Successful Fistula Closure After Treatment with Colostomy and Infliximab in a Patient with Ulcerative Colitis Complicated by Rectovaginal Fistula.

The patient was a 50-year-old Japanese woman who was diagnosed with total-colitis-type ulcerative colitis (UC) at the age of 26 years. She was treated with mesalazine and azathioprine, and her disease activity was well controlled. At the age of 50 years, the patient was experiencing fever, abdominal pain, diarrhea, bloody stool, and anal pain, which led to a diagnosis of a relapse of UC. Although steroid therapy was administered and tended to improve her symptoms, fecaloid vaginal discharge occurred, and rectovaginal fistula (RVF) was confirmed. Colostomy was performed, and infliximab was initiated as maintenance therapy for UC. All symptoms improved, and RVF closure was confirmed 6 months after the initiation of infliximab. To date, she has been free from relapse of UC. There have been only a few reports of UC complicated by RVF, and this condition is often difficult to treat. To the best of our knowledge, no other case of UC complicated by RVF in which the fistula was closed after treatment with colostomy and infliximab has been previously reported; thus, our report of the present case is valuable to the literature.

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.

A Simple Procedure of Epidural Electrode Lead Replacement through a Tissue Sheath in Spinal Cord Stimulation.

Spinal cord stimulation (SCS) is widely performed to treat several types of intractable chronic pain. To maintain lasting SCS, epidural electrode leads must be replaced sometimes due to problems like lead breakage. However, in lead replacement, guiding the new lead to the original position may be difficult because granulation tissue sheath forms around the lead. We encountered a surgical case where we inserted new leads through tissue sheaths forming around the old leads from the epidural space to the thoracolumbar fascia; the lead was smoothly introduced to the original place. This procedure is simpler than previously reported techniques. Here, we report the detailed surgical procedure and review the relevant literature.

A case study of pyloric stenosis caused by metastatic lobular carcinoma of breast.

Metastasis to the gastrointestinal tract is rare. A 59-year-old woman who had a history of an invasive lobular carcinoma of breast with clinical complete response visited our hospital and complained of an upper abdominal pain and distension. We performed an upper gastrointestinal endoscopy which showed only a gastric ulcer without any malignant findings. She experienced a recurrence of symptoms 2 months after this visit. An endoscopy revealed pyloric stenosis, which did not improve with balloon dilatation. We performed a gastro-jejunal and cecal-transverse colonic bypass surgery. Diffuse wall thickening of the antrum was verified during the surgery, and a biopsy sample was collected. The diagnosis of gastric metastasis from breast was confirmed since it showed the same immunohistochemistry pattern as the prior breast lesion. Pyloric stenosis has still been confirmed with an endoscopy, she has been alive with satisfactory oral food intake for >10 years.

Core-Shell Structured Hemoglobin Nanoparticles as Artificial O2 Carriers.

This paper describes the synthesis and O2 binding properties of core-shell structured hemoglobin (Hb) nanoparticles (NPs), artificial O2 carriers of five types, as designed for use as red blood cell (RBC) substitutes. Human adult Hbs were polymerized using α-succinimidyl-ω-maleimide and dithiothreitol in spheroidal shapes to create parent particles. Subsequent covalent wrapping of the sphere with human serum albumin (HSA) yielded 100 nm-diameter Hb nanoparticles (HbNPs). The HbNP showed higher O2 affinity than that of RBC, but NPs prepared under a N2 atmosphere exhibited low O2 affinity. Entirely synthetic particles comprising recombinant human adult Hb and recombinant HSA were also fabricated. Using a recombinant Hb (rHb) variant in which Leu-ß28 of the heme pocket had been replaced with Phe, we found somewhat low O2 affinity of rHb(ßL28F)NP. Particles made of stroma-free Hb (SFHb) containing natural antioxidant enzyme catalase (SFHbNP) formed a very stable O2 complex, even in aqueous H2O2 solution. The SFHbNP showed good blood compatibility and did not affect the blood cell component functionality. The circulation half-life of SFHbNP in rats was considerably longer than that of naked Hb. All results indicate these Hb-based NPs as useful alternative materials for RBC and as a useful O2 therapeutic reagent in diverse medical scenarios.

[A case of idiopathic spinal cord herniation with incomplete Brown-Séquard syndrome].

A 50-year-old man was referred to our hospital with myelitis associated with a 10-months history of progressive muscle weakness in the left leg. Neurological examinations demonstrated diffuse muscle weakness of the left leg, touch hypoesthesia of the right leg, reduced pain sensation below the right nipple, left pyramidal sign, and urinary incontinence. On the basis of thoracic spinal MRI and thoracic CT myelography, revealing anterior displacement of the spinal cord and enlargement of the posterior subarachnoid space at the Th4 vertebral level, we diagnosed the patient as having idiopathic spinal cord herniation with incomplete Brown-Séquard syndrome. After microsurgical release of the spinal cord and subsequent covering of the anterior dural defect with an artificial dura mater, the symptoms improved without progression. Clinicians should consider spinal cord herniation as a cause of slowly progressive thoracic myelopathy with Brown-Séquard syndrome.

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.

Hemoglobin-albumin clusters as an artificial O2 carrier: Physicochemical properties and resuscitation from hemorrhagic shock in rats.

A bovine hemoglobin (HbBv) or human adult hemoglobin (HbA) wrapped covalently by human serum albumins (HSAs), hemoglobin-albumin clusters (HbBv-HSA3 and HbA-HSA3 ), are artificial O2 carriers used as a red blood cell substitute. This article describes the physicochemical properties of the HbBv-HSA3 and HbA-HSA3 solutions, and their abilities to restore the systemic condition after resuscitation from hemorrhagic shock in anesthetized rats. The HbBv-HSA3 and HbA-HSA3 , which have high colloid osmotic activity, showed equivalent solution characteristics and O2 binding parameters. Shock was induced by 50% blood withdrawal. Rats exhibited hypotension and significant metabolic acidosis. After 15 min, the rats were administered shed autologous blood (SAB), HbBv-HSA3 , HbA-HSA3 , or Ringer's lactate (RL) solution. Survival rates, circulation parameters, hematological parameters, and blood gas parameters were monitored during the hemorrhagic shock and for 6 h after administration. All rats in the SAB, HbBv-HSA3 , and HbA-HSA3 groups survived for 6 h. The HbBv-HSA3 and HbA-HSA3 groups restored mean arterial pressure after the resuscitation. No remarkable difference was observed in the time courses of blood gas parameters in any resuscitated group except for the RL group. Serum biochemical tests showed increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the HbBv-HSA3 and HbA-HSA3 groups compared to the SAB group. Therefore, we observed other rats awakened after resuscitation with HbA-HSA3 for 7 days. The blood cell count, AST, and ALT recovered to the baseline values by 7 days. All the results implied that HbBv-HSA3 and HbA-HSA3 clusters provide restoration from hemorrhagic shock as an alternative material for SAB transfusion.

Applicability of Additives for Ground Improvement Utilizing Fine Powder of Waste Glass.

As a solidifying material for ground improvement using inorganic waste as a raw material, the authors have been developing an additive mixture of the fine powder of waste glass containing a large amount of silica generated during the production of glass cullet and an alkaline aid (heat-treating type of "Earth-Silica; ES" additive). Furthermore, a solidifying material that solidifies by mixing this additive with the fine powder of blast furnace slag, which is a by-product of steel production, is also being developed. In this study, the authors reviewed the mixing process of the solidified materials, especially the one made with the heat-treating type of ES additive, omitting the heat treatment of the fine powder of waste glass and the alkaline aid and applying only the mixing treatment. As a result, a mixing type of ES additive was manufactured to simplify the manufacturing process, and the difference in the performance of the solidifying material, depending on the presence or absence of the heat-treating process during the additive manufacturing, was verified in terms of the effect on the solidifying action. Specifically, the solidifying materials to which the heat-treating type of ES additive and the mixing type of ES additive were added, respectively, were applied to the high-pressure injection stirring method, one of the ground-improvement methods. Various tests clarified the changes in viscosity of these solidifying materials over time and the acceleration of their solidifying rates when adding ordinary Portland cement separately.

Effect of Compound Muscle Action Potential After Peripheral Nerve Stimulation Normalization on Anesthetic Fade of Intraoperative Transcranial Motor-Evoked Potential.

PURPOSE: Anesthetic fade refers to the time-dependent decrease in the amplitude of the intraoperative motor-evoked potential. It is thought to be caused by the accumulation of propofol. The authors examined whether normalization by the compound muscle action potential (CMAP) after peripheral nerve stimulation could compensate for anesthetic fade. METHODS: In 1,842 muscles in 578 surgeries, which did not exhibit a motor-neurologic change after the operation, the motor-evoked potential amplitude was normalized by the CMAP amplitude after peripheral nerve stimulation, and the CMAP amplitude and operation times were analyzed. RESULTS: The amplitudes of both motor-evoked potential and CMAP increased over time after peripheral nerve stimulation because of the disappearance of muscle-relaxant action. Especially, after peripheral nerve stimulation, CMAP significantly increased from the beginning to the end of the operation. Anesthetic fade in transcranial motor-evoked potential monitoring seemed to occur at more than 235 minutes of surgery based on the results of a receiver operating characteristic analysis of the operation time and relative amplitudes. Although the mean amplitude without CMAP normalization at more than 235 minutes was significantly lower than that at less than 235 minutes, the mean amplitude with normalization by CMAP after peripheral nerve stimulation at more than 235 minutes was not significantly different from that at less than 235 minutes. CONCLUSIONS: Compound muscle action potential after peripheral nerve stimulation normalization was able to avoid the effect of anesthetic fade. Anesthetic fade was seemed to be caused by a decrease in synaptic transmission at the neuromuscular junction because of propofol accumulation by this result.

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.

Cutoff Points, Sensitivities, and Specificities of Intraoperative Motor-Evoked Potential Monitoring Determined Using Receiver Operating Characteristic Analysis.

BACKGROUND: Although intraoperative motor-evoked potential (MEP) monitoring is widely performed during neurosurgical operations, evaluating its results is controversial. STUDY AIMS: The cutoff point of MEP monitoring should be determined not only to predict but also to prevent postoperative neurologic deficits. MATERIAL AND METHODS: MEP monitoring was performed during 484 neurosurgical operations for patients without definitive preoperative motor palsy including 325 spinal operations, 102 cerebral aneurysmal operations, and 57 brain tumor operations, all monitored by transcranial stimulation, and 34 brain tumor operations monitored under direct cortical stimulation. To exclude the effects of muscle relaxants on MEP, the compound muscle action potential (CMAP), measured immediately after transcranial stimulation or direct cortical stimulation at supramaximal stimulation of the peripheral nerve, was used for normalization. The cutoff points, sensitivity, and specificity of MEP recorded during neurosurgery were examined by receiver operating characteristic (ROC) analyses and categorized according to the type of operation and stimulation. RESULTS: In spinal operations under transcranial stimulation, amplitude reduction of 77.9% and 80.6% as cutoff points for motor palsy with and without CMAP normalization, respectively, provided a sensitivity of 100% and specificity of 96.8% and 96.5%. In aneurysmal operations under transcranial stimulation, cutoff points of 70.7% and 69.6% offered specificities of 95.2% and 95.7% with and without CMAP normalization, respectively. The sensitivities for both were 100%. In brain tumor operations under direct stimulation, cutoff points were 83.5% and 86.3% with or without CMAP normalization, respectively, and the sensitivity and specificity for both were 100%. CONCLUSION: An amplitude decrease of 80% in brain tumor operations, 75% in spinal operations, and 70% in aneurysmal operations should be used as the cutoff points.

Hemoglobin-albumin cluster: physiological responses after exchange transfusion into rats and blood circulation persistence in dogs.

A core-shell protein cluster comprising hemoglobin and human serum albumins, hemoglobin-albumin cluster (Hb-HSA3), was designed and synthesized for use as an artificial O2 carrier and red blood cell (RBC) substitute. For initial preclinical safety evaluation of the Hb-HSA3 solution, we observed blood compatibility in vitro, physiological responses after exchange transfusion into rats and blood circulation lifetime in dogs. Dilution of human whole blood with Hb-HSA3 showed an appropriate decrease in blood cell number, proportional to the mixing volume ratio. Time courses in the circulation parameters and blood gas parameters after 20% exchange transfusion with Hb-HSA3 in anesthetized rats were almost identical to those observed in a sham group (without infusion) and an HSA group (with HSA administration) for 6 h. Serum biochemical tests of the withdrawn blood indicated safety of the protein cluster. Furthermore, fluorescent Hb-HSA3 was infused into beagle dogs to assess blood retention. Fluorescence measurements of the blood samples enabled us to ascertain the cluster half-life within the intravascular space. Histopathologic inspections of the vital organs imply no abnormality in tissues. All these results indicate sufficient initial preclinical safety of Hb-HSA3 as an alternative material for use in RBC transfusion.

Initial experience with transbronchial cryoablation as a novel local treatment for malignant peripheral lung lesions.

INTRODUCTION: Percutaneous cryoablation has been adopted for small, malignant peripheral pulmonary lesions and has yielded favourable results as a less invasive local treatment. A transbronchial approach may reduce the risks of complications, such as pneumothorax and pleural haemorrhage. A fundamental animal experiment on transbronchial cryoablation was performed to examine its immediate safety and effectiveness. METHODS: Experimental cryoablation was performed on swine lungs using a rigid cryoprobe, 2.4 mm in diameter. The probe was introduced from the right main bronchus into the distal bronchus via thoracotomy, perforated the end of the conducting bronchus and reached the lung parenchyma. The temperature of the cryoprobe tip reaches approximately -130°C during freezing and approximately 20°C during thawing. After three freeze-thaw cycles, the cryoprobe was removed. RESULTS: No significant haemorrhage was bronchoscopically observed in the airways throughout the experiment. The chronological changes and spatial distribution of the temperature of the pulmonary tissue circumferential to the point of the cryoprobe were similar to those seen with transpleural cryoablation and the less than -20°C thermal zone seemed to be established within a radius of at least 12 mm. The central destruction zone of alveolar structures was histologically similar to the thermal zone, while the conducting bronchus structure and the accompanying pulmonary artery were not severely affected. CONCLUSION: Experimental transbronchial cryoablation with a rigid cryoprobe could effectively freeze and destroy peripheral lung alveoli without any significant immediate adverse effects. This may suggest the potential clinical application of transbronchial cryoablation for peripheral malignant lung lesions.

Temporal Changes of Inflammatory Cytokine Profiles in Epithelial Lining Fluid in a Canine Lung Transplant Model.

OBJECTIVES: Ischemia-reperfusion injury resulting in post-transplant lung dysfunction involves a complicated network of cytokines that has yet to be fully investigated. We analyzed temporal changes in cytokine levels in epithelial lining fluid (ELF) from the distal airways of a canine lung transplantation model. METHODS: Ischemic time was set to 18 hours to enhance lung injury in a left single-lung transplantation model. ELF was collected via bronchoscopic microsampling, a minimally-invasive technique allowing repeated sampling, hourly up to 5 hours after reperfusion started. We compared levels of pro-inflammatory cytokines in ELF with those at baseline (time zero), and with a sham-operated control group. RESULTS: Concentrations of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) significantly increased immediately after the start of lung reperfusion in the transplant group relative to the sham group (P < 0.005 and P < 0.05, respectively); both were sustained through the 5 hours. Interferon gamma (IFN-γ levels were significantly reduced 3 h after reperfusion started (P < 0.05). CONCLUSIONS: We found time- and cytokine-dependent changes in TNF-α, IL-6, and IFN-γ in ELF from the lung transplantation model. These specific changes in the cytokine profile may relate to the mechanism underlying post-transplant lung dysfunction.

Acute 40% exchange-transfusion with hemoglobin-vesicles in a mouse pneumonectomy model.

OBJECTIVES: Hemoglobin vesicles (HbVs) function as a red blood cell (RBC) substitute and are composed of purified hemoglobin encapsulated in a phospholipid bilayer membrane. The performance of HbVs as a substitute for RBC transfusions was examined in a mouse model of pneumonectomy following acute 40% exchange-transfusion with HbVs. METHODS: Before performing left pneumonectomies, 40% of the blood volume of mice was replaced with a) lactated Ringer's solution (control), b) 5% recombinant human serum albumin (rHSA), c) mouse RBCs shed in rHSA (mRBCs/rHSA), or d) HbV suspended in rHSA (HbV/rHSA). We compared postoperative a) survival, b) functional recovery, and c) histopathological, immunohistochemical, and inflammatory responses among the study groups. RESULTS: In the HbV/rHSA and mRBC/rHSA groups, all mice survived ≥7 days after pneumonectomy, whereas 100% of the control mice died within a few h and 50% of mice in the rHSA group died within 24 h after pneumonectomy. Immunohistochemical staining for hypoxia-inducible factor-1α showed that hepatic and renal hypoxic injuries were prominently mitigated by HbV and mRBCs. CONCLUSIONS: The oxygen-carrying performance of HbV was similar to that of mRBCs, even with impaired lung functions following pneumonectomy. HbV infusion did not interfere with the recovery from surgical injury. In the near future, HbVs could be used clinically as a substitute for the perioperative transfusion of RBCs, when or where donated RBCs are not immediately available.

Ionic Liquid-Mediated Hydrofluorination of o-Azaxylylenes Derived from 3-Bromooxindoles.

The hydrofluorination reaction of 3-bromooxindole using mild HF reagents in an ionic liquid is described. This transformation can operate at room temperature to give a series of 3-substituted 3-fluorooxindole derivatives including racemic BMS 204352 (MaxiPost). The mechanistic study about interactions between HF and 3-butyl-1-methylimidazolium tetrafluoroborate [bmim][BF4] is also discussed on the basis of energy calculations.

Frank-Kasper σ phase in polybutadiene-poly(ε-caprolactone) diblock copolymer/polybutadiene blends.

Microphase-separated structures in a polybutadiene-poly(ε-caprolactone) diblock copolymer (PB-PCL)/polybutadiene homopolymer (PB) blend were investigated by small-angle x-ray scattering (SAXS). Non-equilibrium spherical micelles were observed at temperatures ranging between 60 and 100 °C. An SAXS profile with >60 scattering peaks was recorded at 140 °C. All the peak positions were in good agreement with theoretical Frank-Kasper σ phase peak positions. Thus, these results indicate the formation of a Frank-Kasper σ phase in the PB-PCL/PB blend at 140 °C.

Serial Epithelial Lining Fluid Collection Using Bronchoscopic Microsampling in a Canine Lung Transplantation Model.

OBJECTIVES: As a less invasive alternative to bronchoalveolar lavage (BAL), bronchoscopic microsampling (BMS) was developed to identify molecules present in the epithelial lining fluid (ELF) of the distal airways. Here, we evaluated the utility of BMS for serial collection of ELF in a canine lung transplant model. METHODS: ELF was collected hourly by BMS up to 5 hours after reperfusion in a canine left lung transplant model. Tumor necrosis factor (TNF)-α levels in ELF were measured using an enzyme-linked immunosorbent assay and were compared with those in BAL fluid. RESULTS: Serial collection of ELF by BMS in graft lungs was possible without adverse effects. However, the partial pressure of oxygen was markedly decreased because of ischemia-reperfusion lung injury. Probe ELF absorption ranged from 1-18 µL. TNF-α expression was significantly elevated and detected for 5 hours after reperfusion, whereas it was very low in the sham-operated group (p < 0.05). TNF-α concentration in BAL fluid was less than one-hundredth of that in ELF. CONCLUSIONS: BMS was safe and effective for serial ELF collection in grafted lungs. Temporal changes in TNF-α corresponded with ischemia-reperfusion lung injury. This is the first study to adopt BMS to elucidate pulmonary function after lung transplantation.