Background-A study was undertaken to determine whether swimming training improved aerobic capacity, exercise induced bronchoconstriction (EIB), and bronchial responsiveness to inhaled histamine in children with asthma. Methods-Eight children with mild or moderate asthma participated in swimming training every day for six weeks. The intensity of training was individually determined and set at 125% of the child's lactate threshold (LT), measured using a swimming ergometer. Another group of eight asthmatic children served as control subjects. Aerobic capacity and the degree of EIB were assessed by both cycle ergometer and swimming ergometer before and after swimming training. Results-The mean (SD) aerobic capacity at LT increased by 0.26 (0.11) kp after training when assessed with the swimming ergometer and by 10.6 (4.5) W when assessed with the cycle ergometer, and these changes were significantly diVerent from the control group. The mean (SD) maximum % fall in forced expiratory volume in one second (FEV 1 ) to an exercise challenge (cycle ergometer) set at 175% of LT decreased from 38.7 (15.4)% before training to 17.9 (17.6)% after training, but with no significant diVerence from the control group. There was, however, no difference in histamine responsiveness when compared before and after the training period. Conclusion-A six week swimming training programme has a beneficial eVect on aerobic capacity but not on histamine responsiveness in children with asthma.

Catecholamine concentrations are known to increase sharply in the blood at work rates above the blood lactate threshold (LT); thus, we hypothesized that the double product (DP, heart rate-systolic blood pressure product) may also abruptly increase at work rates above the LT. Ninety healthy students performed a stepwise incremental test on a cycle ergometer. The slopes of the two regression lines below and above the LT for the heart rate (HR), the indirectly measured systolic blood pressure (SBP), and the DP, respectively, were compared using VO2 as an independent variable. For all three parameters the slope of the regression line above the LT was significantly higher than that below the LT. Although either the same or a lower slope was found in the HR (N = 23) or SBP (N = 22) responses in some subjects above the LT as compared with that below the LT, a steeper DP slope above the LT was evident in all 90 subjects. The same results were also obtained during 4-min constant work rate exercise sessions at a variety of submaximal intensities performed in a random order in seven subjects. In addition, we established the DP break point (DPBP) determining protocol with a fairly good test-retest reliability (r = 0.951) and a correlation coefficient between the DPBP and the LT (r = 0.900). These results suggest that the DP increases more steeply above the LT, and, as a result, the DPBP is considered to be a valid and useful parameter as a marker of the LT.

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Background:Anti-programmed cell death 1 antibody nivolumab is a promising agent for various cancers. Immune-related adverse events are recognized; however, bi-cytopenia with nivolumab has not been reported.Case presentation:A 73-year-old man was diagnosed with advanced primary malignant melanoma of the esophagus with liver, lung, and lymph node metastases. Previous therapies including dacarbazine and radiation of 39 Gy to the esophageal region were performed, but the liver metastases deteriorated. The patient was then administered nivolumab (2 mg/kg, every 3 weeks). After 3 cycles, the esophageal tumor and lymph nodes showed marked reductions in size, the lung metastases disappeared, and the liver metastases shrank partially. The treatment continued with 7 cycles for 4 months. However, severe anemia and thrombocytopenia appeared in the 6th cycle, and intermittent blood transfusions were required. The patient received high-dose intravenous methylprednisolone therapy for bi-cytopenia, but it was ineffective. Seven months after the initiation of nivolumab, the patient died of tumor. Although the mechanisms of bi-cytopenia were unclear, it could have been induced by nivolumab.Conclusion:The present case shows a rare but serious life-threatening bi-cytopenia possibly associated with nivolumab and suggests the importance of awareness of hematological adverse events during nivolumab therapy.