Surface Erosions Research Articles

Aortic Atherosclerosis and Embolic Events

Aortic plaques are a manifestation of the general process of atherosclerosis in which there is a progressive accumulation of cholesterol and other lipids in the intimal-medial layer of the aorta with secondary inflammation, repetitive fibrous tissue deposition, and eventually luminal surface erosions and appearance of often mobile thrombi protruding into the lumen of the aorta. Aortic plaques may give rise to two types of emboli: thromboemboli and atheroemboli (cholesterol crystal emboli). Thromboemboli are relatively large, tend to occlude medium to large arteries, and cause strokes, transient ischemic attacks, and renal infarcts and other forms of peripheral thromboembolism. Cholesterol crystal emboli are relatively minute, tend to occlude small arteries and arterioles, and may cause the blue toe syndrome, new or worsening renal insufficiency, gut ischemia, etc. Transesophageal echocardiography remains the gold standard for visualization of aortic plaques in the thoracic aorta. There are no proven therapies for aortic embolism per se; general atherosclerosis management strategies are recommended.

Sonography for Assessment of Elbows in Hemophilic Children: A Systematic Protocol

Evaluation of joints using sensitive non-invasive tools is important for diagnosis and follow-up of hemophilic patients who are continuously at risk of development and/or progression of arthropathy. Because conventional radiography is inadequate for assessing early arthropathic changes in hemophilic patients, there has been an increasing interest in the development of systematic protocols and scoring systems using magnetic resonance imaging (MRI) and ultrasound for evaluating hemophilic arthropathy in recent years. Given some advantages of ultrasound over MRI for this purpose, namely easier access, lower costs and no need for sedation in younger patients, detailed sonographic protocols have recently been proposed for assessment of large joints, most notably knees and ankles, which are most frequently affected by hemophilic arthropathy. Due to the challenges that the elbow joint offers to the reproducibility of positioning of the extremity on ultrasound which is an operator dependent imaging modality, the elbow joint requires dedicated attention. In this paper, we present a systematic protocol for sonographic data acquisition of the elbow in hemophilic children along with examples of findings of joint effusion, synovial hypertrophy, hemosiderin deposition, surface erosions, subchondral cysts and cartilage loss. We also correlate the ultrasound findings with corresponding MR images demonstrating the anatomic planes used for imaging acquisition. The development of a systematic protocol for ultrasound imaging acquisition of elbows in hemophilic children opens avenues for the development/refinement of ultrasound scales for assessment of hemophilic arthropathy which should reduce the opportunity for inter-and intraoperator variability during acquisition of images. Further validation of the proposed systematic protocol for assessment of arthropathic changes in hemophilic elbows is required for its future use in cross-sectional and longitudinal clinical trials. Standardization and validation of such protocols is essential for comparison of results of clinical trials conducted in different hemophilia centres across the world.

674 Confocal Laser Endomicroscopy for In Vivo Diagnosis of Clostridium Difficile Associated Colitis

Confocal Laser Endomicroscopy for In Vivo Diagnosis of Clostridium Difficile Associated Colitis Helmut Neumann, Michael Vieth, Martin Grauer, Raja Atreya, Jonas Mudter, Christoph Becker, Nadine Wittkopf, Markus F. Neurath Department of Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany; Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany Background: Clostridium difficile infection (CDI) is one of the most clinically significant causes of hospital-acquired diarrhea and associated with significant morbidity and mortality. Endomicroscopy (CLE) has recently risen as a new emerging endoscopic imaging modality enabling real time in vivo histology during ongoing endoscopy. Aims: Main objective was to investigate whether CLE has the capability for the in vivo diagnosis of CDI. Second objective of our study was to proof the presence of intramucosal bacteria using CLE. Material & Methods: Prospectively, seventy-eight consecutive patients with diarrhea were included of whom eight patients were diagnosed with CDI based on toxigenic culture. CLE was performed after intravenous injection of fluorescein. Additionally, in three patients topical application of acriflavine hydrochloride was performed. In order to validate the presence of intramucosal bacteria ex vivo CLE was performed in pure C. difficile culture; in addition fluorescence in situ hybridization (FISH) was made. Finally, endomicroscopy with fluorescence labelled eubacterial oligonucleotide probes specific for C. difficile was performed in order to prove the presence of intramucosal bacteria. Results: Overall, 80 lesions were examined using endomicroscopy. CLE could readily identify CDIassociated histological changes in vivo. In early CDI, CLE revealed small surface erosions of the superficial colonic crypts and an increased cellular infiltrate. Microvessels within the lamina propria were slightly dilated but showed no leakage. In advanced CDI, CLE demonstrated massively dense cellular infiltrate. Normal colonic appearance was nearly completely abolished and fragile vessels with leakage became visible. Furthermore, a plaque of loosely cells, fibrin and debris covered the mucosal surface. Sensitivity and specificity of CLE in predicting CDI was 75% and 92.9%, respectively. In addition, intramucosal bacteria were visualized using CLE. The presence of these bacteria could also be proven by CLE with fluorescein-labelled specific C. difficile probes and by using the FISH-technique. Sensitivity and specificity for the presence of intramucosal bacteria on endomicroscopy and afterwards confirmed with FISH was 100%. No adverse events regarding the procedure or the use of fluorescence agents were observed. Conclusions: CLE has the potential for the in vivo diagnosis of CDI associated colitis thus enabling accelerated diagnosis and improved patient management. In addition, CLE enabled the detection of intramucosal bacteria in vivo which could open a plethora of new indications in the near future.

Hand Radiological Damage in Systemic Sclerosis: Comparison with a Control Group and Clinical and Functional Correlations

To define the burden of hand radiological damage in systemic sclerosis (SSc) patients, compared with a control group. Both hands of 167 SSc patients and 168 hands (82 right and 86 left) of age- and gender-matched controls were imaged by conventional radiograph. Two musculoskeletal radiologists semiquantitatively scored the following lesions: tuft acro-osteolysis, tuft calcinosis, joint space narrowings, marginal erosions, surface erosions, collapse arthropathies, periarticular calcifications, and juxta-articular osteoporosis, at the following areas: tufts, distal interphalangeal, proximal interphalangeal, metacarpophalangeal, carpal, and first carpometacarpal joints. Clinical and functional characteristics of the 167 SSc patients were obtained from the Belgian Systemic Sclerosis Cohort database. Tuft acro-osteolysis and calcinosis were the most common findings observed in SSc patients and were almost absent in controls. SSc patients displaying tuft acro-osteolysis/calcinosis suffered from more severe disease. Arthropathies were infrequently detected and mainly consisted of a mixture of osteoarthritis-related changes (joint space narrowing and surface erosions)-also observed in controls-and of 2 types of rare SSc-associated arthropathies: a rheumatoid arthritis-like pattern, characterized by marginal erosions (n = 7 patients), and a collapse arthropathy (n = 6 patients), characterized by pressure erosions and joint subluxation. Although a rheumatoid arthritis-like or a collapse arthropathy can be observed in SSc patients, arthropathies are less common than previously reported.

Gastroesophageal Reflux Might Cause Esophagitis Through a Cytokine-Mediated Mechanism Rather Than Caustic Acid Injury

Reflux esophagitis is believed to be caused by the caustic effects of refluxed gastric acid on esophageal epithelial cells. However, caustic chemical injuries develop rapidly whereas esophagitis might not appear until weeks after the induction of reflux in animal models. We studied early histologic events in the development of reflux esophagitis in a rat model and performed in vitro experiments to determine whether exposure to acidified bile salts causes esophageal epithelial cells to secrete chemokines that might contribute to inflammation. At various time points after esophagoduodenostomy, the rat esophagus was removed and inflammatory changes were analyzed by histologic analyses. Human esophageal squamous cell lines were exposed to acidified bile salts to evaluate their effects on cytokine production and immune-cell migration. Reflux esophagitis started at postoperative day 3 with lymphocytic infiltration of the submucosa that progressed to the epithelial surface-these findings contradicted those expected from a caustic chemical injury. Basal cell and papillary hyperplasia preceded the development of surface erosions. Exposure of squamous cells to acidified bile salts significantly increased the secretion of interleukin-8 and interleukin-1beta; conditioned media from these cells caused significant increases in the migration rates of T cells and neutrophils. These findings support, but do not prove, an alternative concept for the development of reflux esophagitis in which refluxed gastric juice does not directly damage the esophagus, but rather stimulates esophageal epithelial cells to secrete chemokines that mediate damage of esophageal tissue.

Biological relevance of ion energy in performance of human endothelial cells on ion‐implanted flexible polyurethane surfaces

To improve the biocompatibility of polyurethane (PUR), we modified the surface by irradiation with different ions (Carbon; C, Oxygen; O, Nitrogen; N, or Argon; Ar) at 0.3-50 keV energy and doses of 1,00E+13 - 1,00E+15 ions/cm(2). The effects of ion implantation using different ion energies and densities were observed on adhesion, proliferation, and viability of human umbilical vein endothelial cells (HUVECs). The long-term in vitro stability of ion-implanted PUR was also investigated. Ion irradiation moderately affected the surface roughness (R(a)), but strongly enhanced the work of adhesion (W(a)). Cell adhesion was markedly improved on O-, N-, and Ar-, but not on C-implanted PUR surfaces. Medium ion energies and lower ion doses produced the best HUVEC attachment and proliferation, indicating the importance of choosing the proper range of energy applied during ion irradiation. In addition, apoptosis rates were significantly reduced when compared with unmodified PUR (uPUR). N implantation significantly protected the surface, although C implantation led to stronger surface erosions than on uPUR. In total, ion implantation on flexible PUR surfaces strongly improved the material surface characteristics and biocompatibility. Electron beam ion implantation within an appropriate energy window is thus a key to improving flexible PUR surfaces for clinical use to support endothelial cell performance. Thus, it can contribute to designing small-diameter grafts, which are in great demand, towards vascular tissue engineering applications.

Effects of artificial pores and purity on the erosion behaviors of polycrystalline Al2O3 ceramics under fluorine plasma

Microstructure developments under fluorine plasma have been investigated in the Al2O3 ceramics containing artificial pores with controlled purity. The erosion behaviors by fluorine plasma consisted of a uniform erosion throughout the specimen surface and local erosions around the artificial pores and defects such as intrinsic irregular pores and damages formed during the grinding and polishing steps. The effects of the pores on the microstructure development were more distinct in the low purity Al2O3 specimen. The erosions around the pores, in the beginning, showed polygonal or flower-like microstructures in high or low purity Al2O3, respectively, indicating a weak grain boundary of glassy phase under the fluorine plasma. The extended plasma treatment resulted in loose structures around the pores in the low purity specimen, possibly producing contamination particles. In contrast to the polycrystalline Al2O3, single crystalline Al2O3 showed only uniform erosion. Although the microstructure developments were completely different depending on purity, porosity and polycrystallinity, etch depths did not appear so different, implying that the etch depths might not properly represent the plasma resistance of the materials.

Surface erosion and modification by highly charged ions

Analyses were conducted of various models and mechanisms of highly charged ion (HCI) and swift-heavy ion energy transfer into a solid target, such as hollow atom formation, charge screening, neutralization, shock wave generation, crater formation, and sputtering. A plasma model of space charge neutralization based on impact ionization of semiconductors at high electric fields was developed and applied to analyze HCI impacts on Si and W. Surface erosions of semiconductor and metal surfaces caused by HCI bombardments were studied by using a molecular dynamics simulation method, and the results were compared with experimental sputtering data.

Macular corneal dystrophy: mutational spectrum in German patients, novel mutations and therapeutic options

The objective of this study was to investigate genotype-phenotype correlations, the consequences for surgical treatment, and the therapeutical options in patients with macular corneal dystrophy (MCD). We investigated MCD genotype by using polymerase chain reaction followed by direct sequencing in one family and four patients with MCD. Results were confirmed by restriction analysis. Clinical phenotypes, histopathological findings, and therapeutical proceedings of each patient were reported and compared with the molecular genetic results. Five mutations, four missense mutations, and one frameshift mutation, from which three were novel, and one single-nucleotide polymorphism, were identified within the coding region of the CHST6 gene. In three patients, two with a homozygous mutation within the start codon (Met1Leu) and one with a heterozygous mutation (Leu200Arg) and a polymorphism (Arg162Gly), with irregular corneal surface and recurrent erosions a phototherapeutic keratectomy lead to a transient success. An additional fitting of rigid gas permeable contact lenses in one patient could further improve irregular astigmatism. In two patients, one with a frameshift mutation (1734_1735delTG; Arg211Gln) and one with two compound heterozygous mutations (Leu200Arg; Leu173Phe) and an additional polymorphism (Arg162Gly) a penetrating keratoplasty improved BCVA without any recurrence of the opacities within the follow-up time. Different genotypes imply several phenotypes, which influence therapeutical proceedings in MCD patients. Our study shows the wide range of diagnostic findings and therapeutical options in patients suffering from macular corneal dystrophy depending on the genotype.

Surface erosion and modification by energetic ions

Surface erosion and modification by energetic highly charged and cluster ions are important in the development of semiconductor devices, TeV accelerators, fission and fusion reactors, and in the development of extreme ultra-violet lithography devices. Gas cluster ion beam (GCIB) surface treatment can significantly mitigate the high-gradient electric vacuum breakdown of rf-cavities. GCIB can also mitigate Q-slope drop in superconducting Nb-cavities. Various mechanisms of the highly charged ion (HCI) energy transfer into the solid target, such as hollow atom formation, charge screening and neutralization, shock wave generation, and sputtering were analyzed. Surface erosions caused by GCIB, HCI bombardments, and by low energy He + and H + ions typical for fission and fusion devices were studied by using molecular dynamics simulation. A He bubble splashing mechanism of liquid Li containing was developed, and surface erosion was simulated. The mechanism of bubble explosion could significantly contribute to the surface erosion at high ion fluxes and explain the existing experimental results.

Bladder calculi presenting as complete procidentia

Multiple large bladder stones resulting in complete procidentia present unique operative challenges. A 71-year-old postmenopausal multipara was admitted to the intensive care unit for urosepsis. A firm irreducible 15 x 10 x 10 cm procidentia was noted on exam with surface erythema, erosions, and edema. A computed tomography scan of the pelvis reported a staghorn calculus in the right renal pelvis and a large calcified fibroid uterus which had prolapsed completely out of the pelvis. After resolution of her urosepsis, the patient was taken to the operating room for a vaginal hysterectomy and surgical correction of her prolapse. A small uterus weighing 67 g was identified with a large bladder mass. Cystotomy revealed multiple bladder calculi, the largest measuring 8.1 x 6.8 x 4.6 cm. Cystolithiasis should be considered when evaluating patients with large calcified prolapse.

The effect of oral calcitonin on cartilage turnover and surface erosion in an ovariectomized rat model

To investigate whether oral calcitonin treatment influences the increases in type II collagen (CII) degradation and related surface erosions of articular cartilage in ovariectomized rats. Fifty rats were randomly allocated into 1 of the 5 following intervention groups: sham-operated, ovariectomy, ovariectomy plus subcutaneously implanted 17beta-estradiol pellet, ovariectomy plus 2 mg/kg salmon calcitonin plus 50 mg/kg 5CNAC (carrier), or ovariectomy plus 50 mg/kg 5CNAC. Each treatment was administered for 9 weeks after the ovariectomy. Blood samples for biochemical marker analysis were collected from fasting animals at baseline, on day 3, and after 1, 2, 4, 6, and 9 weeks. CII degradation was quantified by specific immunoassay, and the changes in severity scores of articular cartilage erosions were visualized and scored in histologic sections of the knees. Ovariectomy resulted in a marked increase in serum levels of C-telopeptide of type II collagen (CTX-II) (P < 0.001), which could be effectively reversed by 17beta-estradiol supplementation. Oral administration of calcitonin elicited similar decreases in serum levels of CTX-II (P < 0.001). Histologic scoring of cartilage erosion showed significantly less cartilage erosion in calcitonin-treated ovariectomized rats versus control ovariectomized rats that were untreated or treated with 5CNAC alone. (P < 0.01). The in vivo effects of calcitonin in rats suggest that calcitonin is able to counteract CII degradation and the accompanying structural disintegration of articular cartilage promoted by estrogen deficiency. Clinical assessment of the chondroprotective potential of calcitonin in postmenopausal women seems warranted.

Gastrointestinal Stromal Tumor with Dieulafoy Lesion: A Novel Association

A man, 86 years of age, presented with a 4-day history of black loose stools for the 4 days prior to admission. He felt weak and light-headed and reported chronic symptoms of heartburn, but no history of hematochezia. Rectal examination revealed strongly occult-positive stools. Hemoglobin, at presentation, was 8.6 g/dl. Same-day esophagogastroduodenoscopy (EGD) revealed a large smooth submucosal tumor situated at the lesser curvature, distally. It measured 4 cm x 4 cm and was clinically consistent with a gastrointestinal stromal tumor (GIST). Close examination of the lesion revealed a protuberant shiny erythematous blood vessel without any active bleeding (figure 1A ▶). There were no surface ulcers or erosions. Given these characteristics, it was felt we were dealing with a Dieulafoy lesion. We sprayed the lesion with water using a 7 Fr bipolar circumactive probe (BiCAP), which resulted in immediate bleeding (figure 1B ▶). Though difficult, hemostasis was successfully achieved with BiCAP (setting of 4, Valley Lab Force Ez, Boulder, CO) followed by application of 4 clips (QuickClip2, Olympus, Melville, NY), resulting in complete hemostasis and ablation of the Dieulafoy lesion. The patient required 3 units of packed red blood cells. Computerized axial tomographic (CAT) scan of the abdomen showed a heterogeneous, nearly spherical tumor approximately 5 cm in diameter in the lesser curvature of the stomach. The patient subsequently underwent wedge resection of the tumor. Histopathological examination was consistent with a GIST with less than 5 mitoses per 50 HPF. Figure 1. (A) Endoscopic image showing a well-delineated Dieulafoy lesion overlying a large gastrointestinal stromal tumor on the lesser curvature of the stomach. (B) The Dieulafoy lesion demonstrated brisk bleeding with simple irrigation. Dieulafoy lesion was first identified as a rare cause of gastrointestinal bleeds by Gallard in 1884 and later described by Dieulafoy in 1897. The typical lesion is a lentil-sized round mucosal defect with an artery protruding from its base. Such lesions are responsible for 0.3% to 1.5% of major gastrointestinal bleeds and most commonly occur in the stomach on the lesser curvature, within 6 cm of the gastroesophageal junction. Lesions have also been reported in the esophagus, duodenum, ileum and colon. They bleed easily and can cause massive hemorrhage. EGD can readily diagnose most of the gastric lesions. Occasionally, however, they can be elusive, requiring subsequent EGD for definitive diagnosis and therapy. Diagnosis of Dieulafoy lesions in other sites is difficult and can be attempted by selective angiography. Endoscopic therapy includes epinephrine injection, thermocoagulation, laser photocoagulation, band ligation and hemoclips. Surgical management is reserved for patients who fail endoscopic management.1,2 GISTs encompass a heterogeneous group of mesenchymal tumors and constitute approximately 3% of all soft tissue sarcomas. They are very uncommon, affecting approximately 4/1,000,000 people. Seventy percent of GISTs occur in the stomach with peak incidence in the fifth and sixth decades. Malignant potential is predicted by size (>5 cm) and mitotic activity (>10 mitoses/HPF). GISTs are typically asymptomatic. Bleeding from ulcers in the overlying mucosa is the most common manifestation, followed by obstructive symptoms by virtue of tumor size. Surgical resection is the preferred treatment and complete tumor resection can be accomplished in 50% to 80% of cases.3,4 This case of massive gastrointestinal bleed from a Dieulafoy lesion overlying a GIST is, to the best of our knowledge, a novel and unique clinical presentation that has not yet been reported in the literature. While this association did not result in a management change, it does underscore the ubiquitous nature of Dieulafoy lesions.

Rectal carcinoid tumor mimicking colonic adenomatous lesion

A 49-year-old man presented with hematochezia. At colonoscopy, a semipedunculated polyp with surface erosions was observed (A). A 1.8-cm lesion was located at the lower rectum. The colonoscopic view after spraying indigo carmine showed that the pit pattern on the surface of this lesion was an irregular arrangement of tubular and round pits with various sizes (B). These endoscopic findings suggested that this neoplastic lesion might originate from the epithelium. However, biopsy specimens taken because of the unusual findings revealed normal colonic mucosa only.

Pathologic Features and Clinical Significance of ???Backwash??? Ileitis in Ulcerative Colitis

Patients with ulcerative colitis (UC) may develop inflammation in the distal ileum thought to be due to "backwash" of cecal contents ("backwash ileitis"). However, a systematic analysis of ileal changes in UC has never been performed, and the prevalence and criteria for "backwash" ileitis have not been defined. The aim of this study was to evaluate the prevalence and spectrum of inflammatory changes in the ileum in patients with UC and to correlate ileal changes with outcome after total proctocolectomy and ileal pouch-anal anastomosis. Routinely processed ileocolonic resection specimens from 200 consecutive patients with clinically and pathologically confirmed UC were evaluated for a wide variety of pathologic features in the ileum and colon. The ileal data were correlated with both the clinical features and the pathologic findings in the colon. Follow-up data were obtained to confirm absence of Crohn's disease and to evaluate outcome of ileo-anal pouches. Overall, 34 of 200 (17%) UC patients had inflammatory changes in the ileum (male/female ratio, 16/18; mean age, 42 years); 32 of 34 (94%) had pancolitis, which was significantly higher than the rate of pancolitis (39%) in patients without ileal disease (N = 166) (P < 0.001), but there were no other differences between patients with or without ileal pathology. In the colon, 22 of 34 (65%) patients had severe activity. Ileal changes included villous atrophy and crypt regeneration without increased inflammation (N = 3), increased neutrophilic and mononuclear inflammation in the lamina propria (N = 6), patchy cryptitis and crypt abscesses (N = 21) and focal superficial surface erosions (N = 4), some with pyloric metaplasia (N = 2 of 4). In general, the severity of ileal changes paralleled the severity of colonic activity. However, 2 of 4 (50%) patients with superficial erosions in the ileum had subtotal or left-sided colitis only, and had only mild colonic activity. Other cases showed only mild to moderate colonic activity and patchy or discontinuous involvement of the distal ileum. Upon follow-up of patients with erosions (mean, 48.5 months; range, 26-102 months), none developed manifestations of Crohn's disease anywhere in the gastrointestinal tract. The presence of inflammatory changes in the ileum had no effect on the prevalence of pouch complications or on the occurrence of dysplasia or cancer. Ileal changes in UC are not uncommon (prevalence, 17%), are generally mild in nature (villous atrophy, increased inflammation, scattered crypt abscesses), and are not associated with an increased rate of ileo-anal pouch complications, dysplasia, or carcinoma. In some cases, our findings are consistent with a backwash etiology. However, rarely, ileal erosions may occur in patients without cecal involvement, which may indicate that other pathogenetic mechanisms should be considered in the etiology of ileitis in UC patients.

Backwash Ileitis Is Not Associated With an Increased Risk of Neoplasia in Ulcerative Colitis

Introduction: Some patients with chronic ulcerative colitis (CUC) develop inflammatory changes of the distal ileum thought to be related to backwash of colonic contents, termed “backwash ileitis” (BI). One previous study showed a high association between BI and carcinoma in CUC (Gastroentrology 2001;120:841–847). However, in that study, strict pathologic criteria for BI were not utilized. The purpose of this study was to evaluate the risk of dysplasia and/or carcinoma in patients with CUC who have BI. Methods: Ileo-colonic resection specimens from 175 consecutive patients with CUC were evaluated for a wide variety of inflammatory changes in the distal ileum and colon, including the presence and grade of dysplasia and carcinoma. The pathologic features in the colon were compared between patients with BI versus those without BI. Follow-up information was obtained (mean, 32.8 months) to ensure the absence of features of Crohn’s disease. Results: Overall, 35 patients showed inflammatory changes of the distal ileum (M/F ratio, 16/19; mean age, 42 years). Ileal changes included villous atrophy and crypt regeneration without increased inflammation (n = 3), increased neutrophilic and mononuclear inflammation in the lamina propria (n = 6), patchy cryptitis, and crypt abscesses (n = 22), and focal superficial surface erosions (n = 4), some with pyloric metaplasia (n = 2/4). Except for a higher prevalence rate of pancolitis in patients with BI (94% pancolitis vs. 45% pancolitis, P < .001), there were no significant differences in the pathologic features in the colon between patients with or without BI. In general, the severity of ileal inflammatory changes paralleled the severity of colonic activity, except for 4 confirmed CUC patients, who had either subtotal or left-sided colitis in addition to inflammatory changes in the ileum. None of the patients with BI had dysplasia, although 2 had carcinoma (6%), in contrast to 14/140 (10%) control patients who had either low (N = 6) or high-grade dysplasia (N = 5), or carcinoma (N = 3), as their most severe neoplastic lesion. These differences were not statistically significant (P > .05). Conclusion: Ileal inflammatory changes in CUC are not uncommon (prevalence rate; 20%) and, in most cases, are consistent with a “backwash” etiology. The prevalence of dysplasia and/or carcinoma is not increased in CUC patients with BI. Introduction: Some patients with chronic ulcerative colitis (CUC) develop inflammatory changes of the distal ileum thought to be related to backwash of colonic contents, termed “backwash ileitis” (BI). One previous study showed a high association between BI and carcinoma in CUC (Gastroentrology 2001;120:841–847). However, in that study, strict pathologic criteria for BI were not utilized. The purpose of this study was to evaluate the risk of dysplasia and/or carcinoma in patients with CUC who have BI. Methods: Ileo-colonic resection specimens from 175 consecutive patients with CUC were evaluated for a wide variety of inflammatory changes in the distal ileum and colon, including the presence and grade of dysplasia and carcinoma. The pathologic features in the colon were compared between patients with BI versus those without BI. Follow-up information was obtained (mean, 32.8 months) to ensure the absence of features of Crohn’s disease. Results: Overall, 35 patients showed inflammatory changes of the distal ileum (M/F ratio, 16/19; mean age, 42 years). Ileal changes included villous atrophy and crypt regeneration without increased inflammation (n = 3), increased neutrophilic and mononuclear inflammation in the lamina propria (n = 6), patchy cryptitis, and crypt abscesses (n = 22), and focal superficial surface erosions (n = 4), some with pyloric metaplasia (n = 2/4). Except for a higher prevalence rate of pancolitis in patients with BI (94% pancolitis vs. 45% pancolitis, P < .001), there were no significant differences in the pathologic features in the colon between patients with or without BI. In general, the severity of ileal inflammatory changes paralleled the severity of colonic activity, except for 4 confirmed CUC patients, who had either subtotal or left-sided colitis in addition to inflammatory changes in the ileum. None of the patients with BI had dysplasia, although 2 had carcinoma (6%), in contrast to 14/140 (10%) control patients who had either low (N = 6) or high-grade dysplasia (N = 5), or carcinoma (N = 3), as their most severe neoplastic lesion. These differences were not statistically significant (P > .05). Conclusion: Ileal inflammatory changes in CUC are not uncommon (prevalence rate; 20%) and, in most cases, are consistent with a “backwash” etiology. The prevalence of dysplasia and/or carcinoma is not increased in CUC patients with BI.

Compatible scales for progressive and additive MRI assessments of haemophilic arthropathy

The international MRI expert subgroup of the International Prophylaxis Study Group (IPSG) has developed a consensus for magnetic resonance imaging (MRI) scales for assessment of haemophilic arthropathy. A MRI scoring scheme including a 10 step progressive scale and a 20 step additive scale with identical definitions of mutual steps is presented. Using the progressive scale, effusion/haemarthrosis can correspond to progressive scores of 1, 2, or 3, and synovial hypertrophy and/or haemosiderin deposition to 4, 5, or 6. The progressive score can be 7 or 8 if there are subchondral cysts and/or surface erosions, and it is 9 or 10 if there is loss of cartilage. Using the additive scale, synovial hypertrophy contributes 1-3 points to the additive score and haemosiderin deposition contributes 1 point. For osteochondral changes, 16 statements are evaluated as to whether they are true or false, and each true statement contributes 1 point to the additive score. The use of these two compatible scales for progressive and additive MRI assessments can facilitate international comparison of data and enhance the accumulation of experience on MRI scoring of haemophilic arthropathy.

Biology of the skin and dermatological disease

Abstract Accurate diagnosis of skin diseases can be daunting because the complexity of the cellular composition of the skin means that the permutations of clinical presentations and the range of diseases that can arise are wide. An understanding of the anatomy and pathophysiology of normal and diseased skin helps in the diagnosis of skin diseases by providing a framework to relate key physical signs to underlying pathological processes. Many skin diseases are characterized by involvement of the epidermis with disruption of the integrity of the epidermal barrier, seen in abnormal scaling of the skin, alterations in skin surface markings, vesicle formation and/or erosions caused by complete loss of the epithelial layer. In most cases, these changes are secondary to inflammatory processes such as psoriasis or eczema. Certain rare genetic and acquired skin diseases primarily affect the epidermis, and their investigation has provided insights into normal epidermal function. Changes in the dermis such as vasodilatation and accumulation of inflammatory cells also often accompany diseases such as psoriasis, eczema and lichen planus. Recognition of the absence of signs of epidermal involvement and awareness of the cellular composition and pathology of the dermis can be invaluable in diagnosing conditions such as morphoea, sarcoidosis, granuloma annulare, vasculitis and Kaposi's sarcoma. Functional understanding of hair follicle biology and skin immunology is also critical for skin diagnosis and helps in the assessment of new potential therapies for diseases characterized by abnormal hair loss or by disturbances in the cellular trafficking of components of the skin immune system.

Erosive osteoarthritis.

Erosive osteoarthritis (EOA) is believed to be a clinically uncommon subset of generalized osteoarthritis (OA) characterized by a clinical course, which is frequently aggressive. The diagnosis of EOA is accepted only for patients meeting American College of Rheumatology clinical criteria for OA of the hand and showing radiographic aspects of articular surface erosions. Conditions to be considered in the differential diagnosis include primarily nodal generalized OA, psoriatic arthritis and rheumatoid arthritis. It is possible to find erosive changes resembling EOA in endocrine diseases, microcrystal-induced diseases, chronic renal diseases, autoimmune diseases and others. Despite the absence of a clear etiology, immunogenetic studies are useful in identifying a possible predisposition to developing EOA in some subjects. No definitive therapeutic approach to EOA has been reported. It is reasonable to assume that in the presence of a symptomatic EOA our therapeutic approach should differ from that used for common, nodal, non-EOA.

Simulation of Drug Release from Biodegradable Polymeric Microspheres with Bulk and Surface Erosions

New models are developed to account for the kinetics of drug release from porous, biodegradable polymeric microspheres under the schemes of bulk erosion and surface erosion of the polymer matrix, respectively. Three mechanisms of drug release, namely, drug diffusion, drug dissolution, and polymer erosion jointly govern the overall release process. For bulk erosion, the model incorporates an erosion term into the dissolution and diffusion equation and is solved numerically for various boundary conditions. Dissolution and erosion are defined in the model by introducing three equations which take into account the drug concentration in the liquid phase, virtual solid phase, and effective solid phase. For surface erosion, drug concentrations in liquid and solid phases are defined and a substitution is introduced to convert the moving‐boundary problem to a fixed‐boundary problem. The resulting differential equations are solved simultaneously to obtain the concentration profile in the liquid and solid phases, respectively. Numerical solutions are provided to illustrate the effects of drug dissolution constant, drug diffusion coefficient, and erosion rate constant. In general, increasing erosion rate, diffusivity, dissolution, and decreasing particle radius enhance the drug release rate. Predictions from the models are also compared with experimental data to verify their validity and possible improvements are proposed. © 2003 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:2040–2056, 2003