A case of pulmonary aspergillosis presenting pulmonary bulla and eosinophilic pneumonia

A rare case of a 25-year-old man with pulmonary aspergillosis is reported. Pulmonary bulla and eosinophilic pneumonia in the right upper lobe were diagnosed by chest roentgenogram and transbronchial lung biopsy. Because the patient developed infective bullae during steroid therapy, we performed transcutaneous thoracic drainage and right upper lobectomy. The resected lung tissue contained numerous hyphae of Aspergillus. Around the hyphae of Aspergillus, granulomatous reaction and eosinophilic infiltration were observed. Antibodies against Aspergillus were detected in the serum of the patient. The number of peripheral blood eosinophils decreased after right upper lobectomy. These findings suggest that pulmonary bullae and eosinophilic pneumonia may be a rare manifestation of pulmonary aspergillosis.     

Novel positive inotropic agents: synthesis and biological activities of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinone derivatives.

A series of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinones has been synthesized and evaluated for positive inotropic activity on the canine heart. Some of these derivatives have a potent activity with none or negative chronotropic effect in isolated, blood-perfused dog heart preparations. They also display a high selectivity for positive inotropic effect over chronotropic and vasodilatory effects in anesthetized dogs. (+/-)-6-[2-Hydroxy-3-[(3-methoxybenzyl)amino]propoxy]-2(1H)-quinolinone (39) and (+/-)-6-[3-(3,4-dimethoxybenzyl)amino]-2-hydroxypropoxy]-2 (1H)-quinolinone (40) were further investigated in conscious dogs. After iv administration, they did not affect heart rate or mean blood pressure at the dose producing a 50% increase in the peak of the first derivative of the left ventricular pressure. The compounds (39, OPC-18750, and 40, OPC-18790) are the most promising agents with desirable biological activities, and now are currently undergoing clinical evaluation.     

Epidemiological characteristics of acute pulmonary thromboembolism in Japan.

AIM: In Japan, acute pulmonary thromboembolism (APTE) is still rare, but the number of patients with APTE has been steadily increasing. It is important for early diagnosis and early management of APTE to recognize epidemiological characteristics of this condition. METHODS: We investigated the epidemiological characteristics of 252 patients with APTE who were admitted to our institutions between 1975 and 2001. APTE was more prevalent in women that in men. It was observed the most in the age group between 50s to 70s, especially in women. Many patients had prolonged immobilization, recent major operation, obesity, or cancer, as risk factors for venous thromboembolism. One hundred and thirty-eight patients developed APTE in hospital; 60 patients were in Department of Internal Medicine, 28 in General Surgery, 15 in Orthopedics, 15 in Obstetrics and Gynecology, and 20 in other services. RESULTS: Among 58 patients with malignancy, 43% had cancers in digestive organs, 21% in gynecological, and 17% in urological. Among 61 patients who were examined for the presence of thrombophilia, 13 patients had inherited thrombophilia (8 protein C deficiency, 4 protein S deficiency, and 1 antithrombin III deficiency) 11 had antiphospholipid antibodies which indicated thrombophilia. Five out of the above 61 patients (8%) had no obvious risk factors including thrombophilia. CONCLUSION: The findings in our patients were almost the same as those in Western patients, except for some points. These results might be useful to establish a preventive approach for APTE in Japan.     

Reduction of osteoclasts in a critical embryonic period is essential for inhibition of mouse tooth eruption.

Alveolar bone resorption by osteoclasts is essential for tooth eruption. Osteoclast-deficient Csfm(op) homozygous (op/op) mice, which lack functional macrophage colony-stimulating factor (M-CSF), suffer from osteopetrosis and completely lack tooth eruption. Although osteoclasts appear, and osteopetrosis is cured with age in op/op mice, tooth eruption is never seen. This fact suggests that there is a critical period when osteoclasts are required for tooth eruption. In this study, to detect the critical period, we administered an antagonistic antibody directed against c-Fms, a receptor for M-CSF, to inbred C57BL/6 mice for various periods. Administration of this antibody decreased tartrate-resistant acid phosphatase-positive (TRAP) osteoclasts, and incisor eruption was completely inhibited by continual administration of this antibody from embryonic day 15.5 (E15.5) until postnatal day 12.5 (D12.5). A 1-day delay of this administration abolished the inhibition of incisor eruption. The number of TRAP-positive osteoclasts was significantly reduced between E16.5 and E18.5 in the mice treated with antibody from E15.5 compared with those treated from E16.5. These results indicate that this period, during which the number of osteoclasts decreases significantly, is critical for inhibiting incisor eruption in C57BL/6 mice.     

Covalent binding of rofecoxib, but not other cyclooxygenase-2 inhibitors, to allysine aldehyde in elastin of human aorta.

In rats, it has been reported that rofecoxib, a cyclooxygenase-2 (COX-2) inhibitor, reacts with the aldehyde group of allysine in elastin to give a condensation covalent adduct, thereby preventing the formation of cross-linkages in the elastin and causing degradation of the elastic fibers in aortas in vivo. Acid, organic solvent, and proteolytic enzyme treatments of human aortic homogenate after incubation with [(14)C]rofecoxib demonstrated that most of the radioactivity is covalently bound to elastin. The in vitro covalent binding was inhibited in the presence of beta-aminopropionitrile, D-penicillamine, and hydralazine, which suggested that the aldehyde group of allysine in human elastin was relevant to the covalent binding. The in vitro covalent binding of [(14)C]rofecoxib was significantly decreased by the addition of only nonradiolabeled rofecoxib but not the other COX-2 inhibitors, celecoxib, valdecoxib, etoricoxib, and CS-706 [2-(4-ethoxyphenyl)-4-methyl 1-(4-sulfamoylphenyl)-1H-pyrrole], a novel selective COX-2 inhibitor. All the above COX-2 inhibitors except for rofecoxib had no reactivity with the aldehyde group of benzaldehyde used as a model compound of allysine aldehyde under a physiological pH condition. On the other hand, no retention of the radioactivity of [(14)C]rofecoxib was observed in human aortic endothelial cells in vitro, suggesting that rofecoxib is not retained in aortic endothelial cells in vivo. These results suggest that rofecoxib, but not other COX-2 inhibitors, is capable of covalently binding to the aldehyde group of allysine in human elastin. This might be one of the main causes of cardiovascular events by rofecoxib in clinical situations.     

Eosinophilic gastroenteritis in the esophagus, stomach, and small intestine in a patient with a choking feeling in the esophagus]

A 75-year-old man was admitted to our hospital with the chief complaint of a choking feeling around the esophagus. Laboratory examinations revealed eosinophilia, and high levels of serum immunoglobulin (Ig) E. A computed tomography scan (CT) showed wall thickening of the esophagus and terminal ileum, and ascites around the liver. An endoscopic examination revealed mild mucosal edema in the esophagus, stomach, and small intestine. Biopsy specimens showed diffuse eosinophilic infiltration in the mucosa. We therefore diagnosed eosinophilic gastroenteritis. Oral prednisolone relieved clinical conditions and the CT image improved. This case was considered valuable, because there have been few reports of eosinophilic esophagitis in Japan.