Intravenous Shiga toxin 2 promotes enteritis and renal injury characterized by polymorphonuclear leukocyte infiltration and thrombosis in Dutch Belted rabbits.

Enterohemorrhagic Escherichia coli (EHEC) infection causes hemolytic uremic syndrome, a leading cause of acute renal failure in children. Dutch Belted (DB) rabbits are susceptible to EHEC-induced disease. Using real-time quantitative RT-PCR we measured the renal mRNA expression of cytokines and fibrinolytic factors in DB rabbits challenged with intravenous Shiga toxin 2 (Stx2) (1200 ng/kg). Group 1 rabbits received an incremental dose during an 8-day period whereas Group 2 rabbits received a single dose. Group 1 rabbits developed mild disease. In contrast, Group 2 rabbits developed severe diarrhea, higher levels of circulating polymorphonuclear leukocytes, increased mean platelet volume, and increased fibrinogen levels. Group 2 rabbits developed polymorphonuclear leukocyte infiltration in the intestine and kidney as well as glomerular congestion, luminal constriction, and mesangial glomerulonephropathy. These renal lesions were associated with up-regulation of interleukin-8 (P<0.006), plasminogen activator inhibitor-1 (P<0.04), and tissue plasminogen activator (P<0.05). Circulating Stx2 promoted dose-dependent enteritis and renal injury characterized by inflammation and impaired fibrinolysis leading to thrombosis.

Aneurysmal pressure changes with nondetachable balloon placement and fluid infusion: rationale for liquid embolization.

BACKGROUND AND PURPOSE: To improve the safety and efficacy of liquid embolization, we evaluated changes in pressures in experimental aneurysms. METHODS: We created three replicas of a lateral sidewall aneurysm and placed them in a physiologic flow circuit. A 3 x 10-mm nondetachable balloon was positioned in the parent vessel across the aneurysmal neck. Intra-aneurysmal pressures were measured at baseline and after balloon inflation. Fluid was infused into the sac via a 1.45F microcatheter during inflation, and maximal pressures were noted. Measurements were repeated eight times in each aneurysm. RESULTS: After balloon inflation, average intra-aneurysmal pressures increased: 12 mm Hg (13%, sigma(n - 1) = 0.46) for aneurysm 1 (baseline mean arterial pressure [MAP], 94 mm Hg), 15 mm Hg (58%, sigma(n - 1) = 0.88) for aneurysm 2 (baseline MAP, 26 mm Hg), and 15 mm Hg (58%, sigma(n - 1) = 0.92) for aneurysm 3 (baseline MAP, 26 mm Hg). During inflation and infusion, pressures increased slightly: 1.1 (0.94%, sigma(n - 1) = 0.64), 1.6 (3.9%, sigma(n - 1) = 1.1), and 1.9 (4.6%, sigma(n - 1) = 1.2) mm Hg for aneurysms 1, 2, and 3, respectively. Despite complete balloon occlusion of the distal aneurysmal neck, a channel between the proximal aneurysmal neck and the parent-vessel lumen persisted along the microcatheter. Fluid exited the sac via this channel, preventing a concomitant, significant increase in pressure during infusion. CONCLUSION: Intra-aneurysmal pressure modestly increased with inflation of a parent-vessel balloon across the neck. When liquid was infused into the sac during inflation, further increases were minimal.

Stereolithographic vascular replicas from CT scans: choosing treatment strategies, teaching, and research from live patient scan data.

Our goal was to develop a system that would allow us to recreate live patient arterial pathology by using an industrial technique known as stereolithography (or rapid prototyping). In industry, drawings rendered into dicom files can be exported to a computer programmed to drive various industrial tools. Those tools then make a 3D structure shown by the original drawings. We manipulated CT scan dicom files to drive a stereolithography machine and were able to make replicas of the vascular diseases of three patients.

Family Outbreaks of Nontyphoidal Salmonellosis following a Meal of Guinea Pigs.

Salmonella outbreaks have been linked to a wide variety of foods, including recent nationwide outbreaks. Guinea pig (Cavia porcellus), also known as cuy or cobayo, has long been a popular delicacy and ceremonial food in the Andean region in South America. This case report describes three family outbreaks of nontyphoidal salmonellosis, each occurring after a meal of guinea pigs. We believe this case report is the first to describe a probable association between the consumption of guinea pig meat and human salmonellosis. Physicians should be aware of the association of Salmonella and the consumption of guinea pigs, given the increasing immigration of people from the Andean region of South America and the increasing travel to this region.

Reproducibility analysis of a new objective method for measuring arteriovenous malformation nidus size at angiography.

BACKGROUND AND PURPOSE: Currently, no specific method exists to measure arteriovenous malformation (AVM) nidus size, a requirement in assessing the success of treatment. Additionally, the commonly used evaluation provides only a linear one-dimensional measurement of this three-dimensional entity. The purpose of this study was to devise an improved method for measuring AVM nidus size, an irregularly shaped radiologic entity, that provides objective and reproducible results. METHODS: The procedure involved digitizing angiograms obtained before and after treatment, making the gray scale uniform, printing images on standard bond paper, delineating the nidus area, measuring the nidus area with a polar planimeter, and finally, correcting for geometric magnification. Three observers made the measurements. The corrected nidus areas were tabulated, and the mean, standard deviation, interobserver variability, and confidence intervals (CIs) were calculated. RESULTS: On both anteroposterior and lateral views, the Kendall coefficient of concordance (a measure of interobserver variability) was equal to 0.97, signifying excellent agreement. Additionally, these values were within the 95% CIs; this result showed that they were unlikely the result of chance. CONCLUSION: Precise measurements of an AVM nidus are required to properly analyze changes in the lesion after endovascular embolization (ie, to evaluate treatment success). Because of the irregular contours of an AVM nidus, measuring an area with planimetry, rather than with the usual linear dimensions, should yield more exact results.

Aneurysm flow dynamics: alterations of slipstream flow for neuroendovascular treatment with liquid embolic agents.

BACKGROUND AND PURPOSE: The main issue with use of a liquid embolic agent is one of safety. To determine and improve the efficacy of potential neuroendovascular treatment regimens, particularly the use of liquid embolic agents, we evaluated the changes in aneurysm flow dynamics resulting from alterations of parent vessel flow. METHODS: We created silicone replicas of a laboratory-created aneurysm model and a basilar artery aneurysm cast from a human cadaver. Replicas were placed in a circuit of pulsatile non-Newtonian fluid, and flows were adjusted to simulate human physiologic flow velocity, profile, and volume. Individual fluid slipstreams were opacified with isobaric dyes. Images were obtained of the unaltered vascular replica; after placement of a nondetachable balloon in the parent vessel at multiple locations proximal to, across, and distal to the aneurysm neck; and after placement of a stent across the aneurysm neck. Aneurysms were then occluded with a cyanoacrylate liquid embolic agent in association with each device. RESULTS: In the unaltered replica, flow entered the distal aneurysm neck and impacted against the distal lateral aneurysm wall. Disturbed, but nonturbulent, flow then continued along the aneurysm wall in a vortex pattern and exited at the proximal aspect of the aneurysm neck. With the balloon partially inflated in the parent vessel, the slipstream velocity increased. This resulted in more rapid flow in the aneurysm sac, a less favorable condition for deposition of liquid embolic material. The effect was more pronounced with greater degrees of balloon inflation (resulting in greater parent vessel narrowing) and when the balloon was proximal to the aneurysm neck compared with more distal parent vessel positioning. Only with complete occlusion of the parent vessel lumen, either proximal to, across, or distal to the aneurysm sac, was there intraaneurysmal flow reduction (ie, stasis), a more favorable condition for liquid embolic material deposition. Also, with the balloon positioned across the aneurysm neck, not only did the liquid agent remain in the aneurysm sac, but also the surface could be molded to re-create a normal parent vessel lumen. A stent placed across the aneurysm neck caused the slipstreams to lose their coherence as they passed through the stent mesh. This prevented slipstream impact against the aneurysm sidewall and decreased the intraaneurysmal fluid velocity. During deposition of liquid embolic agent through the stent sidewall into the aneurysm sac, the stent mesh appeared to provide a barrier to passage of the embolic agent into the adjacent parent vessel, also a more favorable condition for liquid embolic material deposition. CONCLUSION: Knowledge of aneurysm flow dynamics and the changes incurred after endovascular parent vessel flow alteration provides a basis for safer aneurysm obliteration by using a liquid embolic agent with a neurointerventional technique.

Characterization of hemolytic Escherichia coli strains in ferrets: recognition of candidate virulence factor CNF1.

Diseases associated with Escherichia coli infection are the subject of renewed interest due to emerging conditions such as hemolytic uremia syndrome. A collection of 15 strains of beta-hemolytic E. coli was isolated from diarrheic feces and diseased tissues of ferrets. All 15 strains were positive in specific PCR assays for the presence of hlyA, pap1, and cnf1. Seven of the cnf1-positive isolates were tested and shown to have a cytopathic effect on HeLa cell monolayers. The pathogenesis of these strains warrants future study.

In vitro and in vivo characterization of Helicobacter hepaticus cytolethal distending toxin mutants.

Helicobacter hepaticus expresses a member of the cytolethal distending toxin (CDT) family of bacterial cytotoxins. To investigate the role of CDT in the pathogenesis of H. hepaticus, transposon mutagenesis was used to generate a series of isogenic mutants in and around the cdtABC gene cluster. An H. hepaticus transposon mutant with a disrupted cdtABC coding region no longer produced CDT activity. Conversely, a transposon insertion outside of the cluster did not affect the CDT activity. An examination of these mutants demonstrated that CDT represents the previously described granulating cytotoxin in H. hepaticus. Challenge of C57BL/6 interleukin 10(-/-) mice with isogenic H. hepaticus mutants revealed that CDT expression is not required for colonization of the murine gut. However, a CDT-negative H. hepaticus mutant had a significantly diminished capacity to induce lesions in this murine model of inflammatory bowel disease.

A naturally occurring rabbit model of enterohemorrhagic Escherichia coli-induced disease.

Enterohemorrhagic Escherichia coli (EHEC) causes hemorrhagic colitis and hemolytic-uremic syndrome (HUS) in humans. The exact mechanism by which EHEC induces disease remains unclear because of the lack of a natural animal model for the disease. An outbreak of bloody diarrhea and sudden death was investigated in a group of Dutch belted rabbits. Two of these rabbits harbored enteropathogenic E. coli O145:H(-), and 1 rabbit was coinfected with EHEC O153:H(-). A partial Shiga toxin 1 gene (stx1) fragment from E. coli O153:H(-) was confirmed by Southern blot and sequence analysis. Toxin production was demonstrated by a HeLa cell cytotoxicity assay. Histopathologic findings in all affected rabbits included erosive and necrotizing enterocolitis with adherent bacterial rods, proliferative glomerulonephritis, tubular necrosis, and fibrin thrombi within small vessels and capillaries. Our findings provide evidence for a naturally occurring animal model of EHEC-induced systemic disease that closely resembles human HUS.