In silico evaluation of particle transport and deposition in the airways of individual patients with chronic obstructive pulmonary disease.

Inhalation therapy can effectively treat chronic obstructive pulmonary disease (COPD), but the physical factors determining the appropriate aerosol delivery into the targeted airways remain unclear. The problem is nontrivial because pulmonary structures differ among individual patients with COPD and depend on the severity of the disease. In an in silico evaluation, the present study investigates the differences in particle transport and deposition in the airways of three patients with different degrees of COPD. Specific pulmonary airway models were reconstructed based on the computed tomography data of three patients with a different degree of COPD severity. The transport and deposition of inhaled particles in the airways were evaluated in a computational fluid dynamics simulation and a Lagrangian multiphase model. The sizes of the inhaled particles (1.0, 2.5, 5.5, 8.5, and 10.0 µm) were representative of drug particles delivered from inhalation devices, including dry powder inhalers (DPIs). The deposition behaviors of the inhaled particles strongly depended on the individual geometrical structure of the airways. The largest inhaled particles (10.0 µm) were most strongly affected by inertia and were deposited mostly in the oropharynx; consequently, they were rare in the bronchi. In contrast, the smallest inhaled particles (1.0 µm) were effectively delivered distally with the airflow. The spatial distributions and amounts of deposited particles in the airways obviously differed among the three COPD patients. Small particles are preferred as they can penetrate the inner lung regions. The results can assist the design and development of powder formulations and DPIs for patients with various severities of COPD.

High mobility group AT-hook 2 regulates osteoblast differentiation and facial bone development.

The mutation and deletion of high mobility group AT-hook 2 (Hmga2) gene exhibit skeletal malformation, but almost nothing is known about the mechanism. This study examined morphological anomaly of facial bone in Hmga2-/- mice and osteoblast differentiation of pre-osteoblast MC3T3-E1 cells with Hmga2 gene knockout (A2KO). Hmga2-/- mice showed the size reduction of anterior frontal part of facial bones. Hmga2 protein and mRNA were expressed in mesenchymal cells at ossification area of nasal bone. A2KO cells differentiation into osteoblasts after reaching the proliferation plateau was strongly suppressed by alizarin red and alkaline phosphatase staining analyses. Expression of osteoblast-related genes, especially Osterix, was down-regulated in A2KO cells. These results demonstrate a close association of Hmga2 with osteoblast differentiation of mesenchymal cells and bone growth. Although future studies are needed, the present study suggests an involvement of Hmga2 in osteoblast-genesis and bone growth.

Role of Streptococcus intermedius phosphoglucosamine mutase in bacterial growth, cell morphology, and resistance to polymorphonuclear leukocyte killing.

OBJECTIVES: Streptococcus intermedius is a member of the anginosus group of streptococci, an oral commensal bacterium found in infected root canals, and the causative agent of deep-seated abscesses. This organism has slow clearance when phagocytosed within neutrophils. Here, we investigated the role of its phosphoglucosamine mutase (GlmM), an enzyme associated with peptidoglycan synthesis, in bacterial growth, cell morphology, and resistance to polymorphonuclear leukocyte killing. METHODS: The glmM-deletion (ΔglmM) mutant and the plasmid-borne complementation (ΔglmM/glmM) strain of S. intermedius were generated. The wild type, the ΔglmM mutant, and the ΔglmM/glmM strain were phagocytosed with human polymorphonuclear leukocytes (PMNs), and bacterial viability in PMNs was determined by LIVE/DEAD staining. Additionally, bacterial growth and cell morphology were also compared. RESULTS: The survival rate of the ΔglmM mutant was significant lower than that of the wild type. Although the difference in the survival rate of the ΔglmM/glmM strain compared to that of the wild type or the ΔglmM mutant was not significant, the rate appeared to be restored to the middle level. Compared to the wild type and the ΔglmM/glmM strain, the ΔglmM mutant showed reduced growth potential, a significant increase in the number of bacterial chains, and heterogeneous bacteria. CONCLUSIONS: GlmM is one of the factors responsible for the stable resistance of S. intermedius to clearance by PMNs.

Hmga2 regulation of tooth formation and association with Sox2 and Nanog expression.

Tooth formation is accomplished under strict genetic programs. Although patients with chromosome 12q14 aberration shows tooth phenotype including the size and eruption timing with bone growth anomaly, its etiology is uncertain. Here, we examined expression of Hmga2, which is encoded at chromosome 12q14, in mouse tooth germs and analyzed the involvement in lower first molar (M1) and mandibular bone development. Hmga2 expression was immunohistochemically detected at enamel organ and the surrounding mesenchyme of the M1 germs. The expression was dynamically changed with gestation and rapidly decreased in postnatal mice. In Hmga2-/- mice, the M1 germs and crowns were diminished in size, and formation and eruption of molars were delayed with mandibular bone growth retardation. Hmga2 cDNA or siRNA transfection showed that Hmga2 transcriptionally up-regulates expression of stem cell factors, Sox2 and Nanog. They were co-localized with Hmga2 in the germs, but differentially distributed at enamel organ and mesenchyme in Hmga2-/- mice. These results demonstrate that Hmga2 expressed in tooth germs regulates the growth, sizing and eruption and stem cell factor expression in different compartment of the germ and associates with mandibular bone growth. Although future studies are needed, the present study demonstrates HMGA2 regulation of tooth genesis with skeletal development.

Evaluation of four instruments with different working motion using artificial plastic model with C-shaped single canal.

The purpose of this study was to evaluate four instruments with different working motion for preparation of a C-shaped single canal wall using the same artificial plastic models reproduced from a human tooth. One tooth with root canal morphology C1 (the shape is an uninterrupted "C" with no separation or division) was selected among three-dimensional micro-computed tomography (micro-CT) imaging data of extracted human teeth. Imaging data were then converted into STL form data, and twenty-four C-shaped root canal model blocks were manufactured using this STL form data. These blocks were randomly divided into four groups of six blocks each and instrumented as follows: stainless steel K-files (SSK), Self-Adjusting File (SAF), ProTaper NEXT (PTN) and RECIPROC (REC). Micro-CT images taken before and after canal preparation were superimposed, and instrumented canal area, percentage of instrumented canal area, part of instrumented canal area, volume of instrumented canal and time taken for instrumentation were evaluated for each group. The greatest instrumented canal area, percentage of instrumented canal area and volume of instrumented canal were as follows (in decreasing order): SSK > SAF > PTN > REC (P < 0.05). The longest time taken for instrumentation was as follows (in decreasing order): SAF > SSK > PTN > REC (P < 0.05). The conscious shaping of SSK and the lattice structure of SAF were instrumented all root canal walls equally. PTN and REC required less time taken for instrumentation, but showed unequal instrumentation.

Rupture of renal artery aneurysm during the early post-partum period.

Rupture of renal artery aneurysm associated with pregnancy is an uncommon condition. It is known that almost all previously reported cases have occurred during pregnancy. We experienced a case of rupture of renal artery aneurysm during the early post-partum period which was diagnosed by computed tomography and treated by angiographic embolization. To our knowledge, only two cases of rupture of renal artery aneurysm during the post-partum period have been reported in the English-language published work. An early diagnosis of rupture of renal artery aneurysm during the post-partum period is very challenging because the clinical symptoms of this condition are acute abdominal, flank or back pain, which are relatively common signs caused by more common post-partum complications. However, rupture of renal artery aneurysm is a life-threatening emergency condition requiring prompt diagnosis and treatment. The possibility of a rupture of renal artery aneurysm should be considered in any pregnant women with symptoms of an acute abdomen with hemorrhagic shock.

Angiographic findings after vaginal gauze packing: New insight into an old technique.

We had a transferred case of cervical ectopic pregnancy with hemorrhagic shock at 6 weeks of gestation. Upon arrival at hospital, we performed tight and full vaginal gauze packing to push the uterus upward to control the patient's hemorrhage. Following stabilization of her general condition, she was treated with uterine artery embolization. Using angiography, the effectiveness of vaginal gauze packing for emergency hemostasis by the presumed mechanism of impairing blood flow through the uterine artery was demonstrated. To our knowledge, there are no reports that have previously demonstrated angiographic findings similar to ours after vaginal gauze packing. Vaginal gauze packing is an effective, rapid, and convenient hemostatic procedure able to be carried out in a time-sensitive and challenging situation. As a result, this procedure gives clinicians more time to improve the patients' general status and arrange for transfusion and further definitive treatment.

[Initial report of strontium-89 chloride treatment for painful osseous metastases at Sakai Municipal Hospital].

Strontium-89 chloride has been available at our hospital for painful osseous metastases since October 2008. Of the 17 patients(22 treatments)seen until September 2010, response to initial treatment of 13 patients was analyzed. These included cancers of the lung(5 patients, 6 treatments), breast(4 patients), thyroid(2 patients, 5 treatments), liver, 1, and prostate, 1. Other treatments patients received within 1 month of Sr-89 injection were; chemotherapy, 5 patients; radiotherapy, 3 patients; and bisphosphonate, 9 patients. The treatment effects were assessed 1 month after injection, and for 11 of the 13 patients, pain-relief was obtained in a mild and gradual manner. Transient flare was frequently observed, some of which made assessment of pain-relief in 6 patients difficult. We recognized that the bone marrow function before treatment was well above the 'Optimal Treatment Manual Japan ' criteria. After treatment, bone marrow functions kept above the value of grade 2(CTCAE), and even in 5 patients with recent or concomitant chemotherapy, it remained above grade 3 of the CTCAE criteria. These results led us to the conclusion that the indication and inclusion criteria for strontium-89 chloride treatment should be patients with an earlier bone metastasis burden that is currently manifested, without too much attention to bone marrow function criteria.

Follow-up results of 71 patients undergoing metallic stent placement for the treatment of a malignant obstruction of the superior vena cava.

PURPOSE: To retrospectively clarify the utility of metallic stent placement for the treatment of the malignant obstruction of the superior vena cava (SVC) in 71 patients with VC syndrome (SVCS) on the basis of long-term follow-up data. MATERIALS AND METHODS: Seventy-one patients underwent stent placement and were followed until death. The applicability of the spiral Z-stent (S-Z-stent) mainly used the initial and follow-up results, stent placement for bilateral BCV obstruction and the value of concurrent anticancer therapy were studied. RESULTS: The technical success rate was 100%, the initial clinical success rate was 87% (62/71), the primary clinical patency rate was 88% (57/65), and the secondary clinical patency rate was 95% (62/65). The obstruction rate of the stent was 12% (8/65), and an additional stent was useful for relief of recurrent SVCS. Survival of 57 patients in whom there was no recurrence of SVCS until death ranged from 1 week to 29 months (mean, 5.4 months and the S-Z-stent appeared to be suitable for the treatment of the malignant obstruction of SVC. Unilateral stent placement was effective for relief of SVCS with bilateral BCV obstruction. Patients who received concurrent anticancer therapy survived 2 months longer than those who did not. CONCLUSION: Stent placement is an effective treatment for SVCS. Further, the utility of S-Z-stent for SVCS, an additional stent for recurrence, unilateral stent for patients with bilateral BCV obstruction, and anticancer therapy after stent placement were verified.

Quantitative detection of hepatitis C virus (HCV) RNA in saliva and gingival crevicular fluid of HCV-infected patients.

The search for hepatitis C virus (HCV) in body fluids other than blood is important when assessing possible nonparenteral routes of viral transmission. However, the role of oral fluids in HCV transmission remains controversial. Here we quantitatively determined HCV RNA in saliva and gingival crevicular fluid (GCF) of anti-HCV-positive patients. Most patients (14 of 18; 78%) whose saliva specimens were negative had HCV RNA in their GCF. Most patients (20 of 26; 77%) had higher HCV RNA levels in their GCF than in their saliva. Although there was not a statistically significant correlation between the serum viral load and HCV level in saliva or GCF, patients with low serum HCV loads were less likely to have detectable HCV in their saliva. These findings have important implications for medical personnel and suggest that epidemiological studies designed to understand the significance of the oral route of transmission of HCV are warranted.

[Application of metallic stents for both inferior vena cava and biliary obstruction by lymph node involvement in a patient with recurrent hepatocellular carcinoma].

The authors experienced a case with obstruction of the inferior vena cava (IVC) and the common bile duct due to a recurrent hepatocellular carcinoma. In order to improve severe edema of the lower extremities and obstructive jaundice, IVC metallic stent as well as biliary stent were applied. A Luminexx stent of 8 cm in length was placed in the bile duct via subcutaneous route after biliary drainage. A spiral zigzag stent of 8 cm in length was also inserted into the IVC through the femoral vein following balloon dilatation of the obstructed portion. Subsequently, jaundice and edema were dramatically improved in a short period of time, which resulted in patient discharge from the hospital. Although the patient died of the cancer in 2 months, the quality of life was well maintained until death.

[CT evaluation of response to chemotherapy and/or radiotherapy in primary lung cancer: comparison of response evaluation criteria in solid tumors (RECIST) and the WHO criteria, and comparison of both methods with the histological evaluation].

PURPOSE: The new RECIST criteria for evaluation of tumor response to chemotherapy and/or radiotherapy were proposed in 1999. We compared RECIST with the WHO criteria and also compared both methods with the histological findings, to evaluate RECIST. SUBJECTS AND METHODS: The subjects were 32 primary lung cancer patients operated on after chemotherapy and/or radiotherapy. Two radiologists measured the diameter of the tumors and compared the RECIST and WHO criteria using the McNemar test. We also compared both criteria with the histological results. RESULTS: Using RECIST, partial response (PR) was assessed in 12 cases, stable disease (SD) in 18, and progressive disease (PD) in 2. With the WHO criteria, PR was seen in 15, no change (NC) in 15, and PD in 2. The two evaluations corresponded in 29 of 32 cases, and the p-value was 0.2500. Ef.1b-2 (good histological effect) was much higher in PR, and to evaluate the size of the tumors was useful, although more than half of SD was Ef.1b-2. CONCLUSION: RECIST criteria corresponded almost perfectly with the WHO criteria, suggesting that RECIST is accurate and useful.

Percutaneous modular stent-grafts in the treatment of abdominal aortic aneurysms.

PURPOSE: To describe a newly designed bifurcated modular stent-graft and assess the feasibility and safety of its use in the treatment of abdominal aortic aneurysms (AAA). METHODS: Thirteen patients (10 men; mean age 61.2+/-16 years, range 57-78) with AAAs underwent treatment with a bifurcated stent-graft consisting of 4 components: an unsupported bifurcated stent-graft, an inner bare stent, and 2 stent-grafts. The system was placed sequentially through a percutaneously introduced 12-F sheath; the preloaded bifurcated main body of the stent-graft was deployed first, followed by the inner bare stent and individual stent-graft limbs through separate 10-F sheaths. Spiral computed tomography (CT) was performed before treatment and at 1 week, 3 months, and then at 6-month intervals. RESULTS: The stent-grafts were successfully deployed in all patients, although 3 types of procedure-related adverse events occurred: left limb kinking in 1, postimplantation syndrome (fever, leukocytosis, and decreased platelet count) in 5, and a small access site arteriovenous fistula in 1. Postprocedural angiography and 1-week follow-up CT scanning did not identify any endoleaks. At a mean 9.2+/-4.6-month follow-up, all devices were intact, with complete exclusion of the aneurysms and no endoleaks. CONCLUSIONS: This newly designed bifurcated modular stent-graft appears to be effective for percutaneous AAA repair; further investigation is warranted.

[Percutaneous localization of pulmonary nodules with CT guidance for lung resection: use of dyes].

OBJECTIVE: The purpose of this study was to assess the benefits of computed tomography(CT)-guided marking using dyes in patients undergoing lung resection for peripheral nodules. METHODS: Between January 1997 and August 2002, the location of small pulmonary nodules was identified with the aid of CT-guided marking in 52 patients scheduled for surgery. Dye-injection was performed in 52 patients (indigo carmine, n = 15; indocyanine green, n = 37). The average nodule size was 9.2 mm (range, 3 to 18 mm). RESULTS: The procedure using dyes proved to be easy and safe: the dyes were easily injected near the nodules, and no serious complications ensued. Intraoperatively, indocyanine was superior to indigo carmine with respect to visualization of the dyed pleural surface. CONCLUSION: The preoperative CT-guided injection of indocyanine green proved to be the most useful and safest technique for identifying peripheral pulmonary nodules in patients scheduled for thoracoscopic surgery or minimal thoracotomy.

Post-kidney transplantation iliac artery stenosis due to iatrogenic injury: case report.

We report a case of left external iliac artery lesions as a complication of post-kidney transplantation due to vascular clamp application injury. The lesions were proximal stenosis and distal occlusion just near the graft anastomosis site and they were diagnosed incidentally during the embolization for arteriovenous fistula. Angiography confirmed the diagnosis and it was managed successfully by percutaneous interventional techniques.

Transarterial embolization for large hepatocellular carcinoma with use of superabsorbent polymer microspheres: initial experience.

The authors report the initial experience with transarterial embolization of large hepatocellular carcinoma (HCC) with use of superabsorbent polymer microsphere (SAP-MS) particles. Six patients with nine HCCs (mean diameter, 8.2 cm) underwent 10 embolization procedures. Two patients underwent surgery later. In follow-up, tumor necrosis, postembolization syndrome, and laboratory data were assessed. Complete necrosis in three nodules, nearly complete necrosis in three nodules, and partial necrosis in three nodules were observed. Histologically, SAP-MS occluded intratumoral vessels tightly without ischemic damage of normal hepatic tissue. Postprocedural pain was minimal. No deterioration of liver function occurred. Our initial experience suggests that embolization with use of SAP-MS leads to extensive tumor necrosis of large nodular HCC, sparing use of chemotherapeutic agents.

Temporal subtraction for the detection of hazy pulmonary opacities on chest radiography.

OBJECTIVE: The purpose of this study was to evaluate the accuracy of temporal subtraction with a commercially available computer-assisted diagnosis system for the detection of multifocal hazy pulmonary opacities on chest radiographs, which are sometimes difficult to detect directly on chest radiographs. MATERIALS AND METHODS: Thirty healthy patients and 30 patients with new multifocal hazy pulmonary opacities that were confirmed by serial chest CT examinations were evaluated with and without temporal subtraction images. Chest radiographs were taken from either film-screen or digital radiography images and were digitized with a spatial resolution of 0.171 mm per pixel. Temporal subtraction images were produced by an iterative image-warping technique. We designed an observer performance study in which observers (six chest radiologists and four residents) indicated their confidence level for the presence or absence of hazy pulmonary opacities on two sets of images, current and previous radiographs only (set A), and current and previous radiographs with temporal subtraction images (set B). Receiver operating characteristic curves were generated. RESULTS: For chest radiologists, observer performance with set B (with temporal subtraction images; A(z) = 0.947) was superior to that with set A (without temporal subtraction images; A(z) = 0.916) (p < 0.05). For residents, no statistically significant difference was found between sets A and B. CONCLUSION: The temporal subtraction technique clearly improves diagnostic accuracy for the detection of multifocal hazy pulmonary opacities on chest radiographs, especially when the observers are experienced chest radiologists who have sufficient skill to evaluate the patient's condition as revealed on the images.

Temporal subtraction for detection of solitary pulmonary nodules on chest radiographs: evaluation of a commercially available computer-aided diagnosis system.

PURPOSE: To evaluate the usefulness of a commercially available computer-aided diagnosis (CAD) system that incorporates temporal subtraction for the detection of solitary pulmonary nodules on chest radiographs by readers with different levels of experience. MATERIALS AND METHODS: Sixty pairs of chest radiographs in 30 patients with newly detected solitary pulmonary nodules and 30 normal cases, all confirmed with serial chest computed tomography (CT), were obtained from screen-film or digital radiographic systems and were digitized (spatial resolution, 0.171 mm/pixel). Temporal subtraction images were produced with an iterative image-warping technique. Five chest radiologists and five residents evaluated both image sets for solitary nodules: set A, current and prior radiographs with temporal subtraction images, and set B, current and prior radiographs only. Assessment was performed with receiver operating characteristic (ROC) analysis of the images on a monitor (pixel size, 1,280 x 1,024) equipped with the system. The reading time needed by each reader was recorded in each case. RESULTS: For the chest radiologists, no statistically significant difference was found between set A (area under the ROC curve [A(z)] = 0.934) and set B (A(z) = 0.964). For the residents, however, observer performance in set A (A(z) = 0.907) was superior to that in set B (A(z) = 0.855) (P <.05). For both groups, the mean reading time per case for set A (chest radiologists, 16.7 seconds; residents, 15.7 seconds) was significantly (P <.05) shorter than that for set B (chest radiologists, 20.4 seconds; residents, 26.2 seconds). CONCLUSION: For the detection of solitary pulmonary nodules, the CAD system with temporal subtraction can promote efficiency for established chest radiologists and improvement in accuracy for less experienced readers.

High dose rate endovascular brachytherapy in aorto-iliac lesion for the prevention of restenosis.

This study examined the applicability of endovascular brachytherapy to larger del arteries such as the abdominal aorta and iliac artery. Endovascular brachytherapy using an Ir-192 HDR source was administered 11 times to nine patients who had undergone percutaneous transluminal angioplasty (PTA) between 1995 and 1999. The follow-up lasted 13 to 55 months after treatment (median, 24 months). Eight of the 11 lesions have been controlled so far. Although one case developed thrombus inside the stent five months later, recanalization was achieved by means of retreatment. One patient who underwent low-dose irradiation (6 Gy) without stent implantation showed restenosis five months after treatment. We used a centering catheter that did not block the blood stream for exact centering of the radiation source in larger vessels such as the abdominal aorta. Although endovascular brachytherapy is a promising and safe procedure, careful follow-up is needed to detect untoward reactions such as thrombosis.