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Biomedical subjects

Koichiro Kudo

Publications and source records attributed to Koichiro Kudo.

At least 19 recordsLinked to original sources

Amiodarone pulmonary toxicity: a patient with three recurrences of pulmonary toxicity and consideration of the probable risk for relapse.

A 44-year-old man was treated with amiodarone for dilated cardiomyopathy. After 53 months, he developed amiodarone-induced interstitial pneumonia. Amiodarone treatment was terminated, and the patient was given corticosteroids. These treatments were effective. However, pneumonitis recurred whenever prednisolone was reduced to less than 5 mg per day. Considering the patient's background characteristics, we considered his body mass index (BMI, kg/m(2)) and found his to be high. When four additional patients with amiodarone pulmonary toxicity were reviewed at our institute, a correlation between BMI and the duration of shadow disappearance was found (R(2)=0.8695). Because amiodarone is lipophilic, the patient's high BMI might have influenced the repeated appearance of pulmonary toxicity.

Adult↗

Detection of multidrug resistance in Mycobacterium tuberculosis.

We developed a DNA sequencing-based method to detect mutations in the genome of drug-resistant Mycobacterium tuberculosis. Drug resistance in M. tuberculosis is caused by mutations in restricted regions of the genome. Eight genome regions associated with drug resistance, including rpoB for rifampin (RIF), katG and the mabA (fabG1)-inhA promoter for isoniazid (INH), embB for ethambutol (EMB), pncA for pyrazinamide (PZA), rpsL and rrs for streptomycin (STR), and gyrA for levofloxacin, were amplified simultaneously by PCR, and the DNA sequences were determined. It took 6.5 h to complete all procedures. Among the 138 clinical isolates tested, 55 were resistant to at least one drug. Thirty-four of 38 INH-resistant isolates (89.5%), 28 of 28 RIF-resistant isolates (100%), 15 of 18 EMB-resistant isolates (83.3%), 18 of 30 STR-resistant isolates (60%), and 17 of 17 PZA-resistant isolates (100%) had mutations related to specific drug resistance. Eighteen of these mutations had not been reported previously. These novel mutations include one in rpoB, eight in katG, one in the mabA-inhA regulatory region, two in embB, five in pncA, and one in rrs. Escherichia coli isolates expressing individually five of the eight katG mutations showed loss of catalase and INH oxidation activities, and isolates carrying any of the five pncA mutations showed no pyrazinamidase activity, indicating that these mutations are associated with INH and PZA resistance, respectively. Our sequencing-based method was also useful for testing sputa from tuberculosis patients and for screening of mutations in Mycobacterium bovis. In conclusion, our new method is useful for rapid detection of multiple-drug-resistant M. tuberculosis and for identifying novel mutations in drug-resistant M. tuberculosis.

Antitubercular Agents↗

Mutations in the SLC34A2 gene are associated with pulmonary alveolar microlithiasis.

RATIONALE: Pulmonary alveolar microlithiasis is an autosomal recessive disorder in which microliths are formed in the alveolar space. OBJECTIVES: To identify the responsible gene that causes pulmonary alveolar microlithiasis. METHODS: By means of a genomewide single-nucleotide polymorphism analysis using DNA from three patients, we have narrowed the region in which the candidate gene is located. From this region, we have identified a gene that has mutations in all patients with pulmonary alveolar microlithiasis. MEASUREMENTS AND MAIN RESULTS: We identified a candidate gene, SLC34A2, that encodes a type IIb sodium phosphate cotransporter and that is mutated in six of six patients investigated. SLC34A2 is specifically expressed in type II alveolar cells, and the mutations abolished the normal gene function. CONCLUSION: Mutations in the SLC34A2 gene that abolish normal gene function cause pulmonary alveolar microlithiasis.

Amino Acid Sequence↗

Leflunomide-induced pneumonitis in a patient with rheumatoid arthritis.

Leflunomide is a disease-modifying antirheumatic drug (DMARD) that has been available in Japan since August 2003. Leflunomide-induced interstitial pneumonitis has not been reported as an adverse effect in other countries. We report a suspected case of leflunomide-induced interstitial pneumonitis. A 77-year-old woman with rheumatoid arthritis and a history of methotrexate-induced pneumonitis developed sudden-onset dyspnea on exertion about 2 months after the administration of leflunomide. She maintained a high concentration of an active metabolite of leflunomide for more than 3 weeks after withdrawal of the drug. She did not respond to treatment and died. Leflunomide must be administered with caution to patients with a history of interstitial pneumonitis or drug-induced pneumonitis. If leflunomide-induced pneumonitis is suspected, the plasma concentration must be immediately checked, along with elimination and withdrawal of the medication.

Adjuvants, Immunologic↗

Tuberous sclerosis complex complicated by pulmonary multinodular shadows.

A 41-year-old woman with a history of epilepsy was referred for multiple nodular ground-glass opacities on a chest computed tomography (CT) scan. They were initially suspected of representing atypical adenomatous hyperplasia or well-differentiated adenocarcinoma. However, the subsequent brain CT and magnetic resonance imaging (MRI) scans revealed a coarse nodular calcification and cortical tubers. A subungual fibroma was also noted. Histological examination of a video-assisted thoracoscopic lung biopsy specimen disclosed multiple nodules of type II pneumocyte hyperplasia with septal thickening. Based on all of these findings taken together, a diagnosis of tuberous sclerosis complex with multifocal micronodular pneumocyte hyperplasia (MMPH) was made.

Adult↗

Pneumoconiosis associated with an esophageal ulcer and uptake revealed in FDGPET.

A 76-year-old man with a past history of pneumoconiosis visited the Department of Gastroenterology in our hospital suffering from dysphagia. Gastroscopy revealed an esophageal ulcer on the top of a torus lesion. Chest computed tomography (CT) revealed it was caused by a swollen lymph node in the mediastinum. Squamous cell carcinoma related antigen (SCC) was elevated to 1.8 ng/ml. To rule out malignancy, we performed fluorine-18 deoxyglucose positron emission tomography (FDGPET) which revealed a significantly increased uptake in a nodular lesion in the right upper lobe and mediastinal lymph nodes. Biopsy and cytology of the nodular lesion revealed only pneumoconiosis. We must be careful when we interpret the findings of FDGPET in pneumoconiosis patients.

Aged↗

Emergence of rifampicin resistance in methicillin-resistant Staphylococcus aureus in tuberculosis wards.

To assess whether the occurrence of rifampicin (RFP) resistance in methicillin-resistant Staphylococcus aureus (MRSA) is related to treatment of tuberculosis, we determined the RFP susceptibility of MRSA isolates obtained from tuberculosis patients and screened for mutation(s) in the rpoB gene of these isolates. The MICs of RFP for 84 MRSA isolates obtained from two hospitals in Japan were determined. DNA was sequenced in the region 1318-1602 nucleotides (nt) of the rpoB gene, which includes RFP resistance-determining clusters I (1384-1464 nt, 462-488 amino acids). The majority of MRSA isolates from tuberculosis wards, i.e., 48 of 51 (94%) [33 of 34 in a Tokyo hospital (97%) and 15 of 17 in a Chubu hospital (88%)], were resistant to RFP. Meanwhile, no isolates of 33 from the other wards were resistant to RFP. All RFP-resistant MRSA isolates had a mutation(s), including novel mutation(s) such as Val453-->AEPhe, Asp471-->AEAsn, and Ile527-->AELeu, in rpoB. An emergence of RFP-resistant MRSAs in tuberculosis wards in Japan was strongly suggested.

Amino Acid Sequence↗

Epidemiological and clinical features of idiopathic pulmonary alveolar proteinosis in Japan.

Idiopathic pulmonary alveolar proteinosis (IPAP) is a rare disease characterized by excessive amounts of lipoproteinaceous material in the alveolus. This report presents an interim analysis of nationwide epidemiological data from Japanese patients with pulmonary alveolar proteinosis, and the roles of serum markers for IPAP. (i) The nationwide demographic data from 166 Japanese patients with IPAP are shown. The female to male ratio was 1:2, and the average age was 51 +/- 14 years old (age range: 15-79 years) at registration or diagnosis. A total of 30% of patients with IPAP have a poor clinical course. In total, 30% of patients were treated with whole lung lavage therapy (WLL). Under WLL, the patients significantly improved in the short term, but 40% of the patients who underwent WLL worsened again. A new strategy such as granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy for intractable PAP is required. (ii) The correlation of serum KL-6, carcinoembryonic antigen, surfactant proteins D and A, and LDH with disease severity suggests their potential as disease markers. In contrast, serum anti-GM-CSF antibody did not correlate with disease severity, but is a specific marker for the diagnosis of IPAP. The combined measurements of the serum markers may well prove very useful for both the diagnosis and the management of IPAP patients.

Adolescent↗

[A case of severe falciparum malaria successfully treated with intravenous artesunate and continuous hemodiafiltration].

We report a 54-year-old Japanese man who contracted severe falciparum malaria after visiting West African countries. The patient presented with Plasmodium falciparum parasitemia of 10% on admission and was successfully treated with intravenous artesunate combined with continuous hemodiafiltration. We found that intravenous artesunate had excellent antimalarial activity with rapid parasite clearance and that few adverse effects were observed compared to those reported for intravenous quinine treatment. Supportive therapy was indispensable for saving the life of the patient. Few cases of intravenous artesunate treatment are reported in Japan because the drug has not been legally registered. We wish to emphasize the efficacy of intravenous artesunate with general supportive therapy in the treatment of possible imported severe malaria patients in Japanese medical settings.

Antimalarials↗

[A case of pulmonary tuberculosis complicated with an orthotopic liver transplantation].

The infectious disease is one of the most important complications related to the organ transplantation. Patients using immunosuppressive agents often present atypical tuberculosis and the treatment of such case is far more difficult in some cases due to the liver damage and/or the drug interaction. We report a case of pulmonary tuberculosis in a patient of 60-year-old man using tacrolimus after an orthotopic liver transplantation. He had liver transplanted orthotopically for the long-term history of chronic hepatitis B and subsequent liver failure on January 28, 2004. An abnormal shadow was first detected on his chest X-ray film on October, 2004. He was admitted to our hospital after the smear of the gastric juice showed some acid-fast bacilli and tubercle bacilli were confirmed by polymerase chain reaction (PCR). Tuberculin skin test was positive (erythema 10 x 10) and the computed tomography (CT) scan of his chest revealed a nodular opacity with some smaller nodules scattered around in the right upper lobe. We started four anti-tuberculous drugs other than pyrazinamide (PZA) and rifampicin (RFP), which included isoniazid (INH), ethambutol (EB), streptomycin (SM), levofloxacin (LVFX). The liver enzyme was transiently elevated (AST 123 IU/I, ALT 103 IU/I) but improved after desensitization against INH. The blood concentration of tacrolimus preserved between 5 and 7 ng/ml and there was no need to change the dosage.

Humans↗

[Case of cavitary coccidioidomycosis with fungus balls in the apices of both lungs].

Pulmonary cavitary coccidioidomycosis with a fungus ball was observed in a immunocompetent case. A 32-year-old Japanese man visited Arizona to play golf. After 1 month he consulted a local hospital complaining of a prolonged cough and hematopysis. The laboratory examination revealed eosinophillia and chest radiograph showed 2 cavitary lesions, surrounded by small nodules in the apices of both lungs. Pulmonary tuberculosis was suspected and treated with 4 antituberculosis drugs for 3 months. However, the cavities enlarged and he was admitted to our hospital for further examination and treatment. Transbronchial lung biopsy was performed and serologically, bacteriologically and histologically a diagnosis of chronic coccidioidmycosis was made. It is very rare for fungus ball formation and coexistence of spherules and hyphae of Coccidioides immitis to be seen. Fluconazole was temporarily effective, causing cavities to shrink and eosinophilia to decrease, however Amphotericin B needed to be used later. Eosinophilia was closely related to the severity of the disease gravity.

Adult↗

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2004)].

From October 2004 to September 2005, we collected the specimen from 319 patients with lower respiratory tract infections in 12 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 383 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 381 strains were examined. The breakdown of the isolated bacteria were: Staphylococcus aureus 87, Streptococcus pneumoniae 80, Haemophilus influenzae 78, Pseudomonas aeruginosa (non-mucoid) 35, P. aeruginosa (mucoid) 9, Klebsiella pneumoniae 15, Moraxella subgenus Branhamella catarrhalis 30, etc. Of 87 S. aureus strains, those with 2 microg/mL or less of MIC of oxacillin (methicillin-sensitive S. aureus: MSSA) and those with 4 microg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 40 (46.0%) and 47 (54.0%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all the strains at 0.063 microg/mL. Against MRSA, vancomycin showed the most potent activity and inhibited the growth of all the strains at 1 microg/mL. Arbekacin (ABK) also showed the potent activity and its MIC90 was 2 microg/mL. Carbapenems showed the most potent activities against S. pneumoniae and inhibited the growth of all the strains at 0.25-0.5 microg/mL. Cefozopran (CZOP) also had a preferable activity (MIC90: 1 microg/mL) and inhibited the growth of all the strains at 2 microg/mL. In contrast, there were high-resistant strains (MIC: 128 microg/mL or more) for ABK (2.5%), erythromycin (37.5%), and clindamycin (38.8%). Against H. influenzae, levofloxacin showed the most potent activity and inhibited the growth of all the strains at 0.125 microg/mL. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and inhibited the growth of all the strains at 2 microg/mL. Against P. aeruginosa (non-mucoid), amikacin (AMK) had the most potent activity and its MIC90 was 4 microg/mL. The activity of CZOP against the non-mucoid type also was preferable and its MIC90 was 8 microg/mL. Against K. pneumoniae, CZOP, cefmenoxime, cefpirome, flomoxef were the most potent activity and inhibited the growth of all the strains at 0.063 microg/mL. Also, all the agents generally showed a potent activity against M. (B.) catarrhalis and the MIC90 of them were 4 microg/mL or less. The approximately half the number (57.0%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 50.8% and 23.8% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (21.6%), S. pneumoniae (24.7%) and H. influenzae (20.1%). S. aureus (20.9%), S. pneumoniae (16.1%), and H. influenzae (16.1%) also were relatively frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (22.3%) and H. influenzae (25.1%). The bacteria relatively frequently isolated from the patients treated with macrolides were P. aeruginosa and the isolation frequency was 43.5%.

Aged↗

"Syndromic surveillance within a hospital" for the early detection of a nosocomial outbreak of acute respiratory infection.

We have performed intra-hospital syndromic surveillance to rapidly detect nosocomial acute respiratory infection outbreaks in both inpatients and health care workers in a hospital. Syndromic surveillance allows the rapid detection of sudden outbreaks, including infections caused by unknown pathogens. This approach depends on the identification of specific "symptoms" as signs of a possible outbreak, with no need for specific diagnoses. Moreover, syndromic surveillance is quick, easy, and inexpensive. Nosocomial infection surveillance is usually performed on inpatients only. However, during the outbreaks of SARS and seasonal influenza, for example, many hospital personnel were infected. In cases of this kind, in order to quickly detect the prevalence of such infections, a surveillance system that includes hospital personnel is essential. This surveillance is promising as a strategy to prepare for re-outbreaks of SARS and the emergence of novel influenza pandemics.

Acute Disease↗

Association of rpoB mutations with rifampicin resistance in Mycobacterium avium.

The susceptibility of clinical isolates of Mycobacterium avium to rifampicin (RIF) was examined. All 32 clinical isolates tested, including 18 from Japan, 13 from Poland and 1 from Thailand, were resistant to RIF (minimum inhibitory concentrations (MICs) > or =32 microg/mL for 17 isolates and 2-16 microg/mL for 15 isolates), whereas the type strain of M. avium ATCC 25291 was susceptible to RIF (MIC < or = 0.03 microg/mL). Mutations in nucleotides 1276-1356 of the rpoB gene, termed the 81 bp core region, are associated with RIF resistance in Mycobacterium tuberculosis. No mutations were found in this region in any of the M. avium clinical isolates tested. However, mutation of G-->A to give a Gly544-->Asp substitution was identified within the rpoB gene downstream of the 81 bp region in all clinical isolates. A RIF-resistant strain (ATCC 25291 Rif(r); MIC> or =32 microg/mL) obtained by culturing the type strain in RIF-containing broth possessed a mutation C-->T to give a His445-->Tyr substitution within the 81 bp region. When the rpoB gene of the ATCC 25291 Rif(r) strain and of a clinical isolate were inserted into Mycobacterium smegmatis, organisms with the ATCC 25291 Rif(r) sequence, but not those with the clinical isolate sequence, showed resistance to RIF. These results suggest that mutations of the 81 bp region of rpoB, as well as factors other than rpoB mutation, confer RIF resistance in M. avium.

Amino Acid Sequence↗