receptors, adrenoreceptors, and gap junctions, but not nitric oxide to this non-cholinergic excitation. We also show that the sensitivity of neurons to receptor agonists is increased following the blockade. Data suggest that multiple components contribute to the excitatory activity in hypothalamic neurons during a long-term decrease in glutamate activity.