Papillary Tips Research Articles

Dermatitis Herpetiformis: an Autoimmune Bullous Disease

Dermatitis herpetiformis (DH) is an autoimmune bullous disease characterized by intensely pruritic, chronic, and recurrent vesicles on extensor surfaces such as the elbows, knees, and buttocks. The assortment of neutrophils at the papillary tips is the commonplace histopathological finding, and a trademark analytic element is granular immunoglobulin A statement in the papillary dermis by direct immunofluorescence. DH is firmly connected with gluten touchy enteropathy and is viewed as a cutaneous indication of gluten affectability; i.e., an extra-intestinal show of celiac illness. Gluten free eating routine is the primary line treatment for patients with DH and dispone is likewise compelling. DH specially influences Caucasians who convey human leukocyte antigen (HLA)- DQ2 or HLA-DQ8. The major autoantigen is epidermal transglutaminase. This survey centers around the affirmed highlights of DH and our new discoveries explicit to DH in Japanese patients.

MP36-19 INVESTIGATING RISK FACTORS OF NEPHROLITHIASIS FROM THE CLINICAL IMAGES TO THE GENETIC BIOINFORMATICS

You have accessJournal of UrologyImaging/Radiology: Uroradiology I (MP36)1 Apr 2020MP36-19 INVESTIGATING RISK FACTORS OF NEPHROLITHIASIS FROM THE CLINICAL IMAGES TO THE GENETIC BIOINFORMATICS Zhu Yunpeng* and Zeng Xiaoyong Zhu Yunpeng*Zhu Yunpeng* More articles by this author and Zeng XiaoyongZeng Xiaoyong More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000880.019AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To investigate the correlation among abdominal aortic calcification, the calcification of renal papillary tips and nephrolithiasis though imaging in CT and bioinformatics methods. METHODS: This retrospective study included 163 kidney stone-formers and 168 age- and sex-matched control participants without urolithiasis and histories of urolithiasis. The clinical data including age, gender and comorbidities were collected. Aortic calcification index (ACI) of aorta abdominalis, bone mineral density (BMD) of the first lumbar vertebra and the attenuation of renal papillary tips were measured in CT. Multivariate logistic regression analysis was performed to the correlation among ACI, the attenuation of renal papillary tips and nephrolithiasis. Additionally, through the GEO database, the gene expression analyses of aortic calcification (GSE100927) and nephrolithiasis (GSE100927) were performed to evaluate the inner connection in the level of genetic expression. RESULTS: These data showed that the stone-formers had the higher attenuation of renal papillary tips. There was no significant difference in the prevalence of abdominal aortic calcification, however, ACI of participants with abdominal aortic calcification was significantly higher in the stone group. Multivariate logistic regression analysis showed that ACI and the attenuation of renal papillary tips were significantly correlated with nephrolithiasis. Through bioinformatics methods, the same Differentially Expressed Genes of 8 upregulated genes and 17 downregulated genes were screened out and we found that some important signaling pathways were activated in both nephrolithiasis and arterial calcificatio. CONCLUSIONS: This study demonstrates that the stone-formers have the higher attenuation of renal papillary tips, which gives us a hint that the higher attenuation of renal papillary tips may predict the occurrence nephrolithiasis and is supposed to be a junction between nephrolithiasis and arterial calcification. A significant correlation between aortic calcification and nephrolithiasis was proved again and some important genes and signaling pathways were considered to be the inner connection between nephrolithiasis and arterial calcification. Source of Funding: National Natural Science Foundation of China, Project (No.81570631 and No.81600544) © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e530-e530 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zhu Yunpeng* More articles by this author Zeng Xiaoyong More articles by this author Expand All Advertisement PDF downloadLoading ...

BNP as a Major Player in the Heart-Kidney Connection

Brain natriuretic peptide (BNP) is an important biomarker for patients with heart failure, hypertension and cardiac hypertrophy. Although it is known that BNP levels are relatively higher in patients with chronic kidney disease and no heart disease, the mechanism remains unknown. Here, we review the functions and the roles of BNP in the heart-kidney interaction. In addition, we discuss the relevant molecular mechanisms that suggest BNP is protective against chronic kidney diseases and heart failure, especially in terms of the counterparts of the renin-angiotensin-aldosterone system (RAAS). The renal medulla has been reported to express depressor substances. The extract of the papillary tips from kidneys may induce the expression and secretion of BNP from cardiomyocytes. A better understanding of these processes will help accelerate pharmacological treatments for heart-kidney disease.

A retrospective study of dermatitis herpetiformis from an immunobullous disease clinic in north India.

Indian data on dermatitis herpetiformis (DH) is not available. The aim of this study was to investigate the demographic and clinicopathological characteristics of patients with DH and to study its association with other autoimmune diseases. All data were collected from case record forms of patients registered in immunobullous disease clinic of our institute. The diagnosis was based on characteristic clinical and immuno/histopathological features. A total of 65 patients were included, which constituted 9.47% of the registered patients in the immunobullous disease clinic over 3.5 years. The male to female ratio was 1.4 : 1; the average age was 44.35 ± 15.52 years. Direct immunofluorescence showed granular IgA deposits at the papillary tips in 83.07% and basement membrane zone in 12.3% patients. Sixteen (24.1%) patients had associated celiac disease, and 15 (23.07%) patients had other autoimmune comorbidities such as hypothyroidism. Forty percent of patients on strict gluten-free diet achieved remission in 2 years, while 35.4% had frequent relapses as they continued gluten intake. Dermatitis herpetiformis is not a rare disease in northern India as previously believed. The clinical, histological, and immunopathological characteristics of Indian DH patients are similar to those reported in Caucasian populations. The limitations of our study include an absence of genetic testing for HLA-DQ2 or DQ8, nonavailability of kits for detecting IgA specific for epidermal transglutaminase (IgA eTG), and short follow-up period.

Renal papillary tip extract stimulates BNP production and excretion from cardiomyocytes.

BackgroundBrain natriuretic peptide (BNP) is an important biomarker for patients with cardiovascular diseases, including heart failure, hypertension and cardiac hypertrophy. It is also known that BNP levels are relatively higher in patients with chronic kidney disease and no heart disease; however, the mechanism remains unclear.Methods and resultsWe developed a BNP reporter mouse and occasionally found that this promoter was activated specifically in the papillary tip of the kidneys, and its activation was not accompanied by BNP mRNA expression. No evidence was found to support the existence of BNP isoforms or other nucleotide expression apart from BNP and tdTomato. The pBNP-tdTomato-positive cells were interstitial cells and were not proliferative. Unexpectedly, both the expression and secretion of BNP increased in primary cultured neonatal cardiomyocytes after their treatment with an extract of the renal papillary tip. Intraperitoneal injection of the extract of the papillary tips reduced blood pressure from 210 mmHg to 165 mmHg, the decrease being accompanied by an increase in serum BNP and urinary cGMP production in stroke-prone spontaneously hypertensive (SHR-SP) rats. Furthermore the induction of BNP by the papillary extract from rats with heart failure due to myocardial infarction was increased in cardiomyocytes.ConclusionsThese results suggested that the papillary tip express a substance that can stimulate BNP production and secretion from cardiomyocytes.

Inflammatory Cytokines in the Papillary Tips and Urine of Nephrolithiasis Patients.

Intrarenal inflammation has been implicated in the pathogenesis of nephrolithiasis, with prior work showing increased urine levels of IL-6, IL-8, and CCL-2 in stone patients. However, no studies have assessed for inflammation in the renal papillae. We sought to characterize novel papillary tip and urinary biomarkers in stone patients. Ninety-two patients with nephrolithiasis undergoing percutaneous nephrolithotomy were enrolled. Papillary tip biopsies, kidney urine, and bladder urine were collected, as well as voided urine from eight healthy volunteers. Quantitative polymerase chain reaction was performed to measure inflammatory gene expression. Initial 84-gene polymerase chain reaction array revealed significant elevation of several cytokines in stone patients vs controls (fold change 2.3-694). Twenty-four genes were selected for final analysis. In 41 pairs of urine samples, levels of CCL5, CD40, FasL, RIPK2, SELE, TLR3, and IL-15 were significantly elevated in kidney vs bladder urine (p0.0001-0.04). In 23 triplets of samples, expression of these cytokines plus CCL2, CCL7, CCR2, CSF1, CXCL9, and CXCL10, was significantly greater in papillary tips vs urine samples (p0.001-0.05). Cytokine elevation was independent of maximum postoperative heart rate, respiratory rate, temperature, leukocyte count, urinary tract infection in the past year, presence or absence of antibiotics at the time of surgery, and stone composition (all p > 0.05). Expression of CCL-2, CCL-5, CCL-7, CCR-2, CD40, CSF1, CXCL-9, CXCL-10, Fas-L, RIPK2, SELE, and TLR-3 is markedly elevated in the papillary tips, kidney urine, and bladder urine of nephrolithiasis patients. Cytokine elevation was independent of signs of systemic inflammation. These findings further support the role of inflammation in nephrolithiasis and imply that the inflammatory process likely begins at the renal papillae. These may represent novel biomarkers of stone disease, which may be useful in basic nephrolithiasis research, disease diagnosis, and prognosis.

Evaluation of papillary muscles function in myocardial infarction patients using 2D speckle tracking imaging

Objective To investigate papillary muscle function and construction in myocardial infarction(MI) patients by two-dimensional speckles tracking imaging(2D-STI), and to analyze the influence factors of ischemic mitral regurgitation. Methods Fifty myocardial infarction with ischemic mitral regurgitation(IMR) patients were brought into case group. The patients were divided into two groups: Ant-MI group and Inf-Pos-MI group. Forty-five health volunteers were involved as control group. Anterior, posterior papillary muscle longitudinal strain (ALS, PLS), delay time(DT), fractional shortening (FS), length between the posterior or anterior papillary muscle tips and the contralateral anterior mitral annualr(APM-AMA, PPM-AMA), mitral leaflet closure(MLC), inter distance papillary muscle(IPMD) were aquired respectively. Papillary muscle function and construction among the groups were compared, and the effective factors of IMR were evaluated. Results Between the control group and Ant-MI group, the left ventricular end-diastolic diameter(LVEDD), left ventricular end-diastolic and end-systolic volume(LVEDV, LVESV), left ventricular ejection fraction(LVEF), ALS, delay time(DT), A-FS, IPMD, MLC, APM-AMA, PPM-AMA were significantly different(all P<0.05). Between the control group and Inf-Pos-MI group the LVEDD, LVEDV, LVESV, EF, DT, PPM-AMA, MLC, PLS, P-FS were significantly different(P<0.05). Between the Ant-MI group and Inf-Pos-MI group, the LVEDD, LVEDV, LVESV, EF, MLC, ALS, PPM-AMA, PLS were significantly different(all P<0.05). In the Ant-MI group, LVEDV, ALS, MLC were significantly correated with Gensini score(r=0.71, -0.65, 0.56; P<0.05). In the Inf-Pos-MI group, PPM-AMA, PLS were significantly correated with Gensini score(r=0.65, -0.76; P<0.05). In the Ant-MI group and Inf-Pos-MI group, the ALS, PLS, PPM-AMA were significantly different(P<0.05). Its correlates in Logistic analysis of Ant-MI group included LVEDV, MLC, DT with OR 1.48, 1.72, 1.54(P<0.05), respectively.Its correlates in logistic analysis of Inf-Pos-MI group included PLS, PPM-AMA, DT with OR 1.78, 1.57, 1.56(P<0.05), respectively. Conclusions There are different extent of damage of papillary muscle function and construction in Ant-MI group and Inf-Pos-MI group. The increases of LVEDV and MLC and desynchronization of PMs are risk factors of IMR in Ant-MI group. The increases of PMP-AMA, decrease PLS and desynchronization of PMs are risk factors of IMR inInf-Pos-MI group. Key words: Echocardiography; Mitral vavel regurgitation; Myocardial infarction; Speckle tracking imaging; Papillary muscle function

MP19-07 AUTOFLUORESCENCE OF RANDALL′S PLAQUE PRECURSORS

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology II1 Apr 2017MP19-07 AUTOFLUORESCENCE OF RANDALL′S PLAQUE PRECURSORS Ling Chen, Ryan Hsi, Benjamin Sherer, Marshall Stoller, and Sunita Ho Ling ChenLing Chen More articles by this author , Ryan HsiRyan Hsi More articles by this author , Benjamin ShererBenjamin Sherer More articles by this author , Marshall StollerMarshall Stoller More articles by this author , and Sunita HoSunita Ho More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.3249AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Randall′s plaques at the renal papillary tips are known sites of stone propagation, yet the inciting events leading to Randall′s plaque are poorly understood. Noncollagneous proteins (NCPs) including osteopontin have been identified in the sites of biomineralization and may be critical in the early formation of Randall′s plaques. In contrast to traditional bright-field and polarized microscopy, fluorescence microscopy has the potential to localize and map these proteinaceous regions. This study was undertaken to localize osteogenic noncollagenous proteins in renal papilla as a potential nidus toward stone pathogenesis. METHODS Whole human renal papillae including tissue proximal to the fornix with grossly visible Randall′s plaque were harvested en bloc after nephrectomy. Papillary tissues were processed in a routine fashion and longitudinal histologic sections were characterized using bright field (BF), polarized light (PM), fluorescence (FM), and scanning electron microscopy (SEM) techniques (see Figure) before and after decalcification using EDTA solution. Immunolocalization of NCPs including osteopontin was performed via immunogold labeling of ultrathin sections. RESULTS Mineralized tubules (average diameter 18µm) revealed strong auto-fluorescence in blue, green, and red spectra. After decalcification of the same sections, birefringence visible under polarized light (PM) microscopy disappeared. However, the auto-fluorescence potentially associated with NCPs remained intact. Correlative light and electron microscopy (CLEM) and ultrastructural analyses revealed the mineralized tubular structure in renal papilla is rich in osteopontin (gold particles in Figure). CONCLUSIONS Localization of precursors to Randall′s plaque was detected by auto-fluorescence. NCPs appear to closely associate with tubules of diameter of 18 µm consistent with vascular elements in renal papilla, and may be intimately associated with stone formation. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e231-e232 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Ling Chen More articles by this author Ryan Hsi More articles by this author Benjamin Sherer More articles by this author Marshall Stoller More articles by this author Sunita Ho More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The diagnosis and treatment of dermatitis herpetiformis.

Dermatitis herpetiformis (DH) is an inflammatory cutaneous disease with a chronic relapsing course, pruritic polymorphic lesions, and typical histopathological and immunopathological findings. According to several evidences, DH is considered the specific cutaneous manifestation of celiac disease, and the most recent guidelines of celiac disease have stated that, in celiac patients with a proven DH, a duodenal biopsy is unnecessary for the diagnosis. In this review, the most recent data about the diagnosis and the management of DH have been reported and discussed. In particular, in patients with clinical and/or histopathological findings suggestive for DH, the finding of granular IgA deposits along the dermal–epidermal junction or at the papillary tips by direct immunofluorescence (DIF) assay, together with positive results for anti-tissue transglutaminase antibody testing, allows the diagnosis. Thereafter, a gluten-free diet should be started in association with drugs, such as dapsone, that are able to control the skin manifestations during the first phases of the diet. In conclusion, although DH is a rare autoimmune disease with specific immunopathological alterations at the skin level, its importance goes beyond the skin itself and may have a big impact on the general health status and the quality of life of the patients.

Effect of Congenital Anomalies of the Papillary Muscles on Mitral Valve Function.

Parachute mitral valves (PMVs) and parachute-like asymmetric mitral valves (PLAMVs) are associated with congenital anomalies of the papillary muscles. Current imaging modalities cannot provide detailed biomechanical information. This study describes computational evaluation techniques based on three-dimensional (3D) echocardiographic data to determine the biomechanical and physiologic characteristics of PMVs and PLAMVs. The closing and opening mechanics of a normal mitral valve (MV), two types of PLAMV with different degrees of asymmetry, and a true PMV were investigated. MV geometric data in a patient with a normal MV was acquired from 3D echocardiography. The pathologic MVs were modeled by altering the configuration of the papillary muscles in the normal MV model. Dynamic finite element simulations of the normal MV, PLAMVs, and true PMV were performed. There was a strong correlation between the reduction of mitral orifice size and the degree of asymmetry of the papillary muscle location. The PLAMVs demonstrated decreased leaflet coaptation and tenting height. The true PMV revealed severely wrinkled leaflet deformation and narrowed interchordal spaces, leading to uneven leaflet coaptation. There were considerable decreases in leaflet coaptation and abnormal leaflet deformation corresponding to the anomalous location of the papillary muscle tips. This computational MV evaluation strategy provides a powerful tool to better understand biomechanical and pathophysiologic MV abnormalities.

Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis.

Calcium oxalate (CaOx) kidney stones are formed attached to Randall’s plaques (RPs) or Randall’s plugs. Mechanisms involved in the formation and growth are poorly understood. It is our hypothesis that stone formation is a form of pathological biomineralization or ectopic calcification. Pathological calcification and plaque formation in the body is triggered by reactive oxygen species (ROS) and the development of oxidative stress (OS). This review explores clinical and experimental data in support of ROS involvement in the formation of CaOx kidney stones. Under normal conditions the production of ROS is tightly controlled, increasing when and where needed. Results of clinical and experimental studies show that renal epithelial exposure to high oxalate and crystals of CaOx/calcium phosphate (CaP) generates excess ROS, causing injury and inflammation. Major markers of OS and inflammation are detectable in urine of stone patients as well as rats with experimentally induced CaOx nephrolithiasis. Antioxidant treatments reduce crystal and oxalate induced injury in tissue culture and animal models. Significantly lower serum levels of antioxidants, alpha-carotene, beta-carotene and beta-cryptoxanthine have been found in individuals with a history of kidney stones. A diet rich in antioxidants has been shown to reduce stone episodes. ROS regulate crystal formation, growth and retention through the timely production of crystallization modulators. In the presence of abnormal calcium, citrate, oxalate, and/or phosphate, however, there is an overproduction of ROS and a decrease in the antioxidant capacity resulting in OS, renal injury and inflammation. Cellular degradation products in the urine promote crystallization in the tubular lumen at a faster rate thus blocking the tubule and plugging the tubular openings at the papillary tips forming Randall’s plugs. Renal epithelial cells lining the loops of Henle/collecting ducts may become osteogenic, producing membrane vesicles at the basal side. In addition endothelial cells lining the blood vessels may also become osteogenic producing membrane vesicles. Calcification of the vesicles gives rise to RPs. The growth of the RP’s is sustained by mineralization of collagen laid down as result of inflammation and fibrosis.

Dietary Hydroxyproline Induced Calcium Oxalate Lithiasis and Associated Renal Injury in the Porcine Model

We previously reported hyperoxaluria and calcium oxalate calculi in adult pigs (sows) fed hydroxyproline (HP). The purpose of this study was to grossly and histopathologically characterize intrarenal effects in this model. In the swine facility at our campus, we maintained 21 gestating sows, of which 15 received daily treatment (5% HP mixed with dry feed) and 6 received no treatment (controls). Nine were sacrificed at 21 d (three control, six HP). All kidneys were extracted and examined grossly and for radiographic evidence of stones (GE CT scanner, 80kV, 400MA, 1 sec rotation, 0.625 mm slices). Papillary and cortical samples were processed for histologic analysis. Kidneys from treated sows showed significant calculi distributed within the renal papilla on CT, appeared mottled in the renal cortex and papillary areas, and had less distinct corticomedullary borders. Tiny crystals and mucinous debris lined the papillary tips, calices, and pelvis in kidneys from four of six treated sows, and multiple stones were noted at the papillary tips. Hematoxylin and eosin stain revealed crystals in collecting tubules and papillary tips in treated kidneys and none in controls. Yasue staining confirmed crystals in proximal periglomerular tubules of treated but not control animals. Tubular dilation and inflammatory/fibrotic changes were identified in kidneys from treated animals; none of these changes were evident in control kidneys. We report renal damage as a result of dietary-induced hyperoxaluria in adult sows. Specifically, we found crystalluria in proximal periglomerular tubules and collecting ducts, with tubular damage at all segments.

Real‐Time 3‐Dimensional Dynamics of Functional Mitral Regurgitation: A Prospective Quantitative and Mechanistic Study

BackgroundThree‐dimensional transthoracic echocardiography (3D‐TTE) with dedicated software permits quantification of mitral annulus dynamics and papillary muscle motion throughout the cardiac cycle.Methods and ResultsMitral apparatus 3D‐TTE was acquired in controls (n=42), patients with left ventricle dysfunction and functional mitral regurgitation (LVD‐FMR; n=43) or without FMR (LVD‐noMR, n=35). Annulus in both normal and LVD‐noMR subjects displayed saddle shape accentuation in early‐systole (ratio of height to intercommissural diameter, 10.6±3.7 to 13.5±4.0 in normal and 9.1±4.3 to 12.6±3.6 in LVD‐noMR; P<0.001 for diastole to early‐systole motion, P=NS between those groups). In contrast, saddle shape was unchanged from diastole in FMR patients (10.0±6.4 to 8.0±5.2; P=NS, P<0.05 compared to both other groups). Papillary tips moved symmetrically towards to the midanterior annulus in control and LVD‐noMR subjects, maintaining constant ratio of the distances between both tips to midannulus (PtAR) throughout systole. In LVD‐FMR patients midsystolic posterior papillary tip to anterior annulus distance was increased, resulting in higher PtAR (P=0.05 compared to both other groups). Mechanisms of early‐ and midsystolic FMR differed between different etiologies of LV dysfunction. In patients with anterior MI and global dysfunction annular function and dilatation were the dominant parameters, while papillary muscle motion was the predominant determinant of FMR in patients with inferior MI.ConclusionsInadequate early‐systolic annular contraction and saddle‐shape accentuation in patients with impaired LV contribute to early–mitral incompetency. Asymmetric papillary tip movement towards the midanterior annulus is a major determinant of mid‐ and late‐systolic functional mitral regurgitation.

2303 CALCIUM OXALATE LITHIASIS INDUCES RENAL TUBULAR INJURY AND FIBROSIS IN A PORCINE MODEL

INTRODUCTION AND OBJECTIVES: We have previously reported hyperoxaluria and calcium oxalate calculi in adult sows fed hyroxyproline (HP). The purpose of this study was to grossly and histopathologically characterize intra-renal effects in this paradigm. METHODS: With institutional animal care approval, we maintained 18 pregnant sows in the swine facility at our campus. Treatment was allocated to 14 sows (10% HP mixed with regular dry feed), and 4 were maintained on standard feed with an equal amount of starch (200 g) was mixed (controls). Nine animals were euthanized at 21 d (3 control, 6 HP). All kidneys were extracted and examined in a blinded manner for gross appearance and for CT evidence of stones (GE scanner, 80kV, 400MA, 1 sec rotation, 0.625mm slices). Papillary and cortical samples were processed with HE cortico-medullary borders were less distinct compared to controls. Tiny crystals and mucinous debris lined the papillary tips, calyces and pelvis in 7 of 12 kidneys from treated sows, and multiple stones were noted at the papillary tips in these kidneys. HE none of these changes were evident in control kidneys, which appeared normal. CONCLUSIONS: This is the first report of dietary-induced calcium oxalate stones in adult swine, with crystalluria in proximal periglomerular tubules and collecting ducts, and tubular damage at all levels of tubules. Further studies will allow us to elucidate the etiology of renal damage and identify potential preventive mechanisms. Source of Funding: None

An integrated framework for finite-element modeling of mitral valve biomechanics from medical images: Application to MitralClip intervention planning

Treatment of mitral valve (MV) diseases requires comprehensive clinical evaluation and therapy personalization to optimize outcomes. Finite-element models (FEMs) of MV physiology have been proposed to study the biomechanical impact of MV repair, but their translation into the clinics remains challenging. As a step towards this goal, we present an integrated framework for finite-element modeling of the MV closure based on patient-specific anatomies and boundary conditions. Starting from temporal medical images, we estimate a comprehensive model of the MV apparatus dynamics, including papillary tips, using a machine-learning approach. A detailed model of the open MV at end-diastole is then computed, which is finally closed according to a FEM of MV biomechanics. The motion of the mitral annulus and papillary tips are constrained from the image data for increased accuracy. A sensitivity analysis of our system shows that chordae rest length and boundary conditions have a significant influence upon the simulation results. We quantitatively test the generalization of our framework on 25 consecutive patients. Comparisons between the simulated closed valve and ground truth show encouraging results (average point-to-mesh distance: 1.49 ± 0.62 mm) but also the need for personalization of tissue properties, as illustrated in three patients. Finally, the predictive power of our model is tested on one patient who underwent MitralClip by comparing the simulated intervention with the real outcome in terms of MV closure, yielding promising prediction. By providing an integrated way to perform MV simulation, our framework may constitute a surrogate tool for model validation and therapy planning.

2073 DIETARY HYDROXYPROLINE INDUCES NEPHROLITHIASIS IN THE ADULT PORCINE MODEL

You have accessJournal of UrologyStone Disease: Basic Research I1 Apr 20122073 DIETARY HYDROXYPROLINE INDUCES NEPHROLITHIASIS IN THE ADULT PORCINE MODEL Sutchin R. Patel, Kristina L. Penniston, Thomas D. Crenshaw, and Stephen Y. Nakada Sutchin R. PatelSutchin R. Patel Lake Bluff, IL More articles by this author , Kristina L. PennistonKristina L. Penniston Madison, WI More articles by this author , Thomas D. CrenshawThomas D. Crenshaw Madison, WI More articles by this author , and Stephen Y. NakadaStephen Y. Nakada Madison, WI More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2239AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Our previous studies have shown that a 10% hydroxyproline and gelatin diet can both lead to long-term hyperoxaluria in the adult porcine model. However, no studies have shown nephrolithiasis formation in the adult porcine model. The purpose of our study was to evaluate both diets in the sow model for histologic crystal deposition and gross formation of nephrolithiasis. METHODS Two sows were fed a control diet and six sows were fed a diet of either 10% hydroxyproline or gelatin for 7, 14 and 21 days. Catheters were placed in the sows for 24 hour urine collection prior to the sows being sacrificed at either the 7 day, 14 day or 21 day timepoint. Both kidneys were removed and evaluated for gross stone formation. Renal tissue was fixed in formalin, stained with H&E and von Kossa and evaluated under light microscopy for calcium crystal deposition. Urine was analyzed via ion chromatography for oxalate. RESULTS Mean urinary oxalate concentration for sows on the control diet was 74 mg/L. Urinary oxalate concentrations for the 10% HP diet were 147, 352 and 89 mg/L at 7, 14 and 21 days. Urinary oxalate concentrations for the gelatin diet were 46, 4 and 132 mg/L at 7, 14 and 21 days. Histology revealed calcium crystal formation in the distal collecting ducts and renal papillae in one kidney of the 21 day, 10% hydroxyproline diet sow. Gross pathology revealed 7 renal calculi and calcification at the papillary tips in the same kidney of the 21 day, 10% hydroxyproline diet sow. Chemical analysis of the calculi revealed a composition of 20% calcium oxalate monohydrate, 78% calcium oxalate dihydrate and 2% protein. CONCLUSIONS A long-term 10% hydroxyproline diet leads to calcium oxalate nephrolithiasis in the adult porcine model. This is the first reported case of calcium stone formation in the adult porcine model and has important implications in the development of a dietary porcine model for urolithiasis. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e836 Peer Review Report Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sutchin R. Patel Lake Bluff, IL More articles by this author Kristina L. Penniston Madison, WI More articles by this author Thomas D. Crenshaw Madison, WI More articles by this author Stephen Y. Nakada Madison, WI More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Novel Advances in Dermatitis Herpetiformis

Dermatitis herpetiformis (DH) is an inflammatory cutaneous disease with a chronic-relapsing course that presents with pruritic polymorphic lesions mainly distributed in typical areas such as the extensor aspects of the limbs, the sacral region, and the buttocks. There is growing evidence that DH should be considered the specific phenotypic cutaneous expression of a gluten-sensitive enteropathy indistinguishable from celiac disease (CD). Histologically, DH is characterized by subepidermal blister and accumulation of neutrophils and very few eosinophils at the dermal papillae, while the typical immunopathological finding consists in granular IgA deposits along the basement membrane zone, mainly localized at the papillary tips. Recent studies demonstrated that such IgA are directed against epidermal transglutaminase. However, in the last years, several papers from the literature reported the presence of atypical findings in patients with DH, suggesting that the features described previously probably need a significant revision and leaving many critical points that should be investigated further in the near future. In the present issue, the recent advances of clinical, pathogenetic, and therapeutic aspects of DH will be addressed. About the clinical presentation, an increasing number of papers have recently described uncommon features in patients with DH, as reviewed in the present issue by V. C. Bonciolini et al. Accordingly, Ohata et al. in their paper reported 91 Japanese DH cases showing atypical distribution of the lesions and, interestingly, showed that only two of the eight patients (25%) with DH were biopsied in their case series exhibited histopathological signs of CD. However, patients with DH may present the widest spectrum of histological findings of enteropathy, ranging from normal-appearing epithelium to a flat mucosa; moreover, patients with DH significantly increased the frequency of chronic atrophic gastritis than healthy controls, as demonstrated by A. Alakoski et al. in this issue. From a pathogenetic point of view, the presence of a subepidermal cleft with neutrophilic infiltration at the tips of dermal papillae has been considered the histopathologic hallmark of DH, suggesting a major role for neutrophil granulocytes in the pathogenesis of the skin lesions, as described by D. Bonciani et al. and K. Nakajima in this issue. Besides neutrophils, another cell type has been suggested as a major actor in the pathogenesis of DH, namely, CD4+ T cells. The presence of such cells, with a cytokine expression pattern belonging to the Th2 phenotype, has been documented in recent DH skin lesions as well as in the perilesional skin, suggesting their role in the early phases of DH skin inflammation. Moreover, in this issue, Z. Agnieszka et al. focused the attention on apoptosis, a physiological process that has been shown to play a role in several autoimmune diseases. Finally, in the present issue, A. Fasano reviewed novel therapeutic approaches for DH. Since DH is considered the specific cutaneous manifestation of CD, besides the symptomatic therapies often used in DH patients to control the skin flares at least in the first phases (i.e., dapsone), gluten-free diet (GFD) is still regarded as the only curative approach to the disease. However, a GFD is very hard to comply with, and different approaches are still under investigations. In conclusion, some of the more recent advances in DH are presented in this issue. DH is a complex disease, where the skin represents a clue for the identification of a gluten-sensitive enteropathy. The knowledge of the different clinical and immunopathological features of the disease as well as the understanding of its pathogenesis may lead to a better care of our patients.

Dermatitis herpetiformis in China: a report of 22 cases

Although dermatitis herpetiformis (DH) is a relatively common disease in Caucasian populations, it is very rare in the Far East, including China. To investigate the clinical, histological and immunopathological characteristics of Chinese patients with DH. The clinical data and serum samples of patients with DH diagnosed at Shandong Provincial Institute of Dermatology and Venereology from 2006 to 2010 were collected. Anti-endomysium antibodies (EMA) and anti-tissue transglutaminase (tTG) antibodies were tested using indirect immunofluorescence and enzyme-linked immunosorbent assay respectively. Biopsies of small intestine were performed in those patients who had given informed consent. The study group consisted of 22 patients with DH. The male to female ratio was 2.1:1; the average age was 44 years. Five patients reported mild gastrointestinal symptoms. Dapsone was used to treat 14 patients, who achieved rapid relief. Direct immunofluorescence showed granular IgA deposits at the papillary tips and/or basement membrane zone in 95.5% (21/22) patients. Fibrillar IgA deposition limited to the papillary tips was also seen in one patient (4.5%). IgA antibodies against EMA and tTG were found in 50% (8/16) and 62.5% (10/16) of patient sera respectively. Small-intestinal biopsies of two patients confirmed the presence of coeliac disease. The clinical, histological and immunopathological characteristics of Chinese patients with DH are similar to those seen in Caucasian populations. The positive rates of anti-EMA and anti-tTG antibodies were lower compared with those seen in Western countries. DH is not extremely rare in China and should be actively investigated.

The Utility of the DNA Microarray Scanner to Simplify the Immunofluorescence Evaluation of Autoimmune Bullous Diseases

A DNA microarray scanner was used as a digital fluorescence microscope to simplify the diagnosis of autoimmune bullous diseases. Frozen sections of skin biopsies were taken from 3 patients with bullous pemphigoid and 1 patient each with lichen planus pemphigoides, linear immunoglobulin (Ig) A disease, and dermatitis herpetiformis. After incubation with cyanine-labeled antibodies, the tissues were scanned at 5-mum resolution using an instrument originally designed to study gene expression. The microarray scanner's large field of view, unlike that of fluorescence microscopy, allowed a view of the entire specimen, considerably easing the orientation of tissue. All images were diagnostic and included a linear pattern along the basement membrane zone (BMZ) using anti-IgG and anti-C3 in all cases of bullous pemphigoid, a linear pattern of IgG along the BMZ in lichen planus pemphigoides, and a linear pattern of IgA along the BMZ in linear IgA dermatosis. IgA deposition along dermal papillary tips was seen in dermatitis herpetiformis, but a granular pattern was indiscernible at the 5-mum resolution. The advantages of the microarray scanner over standard fluorescence microscopy include speed, technical ease, large field of view, potential for visualizing multiple antibodies simultaneously in a tissue, and convenience of digital image archiving.

Differences in mitral valve-left ventricle dimensions between a beating heart and during saline injection test☆

Saline injection test performed during mitral valvuloplasty is popular; however, discrepancies are sometimes noticed between the 'naked eye' findings of regurgitation during the saline injection test and the echocardiographic findings after surgery. These discrepancies may arise due to the geometric differences in the mitral valve-left ventricular complex between the saline-injected left ventricle (LV) and the beating LV. Therefore, to elucidate these differences, we compared the three-dimensional geometries between these two conditions. Sonomicrometry crystal markers were implanted in seven mongrel dogs at the mitral annulus, edge of the mitral leaflets between scallops, tips of papillary muscles, and LV apex under cardiopulmonary bypass. Geometric data of the LV were acquired during the saline injection test and in the beating heart. The commissural width was greater and the annular height was lesser during the saline injection test than in the beating heart (20.5+/-5.1mm vs 17.2+/-2.2mm, p<0.01 and 5.5+/-1.8mm vs 7.3+/-2.2mm, p<0.05, respectively), indicating that the saddle-shaped mitral annulus was flattened during the test. Additionally, the middle scallop width and the distance between the papillary tips were greater during the test (14.0+/-4.2mm vs 11.3+/-3.6mm, p<0.05 and 22.9+/-5.9mm vs 11.6+/-5.0mm, p<0.01, respectively), implying that the middle scallop was stretched by the traction of the chordae. The distance between the papillary tips and the mitral annular plane remained constant in both the conditions (19.3+/-2.6mm vs 18.6+/-6.2mm, not significant). The saline injection test could aid in determining the length of the reconstructed chordae. However, the test may provide inaccurate data of the mitral-LV dimensions due to the flattened annulus and overstretched leaflets.