Bilateral leg ulcers secondary to dystrophic calcinosis in a patient with rheumatoid arthritis

Calcinosis cutis can be classified into four subtypes : dystrophic, metastatic, idiopathic, and iatrogenic. Of these subtypes, dystrophic calcinosis (DC) is the most common, and is most frequently associated with connective tissue disease, particularly dermatomyositis and systemic sclerosis, and less commonly with systemic lupus erythematosus. However, DC associated with rheumatoid arthritis (RA) is extremely rare. In this paper, we present a Japanese woman with RA, who suffered from bilateral leg ulcers secondary to DC. To the best of our knowledge, only two cases of DC associated with RA have been reported to date. Similar to this case, the DC lesions were observed in the extremities, including the buttocks in the other two cases. Although the ulcers on her left leg were gradually epithelialized after one year, they may easily recur due to whitish abnormal underlying tissues, and a large ulcer remains on her right leg. Thus, it is important for physicians to identify DC when encountering non-healing leg ulcers associated with connective tissue diseases

Bone Marrow-Derived Cells Implanted into Radiation-Injured Urinary Bladders Reconstruct Functional Bladder Tissues in Rats

The purpose of this study was to determine whether bone marrow-derived cells implanted into radiation-injured urinary bladders could reconstruct functional bladder tissues. The pelvic region of anesthetized female Sprague-Dawley (SD) rats was irradiated with 2 Gy once a week for 5 weeks. After the last irradiation, the rats were maintained for 2 weeks. Bone marrow cells were harvested from the femurs of donor male green fluorescence protein (GFP)-transfected SD rats and cultured for 7 days. Two weeks after the last radiation exposure, the cultured adherent, proliferating bone marrow-derived cells were implanted into the walls of irradiated urinary bladders. For controls, cell-free solutions were similarly injected. Four weeks after donor cell or control implantations, cystometric, histological, and immunohistochemical investigations were performed. Two weeks after the last irradiation, the smooth muscle layers and nerve fibers of the irradiated urinary bladders were disorganized. The proportions of smooth muscle layer and nerve fiber areas were significantly decreased compared with sham-irradiated urinary bladders. In addition, the remaining smooth muscle cells within the irradiated urinary bladders expressed P4HB, an indicator of collagen synthesis. In the cystometric investigations, the voiding interval of irradiated rats was irregularly prolonged, 7.92 +/- 1.09 min, and the residual volume, 0.13 +/- 0.03 mL, was significantly higher compared with the sham-irradiated rats (5.50 +/- 0.43mL and 0.05 +/- 0.01 mL). After 4 weeks, the smooth muscle layers and nerve fibers in the cell-free control urinary bladders remained similar to the pre-implanted irradiated urinary bladders; however, the cell-implanted urinary bladders contained reconstructed smooth muscle layers and nerve fibers, the proportions of each were significantly higher than those in the cell-free injected controls. The expression of P4HB within the cell-implanted urinary bladders decreased. Some GFP-positive implanted cells differentiated into smooth muscle-and nerve-like cells and became organized into the reconstructed tissues. The voiding interval of the cell-implanted rats, 5.46 +/- 0.33 min, was regular and similar to that of the sham-irradiated rats, and significantly less than that of the cell-free injected controls, 7.39 +/- 0.54 min. The residual volume, 0.04 +/- 0.01 mL, was similar to that of the sham-irradiated rats and significantly decreased compared with that of the cell-free injected controls, 0.15 +/- 0.05 mL. Therefore, the implantation of bone marrow-derived cells is a potentially useful treatment for radiotherapy-induced urinary dysfunctions.ArticleTISSUE ENGINEERING PART A. 18(15-16):1698-1709 (2012)journal articl

Precise Three-Dimensional Morphology of the Male Anterior Anorectum Reconstructed From Large Serial Histologic Sections: A Cadaveric Study

BACKGROUND: Deep anatomic knowledge of the male anterior anorectum is important to avoid urethral injury and rectal perforation in intersphincteric resection or abdominoperineal resection for very low rectal cancer. However, its structure is difficult to understand, because the anorectum, muscles, and urogenital organs are complicatedly and 3-dimensionally arranged. OBJECTIVE: The purpose of this study was to revisit the anatomic information of the male anterior anorectum for intersphincteric resection and abdominoperineal resection with a focus on the spatial muscular morphology. DESIGN: This was a descriptive cadaveric study. SETTINGS: The study was conducted at Ehime and Kyoto universities. PATIENTS: Tissue specimens from 9 male cadavers were included. MAIN OUTCOME MEASURES: Specimens around the anterior anorectum were serially sectioned in the horizontal, sagittal, or frontal plane; large semiserial histologic sections were created at 250-μm intervals. The series were stained with Elastica van Gieson, and some sections from the series were studied by immunohistochemistry to detect smooth and striated muscles. Two series were digitalized and reconstructed 3-dimensionally. RESULTS: Two regions without a clear anatomic border were elucidated: 1) the anterior region of the external anal sphincter, where the external anal sphincter, bulbospongiosus muscle, and superficial transverse perineal muscle were intertwined; and 2) the rectourethralis muscle, where the smooth muscle of the longitudinal muscle continuously extended to the posteroinferior area of the urethra, which became closest to the anorectum at the prostatic apex level. A tight connection between the striated and smooth muscles was identified at the anterior part of the upper external anal sphincter and anterolateral part of the puborectalis muscle level. LIMITATIONS: This study involved a small sample size of elderly cadavers. CONCLUSIONS: This study clarified the precise spatial relationship between smooth and striated muscles. The detailed anatomic findings will contribute more accurate step-by-step anterior dissection in intersphincteric resection and abdominoperineal resection, especially with the transanal approach, which can magnify the muscle fiber direction and contraction of striated muscle by electrostimulation. MORFOLOGÍA TRIDIMENSIONAL PRECISA DEL ANORRECTO ANTERIOR MASCULINO RECONSTRUIDO A TRAVÉS DE SECCIONES MAYORES HISTOLÓGICAS EN SERIE: UN ESTUDIO CADAVÉRICO: El conocimiento anatómico amplio del anorrecto anterior masculino es importante para evitar lesiones de uretra y perforación de recto en la resección interesfinterica o la resección abdominoperineal para cáncer de recto bajo. Sin embargo, su estructura es difícil de entender porque el anorrecto, los músculos y los órganos urogenitales están aliñados en forma complexa tridimensional. OBJETIVO: Revisar de nuevo el conocimiento anatómico del anorrecto anterior masculino relevante a la resección interesfinterica y la resección abdominoperineal con un enfoque en la morfología muscular espacial. DISEÑO:: Estudio descriptivo cadavérico. ENTORNO: Ehime y la Universidad de Kyoto. SUJETOS: Tejido especímenes de nueve cadáveres masculinos. PUNTOS FINALES DE VALORACIÓN:: Las muestras alrededor del anorrecto anterior se seccionaron en serie en planos horizontal, sagital y coronal. Se crearon mayores secciones histológicas en serie a intervalos de 250 μm. Los especímenes fueron teñidos con Elástica van Gieson, y algunas secciones de la serie se estudiaron mediante inmunohistoquímica para detectar músculos lisos y estriados. Dos series fueron digitalizadas y reconstruidas tridimensionalmente. RESULTADOS: Se demostraron dos regiones sin un borde anatómico definido: (i) la región anterior del esfínter anal externo, donde se entrelazaron el esfínter anal externo, el músculo bulbospongoso y el músculo perineal transverso superficial; y (ii) músculo rectouretral, donde el músculo liso del músculo longitudinal se extiende continuamente a la zona posteroinferior de la uretra, que se acerca más al anorrecto a nivel del ápice prostático. La conexión estrecha entre los músculos estriados y lisos se identificó en la parte anterior del esfínter anal externo superior y la parte anterolateral del nivel del músculo puborrectal. LIMITACIÓN:: Este estudio incluyó una muestra pequeña de cadáveres ancianos. CONCLUSIÓN:: Este estudio aclaró la relación espacial precisa entre los músculos lisos y estriados. Los hallazgos anatómicos detallados ayudarán para una disección anterior paso a paso más precisa en la resección interesfintérica y la resección abdominoperineal, especialmente con el abordaje transanal, que puede magnificar la dirección de las fibras musculares y la contracción del músculo estriado utilizando electroestimulación

Adult onset IgAV

Immunoglobulin A vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, primarily occurs during childhood between the ages of 3 and 15 years and is the most common form of systemic vasculitis in children ; its occurrence in adults has been rarely reported. Such low incidence could be attributable to either under-diagnosis or misdiagnosis. Thus, not only pediatricians but also physicians should be able to diagnose IgAV accurately to manage the patients appropriately and avoid its associated complications. In addition, treatment of adult onset IgAV with renal involvement has not been fully established yet. We describe here a case of adult onset IgAV complicated by proteinuria and pharyngitis, which was cured by no specific treatment

Bone Marrow-Derived Cells Implanted into Radiation-Injured Urinary Bladders Reconstruct Functional Bladder Tissues in Rats

The purpose of this study was to determine whether bone marrow-derived cells implanted into radiation-injured urinary bladders could reconstruct functional bladder tissues. The pelvic region of anesthetized female Sprague-Dawley (SD) rats was irradiated with 2 Gy once a week for 5 weeks. After the last irradiation, the rats were maintained for 2 weeks. Bone marrow cells were harvested from the femurs of donor male green fluorescence protein (GFP)-transfected SD rats and cultured for 7 days. Two weeks after the last radiation exposure, the cultured adherent, proliferating bone marrow-derived cells were implanted into the walls of irradiated urinary bladders. For controls, cell-free solutions were similarly injected. Four weeks after donor cell or control implantations, cystometric, histological, and immunohistochemical investigations were performed. Two weeks after the last irradiation, the smooth muscle layers and nerve fibers of the irradiated urinary bladders were disorganized. The proportions of smooth muscle layer and nerve fiber areas were significantly decreased compared with sham-irradiated urinary bladders. In addition, the remaining smooth muscle cells within the irradiated urinary bladders expressed P4HB, an indicator of collagen synthesis. In the cystometric investigations, the voiding interval of irradiated rats was irregularly prolonged, 7.92 +/- 1.09 min, and the residual volume, 0.13 +/- 0.03 mL, was significantly higher compared with the sham-irradiated rats (5.50 +/- 0.43mL and 0.05 +/- 0.01 mL). After 4 weeks, the smooth muscle layers and nerve fibers in the cell-free control urinary bladders remained similar to the pre-implanted irradiated urinary bladders; however, the cell-implanted urinary bladders contained reconstructed smooth muscle layers and nerve fibers, the proportions of each were significantly higher than those in the cell-free injected controls. The expression of P4HB within the cell-implanted urinary bladders decreased. Some GFP-positive implanted cells differentiated into smooth muscle-and nerve-like cells and became organized into the reconstructed tissues. The voiding interval of the cell-implanted rats, 5.46 +/- 0.33 min, was regular and similar to that of the sham-irradiated rats, and significantly less than that of the cell-free injected controls, 7.39 +/- 0.54 min. The residual volume, 0.04 +/- 0.01 mL, was similar to that of the sham-irradiated rats and significantly decreased compared with that of the cell-free injected controls, 0.15 +/- 0.05 mL. Therefore, the implantation of bone marrow-derived cells is a potentially useful treatment for radiotherapy-induced urinary dysfunctions.ArticleTISSUE ENGINEERING PART A. 18(15-16):1698-1709 (2012)journal articl

Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Gpnmb is classified as a type 1 membrane protein and its soluble form is secreted by ADAM10-mediated cleavage. Gpnmb mRNA was found in the Kupffer cells and white adipose tissues (WATs) and its upregulation in obesity was recently found. Here, we generated aP2 promoter-driven Gpnmb transgenic (Tg) mice and the overexpression of Gpnmb ameliorated the fat accumulation and fibrosis of the liver in diet-induced obesity model. Soluble form of Gpnmb in sera was elevated in Gpnmb Tg mice and Gpnmb concentrated in hepatic macrophages and stellate cells interacted with calnexin, which resulted in the reduction of oxidative stress. In the patients with non-alcoholic steatohepatitis, serum soluble GPNMB concentrations were higher compared with the patients with simple steatosis. The GPNMB is a promising biomarker and therapeutic target for the development and progression of NAFLD in obesity

Prevention of hypoglycemia by intermittent-scanning continuous glucose monitoring device combined with structured education in patients with type 1 diabetes mellitus : A randomized, crossover trial

Aims: We conducted a randomized, crossover trial to compare intermittent-scanning continuous glucose monitoring (isCGM) device with structured education (Intervention) to self-monitoring of blood glucose (SMBG) (Control) in the reduction of time below range. Methods: This crossover trial involved 104 adults with type 1 diabetes mellitus (T1DM) using multiple daily injections. Participants were randomly allocated to either sequence Intervention/Control or sequence Control/Intervention. During the Intervention period which lasted 84 days, participants used the first-generation FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) and received structured education on how to prevent hypoglycemia based on the trend arrow and by frequent sensor scanning (≥10 times a day). Confirmatory SMBG was conducted before dosing insulin. The Control period lasted 84 days. The primary endpoint was the decrease in the time below range (TBR; <70 mg/dL). Results: The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index >5 was significantly reduced (8.6 % vs 23.7 %, P < 0.001). Conclusions: The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM