Mandibular inferior cortical bone thickness on panoramic radiographs in patients using bisphosphonates.

OBJECTIVE: The goal of this study was to detect dimensional changes in the mandibular cortical bone associated with bisphosphonate (BP) use and to correlate measurements of the cortical bone with the cumulative dose of BPs. STUDY DESIGN: Mandibular inferior cortical bone thickness (MICBT) was measured under the mental foramen on panoramic radiographs of patients with and without bisphosphonate-related osteonecrosis of the jaws (BRONJ) taking BPs and controls. RESULTS: Patients with BRONJ had the highest mean MICBT (6.81 ± 1.35 mm), compared with patients without BRONJ taking BPs (5.44 ± 1.09 mm) and controls (4.79 ± 0.85 mm) (P < .01). Mean MICBT of patients with BRONJ was significantly higher than that of patients without BRONJ taking BPs. There was a correlation between MICBT and cumulative dose of zolendronate. CONCLUSIONS: Measurement of MICBT on panoramic radiographs is a potentially useful tool for the detection of dimensional changes associated with BP therapy.

Intraoral radiography and dental implant restoration.

The usefulness of IOR has been described along with its limitations when considering implant restorations. One major issue is the alignment of the incident x-rays so that they are consistently perpendicular to the implant body, to provide the most reliable information possible. Other limitations include inconsistencies as a result of the inability to verify the nature and extent of bone around an implant, which is subject to variation as a result of type of bone and site. Where implants are concerned, as a diagnostic tool IOR should be considered as part of a multitude of tests-including probing, mobility, symptoms, and other soft-tissue evaluations. It must be emphasized that IOR cannot be relied upon as being the sole diagnostic test.

Mandibular cortical bone evaluation on cone beam computed tomography images of patients with bisphosphonate-related osteonecrosis of the jaw.

OBJECTIVES: The objective of this study was to develop a technique for detecting cortical bone dimensional changes in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ). STUDY DESIGN: Subjects with BRONJ who had cone-beam computed tomography imaging were selected, with age- and gender-matched controls. Mandibular cortical bone measurements to detect bisphosphonate-related cortical bone changes were made inferior to mental foramen, in 3 different ways: within a fixed sized rectangle, in a rectangle varying with the cortical height, and a ratio between area and height. RESULTS: Twelve BRONJ cases and 66 controls were evaluated. The cortical bone measurements were significantly higher in cases than controls for all 3 techniques. The bone measurements were strongly associated with BRONJ case status (odds ratio 3.36-7.84). The inter-rater reliability coefficients were high for all techniques (0.71-0.90). CONCLUSIONS: Mandibular cortical bone measurement is a potentially useful tool in the detection of bone dimensional changes caused by bisphosphonates.

Evaluating craniofacial asymmetry with digital cephalometric images and cone-beam computed tomography.

INTRODUCTION: The aim of this study was to evaluate craniofacial asymmetry by using 2-dimensional (2D) posteroanterior cephalometric images, 3-dimensional cone-beam computed tomography (CBCT), and physical measurements (gold standard). METHODS: Ten dry human skulls were assessed, and radiopaque markers were placed on 17 skeletal landmarks. Twenty linear measurements were taken on each side to compare the right and left sides and to compare these measurements with the physical measurements made with a digital caliper. To acquire the 2D posteroanterior radiographs, an Extraoral Phosphor Storage Plate (Air Techniques, Chicago, Ill) was used as the image receptor with a Eureka x-ray-Duocon Machlett unit (Machlett Laboratores, Chicago, Ill). Three-dimensional imaging data were acquired from a CB MercuRay (Hitachi Medical, Tokyo, Japan). RESULTS: On average, the right side was larger than the left for most of the 20 distances evaluated in the digital 2D and the CBCT images, and there was poor agreement between the digital 2D images and the physical measurements (kappa = 0.0609) and almost perfect agreement (kappa = 0.92) between the CBCT and physical measurements when individual measurements were considered. CONCLUSIONS: Human skulls, with no apparent asymmetry, had some differences between the right and left sides, with dominance for the right side but with no clinical significance. CBCT can better evaluate craniofacial morphology when compared with digital 2D images.

Bone volume, tooth volume, and incisor relapse: a 3-dimensional analysis of orthodontic stability.

INTRODUCTION: Orthodontic relapse is a common and significant problem. Few risk factors have been identified, and the role of bone has only recently been investigated. The purpose of this study was to examine the influence of alveolar bone volume and tooth volume on dental relapse. METHODS: The sample was chosen from the postretention database at the Department of Orthodontics of the University of Washington in Seattle. Based on the 10-year postretention (T3) irregularity index (II), 40 relapse subjects (T3 II > 6 mm) and the 40 most stable subjects (lowest T3 II < 1.5 mm) were identified for the study. Cone-beam computed tomography (CBCT) scans were taken of the posttreatment (T2) models. Total volume (V) was defined laterally by the distal contact points of the canines and vertically by the cusp tips of the canines to a depth 7 mm below the most inferior gingival margin. Alveolar volume (AV) was defined as the region below a vertical line at the most inferior gingival margin and tooth volume (TV) as the region above that line. The ratio TV:AV was calculated. Logistic regression analysis was used to determine the association between relapse and AV, and to adjust for potentially confounding variables (TV, initial II, sex, age, retention time, and postretention time). Mandibular cortical thickness (CT) measured on T2 lateral cephalograms was used as another measure of bone quantity. Nine patients from the graduate orthodontic clinic who had pretreatment CBCT scans were identified. V, AV, and TV were measured on both the in-vivo scans and the scans of their dental casts to verify the method. RESULTS: The relapse group had significantly greater V and AV and significantly lower CT. TV:AV was not different between the groups. T2 II was found to be a significant predictor of relapse based on logistic regression analysis, whereas AV was not. CT was poorly correlated with AV. V and AV were highly correlated between in-vivo scans and dental cast scans, whereas TV approached significance. CONCLUSIONS: Although postretention relapse was associated with increased V and AV, when other variables were controlled, bone volume was not a significant predictor of relapse.

A descriptive study of the radiographic density of implant restorative cements.

STATEMENT OF PROBLEM: Cementation of implant prostheses is a common practice. Excess cement in the gingival sulcus may harm the periodontal tissues. Identification of the excess cement may be possible with the use of radiographs if the cement has sufficient radiopacity. PURPOSE: The purpose of this study was to compare the radiographic density of different cements used for implant prostheses. MATERIAL AND METHODS: Eight different cements were compared: TempBond Original (TBO), TempBond NE (TBN), Fleck's (FL), Dycal (DY), RelyX Unicem (RXU), RelyX Luting (RXL), Improv (IM), and Premier Implant Cement (PIC). Specimen disks, 2 mm in thickness, were radiographed. Images were made using photostimulable phosphor (PSP) plates with standardized exposure values. The average grey level of the central area of each specimen disk was selected and measured in pixels using a software analysis program, ImageTool, providing an average grey level value representative of radiodensity for each of the 8 cements. The radiodensity was determined using the grey level values of the test materials, which were recorded and compared to a standard aluminum step wedge. An equivalent thickness of aluminum in millimeters was calculated using best straight line fit estimates. To assess contrast effects by varying the exposure settings, a second experiment using 1-mm-thick cement specimens radiographed at both 60 kVp and 70 kVp was conducted. The PSP plates with specimens were measured for a grey level value comparison to the standard aluminum step wedge, using the same software program. RESULTS: The highest grey level values were recorded for the zinc cements (TBO, TBN, and FL), with the 1-mm specimen detectable at both 60- and 70-kVp settings. A lower grey level was recorded for DY, indicative of a lower radiodensity compared to the zinc cements, but higher than RXL and RXU. The implant-specific cements had the lowest grey level values. IM could only be detected in 2-mm-thick sections with a lower aluminum equivalence value than the previously mentioned cements. PIC could not be detected radiographically for either the 1-mm or 2-mm thicknesses at either of the kVp settings. CONCLUSIONS: Some types of cement commonly used for the cementation of implant-supported prostheses have poor radiodensity and may not be detectable following radiographic examination.

Isolation and characterization of Vibrio tubiashii outer membrane proteins and determination of a toxR homolog.

Outer membrane proteins (OMPs) expressed by Vibrio tubiashii under different environmental growth conditions were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, N-terminal amino acid sequencing, and PCR analyses. Results showed the presence of a 38- to 40-kDa OmpU-like protein and ompU gene, a maltoporin-like protein, several novel OMPs, and a regulatory toxR homolog.

A model for digital archiving of radiographs into a searchable database.

Digital images are routinely used in orthodontic practices today. Many systems and formats are available for producing, storing, retrieving, viewing, and sharing these images. The digital imaging and communication in medicine (DICOM) standard is designed to ensure that these systems and formats are compatible, so that an image produced in a small private practice today can be viewed next year in a large hospital. The purpose of this article is to describe a method for laser scanning and digitization of analog (film) radiographs that meets DICOM standards and allows for web-based archiving, searching, and retrieval.

Cell-based two-region competition algorithm with a map framework for boundary delineation of a series of 2D ultrasound images.

To ensure the delineated boundaries of a series of 2-D images closely following the visually perceivable edges with high boundary coherence between consecutive slices, a cell-based two-region competition algorithm based on a maximum a posteriori (MAP) framework is proposed. It deforms the region boundary in a cell-by-cell fashion through a cell-based two-region competition process. The cell-based deformation is guided by a cell-based MAP framework with a posterior function characterizing the distribution of the cell means in each region, the salience and shape complexity of the region boundary and the boundary coherence of the consecutive slices. The proposed algorithm has been validated using 10 series of breast sonograms, including seven compression series and three freehand series. The compression series contains two carcinoma and five fibroadenoma cases and the freehand series contains two carcinoma and one fibroadenoma cases. The results show that >70% of the derived boundaries fall within the span of the manually delineated boundaries. The robustness of the proposed algorithm to the variation of regions-of-interest is confirmed by the Friedman tests and the p-values of which are 0.517 and 0.352 for the compression and freehand series groups, respectively. The Pearson's correlations between the lesion sizes derived by the proposed algorithm and those defined by the average manually delineated boundaries are all higher than 0.990. The overlapping and difference ratios between the derived boundaries and the average manually delineated boundaries are mostly higher than 0.90 and lower than 0.13, respectively. For both series groups, all assessments conclude that the boundaries derived by the proposed algorithm be comparable to those delineated manually. Moreover, it is shown that the proposed algorithm is superior to the Chan and Vese level set method based on the paired-sample t-tests on the performance indices at a 5% significance level.

Application of a novel hydrophilic infrared-transparent membrane to the differentiation between microcolonies of Enterobacter sakazakii and Klebsiella pneumoniae.

A proof-of-concept study is reported for the differentiation between microcolonies of Enterobacter sakazakii and Klebsiella pneumoniae by means of a novel sample preparation for infrared (IR) analysis. A disposable, IR-transparent, microporous (0.2-microm pores), hydrophobic, polyethylene (PE) membrane (51 microm thick) was plasma treated under an oxygen atmosphere and used to (i) filter (or print microarrays of) dilute aqueous foodborne bacterial suspensions and (ii) subsequently grow bacterial microcolonies when the treated, hydrophilic PE membrane was placed over brain heart infusion agar medium and incubated. Because this unique membrane is transparent to IR light, isolated microcolonies (200 microm) of bacterial cells grown on this PE substrate for the first time could be directly fingerprinted by IR microspectroscopy in the transmission mode. Hence, time-consuming bacterial cell transfer from culture plates to an IR sample holder for subsequent measurement by IR spectroscopy was eliminated. Multivariate analysis of the observed IR spectra for microcolonies allowed the rapid differentiation between E. sakazakii and K. pneumoniae.

Rugosity in Grimontia hollisae.

Grimontia hollisae, formerly Vibrio hollisae, produces both smooth and rugose colonial variants. The rugose colony phenotype is characterized by wrinkled colonies producing copious amounts of exopolysaccharide. Cells from a rugose colony grown at 30 degrees C form rugose colonies, while the same cells grown at 37 degrees C form smooth colonies, which are characterized by a nonwrinkled, uncrannied appearance. Stress response studies revealed that after exposure to bleach for 30 min, rugose survivors outnumbered smooth survivors. Light scatter information obtained by flow cytometry indicated that rugose cells clumped into clusters of three or more cells (average, five cells) and formed two major clusters, while smooth cells formed only one cluster of single cells or doublets. Fluorescent lectin-binding flow cytometry studies revealed that the percentages of rugose cells that bound either wheat germ agglutinin (WGA) or Galanthus nivalis lectin (GNL) were greater than the percentages of smooth cells that bound the same lectins (WGA, 35% versus 3.5%; GNL, 67% versus 0.21%). These results indicate that the rugose exopolysaccharide consists partially of N-acetylglucosamine and mannose. Rugose colonies produced significantly more biofilm material than did smooth colonies, and rugose colonies grown at 30 degrees C produced more biofilm material than rugose colonies grown at 37 degrees C. Ultrastructurally, rugose colonies show regional cellular differentiation, with apical and lateral colonial regions containing cells embedded in a matrix stained by Alcian Blue. The cells touching the agar surface are packed tightly together in a palisade-like manner. The central region of the colony contains irregularly arranged, fluid-filled spaces and loosely packed chains or arrays of coccoid and vibrioid cells. Smooth colonies, in contrast, are flattened, composed of vibrioid cells, and lack distinct regional cellular differences. Results from suckling mouse studies showed that both orally fed rugose and smooth variants elicited significant, but similar, amounts of fluid accumulated in the stomach and intestines. These observations comprise the first report of expression and characterization of rugosity by G. hollisae and raise the possibility that expression of rugose exopolysaccharide in this organism is regulated at least in part by growth temperature.

Trabecular and cortical bone as risk factors for orthodontic relapse.

INTRODUCTION: Dental relapse of the mandibular incisors after orthodontic treatment is a common problem, and few risk factors have been identified. The purpose of this case-control study was to evaluate whether the amount or the structure of mandibular bone affects the potential for postorthodontic mandibular incisor relapse. METHODS: The subject sample was selected from the postretention database at the University of Washington. Subjects were chosen based on the availability of lateral cephalograms and mandibular periapical radiographs taken approximately 10 years postretention (T3). The mandibular incisor irregularity index (II) was measured on the T3 casts. Two groups were identified: subjects with the II greater than 6 mm (relapse or case) and those with the II less than 3.5 mm (stable or control). Once the case/control status was determined, the II was measured on models taken at the initial orthodontic examination (T1) and at the end of treatment (T2). Sixty relapse and 263 stable subjects were identified. Mandibular cortical thickness measured on both panoramic and lateral cephalometric radiographs was used to assess the amount of mandibular bone, and fractal analysis was used to analyze the trabecular bone structure around the mandibular incisors on the periapical radiographs. Logistic regression analyses were used to determine the association between dental relapse and significant bone parameters. The models were adjusted for potentially confounding variables (initial II, sex, age, and postretention time). RESULTS: The relapse subjects had a larger mean II at T1 and a longer postretention time than the stable subjects. The mean cephalometric mandibular cortical thickness was significantly smaller in the relapse group than in the stable group at T1, T2, and T3. There were no statistically significant differences in the trabecular structure of bone, as measured with fractal analyses, between the relapse and stable groups. CONCLUSIONS: These results indicate that patients with thinner mandibular cortices are at increased risk for dental relapse.

Cell-competition algorithm: a new segmentation algorithm for multiple objects with irregular boundaries in ultrasound images.

Segmentation of multiple objects with irregular contours and surrounding sporadic spots is a common practice in ultrasound image analysis. A new region-based approach, called cell-competition algorithm, is proposed for simultaneous segmentation of multiple objects in a sonogram. The algorithm is composed of two essential ideas. One is simultaneous cell-based deformation of regions and the other is cell competition. The cells are generated by two-pass watershed transformations. The cell-competition algorithm has been validated with 13 synthetic images of different contrast-to-noise ratios and 71 breast sonograms. Three assessments have been carried out and the results show that the boundaries derived by the cell-competition algorithm are reasonably comparable to those delineated manually. Moreover, the cell-competition algorithm is robust to the variation of regions-of-interest and a range of thresholds required for the second-pass watershed transformation. The proposed algorithm is also shown to be superior to the region-competition algorithm for both types of images.

Characterization of Vibrio fluvialis-like strains implicated in limp lobster disease.

Studies were undertaken to characterize and determine the pathogenic mechanisms involved in a newly described systemic disease in Homarus americanus (American lobster) caused by a Vibrio fluvialis-like microorganism. Nineteen isolates were obtained from eight of nine lobsters sampled. Biochemically, the isolates resembled V. fluvialis, and the isolates grew optimally at 20 degrees C; none could grow at temperatures above 23 degrees C. The type strain (1AMA) displayed a thermal reduction time (D value) of 5.77 min at 37 degrees C. All of the isolates required at least 1% NaCl for growth. Collectively, the data suggest that these isolates may embody a new biotype. Pulsed-field gel electrophoresis (PFGE) analysis of the isolates revealed five closely related subgroups. Some isolates produced a sheep hemagglutinin that was neither an outer membrane protein nor a metalloprotease. Several isolates possessed capsules. The isolates were highly susceptible to a variety of antibiotics tested. However, six isolates were resistant to erythromycin. Seventeen isolates harbored plasmids. Lobster challenge studies revealed that the 50% lethal dose of a plasmid-positive strain was 100-fold lower than that of a plasmid-negative strain, suggesting that the plasmid may enhance the pathogenicity of these microorganisms in lobsters. Microorganisms that were recovered from experimentally infected lobsters exhibited biochemical and PFGE profiles that were indistinguishable from those of the challenge strain. Tissue affinity studies demonstrated that the challenge microorganisms accumulated in heart and midgut tissues as well as in the hemolymph. Culture supernatants and polymyxin B lysates of the strains caused elongation of CHO cells in tissue culture, suggesting the presence of a hitherto unknown enterotoxin. Both plasmid-positive and plasmid-negative strains caused significant dose-related intestinal fluid accumulations in suckling mice. Absence of viable organisms in the intestinal contents of mice suggests that these microorganisms cause diarrhea in mice by intoxication rather than by an infectious process. Further, these results support the thermal reduction data at 37 degrees C and suggest that the mechanism(s) that led to fluid accumulation in mice differs from the disease process observed in lobsters by requiring neither the persistence of viable microorganisms nor the presence of plasmids. In summary, results of lobster studies satisfy Koch's postulates at the organismal and molecular levels; the findings support the hypothesis that these V. fluvialis-like organisms were responsible for the originally described systemic disease, which is now called limp lobster disease.

Purification and characterization of a vulnificolysin-like cytolysin produced by Vibrio tubiashii.

An extracellular cytolysin from Vibrio tubiashii was purified by sequential hydrophobic interaction chromatography with phenyl-Sepharose CL-4B and gel filtration with Sephacryl S-200. This protein is sensitive to heat and proteases, is inhibited by cholesterol, and has a molecular weight of 59,000 and an isoelectric point of 5.3. In addition to lysing various erythrocytes, it is cytolytic and/or cytotoxic to Chinese hamster ovary cells, Caco-2 cells, and Atlantic menhaden liver cells in tissue culture. Lysis of erythrocytes occurs by a multihit process that is dependent on temperature and pH. Twelve of the first 17 N-terminal amino acid residues (Asp-Asp-Tyr-Val-Pro-Val-Val-Glu-Lys-Val-Tyr-Tyr-Ile-Thr-Ser-Ser-Lys) are identical to those of the Vibrio vulnificus cytolysin.

Twin carriers of X-linked agammaglobulinemia (XLA) due to germline mutation in the Btk gene.

We report on an X-linked agammaglobulinemia (XLA) family in which mothers of two affected cousins were monozygotic twins. We analyzed the Btk gene of several members in three generations of the family by SSCP analysis, DNA sequencing, and RFLP analysis following polymerase chain reaction-amplification of the individual exons. We identified a missense point mutation, G1817C (R562P), in exon 17 of the Btk gene in the affected cousins. The same mutation was also present in both mothers (twin sisters) of the cousins identifying them as carriers. However, the mutation was absent in all other relatives including the grandmother of the cousins (mother of the twin sisters). This strongly suggests that the mutation in the Btk gene had originated in one of the germ lines or in the zygote. This may be the first demonstration of a germ line (or zygotic) mutation in XLA.

An esophagogastroduodenal anastomosis model for esophageal adenocarcinogenesis in rats and enhancement by iron overload.

The aim of this study is to establish a good animal model for esophageal adenocarcinoma (EAC) and to test the hypothesis that iron over-nutrition enhances EAC formation. With rats, esophagogastroduodenal anastomosis (EGDA) was accomplished by anastomosing the duodenum to the gastroesophageal junction. Iron supplementation was given by i.p. injection of iron dextran (4 mg Fe/kg/week). This model mimics the development of human EAC by introducing mixed reflux of gastric and duodenal contents. At 40 weeks after surgery, the body weight, food intake, hemoglobin, total serum iron, transferrin saturation, serum albumin, and plasma levels of alpha-tocopherol, gamma-tocopherol and retinol of the EGDA rats were not significantly different from those of the non-operated controls. The animals generally had only mild esophagitis, except that the area surrounding the anastomosis opening had more severe esophagitis. Columnar-lined esophagus (CLE), CLE with dysplasia, and EAC were diagnosed in 53.5, 34.9 and 25.6%, respectively, of the 43 rats. Intraperitoneal iron supplementation significantly enhanced esophageal lesions with CLE, CLE with dysplasia, and EAC to 78.0, 53. 7 and 53.7%, respectively, of the 41 rats. All the tumors were well-differentiated mucinous adenocarcinomas at the squamocolumnar junction area, where most iron deposition was observed. EGDA avoids nutritional problems seen in other animal models for EAC. We believe that direct anastomosis of squamous epithelium to columnar epithelium and mixed reflux of gastric and duodenal contents lead to the formation of CLE and EAC. With this model, we demonstrated that iron supplementation significantly enhanced EAC formation, suggesting that iron over-nutrition could also be a risk factor for human EAC.

Studies of iron deposits, inducible nitric oxide synthase and nitrotyrosine in a rat model for esophageal adenocarcinoma.

A rat model was developed recently in our laboratory to study the pathogenesis of Barrett's esophagus (BE) and its progression to esophageal adenocarcinoma (EAC). Eight-week-old male Sprague-Dawley rats underwent esophagoduodenal anastomosis (EDA) to produce gastric and duodenal reflux in their distal esophagi. The rats were given iron dextran (50 mg of Fe/kg, i.p.) starting 2 weeks after surgery and this was continued once a month. BE was observed as early as week 3 and the incidence of BE and EAC increased with time: 58 and 17% at week 23; 91 and 73% at week 31. There was a progression in epithelial cell proliferation and inflammation from mild to severe in the distal one-third of the esophagus. Iron deposition in the esophagus also increased with time. Iron deposits in the stromal tissue adjacent to the epithelium in the distal one-third of the esophagus were associated with areas of severe inflammation. Immunohistochemical analysis showed positive inducible nitric oxide synthase (iNOS) expression in the stromal macrophages directly beneath the epithelium in the distal one-third of the esophagus in 36, 83 and 100% of the rats at weeks 17, 23 and 31, respectively. A significant increasing linear trend (P=0.001) was seen in nitrotyrosine immunostaining (number of positive cells/high power field) in the distal esophagus. Strong positive nitrotyrosine staining was seen in the macrophages and weaker positive staining was seen in the adjacent epithelium starting at week 17. Furthermore, iron supplemented rats killed at week 31 had significantly higher (P < 0.05) levels of inflammation, cell proliferation, iNOS and nitrotyrosine as well as more tumors in their distal esophagi than did rats that received no iron supplement. These results suggest that iron supplementation enhanced inflammation and the production of reactive oxygen and nitrogen species in the esophageal epithelium. These processes could contribute to the formation of BE and its progression to EAC.

Development of esophageal metaplasia and adenocarcinoma in a rat surgical model without the use of a carcinogen.

In order to establish an animal model for studying the cause and prevention of esophageal adenocarcinoma (EAC) and its frequent precursor, Barrett's esophagus (BE), factors affecting the pathogenic processes were investigated in an esophagoduodenal anastomosis model with rats. Experiments by us and others have shown that surgical treatment produced reflux esophagitis with cell hyperproliferation, but not EAC. Additional treatment with a carcinogen has been shown to be necessary for the development of EAC, squamous cell carcinomas (SCC) or EAC/SCC mixtures. We found that the surgically treated animals developed anemia due possibly to reduced iron absorption. When the operated animals were supplemented with iron, EAC occurred at a high rate (73%) after 30 weeks, and treatment with N'-nitrosonornicotine did not enhance the rate of tumorigenesis. Treatment with carcinogen, however, induced SCC in the group of rats killed after 22 weeks. The results suggest that iron overload, which is known to cause oxidative damage, is an enhancing factor for adenocarcinogenesis. The pathogenesis of EAC in the iron-supplemented, non-carcinogen treated group resembles human esophageal adenocarcinogenesis in many features. All the BE was the specialized type with goblet cells (containing sialomucin or sulfomucin) and columnar cells (containing acid or neutral mucin) as well as an incompletely developed brush border. Almost all of the BE was located at the bottom of the esophagus and was continuous with the duodenal mucosa; dysplasia became more frequent at later time points. All of the cancers were well-differentiated mucinous EAC, and most of the EAC had an adjacent area of BE with dysplasia. The results are consistent with the proposed human sequence for pathogenic events of BE progression to 'BE with dysplasia' and then to EAC. Esophagoduodenal anastomosis and iron treatment in rats produces a high rate of BE and EAC which are morphologically similar to human BE and EAC; this may be a useful animal model to study the development and prevention of EAC in humans.