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CONVERT, a randomized, active-controlled, global, Phase 3 trial demonstrated that patients with treatment-refractory Mycobacterium aviumcomplex (MAC) pulmonary disease were more likely to achieve culture conversion with amikacin liposome inhalation suspension (ALIS) plus guideline-based therapy (GBT) versus those continuing on GBT alone. This subgroup analysis reports the efficacy and safety of ALIS in Japanese patients enrolled in CONVERT.

Hypokalemia, an abnormally low level of potassium (K+), is a electrolyte imbalance that commonly occurs in heart failure patients. Hypokalemia is well known to induce lethal ventricular arrhythmia. However, the effects of hypokalemia in failing hearts that have undergone electrophysiological remodeling, i.e., the reactivation of fetal-type ion channels, remain unexplored. We have examined the effect of hypokalemia in the myocytes of transgenic mice overexpressing the hyperpolarization-activated, cyclic nucleotide-sensitive (HCN) channel in the heart (HCN2-Tg mice). Perfusion with a mild hypokalemic solution containing 3 mM K+induced ectopic ventricular automaticity in 55.0% of HCN2-Tg mouse myocytes. In the remaining HCN2-Tg mouse myocytes, the resting membrane potential (RMP) was more depolarized than that of wild-type myocytes subjected to the same treatment and could also be hyperpolarized by an HCN channel blocker. We conclude that in hypokalemia in our mice model, the HCN2 channel was constitutively activated at the hyperpolarized RMP, thereby destabilizing the electrophysiological activity of ventricular myocytes.

We herein reported a 4-month-old boy with transplantation-associated atypical hemolytic uremic syndrome (TA-aHUS) who was successfully treated with eculizumab. The patient diagnosed with type 3 of familial hemophagocytic lymphohistiocytosis underwent cord blood transplantation. After transplantation, he developed TA-aHUS, but plasma exchanges were unsuccessful. We identified deletions in CFH-related gene 1 (del-CFHR1) by the multiplex ligation-dependent probe amplification testing procedure and CFH autoantibodies. Eculizumab has been administered to the patient, with a marked improvement being achieved in thrombocytopenia. He has been well except for the persistent microhematuria for a year after transplantation. Uncontrolled complement activation might be involved in the pathophysiology of TA-aHUS.

The safety of occlusion with Endobronchial Watanabe Spigots (EWS) for the management of hemoptysis associated with chronic respiratory tract infection has not yet been established. A 57-year-old woman diagnosed as having pulmonary Mycobacterium aviumcomplex (MAC) infection presented to our hospital with hemoptysis. She underwent bronchoscopy for bronchial occlusion with EWS, which resulted in the resolution of hemoptysis. Subsequently, she underwent bronchial artery embolization and then EWS were removed. During placement of EWS, no worsening of infection was observed. After removal of EWS, there was no recurrence of hemoptysis. Bronchial occlusion with EWS for hemoptysis associated with pulmonary MAC infection can be performed safely.

ABSTRACTMycobacterium aviumcomplex (MAC) infections are increasing annually in various countries, including Japan, but the route of transmission and pathophysiology of the infection remain unclear. Currently, a variable-number tandem-repeat (VNTR) typing method using the Mycobacterium aviumtandem repeat (MATR) loci (MATR-VNTR) is employed in Japan for epidemiological studies using clinical isolates of M. avium. In this study, the usefulness of this MATR-VNTR typing method was compared with that of the IS1245-restriction fragment length polymorphism (IS1245-RFLP) typing method and a mycobacterial interspersed repetitive-unit (MIRU)-VNTR typing method reported previously (V. C. Thibault, M. Grayon, M. L. Boschiroli, C. Hubbans, P. Overduin, K. Stevenson, M. C. Gutierrez, P. Supply, and F. Biet, J. Clin. Microbiol. 45:2404-2410, 2007). Seventy clinical isolates identified as M. aviumfrom human immunodeficiency virus-negative patients with MAC infections were used. MATR-VNTR typing using 15 loci distinguished 56 patterns of different allele profiles, yielding a Hunter-Gaston discriminatory index (HGDI) of 0.990. However, IS1245-RFLP and MIRU-VNTR typing yielded HGDIs of 0.960 and 0.949, respectively, indicating that MATR-VNTR has an excellent discriminatory power compared with MIRU-VNTR and IS1245-RFLP typing. Moreover, concomitant use of the MATR-VNTR method and IS1245-RFLP typing increased the HGDI to 0.999. MATR-VNTR typing is inexpensive and easy to perform and could thus be useful in establishing a digital multifacility database that will greatly contribute to the clarification of the transmission route and pathophysiology of M. aviuminfections.

We report a case of mediastinal neurofibroma originating from the left phrenic nerve in a 42-year-old woman who was referred to us after a routine chest X-ray showed a smooth, round abnormal shadow in the left middle lung field adjacent to the heart. We resected a 25 × 20 × 20-mm tumor by video-assisted thoracic surgery. Histopathological examination confirmed that the lesion was a mediastinal neurofibroma originating from the left phrenic nerve without von Recklinghausen’s disease. Neurogenic mediastinal tumors originating from the phrenic nerve are very rare, and to the best of our knowledge, no other case of a mediastinal neurofibroma originating from the phrenic nerve in a patient without von Recklinghausen’s disease has ever been reported.

Purpose. Tissue factor (TF), an initiator of the extrinsic coagulation cascade, is also expressed in a wide range of cancer cells and plays an important role in cancer progression and metastasis, as well as in processes independent of the blood coagulation pathway. For example, by acting as an adhesion molecule enabling tissue invasion, TF may play a key role in the metastatic process and angiogenesis in non-small cell lung cancer (NSCLC). Methods. To further investigate the role of TF on tumor cell invasion in NSCLC, we measured the TF mRNA expression in the tumors of 42 NSCLC patients using real-time quantitative reverse transcription — polymerase chain reaction carried out in a LightCycler. We then compared the TF mRNA expression with histological evidence of invasion of blood and lymphatic vessels by tumor cells. Results. Although there was no significant relationship between the TF mRNA expression and the invasion of lymphatic vessels, the TF mRNA expression was significantly higher in tumors that invaded blood vessels (Log 10 TF mRNA/GAPDH mRNA = 2.16 ± 0.18) than in those that did not (1.59 ± 0.16; P = 0.03). Conclusion. These results suggest that TF plays a major role in blood vessel invasion by tumor cells in NSCLC.

Anti-microtubule agents such as vinorelbine and paclitaxel, which are extensively used in the treatment of lung cancers, activate mitotic spindle checkpoint. Although defects of the mitotic spindle checkpoint are thought to play a role in the genesis of chromosome instability, we previously reported its frequent impairment in human lung cancer cell lines. In this study, we examined a panel of 13 human cancer cell lines comprising 11 lung and 2 other cancers and found a significant difference in the resistance to apoptosis induced by anti-microtubule agents between mitotic spindle checkpoint-impaired and -proficient cancer cell lines. This finding was in marked contrast to a lack of such correlation with a DNA damaging agent, cis-platin. Interestingly, anti-microtubule agent-induced apoptosis in mitotic spindle checkpoint-proficient cell lines, NCI-H460 and A549, was shown to be markedly reduced by staurosporine treatment in association with the shortened mitotic arrest, whereas various inhibitors of caspases seemed to have very modest effects. Taken together, these findings suggest the potential involvement of mitotic spindle checkpoint in the induction of apoptosis by anti-microtubule agents in human lung cancers, warranting further studies on the underlying mechanisms.

Objective:Widespread clinical use of helical computed tomography has improved the detection rate for small peripheral pulmonary nodules. As a result, use of thoracoscopic surgery to confirm the diagnosis of small peripheral pulmonary nodules has become more important than ever before. However, if small peripheral pulmonary nodules are too small or located too deeply to detect thoracoscopically, it is necessary to mark the small peripheral pulmonary nodules preoperatively. The purpose of this study was to determine indications for preoperative hookwire marking in thoracoscopic resection of small peripheral pulmonary nodules. Methods:A total of 120 patients underwent thoracoscopic pulmonary resection in our institute from 1999 to 2001. Small peripheral pulmonary nodules were marked preoperatively in 61 of these patients by means of percutaneous placement of a hookwire under computed tomographic guidance. The hookwire-marked small peripheral pulmonary nodules either were smaller than 10 mm or were located more than 10 mm below the pleural surface. Results:Although 9 of the hookwire-marked small peripheral pulmonary nodules were easily identified during thoracoscopy, the other 52 small peripheral pulmonary nodules could not have been identified during thoracoscopy without the hookwire marking. Of the 59 small peripheral pulmonary nodules that were not hookwire marked, 7 required conversion to thoracotomy to locate the nodules. Small peripheral pulmonary nodules from both groups were examined and assigned to either an undetectable or detectable group. Discriminant function analysis indicated that a linear function (ie, depth = 0.836 × size − 2.811) could be used to differentiate between undetectable and detectable small peripheral pulmonary nodules, and preoperative hookwire marking for small peripheral pulmonary nodules should be considered for nodules in the region above those. Conclusion:The results suggest that this formula might serve as an indication for preoperative marking of small peripheral pulmonary nodules in thoracoscopic resection.

ABSTRACTMycobacterium aviumsubsp. hominissuismainly causes disseminated infection in immunocompromised hosts, such as individuals with human immunodeficiency virus (HIV) infection, and pulmonary infection in immunocompetent hosts. However, many aspects of the different types of M. aviumsubsp. hominissuisinfection remain unclear. We examined the antibiotic susceptibilities and genotypes of M. aviumsubsp. hominissuisisolates from different hosts by performing drug susceptibility testing using eight antibiotics (clarithromycin, rifampin, ethambutol, streptomycin, kanamycin, amikacin, ethionamide, and levofloxacin) and variable-number tandem-repeat (VNTR) typing analysis for 46 isolates from the sputa of HIV-negative patients with pulmonary M. aviumsubsp. hominissuisdisease without previous antibiotic treatment and 30 isolates from the blood of HIV-positive patients with disseminated M. aviumsubsp. hominissuisdisease. Interestingly, isolates from pulmonary M. aviumsubsp. hominissuisdisease patients were more resistant to seven of the eight drugs, with the exception being rifampin, than isolates from HIV-positive patients. Moreover, VNTR typing analysis showed that the strains examined in this study were roughly classified into three clusters, and the genetic distance from reference strain 104 for isolates from pulmonary M. aviumsubsp. hominissuisdisease patients was statistically significantly different from that for isolates from HIV-positive patients (P= 0.0018), suggesting that M. aviumsubsp. hominissuisstrains that cause pulmonary and disseminated disease have genetically distinct features. Significant differences in susceptibility to seven of the eight drugs, with the exception being ethambutol, were noted among the three clusters. Collectively, these results suggest that an association between the type of M. aviumsubsp. hominissuisinfection, drug susceptibility, and the VNTR genotype and the properties of M. aviumsubsp. hominissuisstrains associated with the development of pulmonary disease are involved in higher levels of antibiotic resistance.