Evaluation of cardiac autonomic nerves by iodine-123 metaiodobenzylguanidine scintigraphy and ambulatory electrocardiography in patients after arterial switch operations

The autonomic cardiac nerves reach the heart after passing through the vicinity of the aortic root and the pulmonary trunk. The arterial switch operation (ASO) completely transects the ascending aorta and the pulmonary trunk. Therefore, this surgical procedure virtually denerves the heart. Cardiac sympathetic denervation and reinnervation were evaluated in patients after ASO using iodine-123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy and parasympathetic denervation and reinnervation using ambulatory electrocardiography [Holter electrocardiogram (ECG)]. MIBG scintigraphy was performed in 14 patients who underwent ASO (ASO group) and 3 patients who underwent other open heart surgery (control group). All patients in the ASO group underwent the operation in the neonatal or infantile period. Planar and single photon emission computed tomography (SPECT) images of the myocardium were obtained. Defect score was determined by the SPECT images as a semi-quantitative index. The mean interval between ASO and MIBG scintigraphy was 25.6 +/- 14.6 months. Holter ECG was also performed in 14 patients in the ASO group and 19 age-matched normal children. The Holter ECGs were plotted on a Lorenz plot. The H index, which is related to vagal tone for the cardiovascular system, was calculated from the R-R intervals. The mean interval between the ASO and Holter ECG was 8.3 +/- 9.7 months. MIBG scintigraphy in the control group demonstrated an almost normal homogeneous tracer uptake, but showed extremely reduced tracer uptake and significantly higher defect score in the ASO group. The extent and degree of the reduction of MIBG uptake improved with time after the ASO. The heart-to-mediastinum MIBG count ratio tended to increase with time. The H index of the ASO group was lower than that of normal children (< 12 months: Control group 0.0280 +/- 0.0068 vs ASO group 0.0219 +/- 0.0083), and gradually increased with time (1-3 years: 0.0470 +/- 0.0157 vs 0.0314 +/- 0.0124). These results indicate that MIBG scintigraphy reflects the presence of sympathetic denervation and the possibility of reinnervation after ASO, and that H index reflects the presence of parasympathetic denervation and the possibility of reinnervation after ASO. These are simple and useful methods for assessing the extent and degree of autonomic denervation and reinnervation.     

Chronic obstructive pulmonary disease (COPD) burden in Japan--confronting COPD Japan survey

To grasp the burden and management status of COPD in Japan, a large telephone survey was conducted. In initial screening 400 individuals > or =45 years were identified as either having been given a diagnosis of COPD or fulfilling criteria for their respiratory-related symptoms and smoking history (baseline population) and they were recruited for a detailed investigation (interview sample). They were asked about demographic information, exacerbation, impact of COPD on daily life, and management and treatment. Of the 400 interview samples, 209 subjects (52%) had a diagnosis of COPD, and the remaining 191 ones (48%) were not, retrospectively. It was confirmed that proportions of a current smoker in the COPD (35.4%) and non-COPD (35.6%) groups were almost at the same level. The use of inhaled bronchodilators, recommended by guidelines in 157 treated subjects, was 16% or less, whereas respiratory conditions affected daily activities in 70% of all the subjects. In conclusion, COPD in Japanese subjects significantly affects daily life yet is undiagnosed; there is a need to improve COPD diagnosis and management by general practitioners through disseminating guidelines for diagnosis, management, and prevention of COPD in Japan.     

Efficacy of the polo-like kinase inhibitor rigosertib,alone or in combination with Abelson tyrosine kinase inhibitors,against break point cluster region-c-Abelson-positive leukemia cells

The potency of Abelson (ABL) tyrosine kinase inhibitors (TKIs) against chronic myeloid leukemia (CML) has been demonstrated. However, ABL TKI resistance can develop. In this study, we investigated the efficacy of a combination therapy including rigosertib (ON 01910.Na), a polo-like kinase (PLK) and phosphoinositide 3-kinase (PI3K) inhibitor, and ABL TKIs. A 72-h rigosertib treatment was found to inhibit cell growth, induce apoptosis, reduce phosphorylation of the breakpoint cluster region-c (BCR)-ABL and its substrate Crk-L, and increase the activities of caspase 3 and poly (ADP-ribose) polymerase (PARP). This combination therapy also exerted a synergistic inhibitory effect on Philadelphia chromosome (Ph)-positive cell proliferation and reduced the phosphorylation of BCR-ABL and Crk-L while increasing that of cleaved PARP and the H2A.X histone. Rigosertib also potently inhibited the growth of ABL TKI-resistant cells, and cotreatment with ABL TKIs and rigosertib induced higher cytotoxicity. These results indicate that rigosertib treatment may be a powerful strategy against ABL TKI-resistant cells and could enhance the cytotoxic effects of ABL TKIs.     

Current and future perspectives on the TARGET system: the registration system for Glivec® established by the JSH

Since hematology is a highly specialized field, an individual physician may not have much direct treatment experience with a given disease. Therefore, the Japanese Society of Hematology (JSH) has discussed establishing a registry of hematologic disorders, in order to contribute to improving the quality of treatments and clinical outcomes in this field. As a first step, the Timely and Appropriate Registration System for GLIVEC Therapy (TARGET), a registration system for chronic myeloid leukemia (CML) patients treated with imatinib, was established in October 2003. We present the preliminary results of the first 4 years’ experience with this system. CML patients treated with imatinib in Japan were registered through the website and the patient’s clinical course, including parameters and events like imatinib dose, blood counts, adverse events, and efficacy were recorded in months 1, 3, 6, 9, and 12 and then every 6 months thereafter. By September 2007, 862 patients from 176 hospitals were registered. Follow-up period was 0–54 months, and 127 patients were followed-up for more than 36 months. Based on these cumulative data, present imatinib treatment trends were analyzed and safety and efficacy were compared with international trial data. The part of content in this article was presented in the Joint Annual Conference of the 68th Japanese Society of Hematology (JSH) and the 48th Japanese Society of Clinical Hematology (JSCH) in Fukuoka (Japan) at 7 October 2006. Other participants in the TARGET system are listed in the Appendix.     

A case of thoracic empyema with gas formation associated with Streptococcus dysgalactiae subsp. equisimilis

A 63-year-old woman suffering from dyspnea since 1 week earlier underwent a combination therapy of oral corticosteroid and ciclosporin for rheumatic arthritis. Chest radiography showed plural effusion with gas formation in the right thorax. Empyema was diagnosed based on the specimen from pleural effusion. After a chest tube was emplaced to remove and wash out pus, antibiotics were started and empyema improved immediately. Streptococcus dysgalactiae subsp. equisimilis, but not aerobic bacilli, was detected from the pus by repeated culture. Insofar as we know this is the first case of empyema with gas formation associated with Streptococcus dysgalactiae subsp. equisimilis.