Toshimichi Kaneki

Spontaneous Pneumomediastinum in 33 Patients: Yield of Chest Computed Tomography for the Diagnosis of the Mild Type

Background: Spontaneous pneumomediastinum (SPM) usually occurs in young people without an apparent precipitating factor or disease. Although there have been many studies focused on the clinical features and standard chest X-ray (CXR) findings of SPM, few have reviewed the chest computed-tomographic (CT) findings. Objectives: We assessed SPM using CXR and CT, and the relation between them. Methods: We evaluated 33 patients (26 males) diagnosed with SPM on the basis of symptoms and chest radiological findings. Results: Three patients showed normal CXR but a diagnostic CT scan. Seven showed mild pneumomediastinum on CXR. In these 10 patients, pneumomediastinum was easily detected by chest CT. Moderate and severe SPM were easily detected by both CXR and CT. Conclusions: These findings suggested that CXR alone poorly detected approximately 30% of SPM and that chest CT scan was needed to make the diagnosis in these cases. It seems likely that SPM is underdiagnosed by 30% or more in clinical practice.

Churg-Strauss syndrome (allergic granulomatous angitis) presenting with ileus caused by ischemic ileal ulcer

Abstract: We report a rare case of Churg-Strauss syndrome (CSS) in a 41-year-old Japanese man with a history of middle-age onset of bronchial asthma who had severe abdominal pain. He presented with ileus caused by an annular ulcer of the ileum, attributable to mucosal ischemia resulting from necrotizing vasculitis of the mesenteric artery. He also had marked hypereosinophilia (51.5%), elevated serum IgE levels (34040 IU/ml), and generalized enlargement of the superficial cervical lymph nodes, containing eosinophilic granulomas. A stenotic lesion caused by an annular ulcer in the ileum was found and resected by laparotomy. Microscopic examination of the resected specimen revealed luminal narrowing or occlusion of small arteries in the ulcer base, subserosa, and mesenterium resulting from marked fibrotic intimal thickening with fragmentation or lack of the internal elastic lamina. These findings were diagnosed as vasculitis, scar stage. The postoperative course was uneventful, with the patient receiving a maintenance dose of prednisolone (10–15 mg/day) for 7 years subsequently. We must carefully diagnose and treat patients with middle-age onset asthma, because the symptom may be a lung manifestation of CSS, in which various organs including gastrointestinal tract are involved as a result of systemic necrotizing vasculitis.

Direct hemoperfusion with polymyxin B-immobilized fiber improves shock and hypoxemia during endotoxemia in anesthetized sheep

This study evaluates the effect of direct hemoperfusion (DHP) using polymyxin B-immobilized fibers (PMX-F) as an extracorporeal blood filter on systemic hypotension and lung injury during endotoxemia. Sheep were anesthetized, intubated, mechanically ventilated with 50% oxygen and connected to the DHP system between the right femoral artery and left jugular vein. Group 1 (n = 6) sheep were infused with 10 μg/kg Escherichia coli endotoxin over a 30 min period. At the same time, sheep underwent DHP with PMX-F (Toraymyxin®: PMX-20R) for 2 h at a flow rate of 60 ml/h. Group 2 (n = 6) sheep were infused with the same dose of endotoxin and treated with a sham column, in the same manner as those in group 1. DHP with PMX-F significantly improved and restored systemic pressure and arterial oxygen tension in group 1 sheep, although these values never returned to the baseline levels of group 2 sheep. Pulmonary hypertension and leukocytopenia were observed after endotoxin infusion in both groups, but there were no significant differences between these values. DHP with PMX-F significantly decreased the elevation of plasma nitric oxide products. The treatment with PMX-F improves shock and deteriorated oxygenation during endotoxemia, probably through the suppression of nitric oxide production.

Effects of lecithinized superoxide dismutase and a neutrophil elastase inhibitor (ONO-5046) on hyperoxic lung injury in rat

Reactive oxygen and neutrophil metabolites have been implicated in the development of hyperoxic lung injury. We determined the protective effects of either a superoxide dismutase or neutrophil elastase inhibitor and the combination of both agents on the development of hyperoxic lung injury in rats. Two drugs (lecithinized superoxide dismutase and ONO-5046) were used in the present study. Lecithinized superoxide dismutase, a lecithin derivative bound to recombinant CuZn superoxide dismutase, has a higher affinity for cells such as polymorphonuclear leukocytes and endothelial cells than recombinant human superoxide dismutase. N-[2-[4-2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl]¿ aminoacetic acid (ONO-5046), a specific neutrophil elastase inhibitor, which was developed as a low-molecular weight inhibitor, showed protective effects against various lung injuries. Rats were exposed to over 90% oxygen for 72 h, and bronchoalveolar lavage was performed to evaluate the permeability and neutrophil accumulation in the lungs. Rats were treated with lecithinized superoxide dismutase (30,000 U/day, intravenously n=7) or ONO-5046 (10 mg/kg, intramuscularly twice a day, n=7) or a combination of both drugs (n=7). Albumin concentration and neutrophil counts in bronchoalveolar lavage fluid were compared between animals with and without drug treatment. Either lecithinized superoxide dismutase or ONO-5046 treatment significantly decreased albumin concentration and neutrophil counts in bronchoalveolar lavage fluid compared to those in the animals of the hyperoxia-alone group (n=9). However, albumin leakage and neutrophil accumulation in the rat lung treated with combined agents were identical to that of either the lecithinized superoxide dismutase or ONO-5046 treatment. These findings suggest that lecithinized superoxide dismutase and ONO-5046 are useful drugs to protect against hyperoxic lung injury in rats. However, there were no additive effects by the combination in preventing hyperoxic lung injury.

A 21-aminosteroid, U-74006F, attenuates endotoxin-induced lung injury in awake sheep.

The purpose of the present study was to examine the efficacy of U‐74006F, a 21‐aminosteroid, on lung dysfunction induced by endotoxaemia in awake sheep with lung lymph fistula and haemodynamic monitoring. We measured pulmonary haemodynamics, lung lymph balance, circulating leucocyte count, arterial blood gas tensions, and levels of thromboxane (Tx) B2 and 6‐keto‐prostaglandin (PG) F1α in plasma and lung lymph. We performed two experiments. In experiment 1 (n = 6), we intravenously infused Escherichia coli lipopolysaccharide endotoxin (1 μg/kg) over 30 min and observed the parameters over 5 h. In experiment 2 (n = 6), we pretreated sheep with an intravenous bolus of U‐74006F (2 mg/kg) 30 min before the infusion of endotoxin in the same manner of experiment 1, and continuously infused U‐74006F (0.5 mg/kg per h) over 5 h after the bolus during the experiment. The U‐74006F significantly suppressed the early pulmonary hypertension, the late increase in pulmonary permeability and the elevations of TxB2 and 6‐keto‐PGF1α levels in plasma and lung lymph during the early period following endotoxaemia, although the compound did not change the time course of leucocytopenia and hypoxaemia. These findings suggest that the administration of U‐74006F attenuates the lung dysfunction induced by endotoxaemia in awake sheep.

Immunoblastic lymphadenopathy-like T-cell lymphoma complicated by multiple gastrointestinal involvement

Abstract: We report a rare case of immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma complicated by multiple gastrointestinal involvement, which appeared to be ameliorated by chemotherapy but resulted in perforative peritonitis. A 66-year-old Japanese woman who had generalized lymphadenopathy and eruptions was admitted to our hospital because of bloody stool. Colonoscopic examination revealed hemorrhagic ulcers in the terminal ileum and a saucer-like ulcer in the cecum. Gastrointestinal endoscopy revealed several ulcerative or elevated lesions in stomach and duodenum. Biopsy specimens of these lesions and of a lymph node showed characteristic histological features of IBL-like T-cell lymphoma. The initial treatment with prednisolone (PSL) and cyclophosphamide (CPA) was effective. Six months after the treatment, however, she developed bloody stool again caused by multiple ulcerative lesions in the large intestine. The recurrence of the disease was determined histologically, and four courses of CPA, PSL, vinblastine sulfate and doxorubicin hydrochloride (CHOP) therapy were administered. One month after completing the CHOP therapy, she developed intestinal obstruction and then acute peritonitis resulting from perforation at an ulcer scar in the jejunum. Surgical treatment was successful, and histological examination demonstrated no lymphoma cells in the resected specimen. A gastrointestinal perforation should be recognized as a potential complication of IBL-like T-cell lymphoma, even during remission.

Endothelin receptor blockade attenuates air embolization-induced pulmonary hypertension in sheep

We investigated the effects of two types of endothelin receptor antagonists on pulmonary hypertension induced by pulmonary air embolization in awake sheep. We prepared awake sheep with indwelling catheters inserted in blood vessels for continuous monitoring of pulmonary artery pressure, left atrial pressure and systemic arterial pressure. Cardiac output was measured every 30 min. The study consisted of two experiments, one with FR139317 (100 microg/kg/min; (R)2-[(R)-2-[(S)-2-[1-(hexahydro-1H-azepinyl)]-carbonyl]amino-4-++ +methy l-pentanoyl]amino-3-[3-(1-methyl-1H-indolyl)]propionyl)amino-3-(2-pyr idyl)propionic acid), a selective endothelin ET(A) receptor antagonist, and the other with TAK-044 (100 microg/kg/h; cyclo[D-alpha-aspartyl-3-[(4-phenylpiperazin-yl)carbonyl]-L-alanyl -L- alpha- aspartyl-D-2-(2-thienyl) glycyl-L-leucyl-D-tryptophyl] disodium salt), an endothelin ET(A) and ET(B) receptor antagonist. In the paired experiments, air was continuously (4.06 ml/min) infused into the main pulmonary artery for 3 h after the baseline pressures were stabilized. Sheep were treated or not treated with FR139317 or TAK-044. Pulmonary artery pressure was significantly higher than the baseline pressure after the start of air infusion. Both FR139317 and TAK-044 significantly attenuated the increase in pulmonary artery pressure during air embolization. Plasma endothelin -1 levels in both pulmonary and systemic arteries were equally and significantly increased after the start of air infusion. The results indicate that endothelin-1 release is attributable to the development of pulmonary hypertension during the course of air embolization in awake sheep.

Effects of resuscitation with hydroxyethyl starch (HES) on pulmonary hemodynamics and lung lymph balance in hemorrhagic sheep; comparative study of low and high molecular HES

Synthetic starch solution, such as hydroxyethyl starch (HES), has been used clinically to restore cardiovascular volume in patients with hemorrhagic shock. Several HES solutions are available clinically, but each HES has a broad range of molecular mass fractions. We performed comparative studies of extremely low and high molecular HES to evaluate the effects of these HES solutions on lung lymph filtration during resuscitation. We prepared awake sheep with vascular monitoring and lung lymph fistulas. After baseline measurements, animals were bled from an arterial line to maintain shock. After 2 h of hemorrhagic period, the following three solutions were infused over 1 h, respectively. Experiment (Exp) 1 (n=6); low molecular HES; (molecular weight (MW) 70000, substitution fractions 0.5-0.55, Exp 2 (n=6); high molecular HES; (MW 450000, substitution fractions 0.65). Exp 3 (n=6); normal saline (NS). The quantity of solution was determined as the same volume of blood lost to induce hemorrhagic situation in each animal (Exp 1; 940+/-36 ml, Exp 2; 910+/-50 ml, Exp 3; 920+/-42 ml). Both low and high molecular HES could restore the systemic artery pressure and cardiac output, and significantly increased pulmonary microvascular pressure equally, which were significantly higher than those in normal saline. However, actual oncotic pressure gradient (plasma-lymph) rose transiently during low molecular HES infusion, while high molecular HES widened the oncotic pressure gradient even after the cessation of the infusion. Lung lymph flow during and after resuscitation with low molecular HES and NS rose significantly from the pre-shock baseline. There was no significant difference in increased lung lymph flow between low molecular HES and NS. However, lung lymph flow after high molecular HES was significantly less than that after low molecular HES. These data suggest that low molecular HES is as useful a plasma substitute as high molecular HES, but has a possibility to increase lung lymph filtration during the early phase of resuscitation.

Double cancer (lung and colon cancer) that showed complete remission with irinotecan and cisplatin combined chemotherapy.

Abstract: We report a rare case of double (colon and lung) cancer which showed complete remission with chemotherapy with irinotecan (CPT-11) and cisplatin (CDDP). The patient was a 67-year-old man who was diagnosed as having double cancer (stage IIIb pulmonary adenocarcinoma and stage 0 [or 1] well-differentiated adenocarcinoma of the ascending colon). Two courses of chemotherapy (CPT-11, 60 mg/m2, days 1 and 8; CDDP, 30 mg/m2, days 1 and 8) were performed. The combination therapy of CPT-11 and CDDP was very effective. In Japan, there have been few published reports describing the use of CPT-11 for the treatment of gastrointestinal cancer. We think that the use of CPT-11 in gastrointestinal cancer is promising.

Effect of tacrolimus on endotoxin-induced lung injury in sheep.

Since tacrolimus (FK-506) is known to suppress the proliferation and generation of T cells and to inhibit the production of T cell derived cytokines, we examined the effect of FK-506 on endotoxin-induced lung injury. We administered FK-506 (0.1 mg/kg) intravenously before the infusion of endotoxin (1 microgram/kg) into conscious sheep. We measured pulmonary hemodynamics, lung fluid balance, circulating leukocyte count and arterial blood gas tensions. The increase in pulmonary arterial pressure was significantly attenuated by FK-506 during the late period (3-5 h after endotoxin). Arterial oxygen gas tension was significantly higher in the FK-506 treated sheep during this phase. However, no significant differences were observed in lung lymph balance and circulating leukocyte count between the endotoxin alone group and the FK-506 treated group. These findings suggest that FK-506 may improve gas exchange in acute lung injury although there is an increased pulmonary vascular leakage. It is probable that FK-506 may have a beneficial potential on endotoxin-induced lung injury in sheep.