Evaluation of incidence, predictive factors and treatment considerations for asymptomatic genitourinary granulomas after intravesical bacillus Calmette-Guérin therapy.

INTRODUCTION AND OBJECTIVES: Although the complications of intravesical BCG treatment are well described, asymptomatic genitourinary granulomas after BCG therapy have rarely been reported and management strategy for these conditions remains controversial. The objective of this study is to evaluate the incidence rate of asymptomatic genitourinary granuloma formation mimicking bladder cancer recurrence after intravesical bacillus Calmette-Guérin (BCG) therapy and to identify the diagnostic and treatment strategies according to patient conditions. PATIENTS AND METHODS: A retrospective review was conducted on 162 patients who underwent intravesical BCG therapy. For patients who developed granulomas, we evaluated the time interval between BCG instillation and the development of granuloma, the presence of acid-fast bacteria on pathology specimens, culture/polymerase chain reaction results, management strategies for the lesions, and clinical outcomes. RESULTS: Asymptomatic genitourinary masses developed in 14 patients, of whom 5 underwent histological examinations and all were confirmed to have granulomatous inflammation. The affected organs included the kidney, bladder, prostate, and penis. While four of the five patients did not receive treatment for their granulomas, one patient was administered antituberculous medication to prevent worsening of the lesion during the perioperative period of the scheduled cystoprostatectomy. None of the patients experienced worsening or recurrence of granulomatous lesions. Patients who developed asymptomatic masses (n = 14) were significantly younger than those who did not (p = 0.0076) and multivariate analysis also showed that younger age was independently associated with the development of clinically suspicious lesions (p = 0.032); however, none of the parameters were associated with histologically confirmed granuloma formation. CONCLUSIONS: Genitourinary granulomas mimicking recurrence of carcinoma may develop in nearly 10% of patients after intravesical BCG therapy. Most patients can be managed without potentially toxic antituberculosis therapy.

Evaluación de la incidencia, factores predictivos y consideraciones sobre el tratamiento de los granulomas genitourinarios asintomáticos después de la terapia intravesical con bacilo de Calmette-Guérin / Evaluation of incidence and predictive factors, and treatment considerations for asymptomatic genitourinary granulomas after intravesical bacillus Calmette-Guérin therapy

Introducción y objetivos Aunque las complicaciones de la terapia intravesical con el bacilo de Calmette-Guérin (BCG) están bien descritas, pocas veces se ha comunicado la formación posterior de granulomas genitourinarios asintomáticos, y su estrategia de tratamiento sigue siendo controvertida. El objetivo de este estudio es evaluar la tasa de incidencia de la formación de granulomas genitourinarios asintomáticos que imitan la recurrencia del cáncer de vejiga tras el tratamiento intravesical con el BCG, así como identificar las estrategias de diagnóstico y tratamiento según las características de los pacientes. Pacientes y métodos Se realizó una revisión retrospectiva de 162 pacientes sometidos a terapia intravesical con BCG. En los pacientes que desarrollaron granulomas, se evaluó el intervalo de tiempo entre la instilación de BCG y el desarrollo del granuloma, la presencia de bacterias acidorresistentes en las muestras de patología, los resultados del cultivo/reacción en cadena de la polimerasa, las estrategias de tratamiento de las lesiones y los resultados clínicos. Resultados Se desarrollaron masas genitourinarias asintomáticas en 14 pacientes, de los cuales 5 se sometieron a evaluaciones histológicas confirmando en todos los casos una inflamación granulomatosa. Los órganos afectados fueron el riñón, la vejiga, la próstata y el pene. Aunque 5 de los 5 pacientes no recibieron tratamiento para los granulomas, a uno de ellos se le administró medicación antituberculosa para evitar el empeoramiento de la lesión durante el periodo perioperatorio de la cistoprostatectomía programada. Ninguno de los pacientes experimentó empeoramiento o recurrencia de las lesiones granulomatosas. Los pacientes que desarrollaron masas asintomáticas (n=14) eran significativamente más jóvenes que ...(AU)

Introduction and objectives Although the complications of intravesical BCG treatment are well described, asymptomatic genitourinary granulomas after BCG therapy have rarely been reported and management strategy for these conditions remains controversial. The objective of this study is to evaluate the incidence rate of asymptomatic genitourinary granuloma formation mimicking bladder cancer recurrence after intravesical bacillus Calmette-Guérin (BCG) therapy and to identify the diagnostic and treatment strategies according to patient conditions.Patients and methods A retrospective review was conducted on 162 patients who underwent intravesical BCG therapy. For patients who developed granulomas, we evaluated the time interval between BCG instillation and the development of granuloma, the presence of acid-fast bacteria on pathology specimens, culture/polymerase chain reaction results, management strategies for the lesions, and clinical outcomes. Results Asymptomatic genitourinary masses developed in 14 patients, of whom 5 underwent histological examinations and all were confirmed to have granulomatous inflammation. The affected organs included the kidney, bladder, prostate, and penis. While four of the five patients did not receive treatment for their granulomas, one patient was administered antituberculous medication to prevent worsening of the lesion during the perioperative period of the scheduled cystoprostatectomy. None of the patients experienced worsening or recurrence of granulomatous lesions. Patients who developed asymptomatic masses (n=14) were significantly younger than those who did not (P=.0076) and multivariate analysis also showed that younger age was independently associated with the development of clinically suspicious lesions (P=.032); however, none of the parameters were associated with histologically confirmed granuloma formation...(AU)

Mice with cleavage-resistant N-cadherin exhibit synapse anomaly in the hippocampus and outperformance in spatial learning tasks.

N-cadherin is a homophilic cell adhesion molecule that stabilizes excitatory synapses, by connecting pre- and post-synaptic termini. Upon NMDA receptor (NMDAR) activation by glutamate, membrane-proximal domains of N-cadherin are cleaved serially by a-disintegrin-and-metalloprotease 10 (ADAM10) and then presenilin 1(PS1, catalytic subunit of the γ-secretase complex). To assess the physiological significance of the initial N-cadherin cleavage, we engineer the mouse genome to create a knock-in allele with tandem missense mutations in the mouse N-cadherin/Cadherin-2 gene (Cdh2 R714G, I715D, or GD) that confers resistance on proteolysis by ADAM10 (GD mice). GD mice showed a better performance in the radial maze test, with significantly less revisiting errors after intervals of 30 and 300 s than WT, and a tendency for enhanced freezing in fear conditioning. Interestingly, GD mice reveal higher complexity in the tufts of thorny excrescence in the CA3 region of the hippocampus. Fine morphometry with serial section transmission electron microscopy (ssTEM) and three-dimensional (3D) reconstruction reveals significantly higher synaptic density, significantly smaller PSD area, and normal dendritic spine volume in GD mice. This knock-in mouse has provided in vivo evidence that ADAM10-mediated cleavage is a critical step in N-cadherin shedding and degradation and involved in the structure and function of glutamatergic synapses, which affect the memory function.

Diagnostic Value of Brain Calcifications in Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is a rare neurodegenerative disease resulting from mutations in the colony stimulating factor 1 receptor gene. Accurate diagnosis can be difficult because the associated clinical and MR imaging findings are nonspecific. We present 9 cases with intracranial calcifications distributed in 2 brain regions: the frontal white matter adjacent to the anterior horns of the lateral ventricles and the parietal subcortical white matter. Thin-section (1-mm) CT scans are particularly helpful in detection due to the small size of the calcifications. These calcifications had a symmetric "stepping stone appearance" in the frontal pericallosal regions, which was clearly visible on reconstructed sagittal CT images. Intrafamilial variability was seen in 2 of the families, and calcifications were seen at birth in a single individual. These characteristic calcification patterns may assist in making a correct diagnosis and may contribute to understanding of the pathogenesis of leukoencephalopathy.

The relationship between the daily step counts and low back pain during pregnancy.

PURPOSE: To investigate the relationship between the change of daily step counts and low back pain (LBP) during pregnancy. Materials and METHODS: Pregnant women at less than eight weeks of gestation (WG) were recruited. Daily step counts were measured with a pedometer. To assess LBP, the Oswestry disability index (ODI) score was recorded. Thirty-six individuals were divided into the LBP and non-LBP groups. The effect of step counts on LBP between the two groups was analyzed. RESULTS: At 16-19 WG, step counts were not considerably changed in the non-LBP group but were significantly increased in the LBP group. At 24-27 and 32-35 WG, step counts were increased in the non-LBP group but were significantly decreased in the LBP group. CONCLUSIONS: Acute increase of daily step counts in early pregnancy is a risk for LBP, and gradual increases of step counts after mid-pregnancy is recommended for women.

Correction of coronal alignment correlates with reconstruction of joint height in unicompartmental knee arthroplasty.

OBJECTIVES: Because there have been no standard methods to determine pre-operatively the thickness of resection of the proximal tibia in unicompartmental knee arthroplasty (UKA), information about the relationship between the change of limb alignment and the joint line elevation would be useful for pre-operative planning. The purpose of this study was to clarify the correlation between the change of limb alignment and the change of joint line height at the medial compartment after UKA. METHODS: A consecutive series of 42 medial UKAs was reviewed retrospectively. These patients were assessed radiographically both pre- and post-operatively with standing anteroposterior radiographs. The thickness of bone resection at the proximal tibia and the distal femur was measured radiographically. The relationship between the change of femorotibial angle (δFTA) and the change of joint line height, was analysed. RESULTS: The mean pre- and post-operative FTA was 180.5° (172.2° to 184.8°) and 175.0° (168.5° to 178.9°), respectively. The mean δFTA was 5.5° (2.3° to 10.1°). The joint line elevation of the tibia (JLET) was 4.4 mm (2.1 to 7.8). The δFTA was correlated with the JLET (correlation coefficient 0.494, p = 0.0009). CONCLUSIONS: This study indicated that there is a significant correlation between the change of limb alignment and joint line elevation. This observation suggests that it is possible to know the requirement of elevation of the joint line to obtain the desired correction of limb alignment, and to predict the requirement of bone resection of the proximal tibia pre-operatively. Cite this article: Bone Joint Res 2015;4:128-133.

Inhibition of plasmin attenuates murine acute graft-versus-host disease mortality by suppressing the matrix metalloproteinase-9-dependent inflammatory cytokine storm and effector cell trafficking.

The systemic inflammatory response observed during acute graft-versus-host disease (aGVHD) is driven by proinflammatory cytokines, a 'cytokine storm'. The function of plasmin in regulating the inflammatory response is not fully understood, and its role in the development of aGVHD remains unresolved. Here we show that plasmin is activated during the early phase of aGVHD in mice, and its activation correlated with aGVHD severity in humans. Pharmacological plasmin inhibition protected against aGVHD-associated lethality in mice. Mechanistically, plasmin inhibition impaired the infiltration of inflammatory cells, the release of membrane-associated proinflammatory cytokines including tumor necrosis factor-α (TNF-α) and Fas-ligand directly, or indirectly via matrix metalloproteinases (MMPs) and alters monocyte chemoattractant protein-1 (MCP-1) signaling. We propose that plasmin and potentially MMP-9 inhibition offers a novel therapeutic strategy to control the deadly cytokine storm in patients with aGVHD, thereby preventing tissue destruction.

Initial dose of vancomycin based on body weight and creatinine clearance to minimize inadequate trough levels in Japanese adults.

Our aims were to elucidate the factors that affected vancomycin (VCM) serum trough levels and to find the optimal initial dose based on creatinine clearance (CrCl) and body weight (BW) to minimize inadequate trough levels in a retrospective observational study among Japanese adults. One hundred and six inpatients, in whom VCM trough levels were measured after completing the third dosing, were consecutively recruited into our study in a tertiary hospital. We considered the frequency of <30% as low. In the generalized linear model, initial VCM total daily dose, CrCl, and BW were independent risk factors of VCM trough levels. In patients with CrCl ≥30 and <50 mL/min, 1 g/day yielded low frequencies of a trough level of ≥20 mcg/mL, regardless of BW. In patients with CrCl ≥50 mL/min, 2 g/day yielded low frequencies of a trough level of <10 mcg/mL in patients weighing <55 kg, but not in patients weighing ≥55 kg. Optimal VCM initial total daily dose may be 1 g/day in patients with CrCl ≥30 and <50 mL/min regardless of BW and 2 g/day in patients weighing <55 kg with CrCl ≥50 mL/min among Japanese adults.

Plasmin inhibitor reduces T-cell lymphoid tumor growth by suppressing matrix metalloproteinase-9-dependent CD11b(+)/F4/80(+) myeloid cell recruitment.

Activation of the fibrinolytic system during lymphoma progression is a well-documented clinical phenomenon. But the mechanism by which the fibrinolytic system can modulate lymphoma progression has been elusive. The main fibrinolytic enzyme, plasminogen (Plg)/plasmin (Plm), can activate matrix metalloproteinases (MMPs), such as MMP-9, which has been linked to various malignancies. Here we provide the evidence that blockade of Plg reduces T-cell lymphoma growth by inhibiting MMP-9-dependent recruitment of CD11b(+)F4/80(+) myeloid cells locally within the lymphoma tissue. Genetic Plg deficiency and drug-mediated Plm blockade delayed T-cell lymphoma growth and diminished MMP-9-dependent CD11b(+)F4/80(+) myeloid cell infiltration into lymphoma tissues. A neutralizing antibody against CD11b inhibited T-cell lymphoma growth in vivo, which indicates that CD11b(+) myeloid cells have a role in T-cell lymphoma growth. Plg deficiency in T-cell lymphoma-bearing mice resulted in reduced plasma levels of the growth factors vascular endothelial growth-A and Kit ligand, both of which are known to enhance myeloid cell proliferation. Collectively, the data presented in this study demonstrate a previously undescribed role of Plm in lymphoproliferative disorders and provide strong evidence that specific blockade of Plg represents a promising approach for the regulation of T-cell lymphoma growth.

Enlarged post-operative posterior condyle tightens extension gap in total knee arthroplasty.

We investigated whether the extension gap in total knee replacement (TKR) would be changed when the femoral component was inserted. The extension gap was measured with and without the femoral component in place in 80 patients with varus osteoarthritis undergoing posterior-stabilised TKR. The effect of a post-operative increase in the size of the femoral posterior condyles was also evaluated. The results showed that placement of the femoral component significantly reduced the medial and lateral extension gaps by means of 1.0 mm and 0.9 mm, respectively (p < 0.0001). The extension gap was reduced when a larger femoral component was selected relative to the thickness of the resected posterior condyle. When the post-operative posterior lateral condyle was larger than that pre-operatively, 17 of 41 knees (41%) showed a decrease in the extension gap of > 2.0 mm. When a specially made femoral trial component with a posterior condyle enlarged by 4 mm was tested, the medial and lateral extension gaps decreased further by means of 2.1 mm and 2.8 mm, respectively. If the thickness of the posterior condyle is expected to be larger than that pre-operatively, it should be recognised that the extension gap is likely to be altered. This should be taken into consideration when preparing the extension gap.

[Three cases of spontaneous mediastinal emphysema].

We report 3 cases of spontaneous mediastinal emphysema. All patients were young males, and had predisposing episodes for development of spontaneous mediastinal emphysema; sports in 2, loud voice in 1. The each chief complaint was dyspnea, throat pain, and epigastric pain. Two patients were admitted, but 1 rejected admission despite sufficient informed consent. All patients became asymptomatic with mediastinal air reabsorption within a week. We should recognize spontaneous mediastinal emphysema as one cause of chest, back, neck and epigastric pain.

[Successful surgical treatment of acute pulmonary thromboembolism caused by giant intra-pervic tumor; report of a case].

A 40-year-old woman was admitted to our hospital because of operation for giant intra-pervic tumor. She had a history of deep vein thrombosis. Suddenly she complained severe dyspnea while having a bath, and subsequently cardiogenic shock occurred. Immediately we set up percutaneous cardiopulmonary support (PCPS) for acute pulmonary thromboembolism. Despite thrombolytic therapy including the administration of urokinase and rt-PA, hemodinamics were not improved. Emergent pulmonary embolectomy was performed on-pump beating. Postoperative course was uneventful. The intra-pervic tumor was removed on the 24th postoperative day. She was discharged in good condition on the 38th postoperative day. Quick diagnosis and appropriate therapy are essential in patient with acute massive pulmonary thromboembolism.

Graft-versus-adult T-cell leukemia/lymphoma effect following allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has proven effective in adult T-cell leukemia/lymphoma (ATL) patients. To study the graft-versus-ATL (Gv-ATL) effects after allo-HSCT, we analyzed 21 ATL patients who had been treated at our hospital. Of these, 18 had acute-, 2 had lymphoma- and 1 had chronic-type ATL; at allo-HSCT, seven patients were in CR, one was in PR, five had stable disease (SD) and eight had progressive disease (PD). Disease state after allo-HSCT was CR in 14, PR in 3, SD in 1 and PD in 3 patients. Among 15 patients who survived longer than 100 days, ATL relapsed in 10 patients, skin relapsed in 9 patients and 5 had relapsed on the skin alone. After we discontinued immunosuppressant therapy in these 10 patients, 8 manifested GVHD; ATL was ameliorated to CR in 6 patients. Donor lymphocytes were infused into two patients who did not show GVHD; one obtained CR. In five patients with skin relapse alone, four patients achieved CR following the discontinuation of the immunosuppressants. Our results demonstrate that relapse of ATL after allo-HSCT tends to develop on skin, and Gv-ATL effects played a critical role in the outcome of allo-HSCT for ATL.

Gelation mechanism of surimi studied by 1h NMR relaxation measurements.

In order to elucidate the gelation mechanism of surimi, the temperature dependence of water proton spin-spin relaxation time ((1)H T(2)) has been described by a theoretical approach, in which the exposed protein surface is taken into account. Water (1)H T(2) measured for horse mackerel surimi in the presence of 2.5% NaCl was analyzed on the basis of the consideration for the denaturation and the aggregation of protein in order to explain the macroscopic structural change during the heating and the cooling processes. The temperature dependence of water (1)H T(2) and the fraction of rigid component gave a clear explanation for the gelation mechanism of surimi. Differential scanning calorimetry thermogram and dynamic viscoelastic measurements supported the results of nuclear magnetic resonance (NMR) measurements. It has been demonstrated that the measurement of NMR relaxation times is useful to describe the gelation mechanism of surimi.

Nasal natural killer/T-cell lymphoma and its association with type "i"/XhoI loss strain Epstein-Barr virus in Chile.

BACKGROUND: Nasal T/natural killer (NK)-cell lymphoma is an aggressive type of non-Hodking's lymphoma associated with Epstein-Barr virus (EBV) and striking geographical variations worldwide. AIM: To characterise nasal NK/T-cell lymphoma associated with genotypes of EBV in Chile, a Latin American country, where multiple strains of EBV, including two new recombinant strains, in healthy individuals were recently found. METHODS: Cases with diagnosis of primary nasal lymphoma were selected for histological and immunohistochemical analysis (CD3, CD3e, CD4, CD8, CD79a, CD56, CD57 and TIA-1) and in-situ hybridisation, serology and genotyping analysis for EBV. RESULTS: Out of 22 cases, 9 (41%) cases fulfilled the World Health Organization criteria for nasal NK/T-cell lymphoma; of these 7 (78%) cases were positive for EBV. Genotyping analysis revealed 6 cases of type 1 EBV and wildtype F at the BamHI-F region, 4 cases type "i" EBV at the BamHI-W1/I1 region; XhoI wild type was found in 2 and XhoI loss in 4 cases, respectively. Cosegregation analysis of the BamHI-W1/I1 region and XhoI restriction site showed the new recombinant strain type "i"/XhoI loss in 3 cases and type "i"/XhoI wild-type strain in 1 case. Most patients were treated with combined anthracycline-containing regimens. Half of the cases attained complete remission. CONCLUSION: Although nasal NK/T-cell lymphomas from Chile share similar clinicopathological features, high association with EBV and unfavourable prognosis with those described elsewhere, genotype analysis shows that the new recombinant type "i"/XhoI loss strain might contribute to explain the intermediate incidence of nasal NK/T-cell lymphomas in Latin America.

Chemical removal and recovery of phosphorus from excess sludge in a sewage treatment plant.

We describe a process for the recovery of phosphorus from excess sludge in a sewage treatment plant that currently uses polyaluminium chloride for chemical phosphorus removal. Instead, we employed alkaline dissolution of excess sludge with calcium phosphate precipitation to recover phosphorus from sewage. The recovery ratio for phosphorus from sewage using the phosphorus recovery system is approximately 50%. In addition, the amount of excess sludge in the phosphorus recovery system is approximately half that of conventional chemical phosphorus removal. Alkaline dissolution of excess sludge resulted in dissolution of aluminium into the supernatant. Furthermore, since dissolved aluminium can be reused as a coagulant, the phosphorus recovery system could be used to economize coagulant consumption. Operation and maintenance costs of the phosphorus recovery system are 25.9 U.S. cents per 1 m3 of sewage compared to 32.0 U.S. cents per 1 m3 of sewage for conventional chemical phosphorus removal, representing a decrease of 20% in the operation and maintenance costs.

Identification and production of a bacteriocin from Enterococcus mundtii QU 2 isolated from soybean.

AIMS: Identification of the bacteriocin produced by Enterococcus mundtii QU 2 newly isolated from soybean and fermentative production of the bacteriocin. METHODS AND RESULTS: The bacteriocin produced by Ent. mundtii QU 2 inhibited the growth of various indicator strains, including Enterococcus, Lactobacillus, Leuconostoc, Pediococcus and Listeria. The bacteriocin activity was stable at wide pH range and against heat treatment, but completely abolished by proteolytic enzymes. The bacteriocin was purified from the culture supernatant by the three-step chromatographic procedure. Mass spectrometry, amino acid sequencing and DNA sequencing revealed that the bacteriocin was similar to class IIa bacteriocins produced by other Ent. mundtii strains. The bacteriocin production decreased in the absence of glucose, nitrogen sources, or Tween 80 in MRS medium. Additionally, it was strongly suppressed by addition of Ca(2+) (CaCO(3) or CaCl(2)). In pH-controlled fermentations, the highest bacteriocin production was achieved at pH 6.0, whereas the highest cell growth was obtained at pH 7.0. CONCLUSIONS: Ent. mundtii QU 2 produced a class IIa bacteriocin. Some growth factors (e.g. Ca(2+) and pH) influenced the bacteriocin production. SIGNIFICANCE AND IMPACT OF THE STUDY: A new soybean isolate, Ent. mundtii QU 2 was found to be a class IIa bacteriocin producer. Factors influencing the bacteriocin production described herein are valuable for applications of the bacteriocins from Ent. mundtii strains.

Transmission of alien chromosomes from selfed progenies of a complete set of Allium monosomic additions: the development of a reliable method for the maintenance of a monosomic addition set.

Selfed progeny of a complete set of Allium fistulosum - Allium cepa monosomic addition lines (2n = 2x + 1 = 17, FF+1A-FF+8A) were produced to examine the transmission rates of respective alien chromosomes. All eight types of the selfed monosomic additions set germinable seeds. The numbers of chromosomes (2n) in the seedlings were 16, 17, or 18. The eight extra chromosomes varied in transmission rate (%) from 9 (FF+2A) to 49 (FF+8A). The complete set of monosomic additions was reproduced successfully by self-pollination. A reliable way to maintain a set of Allium monosomic additions was developed using a combination of two crossing methods, selfing and female transmission. FF+8A produced two seedlings with 18 chromosomes. Cytogenetical analyses, including GISH, showed that the seedlings were disomic addition plants carrying two entire homologous chromosomes from A. cepa in an integral diploid background of A. fistulosum. Flow cytometry analysis showed that a double dose of the alien 8A chromosome caused fluorescence intensity values spurring in DNA content, and isozyme analysis showed increased glutamate dehydrogenase activity at the gene locus Gdh-1.