Successfully treated bronchopulmonary oxalosis caused by Aspergillus tubingensis in a non-neutropenic patient: A case report and review of the literature.

Pulmonary oxalosis can be fatal, and Aspergillus tubingensis is commonly resistant to azoles in Japan. We report a case of bronchopulmonary oxalosis caused by A. tubingensis in a non-neutropenic patient who was successfully treated with voriconazole monotherapy. The susceptibility of the isolates to voriconazole and the effective elimination of contagious necrotic tissue by expectoration seemed to be two major factors contributing to the patient's survival. According to the literature review, pulmonary oxalosis is associated with a high mortality rate over a short term. An exploration of detailed information about the genomic characteristics and drug susceptibility of Aspergillus isolates is important for the development of treatment strategies for this life-threatening disease.

Primary and secondary immune responses to keyhole limpet hemocyanin in rats after infusion of hemoglobin vesicle, an artificial oxygen carrier.

Hemoglobin vesicles (HbVs), artificial oxygen carriers encapsulating concentrated Hb solution on phospholipid vesicles (liposomes), are promising candidates for clinically useful transfusion. Although HbV infusion transiently suppressed the proliferative response of rat splenic T-cells to concanavalin A or keyhole limpet hemocyanin (KLH), a T-cell-dependent antigen, in ex vivo culture conditions, HbV infusion did not affect the primary IgG antibody response. We extended our assessment of the effects of HbV infusion on the systemic immune response using primary and secondary responses to KLH in rats. We observed that the generation of primary anti-KLH IgM antibody in HbV-infused rats was not suppressed but was instead higher than those in saline-infused rats. Furthermore, HbV infusion did not suppress the increase of IgG subclass of KLH antibody in secondary response. The T cell response to KLH of bulk spleen cells, as derived from 2-3 months after secondary KLH immunization, was unaffected by infusion of HbV, suggesting that HbV loading has no suppressive effect on homeostatic survival of memory T-cells against KLH. These results indicate that HbV is highly biocompatible in systemic immune responses in rats.

[Resection and reconstruction of sternum].

We have experienced 6 cases with resection and reconstruction of sternum. They were 1 with osteosarcoma, 1 with synovial sarcoma, 1 with sternal metastasis of fallopian tube cancer, 1 with sternal metastasis of thyroid cancer, 1 with desmoid tumor, and 1 with dermatofibrosarcoma protuberance. Resection of both manubrium and sternum was performed in 3 cases and sternum resection in 3. There was no total resection. We used a titanium reconstruction plate and titanium mesh in 3 cases, a titanium reconstruction plate and polypropylene mesh in 2, titanium mesh in 1 for reconstruction of bony defect, and rectus abdominis myocutaneous flap in 3, pectralis major muscle flap in 2, latissimus doris myocutaneous flap in 1 for reconstruction of soft tissue defect. Postoperative courses were uneventful, and flail chest was not observed. Reconstruction of the bony defect of the anterior chest wall with the titanium reconstruction plate and titanium mesh or polypropylene mesh was effective by providing sufficient rigidity as well as protection of the thoracic organs.

Using hemoglobin vesicles to treat operative hemorrhagic shock after pneu- monectomy in dog models: an experimental study.

Hemoglobin vesicles (HbVs), considered as red blood cell substitutes, are liposomes encapsulating purified hemoglobin, with a phospholipid bilayer membrane (diameter: 250 nm; P50, 28 Torr). In this study, we aimed to investigate HbV function during hemorrhagic shock in lung resection and analyze the details of oxygen delivery. Left pneumonectomy was performed in dogs under mechanical ventilation, followed by rapid exsanguination of approximately 30% of the total circulating blood volume, which led to shock, reducing the mean arterial pressure (MAP) by approximately 60% of baseline. Subsequently, either 5% human serum albumin (HSA) or HbVs suspended in 5% HSA were infused for resuscitation. The MAP only recovered to 75% of baseline after HSA administration, but fully recovered (100%) after HbV administration, with significant differences between the groups (P < 0.005). Oxygen delivery was restored in the HbV group and was significantly higher than that in the HSA group (P < 0.0001). The infusion of HbVs dispersed in a 5% HSA solution compensated for the rapid loss of approximately 30% of the total circulating blood volume in a dog pneumonectomy model, even with impaired lung function. Thus, HbVs can be used for resuscitation from hemorrhagic shock during thoracic surgery.

Removal of cellular-type hemoglobin-based oxygen carrier (hemoglobin-vesicles) from blood using centrifugation and ultrafiltration.

The hemoglobin-vesicle (HbV) is an artificial oxygen carrier encapsulating a concentrated hemoglobin solution in a phospholipid vesicle (liposome). During or after transporting oxygen, macrophages capture HbVs in the reticuloendothelial system (RES) with an approximate circulation half-life of 3 days. Animal studies show transient splenohepatomegaly after large doses, but HbVs were completely degraded, and the components were excreted in a few weeks. If a blood substitute is used for emergency use until red blood cell transfusion becomes available or for temporary use such as a priming fluid for an extracorporeal circuit, then one option would be to remove HbVs from the circulating blood without waiting a few weeks for removal by the RES. Using a mixture of beagle dog whole blood and HbV, we tested the separation of HbV using a centrifugal Fresenius cell separator and an ultrafiltration system. The cell separator system separated the layers of blood cell components from the HbV-containing plasma layer by centrifugal force, and then the HbV was removed from plasma phase by the ultrafiltration system. The HbVs (250-280 nm) are larger than plasma proteins (< 22 nm diameter) but smaller than blood cell components (> 3 µm). The size of HbVs is advantageous to be separated from the original blood components, and the separated blood components can be returned to circulation.

Fluid resuscitation of hemorrhagic shock with hemoglobin vesicles in Beagle dogs: pilot study.

Resuscitation of hemorrhagic shock requires volume replacement and restoration of oxygen metabolism. Artificial oxygen carriers that can both expand blood volume and deliver oxygen have been developed as resuscitation fluids. We employed hemoglobin vesicles (HbV), a cellular-type artificial oxygen carrier, in a Beagle dog hemorrhagic shock model to prove the efficacy of HbV. Hemorrhagic shock was introduced in splenectomized Beagle dogs by withdrawing 50% of circulating blood from the femoral artery. Shock was maintained for 60 minutes before isovolemic resuscitation with HbV dispersed in 5% albumin in saline (HbV), lactated Ringer's solution (LR), 5% human serum albumin in saline (HSA), or autologous shed blood (ASB). One animal in the LR group died 150 min after resuscitation. All other animals survived 4 h of the experiment. The mean arterial pressure remained significantly lower in the LR group than in the HbV group but did not differ significantly among the HbV, Alb, and ASB groups. Immediately after resuscitation, the HbV group showed a significantly higher mean pulmonary arterial pressure, which decreased within 10 minutes to the baseline level. The cardiac output was significantly higher in the Alb group than in the others, indicating compensation for low oxygen delivery per unit blood. The post-resuscitation hematocrit was 36% in the ASB group and decreased in the other groups (20-22%). Serum chemistry data from the HbV group were unremarkable. HbV contributed 32% of the post-resuscitation oxygen delivery. Collectively, HbV is comparable to ASB and HSA as a resuscitation fluid and is an effective oxygen carrier.

Uniportal VATS combined subsegmentectomy of the left S1+2c+S3a guided by 3D computed tomography simulation.

When a tumor to be resected is located close to or extending beyond the intersegmental plane, combined segmentectomy or subsegmentectomy is an option to ensure a sufficient surgical margin. The segmental and subsegmental anatomy of the lungs varies greatly from case to case. Therefore, there is no standardized procedure for combined subsegmentectomy, and surgical planning based on individual anatomy using three-dimensional computed tomography is essential. This video tutorial presents the surgical technique for uniportal video-assisted thoracic surgery of the left S1+2c+S3a combined subsegmentectomy for tumors located at the border of the S1+2c and S3a segments of the left upper lobes, with preoperative three-dimensional simulation and intraoperative navigation images.

Early reperfusion with hemoglobin vesicles into tracheal subepithelial capillaries in a mouse tracheal transplant model.

Hemoglobin vesicles (HbVs), liposomes containing concentrated hemoglobin extracted from outdated human red blood cells (RBC), are artificial oxygen carriers with a small particle size. To evaluate the reperfusion of capillaries with HbVs in a tracheal transplant model and compare it with that of RBC. Isogenic mice were used as donors and recipients in a parallel trachea transplant model. Both ends of the donor trachea were anastomosed end-laterally to the recipient trachea to form in parallel. After transplantation, 0.3 mL of HbV solution (Hb concentration, 10 g/dL) was administered via the tail vein. The recipients were euthanized 1, 4, 6, and 8 h after surgery (n = 5 in each group). The tracheas were harvested, and tracheal subepithelial capillaries (SEC) reperfusion was histologically evaluated. A significant number of particles defined as HbV by electron microscopy were observed in the SEC of the grafted tracheas 4 h after the transplant surgery and HbV administration when no RBC were found in the SECs. The number increased 6 and 8 h later. Our findings suggest that HbVs, which are smaller than RBC, can reperfuse the capillaries of grafts earlier than RBCs after transplantation and contribute to the oxygenation of transplanted tissues.

Phagocytosis of liposome particles by rat splenic immature monocytes makes them transiently and highly immunosuppressive in ex vivo culture conditions.

Liposomes reportedly accumulate in monophagocytic systems (MPSs), such as those of the spleen. Accumulation of considerable amounts of liposome in a MPS can affect immunologic response. While developing a liposomal oxygen carrier containing human hemoglobin vesicle (HbV), we identified its suppressive effect on the proliferation of rat splenic T cells. The aim of this study was to elucidate the mechanism underlying that phenomenon and its effect on both local and systemic immune response. For this study, we infused HbV intravenously at a volume of 20% of whole blood or empty liposomes into rats, removed their spleens, and evaluated T cell responses to concanavalin A (Con A) or keyhole limpet hemocyanin (KLH) by measuring the amount of [(3)H]thymidine incorporated into DNA. Cells that phagocytized liposomal particles were sorted using flow cytometry and analyzed. Serum anti-KLH antibody was measured after immunizing rats with KLH. Results showed that T cell proliferation in response to Con A or KLH was inhibited from 6 h to 3 days after the liposome injection. Direct cell-to-cell contact was necessary for the suppression. Both inducible nitric-oxide synthase and arginase inhibitors restored T cell proliferation to some degree. The suppression abated 7 days later. Cells that trapped vesicles were responsible for the suppression. Most expressed CD11b/c but lacked class II molecules. However, the primary antibody response to KLH was unaffected. We conclude that the phagocytosis of the large load of liposomal particles by rat CD11b/c+, class II immature monocytes temporarily renders them highly immunosuppressive, but the systemic immune response was unaffected.

Fluid resuscitation with hemoglobin vesicles prevents Escherichia coli growth via complement activation in a hemorrhagic shock rat model.

Hemoglobin vesicles (HbVs) could serve as a substitute for red blood cells (RBCs) in resuscitation from massive hemorrhage. A massive transfusion of RBCs can increase the risk of infection, which is not caused by contaminating micro-organisms in the transfused RBCs but by a breakdown of the host defense system. We previously found that complement activity was increased after resuscitation with HbVs at a putative dose in a rat model of hemorrhagic shock. It is known that complement system plays a key role in host defense in the embryonic stage. Therefore, the objective of this study was to address whether the suppression of bacterial infections in hemorrhagic shock rats was a result of increased complement activity after massive HbV transfusion. For this purpose, Escherichia coli were incubated with plasma samples obtained from a rat model of hemorrhagic shock resuscitated by HbVs or RBCs, and bacterial growth was determined under ex vivo conditions. As a result, E. coli growth was found to be suppressed by increased complement activity, mediated by the production of IgM from spleen. However, this antibacterial activity disappeared when the E. coli were treated with complement-inactivated plasma obtained from splenoctomized rats. In addition, the resuscitation of HbVs from hemorrhagic shock increased the survival rate and viable bacterial counts in blood in cecum ligation and puncture rats, a sepsis model. In conclusion, the resuscitation of HbVs in the rat model of hemorrhagic shock suppresses bacterial growth via complement activation induced by IgM.

Repeated injection of high doses of hemoglobin-encapsulated liposomes (hemoglobin vesicles) induces accelerated blood clearance in a hemorrhagic shock rat model.

The hemoglobin vesicle (HbV) is an artificial oxygen carrier in which a concentrated hemoglobin solution is encapsulated in a liposome. To apply liposome preparations in clinics, it is important to consider the accelerated blood clearance phenomenon (ABC phenomenon), which involves a loss in the long-circulation half-life after being administered repeatedly to the same animals. The objective of this study was to determine whether the ABC phenomenon is induced by repeated injection of HbV under conditions of hemorrhagic shock. We created a rat model of hemorrhagic shock and performed a pharmacokinetic study using (125)I-HbV, in which the Hb inside of HbV was labeled with (125)I. At 4 and 7 days after resuscitation from hemorrhagic shock by nonlabeled HbV (1400 mg Hb/kg), the second dose of (125)I-HbV (1400 mg Hb/kg) was rapidly cleared from the circulation compared with normal rats. Of interest, IgM against HbV was produced at 4 days after the first injection of HbV, but decreased at 7 days. In addition, phagocyte activity was increased at both 4 and 7 days after the first injection of HbV. These results suggest that repeated injections of HbV at a dose of 1400 mg Hb/kg induce the ABC phenomenon under conditions of hemorrhagic shock, which is strongly related to both the production of anti-HbV IgM and enhanced phagocyte activity. We thus conclude that it might be necessary to consider the ABC phenomenon in the dose regimen of HbV treatment in clinical settings.

Hemoglobin vesicle improves recovery of cardiac function after ischemia-reperfusion by attenuating oxidative stress in isolated rat hearts.

Hemoglobin vesicle (HbV) could be a useful blood substitute in emergency medicine. The aim of this study was to clarify the effects of HbV on cardiac function after ischemia-reperfusion (I/R) ex vivo. Isolated rat hearts were perfused according to the Langendorff method. An ischemia-reperfusion group (n = 6) was subjected to 25 minutes of global ischemia and 30 minutes of reperfusion. HbV (hemoglobin, 0.33 g/dL) was perfused before ischemia-reperfusion for 10 minutes (HbV group, n = 6). Hemodynamics were monitored, and tissue glutathione contents were measured. The redox state of reactive thiols in cardiac tissues was assessed by the biotinylated iodoacetamide labeling method. Left ventricular developed pressure was significantly recovered in the HbV group after 30 minutes of reperfusion (56.3 ± 2.8 mm Hg vs. ischemia-reperfusion group 27.0 ± 8.0 mm Hg, P < 0.05). Hemodynamic changes induced by HbV were similar to those observed when N-nitro-L-arginine methyl ester was perfused for 10 minutes before ischemia-reperfusion (L-NAME group). The oxidized glutathione contents of cardiac tissues significantly decreased, and biotinylated iodoacetamide labeling of thiols was maintained in both the HbV and the L-NAME groups. HbV improved the recovery of cardiac function after ischemia-reperfusion in isolated rat hearts. This mechanism is dependent on functional protection against thiol oxidation.

KL-6 and CEA levels in epithelial lining fluid microsamples predict response to gefitinib in patients with advanced non-small cell lung cancer.

BACKGROUND AND OBJECTIVE: Both Krebs von den Lungen-6 (KL-6) and carcinoembryonic antigen (CEA) are known to be tumour markers in non-small cell lung cancer (NSCLC). The aim of the present study was to assess whether or not intrabronchial epithelial lining fluid (ELF) levels of these markers predicted tumour response better than serum levels in patients with advanced NSCLC treated with gefitinib. METHODS: ELF samples were obtained both from near the tumour and from the contralateral lung using a bronchoscopic microsampling technique, before and 2 weeks after the start of gefitinib treatment. Serum samples were taken concurrently. Among the 22 patients enrolled in the study, 14 (64%) showed partial responses or stabilization of disease with gefitinib treatment (treatment responders), while 8 (36%) showed progression of disease (treatment non-responders), 4 weeks after the start of treatment. RESULTS: ELF KL-6 levels near the tumour decreased significantly after 2 weeks in the treatment responders group (P = 0.011), whereas there was a marginal increase in the treatment non-responders group (P = 0.049). ELF CEA levels near the tumour decreased significantly after 2 weeks in the treatment responders group (P = 0.004), whereas there was no significant change in the treatment non-responders group. For both markers, neither the serum levels nor the levels in contralateral ELF showed any significant changes in either group of patients. CONCLUSIONS: Both KL-6 and CEA levels in ELF near the tumour predicted tumour response in NSCLC patients treated with gefitinib, whereas serum levels did not.

How many pathological T1N0M0 non-small cell lung cancers can be completely resected in one segment? Special reference to high-resolution computed tomography findings.

PURPOSE: Although segmentectomy is attempted for small non-small cell lung cancer (NSCLC) tumors, no reports have so far described how many of these tumors can be candidates for a successful resection by single segmentectomy. METHODS: In all, 135 patients with peripheral p-T1N0M0 NSCLC were examined. The tumors were classified into five groups divided by every 0.5-cm increase in size. Tumor locations were classified into two groups - limited to within one segment and extended beyond one segment - based on the identification of whether pulmonary vessels and the bronchi were involved in the tumors on high-resolution computed tomography. Differences in the proportion of tumors limited within one segment between tumors smaller and larger than each class of tumor size were assessed. RESULTS: The tumor sizes were 0-1.0 cm in 8 tumors, 1.1-1.5 cm in 27, 1.6-2.0 cm in 35, 2.1-2.5 cm in 34, and 2.6-3.0 cm in 31 tumors. Of these 135 tumors, 92 (65%) were limited to one segment, whereas 48 (35%) had extended beyond one segment. When the tumor size was less than 30 mm, the proportion of tumor limited within one segment did not show any significant difference depending on the size of the tumor. CONCLUSIONS: More than one-third of p-T1N0M0 NSCLC tumors extended beyond one segment, irrespective of size. It is therefore noteworthy that resection of up to two segments or lobectomy should be undertaken for prevention of local recurrence in patients with p-T1N0M0 peripheral NSCLC.

ADAM28 is a serological and histochemical marker for non-small-cell lung cancers.

ADAM28 (a disintegrin and metalloproteinase 28) is over-expressed in non-small-cell lung cancer (NSCLC) with correlation to cancer cell proliferation, tumor size and lymph node metastasis. The present study was aimed to develop an enzyme-linked immunosorbent assay (ELISA) system for diagnosis and monitoring of NSCLC. Our ELISA specifically measured ADAM28, showing negligible cross-reactivity with other metalloproteinases. The ADAM28 level in the NSCLC tissue was remarkably 36.9-fold higher than that in the non-neoplastic lung tissue (p < 0.001). The serum level was significantly 4.6-fold higher in the NSCLC patients (5.41 +/- 8.62 ng/ml; n = 102) than in the control subjects (1.17 +/- 0.93 ng/ml; n = 20) (p < 0.001), and increased with progress of tumor stage (p < 0.001). The level was also significantly higher in the patients with recurrent carcinoma than the control (p < 0.001) and in the patients with lymph node metastasis than those without metastasis (p < 0.001). The sensitivity, false-negative rate and AUC for ADAM28 were better than those for carcinoembryonic antigen. The combination of both assays improved the sensitivity, specificity, false-positive and false-negative rates for NSCLC. There was a positive correlation between the ADAM28 level measured by ELISA system and the degree of immunostaining in the lung adenocarcinomas with a size of

Hepatically-metabolized and -excreted artificial oxygen carrier, hemoglobin vesicles, can be safely used under conditions of hepatic impairment.

The hemoglobin vesicle (HbV) is an artificial oxygen carrier in which a concentrated Hb solution is encapsulated in lipid vesicles. Our previous studies demonstrated that HbV is metabolized by the mononuclear phagocyte system, and the lipid components are excreted from the liver. It is well-known that many hepatically-metabolized and -excreted drugs show altered pharmaceutics under conditions of liver impairment, which results in adverse effects. The aim of this study was to determine whether the administration of HbV causes toxicity in rats with carbon tetrachloride induced liver cirrhosis. Changes in plasma biochemical parameters, histological staining and the pharmacokinetic distribution of HbV were evaluated after an HbV injection of the above model rats at a putative clinical dose (1400 mgHb/kg). Plasma biochemical parameters were not significantly affected, except for a transient elevation of lipase, lipid components and bilirubin, which recovered within 14 days after an HbV infusion. Negligible morphological changes were observed in the kidney, liver, spleen, lung and heart. Hemosiderin, a marker of iron accumulation in organs, was observed in the liver and spleen up to 14 days after HbV treatment, but no evidence of oxidative stress in the plasma and liver were observed. HbV is mainly distributed in the liver and spleen, and the lipid components are excreted into feces within 7 days. In conclusion, even under conditions of hepatic cirrhosis, HbV and its components exhibit the favorable metabolic and excretion profile at the putative clinical dose. These findings provide further support for the safety and effectiveness of HbV in clinical settings.

Hemoglobin-vesicle, a cellular artificial oxygen carrier that fulfils the physiological roles of the red blood cell structure.

Hb-vesicles (HbV) are artificial O(2) carriers encapsulating concentrated Hb solution (35 g/dL) with a phospholipid bilayer membrane (liposome). The concentration of the HbV suspension is extremely high ([Hb] = 10 g/dL) and it has an O(2) carrying capacity that is comparable to that of blood. HbV is much smaller than RBC (250 vs. 8000 nm), but it recreates the functions of RBCs; (i) the slower rate of O(2) unloading than Hb solution; (ii) colloid osmotic pressure is zero; (iii) the viscosity of a HbV suspension is adjustable to that of blood; (iv) HbV is finally captured by and degraded in RES; (v) co-encapsulation of an allosteric effector to regulate O(2) affinity; (vi) the lipid bilayer membrane prevents direct contact of Hb and vasculature; (vii) NO-binding is retarded to some extent by an intracellular diffusion barrier, and HbV does not induce vasoconstriction. (viii) Both RBC and HbV can be a carrier of not only O(2) but also exogenous CO. However, HbV has limitations such as a shorter functional half-life when compared with RBCs. On the other hand, the advantages of HbV are that it is pathogen-free and blood-type-antigen-free; moreover, it can withstand long-term storage of a few years, none of which can be achieved by the RBC transfusion systems.

Immediate effects of systemic administration of normal and high O2-affinity haemoglobin vesicles as a transfusion alternative in a rat pneumonectomy model.

BACKGROUND: Haemoglobin vesicles (HbVs) are red blood cell (RBC) substitutes with a phospholipid bilayer membrane and a polyethylene modified surface (diameter=250 nm; P50=28 Torr). They can be preserved for years and can be used in patients of all blood types without the risk of infection. Their oxygen affinity can be modified by changing the allosteric effectors. METHODS: Left pneumonectomy was performed under mechanical ventilation on rats, followed by rapid exsanguination of ~30% of the total circulating blood volume. Rat RBCs shed in 5% human serum albumin (HSA) solution (rat RBC), HbV with high oxygen affinity in 5% albumin solution (low-P50 HbV, P50=9 Torr), normal HbV suspended in 5% albumin (HbV, P50=28 Torr) or 5% HSA was infused for resuscitation. Haemodynamics and oxygenation were evaluated. RESULTS: Systemic arterial blood pressure significantly decreased after exsanguination and increased after each infusion. In the HbV, low-P50 HbV and rat RBC groups, all rats were liberated from mechanical ventilation and blood pressure was stabilised, whereas 50% of the rats in the HSA group died within 1 hour after weaning from mechanical ventilation. The PaO2 in arterial blood for 1 hour after liberation from mechanical ventilation in the rat RBC, HbV and low-P50 HbV groups was 59.4±12.5, 58.3±10.1 and 70.5±14.5 mm Hg, respectively. The PaO2 in the low-P50 HbV group was significantly higher than those in the rat RBC and HbV groups (p=0.05 for both). Serum lactate elevations due to hypoxic damage were minimised by HbV, low-P50 HbV as well as rat RBCs. CONCLUSIONS: The oxygen-carrying ability of HbV was comparable to that of rat RBCs, even under impaired lung function after pneumonectomy. HbVs with high oxygen affinity may have more beneficial effects on oxygenation in pulmonary resection.

The Incidence of Hemorrhagic Complications Was Lower With the Guide Sheath Than With the Conventional Forceps Biopsy Method: Results of Bronchoscopy in the 2016 Nationwide Survey by the Japan Society for Respiratory Endoscopy.

BACKGROUND: The Japan Society for Respiratory Endoscopy performed a nationwide survey to evaluate the current status and complications of bronchoscopy. Data on deaths due to bronchoscopy, complications after bronchoscopy, and particularly, complications of forceps biopsy were surveyed. METHODS: The survey form was mailed to 532 facilities accredited by the society. The numbers of procedures, complications, and deaths were investigated. RESULTS: The response rate was 79.1% (421 facilities). Deaths attributable to diagnostic bronchoscopy occurred in 11 (0.011%) of 98,497 cases.In regards to forceps biopsy, the guide sheath method was applied in 23,916 cases and the conventional method in 31,419 cases was done with conventional method. Complications of forceps biopsy developed in 1019 cases in total, with an incidence rate of 1.84%. The most frequent complication was pneumothorax (0.70%), followed by pneumonia/pleurisy (0.46%) and hemorrhage (0.45%). The incidence of hemorrhagic complication was significantly lower in the guide sheath group than in the non-guide sheath group (0.29% vs. 0.58%; P<0.001). The overall incidence of complications (1.63% vs. 2.00%; P=0.002) and the mortality rate (0% vs. 0.02%; P=0.04) were significantly lower in the guide sheath group. CONCLUSION: The incidence of hemorrhagic complications in forceps biopsy of peripheral pulmonary lesions was lower when the guide sheath method was applied. It is necessary to increase the awareness for safety control in diagnostic bronchoscopy for new procedures.

Hemoglobin vesicles, polyethylene glycol (PEG)ylated liposomes developed as a red blood cell substitute, do not induce the accelerated blood clearance phenomenon in mice.

The hemoglobin vesicle (HbV) is an artificial oxygen carrier encapsulating a concentrated hemoglobin solution in a liposome of which the surface is covered with polyethylene glycol (PEG). It was recently reported that repeated injections of PEGylated liposomes induce the accelerated blood clearance (ABC) phenomenon, in which serum anti-PEG IgM plays an essential role. To examine this issue, we investigated whether HbV induces the ABC phenomenon in mice at a dose of 0.1 mg Hb/kg, a dose that is generally known to induce the ABC phenomenon, or at 1400 mg Hb/kg, which is proposed for clinical use. At 7 days after the first injection of nonlabeled HbV (0.1 mg Hb/kg), the mice received HbV in which the Hb had been labeled with (125)I. After a second injection, HbV was rapidly cleared from the circulation, and uptake clearances in liver and spleen were significantly increased. In contrast, at a dose of 1400 mg Hb/kg, the pharmacokinetics of HbV was negligibly affected by repeated injection. It is interesting to note that IgM against HbV was produced 7 days postinjection at both of the above doses, and their recognition site was determined to be 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine-N-PEG in HbV. These results suggest that a clinical dose of HbV does not induce the ABC phenomenon, and that suppression of ABC phenomenon is caused by the saturation of phagocytic processing by the mononuclear phagocyte system. Thus, we conclude that induction of the ABC phenomenon would not be an issue in the dose regimen used in clinical settings.