Tetsuya Urano

Therapeutic Effects of Various Initial Combinations of Chemotherapy Including Clarithromycin Against Mycobacterium avium Complex Pulmonary Disease

BACKGROUND The objective of this study was to find an optimal initial combination chemotherapy that includes clarithromycin (CAM) for treatment-naive patients with Mycobacterium avium complex (MAC) pulmonary disease, as assessed by microbiological conversion using a Mycobacterium growth indicator tube (MGIT). METHODS Thirty-four patients with treatment-naive MAC pulmonary disease (determined using 1997 American Thoracic Society criteria) were evaluated retrospectively. They demonstrated a nodular and bronchiectatic pattern without cavity on high-resolution CT (HRCT) scans. The following three regimens were administered: regimen A (n = 9) consisted of CAM (400 mg/d), ethambutol (EB) [750 mg/d], and rifampicin (RFP) [450 mg/d]; regimen B (n = 12) consisted of CAM (800 mg/d), EB (750 mg/d), and RFP (450 mg/d); and regimen C (n = 13) consisted of CAM (800 mg/d), EB (1,000 mg/d), and RFP (600 mg/d) during the first 2 months followed by a reduction of the dosage of EB from 1,000 to 750 mg/d. Gender, age, BMI, and HRCT scan finding scores were not significantly different among the three groups. Chemotherapy was continued for 18 months. Sputum culture was periodically assessed by MGIT. RESULTS Culture conversion at 18 months in regimen A (55.6%), which included a daily dosage of 400 mg of CAM (9.5 mg/kg), was significantly inferior to that in regimen B (91.7%), which included daily 800 mg of CAM (17.6 mg/kg; p < 0.05), but regimen B and C (92.3%) showed no between-group difference after > 18 months of chemotherapy. CONCLUSIONS The higher dose of CAM allowed for better culture conversion. Daily combination chemotherapy that includes CAM (800 mg) seems appropriate as an initial treatment against treatment-naive patients with nodular and bronchiectatic MAC pulmonary disease.

Relationship between IL-1β gene polymorphism and gastric mucosal IL-1β levels in patients with Helicobacter pylori infection

BackgroundInterkeukin-1 (IL-1) gene cluster polymorphisms that are thought to enhance the production of IL-1β are associated with an increased risk of gastric cancer. To determine the role of host genetic factors in Helicobacter pylori infection, we examined the relationship between gastric mucosal IL-1β levels and IL-1B polymorphisms in patients with H. pylori infection.MethodsBiopsy tissues obtained from 99 patients were homogenized and gastric mucosal IL-1β levels were measured by enzyme-linked immunosorbent assay (ELISA). Single-base polymorphisms at positions −511 and −31 in IL-1B were analyzed.ResultsThe IL-1β level in the antrum was significantly higher in genotype IL-1B-511C/C than in H. pylori-negative patients (P < 0.05). The IL-1B polymorphism did not influence the degree of gastric neutrophil and mononuclear cell infiltration, or gastric atrophy. IL-1β levels in the corpus, but not those in the antrum, correlated to the severity of gastric atrophy.ConclusionsThese findings indicate that IL-1B polymorphisms enhance IL-1β production in the antrum; however, other factors might regulate the production of IL-1β in the corpus of the stomach, regardless of IL-1B polymorphisms, and high IL-1β production may be associated with the grade of gastric atrophy in the corpus mucosa in patients with H. pylori infection.

Rapid Response to Inhaled Frusemide in Severe Acute Asthma with Hypercapnia

We report 7 patients with severe acute asthma unresponsive to standard medication, including sympathomimetic agents, aminophylline and corticosteroids, who responded to inhaled frusemide. All were hypercapneic with a mean PaCO2 of 7.7 kPa (57.7 mm Hg) [range 6.2-8.8 kPa (46.2-66.3 mm Hg)]. Following nebulization of 20 mg frusemide, clinical response was rapid, and the mean PaCO2 fell significantly to 5.4 kPa (40.6 mm Hg) [range 5.0-6.2 kPa (37.5-46.5 mm Hg)] within 20-60 min. No adverse effect was recognized. Inhaled frusemide should be considered for treatment of acute asthma refractory to conventional therapy.

Effects of long-term low-dose oxygen supplementation on the epithelial function, collagen metabolism and interstitial fibrogenesis in the guinea pig lung

BackgroundThe patient population receiving long-term oxygen therapy has increased with the rising morbidity of COPD. Although high-dose oxygen induces pulmonary edema and interstitial fibrosis, potential lung injury caused by long-term exposure to low-dose oxygen has not been fully analyzed. This study was designed to clarify the effects of long-term low-dose oxygen inhalation on pulmonary epithelial function, edema formation, collagen metabolism, and alveolar fibrosis.MethodsGuinea pigs (n = 159) were exposed to either 21% or 40% oxygen for a maximum of 16 weeks, and to 90% oxygen for a maximum of 120 hours. Clearance of inhaled technetium-labeled diethylene triamine pentaacetate (Tc-DTPA) and bronchoalveolar lavage fluid-to-serum ratio (BAL/Serum) of albumin (ALB) were used as markers of epithelial permeability. Lung wet-to-dry weight ratio (W/D) was measured to evaluate pulmonary edema, and types I and III collagenolytic activities and hydroxyproline content in the lung were analyzed as indices of collagen metabolism. Pulmonary fibrotic state was evaluated by histological quantification of fibrous tissue area stained with aniline blue.ResultsThe clearance of Tc-DTPA was higher with 2 week exposure to 40% oxygen, while BAL/Serum Alb and W/D did not differ between the 40% and 21% groups. In the 40% oxygen group, type I collagenolytic activities at 2 and 4 weeks and type III collagenolytic activity at 2 weeks were increased. Hydroxyproline and fibrous tissue area were also increased at 2 weeks. No discernible injury was histologically observed in the 40% group, while progressive alveolar damage was observed in the 90% group.ConclusionThese results indicate that epithelial function is damaged, collagen metabolism is affected, and both breakdown of collagen fibrils and fibrogenesis are transiently induced even with low-dose 40% oxygen exposure. However, these changes are successfully compensated even with continuous exposure to low-dose oxygen. We conclude that long-term low-dose oxygen exposure does not significantly induce permanent lung injury in guinea pigs.

High-flow nasal cannula oxygen therapy for acute exacerbation of interstitial pneumonia: A case series

We report 3 cases (all men, age: 69-81 years) of acute exacerbation of interstitial pneumonia (AEIP) that were successfully treated with a high-flow nasal cannula (HFNC), which delivers heated, humidified gas at a fraction of inspired oxygen (FIO2) up to 1.0 (100%). Oxygenation was insufficient under non-rebreathing face masks; however, the introduction of HFNC with an FIO2 of 0.7-1.0 (flow rate: 40 L/min) improved oxygenation and was well-tolerated until the partial pressure of oxygen in blood/FIO2 ratio increased (between 21 and 26 days). Thus, HFNC might be an effective and well-tolerated therapeutic addition to the management of AEIP.

Augmentation of endotoxin-induced pulmonary responses by mononuclear cell phagocytosis in the reticuloendothelial system.

OBJECTIVE To test the hypothesis that the effects of intravenous injection of latex particles would demonstrate the contribution of phagocytosis by mononuclear phagocytes to the development of Escherichia coli-induced acute lung injury in neutropenic guinea pigs. DESIGN Prospective, controlled, experimental study. Intravenously injected the latex particles into 41 guinea pigs to investigate the contribution of the phagocytosis in acute lung injury. SUBJECTS Forty-one guinea pigs. INTERVENTIONS Forty-one guinea pigs were divided into five experimental groups: a saline group (n=9); an endotoxin group (n=10) receiving 2 mg/kg of intravenous E. coli endotoxin; a latex group (n=7) receiving 2 x 10(9)/kg of intravenous polystyrene latex (mean diameter 3.19 micrometers); an endotoxin + latex group (n=8); and an E. coli group (n=7) receiving 2 x 10(9) live E. coli/kg. MEASUREMENTS AND MAIN RESULTS The lung wet/dry ratio was increased in the live E. coli-treated guinea pigs (6.71 +/- 0.16 [SEM], p < .01) as compared with the saline control (5.40 +/- 0.16, whereas the ratio was not increased in the endotoxin (5.52 +/- 0.14) or latex (5.58 +/- 0.20) groups. However, the lung wet/dry ratio was greater in the endotoxin + latex group (6.11 +/- 0.16, p < .05) than in the saline control. The 125I albumin lung tissue/plasma ratio was greater in the E. coli (2.00 +/- 0.29, p < .01) and endotoxin + latex (0.84 +/- 0.12, p < .05) groups than in the saline group (0.18 +/- 0.07), whereas no increases were observed in the endotoxin group (0.22 +/- 0.10) and the latex (0.34 +/- 0.13) group. More than 40% of the injected radiolabeled latex was observed to have accumulated in the reticuloendothelial system (liver and spleen), in both the saline control (40.1 +/- 2.3%, n=4) and endotoxin (57.3 +/- 6.8%, n=5) groups, with 2.6 +/- 1.5% and 3.1 +/- 1.7% in the lungs for the saline control and the endotoxin groups, respectively. The percent deposition of radiolabeled latex in the liver was greater in the endotoxin group (51.7 +/- 3.8%, p < .05) than in the saline group (37.6 +/- 5.9%). CONCLUSIONS These findings suggest that, in neutropenic guinea pigs: a) the combination of endotoxin and latex particles induces acute lung injury; and b) the phagocytic properties of mononuclear phagocytes in the reticuloendothelial system augment endotoxin-induced pulmonary responses and may play a role in the development of live E. coli-induced acute lung injury.

Clinical contributions of exhaled volatile organic compounds in the diagnosis of lung cancer

Background Exhaled volatile organic compounds (VOC) are being considered as biomarkers for various lungs diseases, including cancer. However, the accurate measurement of extremely low concentrations of VOC in expired air is technically challenging. We evaluated the clinical contribution of exhaled VOC measured with a new, double cold-trap method in the diagnosis of lung cancer. Methods Breath samples were collected from 116 patients with histologically confirmed lung cancer and 37 healthy volunteers (controls) after inspiration of purified air, synthesized through a cold-trap system. The exhaled VOC, trapped in the same system, were heat extracted. We analyzed 14 VOC with gas chromatography. Results The concentrations of exhaled cyclohexane and xylene were significantly higher in patients with lung cancer than in controls (p = 0.002 and 0.0001, respectively), increased significantly with the progression of the clinical stage of cancer (both p < 0.001), and decreased significantly after successful treatment of 6 patients with small cell lung cancer (p = 0.06 and 0.03, respectively). Conclusion Measurements of exhaled VOCs by a double cold-trap method may help diagnose lung cancer and monitor its progression and regression.

Endobronchial Hamartoma as a Cause of Pneumonia

Patient: Male, 66 Final Diagnosis: Endobronchial hamartoma Symptoms: Fever Medication: — Clinical Procedure: Flexible bronchoscopy • surgical resection Specialty: Pulmonology Objective: Unusual clinical course Background: Post-obstructive pneumonia occurs in the presence of airway obstruction, usually caused by lung cancer. However, there are cases of bronchial obstruction due to benign origin such as foreign bodies and benign endobronchial tumors, which are often misdiagnosed. Case Report: A 66-year-old man was referred to our hospital due to high fever with abnormal shadow in the right lung. Chest computed tomography after a course of antibiotic treatment showed an intra-bronchial tumor obstructing the right upper bronchus. Part of the tumor was removed with flexible bronchoscopy, and histopathological examination revealed cartilage tissue but not fat or other components. Lobectomy of the right upper lobe of the lung was performed to make a definite diagnosis and prevent recurrent obstructive pneumonia. The resected tumor contained mature cartilage and fat tissues, and was diagnosed as endobronchial hamartoma. Conclusions: Benign endobronchial tumors such as hamartomas should be considered in the differential diagnosis of post-obstructive pneumonia.

Lung Cancer Associated with Seronegative Myasthenia Gravis

A 64-year-old man presented with diplopia, muscle weakness, a pulmonary nodule and mediastinal widening on a chest radiograph. He was diagnosed with clinical stage IIIA (T2aN2M0) lung cancer. His neurological symptoms worsened following the initiation of thoracic radiation therapy (60 Gy) and chemotherapy. A diagnosis of myasthenia gravis (MG) was confirmed with a repetitive nerve stimulation test that showed a waning pattern, and a positive edrophonium test, although neither anti-acetylcholine receptor antibodies nor anti-muscle-specific tyrosine kinase antibodies were detected. The ptosis and limb muscle weakness improved with prednisolone and acetylcholinesterase inhibitor treatment, and a partial response of the lung cancer to chemoradiotherapy was obtained. However, the ptosis and limb muscle weakness worsened again following a recurrence of the lung cancer. The herein described case, in which lung cancer and MG occurred and recurred simultaneously, suggests that MG can develop as a paraneoplastic syndrome of lung cancer.

Development of a new measurement system to detect selectively volatile organic compounds derived from the human body

A new concept expired gas measurement system used double cold-trap method was developed. The system could detect selectively volatile organic compound (VOC) derived from the human body. The gas chromatography (GC) profiles of healthy volunteers expired gas collected by our system were analyzed. As a result, 60 VOCs were detected from the healthy volunteers expired gas. We examined 14 VOCs among them further, which could be converted to the concentration from the GC profiles. The concentration of almost VOCs decreased when the subjects inspired purified air compared with the atmosphere. On the other hand, isoprene was almost the same. It was strongly suggested that these VOCs were derived from the human body because the concentration of these VOCs in the atmosphere were nearly zero. Expired gas of two sleep apnea syndrome (SAS) patients were analyzed as preliminary study. As a result of the study, the concentration of some VOCs contained in the expired gas of the SAS patients showed higher value than a healthy controls.