High-dose methotrexate-based chemotherapy has extended survival in patients with primary central nervous system lymphoma (PCNSL). However, although salvage treatment is necessary in recurrent and refractory PCNSL, this has not been standardized. We herein describe the efficacy of a combination of rituximab and temozolomide (TMZ) in two consecutive patients with recurrent and refractory PCNSL. Based on the immunohistochemical study, case 1 had a non-germinal center B-cell-like (non-GCB) subtype, was positive for bcl-2 and negative for O6-methylguanine-DNA methyltransferase (MGMT). Case 2 was GCB subtype, bcl-2-, and MGMT+. Because of the positive expression of MGMT, interferon-beta was additionally given in case 2. Complete responses and partial responses were obtained after the third and fourth cycles of combination therapy, respectively. This was maintained for 12 months, with acceptable toxicity. The combination of rituximab and TMZ was effective in tumors with different immunohistochemical profiles. This combination therapy warrants further study in a larger population.
Aged ; Antibodies, Monoclonal, Murine-Derived/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Central Nervous System Neoplasms/*drug therapy ; Dacarbazine/*analogs & derivatives/therapeutic use ; Drug Therapy, Combination/*methods ; Humans ; Lymphoma/*drug therapy ; Male ; Middle Aged ; Neoplasm Recurrence, Local/drug therapy

To estimate how much physical activity is needed to improve overall health status in female patients with ischemic heart disease (IHD), the dose-response relationship between the duration of daily aerobic exercise and change in vital age (VA) was assessed for 4 months of exercise training. VA was considered as an index of physical health status and was computed from various coronary risk facotrs and physical fitness elements. Eighteen female patients with IHD, aged 54.3±9.1 yrs, continued the supervised exercise training 1-2 d/wk and the self-controlled exercise training 1-5 d/wk for 4 months. The intensity of exercise was set at individually determined lactate threshold. Daily duration of aerobic type exercise calculated for each patient averaged 21.1±11.0min/d, rang ing from 4.6 to 46.7 min/d. After the 4-month exercise training, VA decreased from 59.6±12.1 yrs to 54.2±11.8 yrs (P<0.05) . Significant correlation was found between daily duration of exercise and the change in VA (Spearman's rho=-0.60 ; Pearson's r=-0.62) . In this relationship, 10 min/d of exercise induced the decrease in VA and no further decrease in VA was found over the 30 min/d of exercise. In the 11 variables which constitute the equation of VA, oxygen uptake at lactate threshold (Spearman's rho=0.65; Pearson's r=0.64) and balancing on one leg with eyes closed (Spearman's rho=0.48; Pearson's r=0.51) significantly correlated with daily duration of aerobic exercise. From these results, it is suggested that the amount of moderate intensity exercise required to improve physical health status in female patients with IHD may be 10-30 minutes per day.

To determine the minimum duration of exercise for improving the aerobic capacity of patients with coronary heart disease (CHD), 23 female patients with CHD and/or hypertension, aged 52.8±8.7 years, were studied. After pre-testing, all the patients were conditioned for 4 months in order to elicit improvements in their aerobic capacity and other healthrelated factors. Duration and contents of daily activities were recorded by each patient. After 4 months, oxygen uptake at lactate threshold (VO_2LT) and VO_2peak were increased significantly from 12.9±2.6 to 16.0±3.4ml/kg/min and from 18.5±4.2 to 22.3±5.6ml/kg/min, respectively. Duration of exercise conditioning for the 4 months averaged 23.8±12.2min per day, ranging from 4.6 to 49.7min. Correlational analyses were applied in order to determine the extent to which the improvement in aerobic capacity was associated with the individual mean duration of exercise conditioning. As a result, changes in VO_2LT and VO_2peak correlated significantly with the exercise duration (Pearson's r=0.51, Spearman's rho=0.47 for VO_2LT; Spearman's rho=0.58 for VO_2peak) . Both VO_2LT and VO_2peak tended to improve markedly when daliy exercise duration was 20 min or longer. Furthermore, it was shown that the improvement in aerobic capacity remained almost the same within a range of exercise duration of 20 to 60min. We suggest that the minimum exercise duration for improving the aerobic capacity of cardiac patients is 20 to 30min per day or 140min or more per week.

Biological age based on the assessment of various physiological factors measured in a resting state has been proposed as an appropriate index of aging. We have recently developed an equation for estimation of physical fitness age (PFA), which is composed of eight age-related physical fitness variables. These include oxygen uptake corresponding to lactate threshold (Vo₂@LT), maximal oxygen uptake (Vo₂max), side step, grip strength, vertical jump, foot balance with eyes closed, trunk extension, and trunk flexion. In this study, the validity of PFA as a critical index of physical health and/or aging status was investigated from a longitudinal standpoint on the assumption that exercise habituation does contribute to health promotion. The subjects were 14 Japanese middle-aged and elderly men, aged 50 to 70 years, all of whom were patients with coronary heart disease (CHD) . The subjects participated in a supervised exercise conditioning program for 90 to 120 min each session, 2 times weekly for 4 months. Analyses of the data indicated that the mean PFA of the subjects (66.0±9.0 yr) after conditioning was significantly (P<0.05) lower than the mean PFA (72.8±8.6 yr) obtained before conditioning. After the exercise program, significant increases were documented in Vo₂@LT (17%), Vo₂max (12%), side step (26%), trunk flexion (109%), trunk extension (7%), vertical jump (12%), and foot balance with eyes closed (31%) . Therefore, we conclude that our exercise conditioning program may alter the overall physical fitness of patients with CHD, and that PFA could be a valid physical health and/or aging index.

Athletic women often exhibit menstrual disorders such as luteal insufficiency, oligomenorrhea and amenorrhea are often seen. It has been suggested that such disorders are related to prolactin release caused by physical activity. To investigate the mechanism by which the disorders are promoted, prolactin secretion was studied in 10 athletic women (5 with normal ovulatory periods, and 5 with short luteal periods) and 6 non-athletic controls. Blood samples were obtained during the early follicular phase of the menstrual cycle through an indwelling venous catheter at 15-minute intervals for 4 hours. The concentration of prolactin was measured by radioimmunoassay.
The mean prolactin concentration in the athletic group was lower than that in the control group (p<0.001), and pulse frequency in the athletic group was higher than that of the control group (p<0.01) . Pulse amplitude in the athletic women with short luteal periods was higher than that of those with normal ovulation. Pulse duration in the athletic women with short luteal periods was significantly longer than that of those with normal ovulation (p<0.01) .
These findings suggest that prolactin is one of the most important factors in menstrual disorders in athletic women.

Ten athletic women (5 normal ovulatory cycles, 5 short luteal phases) and 6 non-athletic women with normal ovulatory cycles were subjected to an investigation of episodic gonadotropin secretion. In the middle follicular phase, blood samples were obtained via an indwelling venous catheter every 15 minutes for 4 hours.
Mean levels of gonadotropins in both athletic groups were lower (p<0.001) than in the control group. LH pulse frequencies in the short luteal group were significantly lower than in the control group (p<0.001) . LH pulse amplitudes were similar in all groups. FSH dynamics were the same as those for LH.
In athletic women, low mean levels and infrequent episodic secretion of gonadotropins were obvious. These data suggest that strenuous athletic activity may cause hypothalamic-pituitary insufficiency, especially that of hypothalamic origin.

The purpose of this study was to investigate the kinetics of Vco₂during incremental exercise. The subjects were 7 males, age 21-28 years, exercised at two steady state work loads (540 kpm/min, 810 kpm/min) and incremental work load which was increased stepwise by every 1 min from 180 kpm/min to exhaustion. The Vo₂and Vco₂during steady state exercise (4 to 5 min) were determined by the Douglas bag method and arterialized blood samples were taken for lactate (LA) analysis and blood gas analysis. The Vo₂, Vco₂, and blood lactate were also determined throughout the incremental exercise. At exhaustion, mixed venous Pco₂ (PVco₂) was determined by the CO₂rebreathing method.
1) The Vco₂values at rest and during steady state exercise were linearly related to the Vo₂values. When the regression line was compared with Vco₂during the incremental exercise on the same Vo₂, the Vco₂during the incremental exercise below the anaerobic threshold showed lower values.
2) The total sum of the difference in Vco₂between steady state and incremental exercise was defined as CO₂store. The calculated CO₂store and CO₂store per body weight were significantly related to PVco₂at exhaustion in incremental exercise, respectively (r=0.954, r=0.954) .
3) At work load below the anaerobic threshold, Vco₂was linearly related to Vo₂. If the Vco₂above the anaerobic threshold is estimated from Vo₂using the regression line obtained at work load below the anaerobic threshold, the estimated Vco₂will be lower than the measured Vco₂. The total sum of the difference in the Vco₂was defined as CO₂excess. The CO₂excess and the CO₂excess per body weight were significantly related to ΔLAmax (the difference between LA at 3rd min after exhastion and LA at exercise below the anaerobic threshold), respectively (r=0.870, r=0.930) .
4) HCO₃^-calculated from blood gases (pH and Pco₂) was significantly related to LA (r=-0.902) . The increase of 1 mM/1 in LA was corresponding to the decrease of 0.843 mEq/l in HCO₃^-.
5) From these results, it appeared that the expired Vco₂during the incremental exercise consisted of the stored Vco₂, the exceeded Vco₂, and the produced Vco₂ (Vco₂metabolically produced from Vo₂) .

Preliminary studies on the blood composition were carried out with 40- to 82-year-old runners when they were at rest. 790 male subjects who had kept the routine training of running over a year were examined. And the results were compared those with the corresponding control groups who had no particular routine training.
The results were as follows:
1. Runners' values for Red blood cell count and Hematocrit were decreased with age.
2. Runners' values for Red blood cell count, Hemoglobin and Hematocrit were approximately 10%, 9% and 4% lower than those of the corresponding control groups of almost all age groups. On the other hand runners' values for MCH (Mean Corpuscular Hemoglobin) were approximately 8% higher than the control group values for all age groups.
3. Runners' values for reticulocyte count and osmotic fragility of the blood were within normal range.
4. Comparison between runners of 10 km group and 25 km group of blood composition was made; the age group of forties of 25 km group of both Red blood cell count and Hematocrit were significantly lower than the corresponding 10 km group.
5. Dailly training programs of 25 km runners were significantly longer than those of 10 km runners for all age groups.

Physiological characteristics of middle-aged and old runners, who competed in the international 10km or 25 km race, were investigated. All of 2260 runners were aged 40 to 86 years. They have been trained for at least one years. Body composition, resting blood pressure, blood composition, serum metabolites, serum enzymes and pulmonary function were measured. The runners who competed in 10 km race were compared with those competed in 25 km race. Relation between running performance and physioloigical parameters were discussed.
1) Average running speed was faster in 25 km group than in 10 km group, although 25 km group ran a longer distance. In daily training, 25 km group also showed longer running distance than in 10 km group.
2) Body weight averaged 55.9±6.82 kg in a whole group of 2260 runners. Skinfold thickness averaged 6.1±2.50 mm in triceps, and 10.9±3.78 mm in subscuplar. These values were remarkably lower than normal values of corresponding age of the Japanese. 25 km group showed significantly lower values in these parameters than 10 km group. The runner who made better performance also showed lower values in these parameters.
3) Resting blood pressure of the runners averaged 144.3±17.0 mmHg in systole, and 86.2±11.0 mmHg in diastole. No difference were found between 10 km group and 25 km group in blood pressure.
4) RBC, Ht, Hb of 645 runners averaged 411.8±37.4×10⁴/mm³, 40.3±3.70%, 14.5 ±1.25g/dl, respectively. These values were lower than in normals. Among age group of 40-49yrs, negative correlation between running speed and these heamatological parameters were found. Better runner showed lower values in these parameters.
5) Blood glucose, serum choresterol, LDH and CPK were not different from normal values.
6) Pulmonary function were not different from normal values. Remarkable decrease with increasing age were found in pulmonary function.

It was the purpose of this study to elucidate the difference between endurance runners and normal men in respiratory and circulatory adjustments during prolonged exercise, and to evaluate the relationship between the magnitude of the respiratory and circulatory“drift”and the endurance exercise capacity.
Ten male endurance runners (runner group), aged 19-23 years, and nine normal men (control group), aged 19-28 years, exercised on a bicycle ergometer for 60 min at a constant work load requiring 60% of Vo₂max for each subject.
In the control group, VE increased approximately 20% from 10th to 60th min of prolonged exercise (P<0.05), with a corresponding decrease in PAco₂ (P<0.05), whereas in the runner group VE and PAco₂were remained constant throughout prolonged exercise. The above differences of VE and PAco₂responses between the control and the runner group could not be accounted for by a rising body temperature and lactic acidosis, because it was found that the magnitude of the rise in rectal temperature (Tre) and the behavior in lactic acid (LA) were not different for the two groups. On the other hand, we failed to find the difference of the pattern in HR and SV responses to prolonged exercise in the runner group as compared with the control group. At each comparable time period during prolonged exercise, however, the percentage changes from the values at the 10th min in HR and SV were less in the runner group than in the control group. In addition, Vo₂max (ml/kg/min) correlated significantly with the percentage changes in VE (r=-0.534, P<0.05), HR (r=-0.565, P<0.05), and SV (r=0.588, P<0.01) from 10th to 60th min of prolonged exercise.
The results of this study suggest that the endurance training may improve the magnitude of the respiratory and circulatory “drift”, which appears to become a limiting factor to endurance performance.