Rapid Turnover and High Production Rate of Myeloid Cells in Adult Rhesus Macaques with Compensations during Aging.

Neutrophils, basophils, and monocytes are continuously produced in bone marrow via myelopoiesis, circulate in blood, and are eventually removed from circulation to maintain homeostasis. To quantitate the kinetics of myeloid cell movement during homeostasis, we applied 5-bromo-2'-deoxyuridine pulse labeling in healthy rhesus macaques (Macaca mulatta) followed by hematology and flow cytometry analyses. Results were applied to a mathematical model, and the blood circulating half-life and daily production, respectively, of each cell type from macaques aged 5-10 y old were calculated for neutrophils (1.63 ± 0.16 d, 1.42 × 109 cells/l/d), basophils (1.78 ± 0.30 d, 5.89 × 106 cells/l/d), and CD14+CD16- classical monocytes (1.01 ± 0.15 d, 3.09 × 108 cells/l/d). Classical monocytes were released into the blood circulation as early as 1 d after dividing, whereas neutrophils remained in bone marrow 4-5 d before being released. Among granulocytes, neutrophils and basophils exhibited distinct kinetics in bone marrow maturation time and blood circulation. With increasing chronological age, there was a significant decrease in daily production of neutrophils and basophils, but the half-life of these granulocytes remained unchanged between 3 and 19 y of age. In contrast, daily production of classical monocytes remained stable through 19 y of age but exhibited a significant decline in half-life. These results demonstrated relatively short half-lives and continuous replenishment of neutrophils, basophils, and classical monocytes during homeostasis in adult rhesus macaques with compensations observed during increasing chronological age.

[A case of bladder cancer with metastasis to the bone of the hand].

Metastasis to the bone of the hand is rare. In addition, metastasis to the bone of the hand from bladder cancer is extremely rare. We herein report a case of distal phalanx metastasis from bladder cancer. A 64- year-old man who was diagnosed with bladder cancer (cT2bN0M0) received total cystectomy (pT3bN2). Two months after the surgery, a roentgenogram revealed lung metastasis. Then we administered 2 cycles of chemotherapy using gemcitabine and cisplatin. Computed tomography revealed a partial response. However, several months after chemotherapy, we noted that his left ring finger was swollen and showed erythema. We made a diagnosis of metastasis to the distal phalanx of the left ring finger and amputated the finger. Pathological findings showed no conflict with metastasis from bladder cancer. Postoperative course was good, but he died about three months after the diagnosis of metastasis.

Full-lung simulations of mechanically ventilated lungs incorporating recruitment/derecruitment dynamics.

This study developed and investigated a comprehensive multiscale computational model of a mechanically ventilated ARDS lung to elucidate the underlying mechanisms contributing to the development or prevention of VILI. This model is built upon a healthy lung model that incorporates realistic airway and alveolar geometry, tissue distensibility, and surfactant dynamics. Key features of the ARDS model include recruitment and derecruitment (RD) dynamics, alveolar tissue viscoelasticity, and surfactant deficiency. This model successfully reproduces realistic pressure-volume (PV) behavior, dynamic surface tension, and time-dependent descriptions of RD events as a function of the ventilation scenario. Simulations of Time-Controlled Adaptive Ventilation (TCAV) modes, with short and long durations of exhalation (T Low - and T Low +, respectively), reveal a higher incidence of RD for T Low + despite reduced surface tensions due to interfacial compression. This finding aligns with experimental evidence emphasizing the critical role of timing in protective ventilation strategies. Quantitative analysis of energy dissipation indicates that while alveolar recruitment contributes only a small fraction of total energy dissipation, its spatial concentration and brief duration may significantly contribute to VILI progression due to its focal nature and higher intensity. Leveraging the computational framework, the model may be extended to facilitate the development of personalized protective ventilation strategies to enhance patient outcomes. As such, this computational modeling approach offers valuable insights into the complex dynamics of VILI that may guide the optimization of ventilation strategies in ARDS management.

Splitting of a three-dimensional liquid plug at an airway bifurcation.

Employing the moving particles' semi-implicit (MPS) method, this study presents a numerical framework for solving the Navier-Stokes equations for the propagation and the split of a liquid plug through a three-dimensional air-filled bifurcating tube, where the inner surface is coated by a thin fluid film, and surface tension acts on the air-liquid interface. The detailed derivation of a modified MPS method to handle the air-liquid interface of liquid plugs is presented. When the front air-liquid interface of the plug splits at the bifurcation, the interface deforms quickly and causes large wall shear stress. We observe that the presence of a transverse gravitational force causes asymmetries in plug splitting, which becomes more pronounced as the capillary number decreases or the Bond number increases. We also observe that there exists a critical capillary number below which the plug does not split into two daughter tubes but propagates into the lower daughter tube only. In order to deliver the plug into the upper daughter tube, the driving pressure to push the plug is required to overcome the hydrostatic pressure due to gravity. These tendencies agree with our previous experimental and theoretical studies.

Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems.

We describe a microfabricated airway system integrated with computerized air-liquid two-phase microfluidics that enables on-chip engineering of human airway epithelia and precise reproduction of physiologic or pathologic liquid plug flows found in the respiratory system. Using this device, we demonstrate cellular-level lung injury under flow conditions that cause symptoms characteristic of a wide range of pulmonary diseases. Specifically, propagation and rupture of liquid plugs that simulate surfactant-deficient reopening of closed airways lead to significant injury of small airway epithelial cells by generating deleterious fluid mechanical stresses. We also show that the explosive pressure waves produced by plug rupture enable detection of the mechanical cellular injury as crackling sounds.

[Early initiation of antiplatelet therapy after urological surgery : a prospective study].

In recent times, the number of patients receiving antiplatelet drugs for the prevention of cardiovascular and cerebrovascular diseases has been increasing. We examined the possibility of early initiation of antiplatelet therapy after urological operations. Between April 2008 and February 2009, 62 patients who received antiplatelet drugs and underwent urological surgeries (open surgery, transurethral surgery and laparoscopic surgery) and prostate biopsies were examined. Of the 62 patients, 59 were randomized into 2 groups ; 32 patients receiving antiplatelet treatment initiation within 24 hours (early group) and 29 patients receiving this treatment more than 24 hours (late group) after the urological operation. The end point of this study was the re-cessation of antiplatelet therapy because of the development of postoperative complications (hematuria, blood loss, etc.) and cardiovascular and cerebrovascular events within 1 month. There was no significant difference in the urological events observed between these groups, including 2 of the 32 (6.3%) patients in the early group and 3 of the 27 (11.1%) in the late group. Cardiovascular and cerebrovascular diseases were not noted in any of the patients within 1 month. In conclusion, we think that it is possible to initiate antiplatelet therapy within 24 hours after urological operations and prostate biopsies in the absence of active blood loss. Early initiation may prevent the risk of cardiovascular and cerebrovascular disease in the future.

[Clinical studies on renal cell carcinoma].

PURPOSE: We reviewed 193 patients of renal cell carcinoma treated at Osaka Police Hospital between 1990 and 2006. METHODS: The patients consisted of 140 males and 53 females. The median age was 62 years, ranging from 26 to 88 years. Median follow-up period was 53 months. TNM system and pathologic findings were classified in accordance with the Japanese General Rules for Clinical and Pathological Studies on Renal Cell Carcinoma. Survival rates were calculated using the Kaplan-Meier method, and differences in survival curves were estimated with the log-rank test. Independent prognostic factors were analyzed using the Cox proportional hazards model. RESULTS & CONCLUSIONS: The overall 3, 5, 10 and 15-year cause-specific survival rates were 92.6, 91.1, 86.1, 72.2%, respectively. Univariate analysis indicated age, chief complaint, performance status, tumor size, anemia, CRP, tumor extent, grade, infiltrating pattern, venous involvement, lymph node metastasis, distant metastasis, stage to be significant prognostic factors. Moreover, multivariate analysis with Cox's proportional hazard model revealed high age (60 < or =), positive CRP, and T4 to be independent poor prognosticators for cause specific survival. Using these three risk factors, patients with 0, 1, 2, and 3 poor risk factors were classified as 0, 1, 2, and 3 risk groups, respectively. The overall 5 and 10-year cause specific survival rates in 0, 1, 2, and 3 risk groups were 100 and 100%, 90.8 and 83.8%, 71.6 and 34.1%, 0 and 0%, respectively. The overall 5 and 10-year cause specific survival rates (69.2 and 33.0%) especially in 2 and 3 risk groups were significantly poor prognosis, comparing with those (94.8 and 91.9%) in 0 and 1 risk group (p< 0.0001). Thus, the intensity of the follow up period and the necessity of postoperative adjuvant therapy for a patient are recommended for 2 and 3 risk groups.

Surfactant-Mediated Airway and Acinar Interactions in a Multi-Scale Model of a Healthy Lung.

We present a computational multi-scale model of an adult human lung that combines dynamic surfactant physicochemical interactions and parenchymal tethering between ~16 generations of airways and subtended acini. This model simulates the healthy lung by modeling nonlinear stress distributions from airway/alveolar interdependency. In concert with multi-component surfactant transport processes, this serves to stabilize highly compliant interacting structures. This computational model, with ~10 k degrees of freedom, demonstrates physiological processes in the normal lung such as multi-layer surfactant transport and pressure-volume hysteresis behavior. Furthermore, this model predicts non-equilibrium stress distributions due to compliance mismatches between airway and alveolar structures. This computational model provides a baseline for the exploration of multi-scale interactions of pathological conditions that can further our understanding of disease processes and guide the development of protective ventilation strategies for the treatment of acute respiratory distress syndrome (ARDS).

[Primary signet-ring cell carcinoma of the urinary bladder: a case report].

We report a case of signet-ring cell carcinoma of the urinary bladder. A 60-year-old man was hospitalized because of total macrohematuria. Cystoscopic examination revealed a non-papillary sessile tumor on the posterior wall of the urinary bladder. The pathological diagnosis was stage pT1 signet ring cell carcinoma. Upper gastrointestinal endoscopy and computed tomographic scanning revealed no involvement of other organs. Radical cystectomy and creation of an ileal neobladder were performed. The histopathological stage was pT3aN0M0. Adjuvant chemotherapy (TS-1) was performed and the patient is currently free from disease at eight months after the surgery. This disease is usually diagnosed at an advanced stage and has a poor prognosis. To our knowledge, this is the first case report on the creation of an ileal neobladder for the treatment of primary signet-ring cell carcinoma of the urinary bladder.

[Scrotal hematoma associated with idiopathic thrombocytosis: a case report].

We report a case of acute scrotal hematoma associated with idiopathic thrombocytosis. A 75-year-old man visited our hospital for the treatment of a left scrotal mass that had been increasing in size; the mass had developed after the puncture of left testicular hydrocele. The patient was diagnosed with acute scrotal hematoma on the basis of ultrasonography findings. The patient underwent an emergency operation for the removal of the hematoma. On 2 days after the surgery we noticed an increase in the size of the hematoma. The patient had a 4-year clinical history of idiopathic thrombocytosis for which he had not received any treatment. Although the platelet count was slightly high at the time of the operation, complete hemostasis did not occur because of the existence of platelet dysfunction. The second hematoma was treated conservatively. To our knowledge, this is the first case report on the acute scrotal hematoma associated with idiopathic thrombocytosis.

[A case report: retroperitoneoscopic nephrectomy for a giant hydronephrosis of a horseshoe kidney].

A 30-year-old female was referred to our hospital complaining of left flank pain. She was diagnosed with a giant hydronephrosis in a horseshoe kidney. We performed a retroperitoneoscopic nephrectomy on the non-functioning moiety of the horseshoe kidney. After the placement of a ureteral catheter, she underwent a retroperitoneal nephrectomy. The feeding vessels consisted of four arteries and four veins. The thin isthmus of the horseshoe kidney was divided using scissors, without the need for electrocautery, and hemostasis was achieved using monopolar shears. Laparoscopic nephrectomy on a horseshoe kidney is a difficult surgery given the aberrant vessels and isthmus, so it tends to be avoided for reasons of safety. However, if appropriate preoperative imaging is carried out and the procedure is conducted in a careful manner, it can be made a safe and minimally invasive operation.

Cell trapping in Y-junction microchannels: A numerical study of the bifurcation angle effect in inertial microfluidics.

The majority of microfluidic technologies for cell sorting and isolation involve bifurcating (e.g., Y- or T-shaped junction) microchannels to trap the cells of a specific type. However, the microfluidic trapping efficiency remains low, independently of whether the cells are separated by a passive or an active sorting method. Using a custom computational algorithm, we studied the migration of separated deformable cells in a Y-junction microchannel, with a bifurcation angle ranging from 30° to 180°. Single or two cells of initially spherical shape were considered under flow conditions corresponding to inertial microfluidics. Through the numerical simulation, we identified the effects of cell size, cytoplasmic viscoelasticity, cortical tension, flow rate, and bifurcation angle on the critical separation distance for cell trapping. The results of this study show that the trapping and isolation of blood cells, and circulating tumor cells in a Y-junction microchannel was most efficient and least dependent on the flow rate at the bifurcation angle of 120°. At this angle, the trapping efficiency for white blood cells and circulating tumor cells increased, respectively, by 46% and 43%, in comparison with the trapping efficiency at 60°. The efficiency to isolate invasive tumor cells from noninvasive ones increased by 32%. This numerical study provides important design criteria to optimize microfluidic technology for deformability-based cell sorting and isolation.

Microscale to mesoscale analysis of parenchymal tethering: the effect of heterogeneous alveolar pressures on the pulmonary mechanics of compliant airways.

In the healthy lung, bronchi are tethered open by the surrounding parenchyma; for a uniform distribution of these peribronchial structures, the solution is well known. An open question remains regarding the effect of a distributed set of collapsed alveoli, as can occur in disease. Here, we address this question by developing and analyzing microscale finite-element models of systems of heterogeneously inflated alveoli to determine the range and extent of parenchymal tethering effects on a neighboring collapsible airway. This analysis demonstrates that micromechanical stresses extend over a range of ∼5 airway radii, and this behavior is dictated primarily by the fraction, not distribution, of collapsed alveoli in that region. A mesoscale analysis of the microscale data identifies an effective shear modulus, Geff, that accurately characterizes the parenchymal support as a function of the average transpulmonary pressure of the surrounding alveoli. We demonstrate the use of this formulation by analyzing a simple model of a single collapsible airway surrounded by heterogeneously inflated alveoli (a "pig-in-a-blanket" model), which quantitatively demonstrates the increased parenchymal compliance and reduction in airway caliber that occurs with decreased parenchymal support from hypoinflated obstructed alveoli. This study provides a building block from which models of an entire lung can be developed in a computationally tenable manner that would simulate heterogeneous pulmonary mechanical interdependence. Such multiscale models could provide fundamental insight toward the development of protective ventilation strategies to reduce the incidence or severity of ventilator-induced lung injury. NEW & NOTEWORTHY A destabilized lung leads to airway and alveolar collapse that can result in catastrophic pulmonary failure. This study elucidates the micromechanical effects of alveolar collapse and determines its range of influence on neighboring collapsible airways. A mesoscale analysis reveals a master relationship that can that can be used in a computationally efficient manner to quantitatively model alveolar mechanical heterogeneity that exists in acute respiratory distress syndrome (ARDS), which predisposes the lung to volutrauma and/or atelectrauma. This analysis may lead to computationally tenable simulations of heterogeneous organ-level mechanical interactions that can illuminate novel protective ventilation strategies to reduce ventilator-induced lung injury.

Liquid and surfactant delivery into pulmonary airways.

We describe the mechanisms by which liquids and surfactants can be delivered into the pulmonary airways. These are instilled and transported throughout the lung in clinical therapies such as surfactant replacement therapy, partial liquid ventilation and drug delivery. The success of these treatments is contingent on the liquid distribution and the delivery to targeted regions of the lung. The targeting of a liquid plug can be influenced by a variety of factors such as the physical properties of the liquid, the interfacial activity, the gravitational orientation, instillation method and propagation speed. We provide a review of experimental and theoretical studies that examine these effects in single tubes or channels, in tubes with single bifurcations and in the whole lung.

[Renal transection conservatively treated three times by selectively transarterial embolization (TAE): a case report].

A 12-year-old-man presented with left flank pain after a traffic accident on October 14, 2006. Computed tomography (CT) revealed major left renal hematoma and transection (IIIb). Selectively transarterial embolization (TAE) was performed to control upper transected renal bleeding on the same day, and again to do rebleeding two days later. Because CT revealed left perirenal urinoma caused by upper transected kidney on October 18, TAE was performed for the upper transected kidney not to function. Five months after left renal injury, CT demonstrated the left kidney successfully preserved without hydronephrosis, urinoma and hematoma. The patient was well and could be conservatively treated without hypertension and other complications. In previous reports, only a part of renal injury (III) cases with conservative treatment converted to nephrectomy, whereas approximately half of them with surgical treatment resulted in nephrectomy. Therefore, it is important to treat them as conservatively as possible and to preserve renal function, even in cases of major renal blunt injury.

[Immunohistochemical studies of p53, Ki-67, E-cadherin and beta-catenin on renal pelvic and ureteral cancers].

PURPOSE: We reviewed prognosis and bladder recurrence of 31 patients with renal pelvic and ureteral cancer concerning clinicopathological and immunohistochemical factors. METHODS: The patients consisted of 19 males and 12 females. The median age was 69 years, ranging from 43 to 84 years. Median follow-up period was 79 months. Immunohistochemistry for p53, Ki-67, E-cadherin and beta-catenin was performed on sections from tumor tissue. RESULTS & CONCLUSIONS: The overall 5-year cause-specific survival rate was 77.4%. Univariate analysis indicated tumor number, grade, infiltrating pattern, lymphatic involvement to be significant prognostic factors. Moreover, multivariate analysis with Cox's proportional hazard model revealed tumor number and lymphatic involvement to be independent prognostic factors for cause-specific survival rate. The overall 5-year bladder recurrence free rate was 60.9%. Univariate analysis revealed expression of E-cadherin to be a significant factor for bladder recurrence free rate.

[Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the urinary bladder associated with left renal pelvic carcinoma: a case report].

We report a case of primary mucosa-associated lympoid tissue (MALT) lymphoma of the urinary bladder associated with left renal pelvic carcinoma. A 84-year-old woman showed microscopic hematuria during follow up for hypertention. Left renal pelvic tumor was found and she was referred to our hospital for further evaluation and managemant. She showed pyuria and Escherichia coli was detected by urine culture. Intravenous pyelography and computed tomography revealed the left renal pelvic tumor and solid bladder tumor. Transurethral resection of bladder tumor and left total nephroureterectomy were performed. Histologically, the left renal pelvic tumor was urothelial carcinoma > > adenocarcinoma, G2, pT2 and the bladder tumor was MALT lymphoma. Ga-scintigraphy showed no hot uptake suspicious of metastatic lesion. Then, external beam radiotherapy (36 Gy) was performed to the urinary bladder. She has been alive for 14 months with neither renal pelvic tumor nor MALT lymphoma showing any evidence of disease progression.

Papillary cystadenocarcinoma of the prostate: a case report.

A 91-year-old man presented with nocturnal frequency and urge incontinence of a few days duration due to involvement of prostate cancer (PCa) accompanied by a large cyst in the left lobe of the prostate gland and urinary bladder wall. Channeling transurethral resection of prostate was performed to relieve the main symptoms and the resected material was histologically diagnosed as papillary cystadenocarcinoma arising from the epithelium of microscopic retention cysts. Following shrinkage of the large cyst, the patient is doing well on a combination regimen of a luteinizing hormone-releasing hormone analogue and bicaltamide. Papillary cystadenocarcinoma of the prostate was originally defined as papillary PCa arising from, not accompanied by, prostatic cysts. Cysts associated with PCa are subdivided into primary (or true) and secondary (or pseudo) cysts. Cancer cells in primary cysts originate from the epithelial lining. Papillary growth type cysts belong to this group and are regarded as papillary cystadenocarcinoma. The secondary (or pseudo) cysts, which have no epithelial lining and consist of hemorrhagic and/or necrotic contents are associated with invasive PCa. In the present case, the microscopic retention cysts revealed by histologic examination were of the primary type. This case of papillary cystadenocarcinoma, arising from a primary cyst, is the 13th such report from among previously reported cases in Japan.

[Local recurrent aggressive angiomyxoma presenting as a para urethral tumor 64 months after the first resection: a case report].

We report a case of local recurrent aggressive angiomyxoma presenting as a para-urethral tumor. A 28-year-old woman visited our hospital with a complaint of a painless vulval mass. Magnetic resonance imaging (MRI) of the pelvis showed the para-urethral tumor to be 2.5 x 3.0 cm. The tumor was resected, and diagnosed histopathologically as aggressive angiomyxoma. The patient showed a painless vulval mass again at 64 months after the first resection. MRI of the pelvis showed the paraurethral tumor to be 2.5 x 3.0 cm. The tumor was resected, and diagnosed histopathologically as aggressive angiomyxoma. The patient showed no recurrence at 4 months after the second resection.

[Liposarcoma of the spermatic cord associated with rectum cancer: a case report].

We report a case of liposarcoma of the spermatic cord associated with rectum cancer. A 78-year-old man visited our hospital with a complaint of painless left inguinal mass. He also showed constipation and bloody bowel discharge, rectum cancer was diagnosed by further evaluation. Ultrasonography, computed tomography and magnetic resonance imaging revealed a 2 x 4 x 6 cm mass in the left spermatic cord. Left high orchiectomy for the left inguinal tumor and Hartmann's procedure for rectum cancer was performed. Histologically, the mass in the left spermatic cord was well differentiated liposarcoma and rectum cancer was poorly differentiated adenocarcinoma. He died from rectum cancer with no evidence of recurrence of liposarcoma of the left spermatic cord after follow up for 6 months.