Extramedullary progression of multiple myeloma following GM-CSF treatment--grounds for caution?
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Biomedical subjects
Publications and source records attributed to F Celsing.
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Ten hyperthyroid patients were assessed for muscle strength before and after a period of medical treatment that averaged 12 months. The subjects did not change their habitual level of physical activity between the two test occasions. Maximal voluntary isokinetic knee extensor muscle strength was determined during various concentric, eccentric and isometric conditions. Average increases in strength from before to termination of treatment ranged from 25 to 41% for the concentric and isometric tests (P less than 0.01, n = 10), and from 19 to 35% for the eccentric tests (P less than 0.01, n = 6). The present study demonstrates that medical treatment of hyperthyroid patients results in a marked increase in muscle strength.
The influence of chronic iron deficiency anaemia on myoglobin content, maximal enzyme activities and capillarization in the human skeletal muscle was investigated. Muscle samples from musculus vastus lateralis were screened in an Indonesian population. The causes of iron deficiency were chronic intestinal bleeding or repeated pregnancy combined with low iron intake. The maximal activities of iron-dependent and non-iron-dependent glycolytic and oxidative enzymes as well as myoglobin showed similar values in the iron-deficient group and the matched control group. The activities of the oxidative enzymes in both the iron-deficient group and the controls were lower, however, compared even to untrained Swedish subjects. The capillary density was essentially within a normal range in both groups. It is concluded that chronic iron deficiency anaemia of a moderate or severe degree, with Hb concentrations of about 80-100 g.1(-1), does not cause an impaired biochemical function of the human skeletal muscle.
The plasma concentrations of branched-chain and aromatic amino acids have been measured in two different types of sustained dynamic exercise. Twenty-two subjects participated in the 1986 Stockholm Marathon and eight subjects took part in an army training programme of approximately 1.5-h duration. Both types of exercise caused a significant decrease in the plasma concentration of branched-chain amino acids, while there was no change in the concentration of total (free plus bound to albumin) tryptophan. The plasma concentration of free tryptophan, which was measured in the marathon runners, was found to increase 2.4-fold during the race. This increase is probably caused by a pronounced elevation in the concentration of plasma free fatty acids during exercise, since these are known to displace tryptophan from albumin. The observed increase in plasma free tryptophan concentration, together with the decrease in plasma concentration of branched-chain amino acids, gives rise to a marked increase in the plasma concentration ratio of free tryptophan/branched-chain amino acids. This should lead to an increase in the rate of transport of tryptophan across the blood-brain barrier and hence to an increase in the rate of synthesis of 5-hydroxytryptamine (5-HT) in the brain. An elevated concentration of 5-HT in specific areas of the brain may be responsible, at least in part, for the development of physical, and/or mental fatigue during prolonged exercise.
Increasing the haemoglobin concentration ([Hb]) improves the oxygen transport capacity but it also increases the viscosity of the blood. The influence of changes in [Hb] and viscosity on submaximal exercise capacity and maximal aerobic power was investigated in eight healthy males in varying states of training and with a normal resting [Hb] ([Hb]r), ranging from 123 to 178 g l-1. The subjects were venesected five times (450 ml per unit) and exercise tests were performed in the anaemic state. After 5-7 weeks, when [Hb] had returned to the 'normal' value, a stepwise re-transfusion of three to five units of blood was performed with exercise tests after each transfusion. The [Hb]r was 137 +/- 15 g l-1 in the anaemic state (A) and 170 +/- 16 g l-1 after the last re-transfusion (LT). The VO2max rose from 3.94 +/- 0.35 in A to 4.68 +/- 0.30 l min-1 after LT. Individual regression lines for [Hb] and VO2max revealed a mean increase in VO2max of 19 +/- 6 ml min-1 per g l-1 change in [Hb]. This value did not differ between individuals with high and low normal [Hb]. Furthermore, in intra-individual comparisons the relationship between [Hb] and VO2max in high and low individual [Hb] ranges was not found to be statistically different despite a 40% increase in the in vitro viscosity from the anaemic to the polycythaemic state.(ABSTRACT TRUNCATED AT 250 WORDS)
The purpose of the present study was to examine to what degree a reduction in systemic oxygen transport capacity influences the absolute and relative levels (% of maximal oxygen uptake) of submaximal blood lactate accumulation. Anemia was induced by repeated venesections in eight healthy males. After 9-10 weeks of anemia, hemoglobin concentration [Hb] was restored by retransfusion of packed erythrocytes. The [Hb] values obtained were, before venesections, in control (C) = 145 +/- 10, in the anemic state (A) = 110 +/- 8, and after retransfusion (R) = 143 +/- 8 g X l-1 respectively. In all states, muscle biopsies were taken and measurements made of VO2max and VO2 at a running velocity corresponding to a blood lactate concentration of 4 mM (upsilon Hla 4.0). In the A condition Vo2max decreased by 19% as compared to C (P less than 0.01). upsilon Hla 4.0 was 14% lower in A as compared to C and R (p less than 0.01). VO2 at upsilon Hla 4.0 was 13% lower in A as compared to C (P less than 0.01). However, VO2 at upsilon Hla 4.0 expressed as a percentage of VO2max was increased (P less than 0.01) in the anemic state, the values obtained being C = 83.3%, A = 89.8% and R = 84.8%. Ventilation at upsilon Hla 4.0 was higher in A as compared to C and R (P less than 0.05). R and C values were not significantly different for any of the values presented above. The maximal activity of citrate synthase in muscle did not differ between the three different conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Seven hyperthyroid patients were studied by repeated muscle biopsies (vastus lateralis) before and after a period of medical treatment which averaged 10 months. The biopsies were analysed with regard to fibre-type composition, fibre area, capillary density, glycogen content and enzyme activities representing the glycolytic capacity (hexokinase, 6-phosphofructokinase), oxidative capacity (oxoglutarate dehydrogenase, citrate synthase) and Ca2+- and Mg2+-stimulated ATPase in muscle. In the pretreatment biopsy (hyperthyroid state), there was a significantly lower proportion of type I fibres (30% vs. 41%), a higher capillary density (23%), lower glycogen content (33%), and higher hexokinase activity (32%) compared with the post-treatment biopsy. No significant changes in the activity of the remaining enzymes were observed. The present study indicates that hyperthyroidism induces a transformation from type I to type II fibres in human skeletal muscle. The increase in hexokinase activity probably reflects a higher glucose utilization by skeletal muscle in order to compensate partially for the reduced glycogen content.
In order to evaluate a computerized modified acetylene rebreathing method for the determination of cardiac output, 15 healthy subjects were studied at different levels of their maximal oxygen uptake (VO2max). Submaximal exercise was performed on a cycle ergometer and maximal exercise on a treadmill. Oxygen uptake, heart rate, and cardiac output (acetylene method) were determined in all test situations. In seven subjects simultaneous determinations of cardiac output were made by a modified acetylene rebreathing method (QA) and a dye dilution method (QD). Furthermore, a new resting rebreathing technique was used. The methodological error for QA (means of double samples) was 0.37 litre min-1 (2.8%) in the same individual at 150 W. The corresponding values between individuals were 0.71 (rest), 0.41 (50 W), 0.69 (150 W), and 0.40 litre min-1 (VO2max). Thus the methodological error of the modified acetylene method was very low. There was a significant difference (P less than 0.01), however, between the acetylene method and the dye dilution method, which showed a lower value for QA at all levels. This was probably due to the long response time of the mass spectrometer combined with anatomical and physiological arteriovenous shunt effects in the lungs during exercise. When these factors were considered the correcting formula was: QAc = QA + 0.005 X Q2A. There was no significant difference between the corrected cardiac output values (QAc), and the corresponding QD values. In conclusion, this modified acetylene rebreathing method is a very useful non-invasive method for measuring cardiac output at rest as well as during heavy exercise.
The purpose of this study was to evaluate the effect of long-term anemia and subsequent retransfusion of erythrocytes on various circulatory parameters. Anemia was induced in nine healthy male subjects by repeated venesections. The stored blood was retransfused after 9 wk (range 8-11 wk). Exercise tests were performed before venesection in the control state (C), in the anemic state (A), and 48 h after retransfusion (R). Hemoglobin concentration levels were 146 +/- 10 g/l in C, 110 +/- 7 g/l in A, and 145 +/- 9 g/l in R. Maximal O2 uptake was 4.55 +/- 0.6, 3.74 +/- 0.7, and 4.45 +/- 0.6 l/min in C, A, and R, respectively. A decrease in heart rate of 7 beats/min (P less than 0.01) and in cardiac output of 2 l/min (P less than 0.05) at maximal exercise occurred in the anemic state compared with control values. These decreases were not reversed but, rather, were further accentuated after retransfusion. The adaptive response to submaximal exercise (cycling at 150-175 W) in anemia was mediated to the amount of 50% by an increase in cardiac output (mainly an increase in heart rate) and 50% was due to increased O2 extraction in the peripheral tissue. In conclusion, long-term anemia was found to decrease the heart rate and cardiac output at maximal exercise. Furthermore the close correlation between hemoglobin concentration and maximal O2 uptake in humans is confirmed.
The purpose of the present study was to evaluate the effects of iron deficiency on enzyme activities and endurance. Iron deficiency was induced in 9 healthy male subjects by repeated venesections. After a period of 9 wk (range, 8-11 wk) when the subjects had become iron deficient as defined by laboratory parameters, blood was retransfused to reestablish the control hemoglobin concentration. In this state it was possible to evaluate the effect of iron deficiency isolated from anemia. In samples secured by muscle biopsies, glycolytic, oxidative, and iron depending enzymes were analyzed in the control (C) and anemic (A) states and after retransfusion (R). There were no significant changes in the maximal activities of any of the enzymes studied. The capillary/fiber ratio remained unchanged between C (1.92) and R (1.94). Times to exhaustion on treadmill tests were 49 min, 11 s in C, 26 min, 33 s in A, and 52 min, 3 s in R. Vo2max was 4.55 1 X min-1 in C, 3.74 1 X min-1 in A, and 4.45 1 X min-1 in R. An artificially induced iron deficiency defined by conventional laboratory parameters did not affect endurance when transfusion of red blood cells was performed in order to exclude the influence of a low hemoglobin concentration. A 4-wk period of severely depleted or absent tissue iron stores did not affect the maximal activities of various enzymes in human skeletal muscle.