Yasuji Arimura

Ghrelin Treatment of Cachectic Patients with Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

Background Pulmonary cachexia is common in advanced chronic obstructive pulmonary disease (COPD), culminating in exercise intolerance and a poor prognosis. Ghrelin is a novel growth hormone (GH)-releasing peptide with GH-independent effects. The efficacy and safety of adding ghrelin to pulmonary rehabilitation (PR) in cachectic COPD patients were investigated. Methodology/Principal Findings In a multicenter, randomized, double-blind, placebo-controlled trial, 33 cachectic COPD patients were randomly assigned PR with intravenous ghrelin (2 µg/kg) or placebo twice daily for 3 weeks in hospital. The primary outcomes were changes in 6-min walk distance (6-MWD) and the St. George Respiratory Questionnaire (SGRQ) score. Secondary outcomes included changes in the Medical Research Council (MRC) scale, and respiratory muscle strength. At pre-treatment, serum GH levels were increased from baseline levels by a single dose of ghrelin (mean change, +46.5 ng/ml; between-group p<0.0001), the effect of which continued during the 3-week treatment. In the ghrelin group, the mean change from pre-treatment in 6-MWD was improved at Week 3 (+40 m, within-group p = 0.033) and was maintained at Week 7 (+47 m, within-group p = 0.017), although the difference between ghrelin and placebo was not significant. At Week 7, the mean changes in SGRQ symptoms (between-group p = 0.026), in MRC (between-group p = 0.030), and in maximal expiratory pressure (MEP; between-group p = 0.015) were better in the ghrelin group than in the placebo group. Additionally, repeated-measures analysis of variance (ANOVA) indicated significant time course effects of ghrelin versus placebo in SGRQ symptoms (p = 0.049) and MEP (p = 0.021). Ghrelin treatment was well tolerated. Conclusions/Significance In cachectic COPD patients, with the safety profile, ghrelin administration provided improvements in symptoms and respiratory strength, despite the lack of a significant between-group difference in 6-MWD. Trial Registration UMIN Clinical Trial Registry C000000061

Acute Respiratory Distress Syndrome Induced by Rifampicin with High Levels of Neutrophil and Eosinophil Products in Bronchoalveolar Lavage Fluid

We reported a case with acute respiratory distress syndrome (ARDS) caused by rifampicin during therapy for pulmonary tuberculosis. A high level of eosinophil cationic protein in bronchoalveolar lavage fluid (BALF) was detected as well as interleukin-8 and neutrophil elastase. Based on these results together with the positive result of the drug lymphocyte-stimulating test, we concluded that rifampicin was the causative drug leading to ARDS. Corticosteroid therapy resulted in clinical improvement and resolution of the pulmonary infiltrates on the chest radiograph without the recurrence of pulmonary tuberculosis.

A Possible Role of Galectin-9 in the Pulmonary Fibrosis of Patients with Interstitial Pneumonia

BackgroundGalectin-9 (Gal-9) is a β-galactoside-binding protein that induces biological reactions, such as cell activation, chemoattraction, and apoptosis. We evaluated the role of Gal-9 in the pathogenesis of interstitial pneumonia (IP).MethodsGal-9 levels in the bronchoalveolar lavage fluid (BALF) of patients with IP associated with collagen vascular disease (CVD-IP) and with idiopathic interstitial pneumonias (IIPs), including idiopathic pulmonary fibrosis (IPF) and idiopathic nonspecific interstitial pneumonia (idiopathic NSIP), were estimated by enzyme-linked immunosorbent assay. Gal-9 expression in the lungs of these patients was evaluated using immunohistochemistry. The effect of Gal-9 on the growth and apoptosis of human lung fibroblast cells was assessed in vitro.ResultsGal-9 levels in the BALF were significantly higher in patients with CVD-IP than in patients with IIPs. Gal-9 levels significantly correlated with both the total cell count and the absolute number of lymphocytes in the BALF of patients with IIPs and CVD-IP. Strong reactivity with anti-Gal-9 antibody was observed in the cytoplasm of alveolar macrophages, lymphocytes, and type II pneumocytes in the lungs of patients with IP. Gal-9 expression in those cells was more remarkable in patients with CVD-IP than in patients with IPF and idiopathic NSIP. Gal-9 suppressed the growth of human lung fibroblast cells in a dose- dependent manner. Gal-9 induced apoptosis of human lung fibroblast cells in a dose-dependent manner.ConclusionsOur findings suggest that the expression level of Gal-9 in the lung is increased in patients with CVD-IP and that Gal-9 may have a protective role against pulmonary fibrosis of these patients.

Cutaneous paragonimiasis due to triploid Paragonimus westermani presenting as a non-migratory subcutaneous nodule: a case report

IntroductionParagonimiasis is a food-borne infection caused by Paragonimus parasites. The lungs and pleura are the primary sites for the infection; however, ectopic infection can occur in other organs such as skin, liver and brain. It is difficult to make a diagnosis of ectopic paragonimiasis due to an ignorance of, and unfamiliarity with the disease. We report the case of a patient with subcutaneous paragonimiasis diagnosed by histopathological analysis and serological testing.Case presentationA 39-year-old Chinese immigrant woman presented with a subcutaneous nodule in her left lower back. The nodule was initially suspected of lipoma and she was followed up on without any treatment. However, it gradually indurated and the nodule was resected surgically. A magnetic resonance imaging scan revealed a polycystic lesion with inhomogeneous low or high intensity on T1- or T2-weighted images, respectively. The rim of the lesion was enhanced after contrast enhancement, but the inside did not show high-signal intensity. A histological analysis of the surgically resected specimen revealed variable-sized tubulo-cystic structures. The cyst wall showed a granulomatous change with scant eosinophilic infiltration. A number of parasite ova were observed in the necrotic tissue inside the cysts, and a parasite body with a presumed oral sucker and reproductive organ was also detected, suggesting a trematode infection. A subsequent serological examination showed a positive reaction of her serum to the Paragonimus westermani antigen. No abnormal findings were found on her chest computed tomography scan. The diagnosis of subcutaneous paragonimiasis caused by Paragonimus westermani was made.ConclusionsWe report a case presenting only as a non-migratory subcutaneous nodule without any pleuropulmonary lesion, which was initially suspected of lipoma but denied by magnetic resonance imaging scan results. The case was subsequently diagnosed as subcutaneous paragonimiasis from the results of histopathological analysis and serological testing.

Clinical application of ghrelin for chronic respiratory failure

Chronic respiratory failure, which is often caused by chronic obstructive pulmonary disease, chronic lower respiratory tract infection, or interstitial pneumonia, often leads to cachexia with disease progression. Patients who have chronic respiratory failure with cachexia exhibit increased morbidity. Although cachectic status is an important clinical problem, there are no effective therapies for cachexia. Ghrelin has various effects, including increasing food intake, attenuating sympathetic nerve activity, inhibiting inflammation, increasing cardiac output, and controlling fat utilization. These effects of ghrelin are ideal targets for the treatment of severely wasting chronic respiratory disease. In a few clinical studies, including a small randomized controlled trial, ghrelin administration to cachectic patients with chronic respiratory failure improved exercise tolerance, dyspnea, and appetite. The patients in these studies gained muscle mass and weight. In another study of chronic lower respiratory tract infection with cachexia, ghrelin suppressed airway inflammation by decreasing neutrophil accumulation in the airway, resulting in improvements in oxygenation and exercise tolerance. Although further clinical investigations are needed to clarify its usefulness, ghrelin is expected to become a novel therapy for cachectic patients with chronic respiratory failure.

Hepatic portal venous gas in a patient undergoing chemotherapy for non-small cell lung cancer

A 71-year-old man was diagnosed with c-stage IV non-small cell lung cancer and treated with anticancer chemotherapy. On the 29th day of chemotherapy, the patient had slight upper abdominal fullness and pain. Ultrasonography showed gas flow in the portal vein and computed tomography confirmed the presence of gas in the peripheral lesion of the liver. We made a diagnosis of hepatic portal venous gas. He was successfully treated with conservative management. No mechanical or bacterial factors were identified, and the occurrence of HPVG in our case was considered to be related to his cancer-bearing condition and the chemotherapy agents. Although HPVG during chemotherapy is extremely rare, we should be aware of this complication in patients undergoing chemotherapy.

Successful treatment of sepsis due to Pantoea agglomerans by polymyxin B-immobilized fiber column direct hemoperfusion therapy in a small cell lung carcinoma patient.

Sepsis is a life-threatening condition caused by the inflammatory response to invading organisms. Polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) is used to reduce blood endotoxin levels and modulate circulating inflammatory cytokine levels in sepsis patients. Here we report that severe sepsis caused by an infection of the gram-negative bacterium Pantoea agglomerans in a patient with small cell lung carcinoma was treated successfully with antibiotics and PMX-DHP. The patient, a 49-year-old Japanese male smoker whose condition was complicated with hyponatremia due to SIADH (syndrome of inappropriate secretion of antidiuretic hormone), rapidly developed sepsis and disseminated intravascular coagulation (DIC) after the administration of cisplatin and irinotecan. Despite initial antibiotics therapy, severe host responses including hypotension, high body temperature and tachycardia were noted. We initiated PMX-DHP, and the patients Sequential Organ Failure Assessment score was greatly reduced and his DIC improved immediately. To our knowledge, this is the first reported case of PMX-DHP therapy for severe sepsis caused by P. agglomerans infection. Although the efficacy of PMX-DHP in sepsis is not well defined, PMX-DHP therapy should be considered in cases of sepsis from gram-negative infections.