Oscillation of pain intensity during adenosine infusion. Relationship to beta-endorphin and sympathetic tone.

Adenosine is a neuromodulator with both excitatory and inhibitory effects dependent in part upon preconditions; it can act as an algesic or an analgesic agent. Previously we found variations of pain intensity during constant infusion of adenosine. We therefore quantified pain intensity during constant infusion of adenosine at a rate of 140 microg/kg/min intravenously in healthy volunteers, placebo controlled, double blind, and the relation to hemodynamic, vasomotor and sudomotor responses of the sympathetic nervous system and to the role of peripheral beta-endorphin response. The perceived chest pain during adenosine infusion showed an oscillatory pattern. Painful periods of about 30s were interrupted by painfree periods, and pain was always preceded by an increase in vasomotor sympathetic activity and by increased sudomotor activity. Plasma beta-endorphin values were heterogenous but exhibited an increase during infusion.

Physical training in Syndrome X: physical training counteracts deconditioning and pain in Syndrome X.

OBJECTIVES: The aim of this study was to evaluate the effects of exercise training and body-awareness training in female patients with Syndrome X. BACKGROUND: Patients with Syndrome X, defined as effort-induced angina pectoris, a positive exercise test and a normal coronary angiogram, suffer from a chronic pain disorder. We hypothesized that this disorder results in physical deconditioning with decreased exertional pain threshold. METHODS: Twenty-six patients were randomly assigned to two training groups (A, B) and a control group (C). Group A (n = 8) started, after baseline measurements, with eight weeks of body-awareness training followed by eight weeks of exercise training on a bicycle ergometer three times a week for 30 min at an intensity of 50% of peak work rate. Group B (n = 8) performed only eight weeks of exercise training. Group C (n = 10) acted as controls without any intervention whatsoever. The effects on exercise performance, hormonal secretion, vascular function, adenosine sensitivity and quality of life were evaluated. RESULTS: Body-awareness training did not change the pain response. The two training groups did not differ in effects of exercise training. Exercise capacity before training was below the gender- and age-matched reference range and improved by 34% with training to a level not different from the reference range. Onset of pain was delayed by 100% from 3 +/- 2 to 6 +/- 3 min (p < 0.05) while maximum pain did not change. Thus the pain-response-to-exercise curve was shifted to the right. Syndrome X patients showed a hypersensitivity to low-dose adenosine infusion compared to healthy age- and gender-matched controls (p < 0.0001) that did not change with exercise training. Endothelium-dependent blood flow increase was at baseline within reference range and tended to increase (p < 0.06) following training. In Group A the concentration of cortisol in urine decreased by 53% after body-awareness training (p < 0.05), and this change from baseline remained after physical exercise training (p < 0.05). A similar decrease occurred with only exercise training (Group B). CONCLUSIONS: Physical deconditioning with lower exertional threshold for pain is a prominent feature in Syndrome X. Physical training in Syndrome X results in an increased exercise capacity with lesser anginal pain. We suggest physical training as an effective treatment in Syndrome X.

Analgesic effects of adenosine in syndrome X are counteracted by theophylline: a double-blind placebo-controlled study.

It has been proposed that adenosine mediates ischaemic pain in humans. Patients with cardiac Syndrome X are hypersensitive to potential pain stimuli, including adenosine. On the other hand, recent findings suggest that low-dose adenosine infusion may have analgesic effects. Our aim was to test two hypotheses: (1) that the analgesic effect of adenosine is peripheral in origin, and (2) that part of the hypersensitivity to pain of patients with cardiac Syndrome X results from a disturbed mechanism of adenosine analgesia. A total of 12 female Syndrome X patients and eight healthy age-matched female controls were studied in a randomized, double-blind and placebo-controlled study. Adenosine (70 microg/min) or placebo was infused into the forearm via an intra-arterial catheter. After 15 min of infusion, a tourniquet on the upper arm was inflated to 225 mmHg to ensure arterial occlusion. The patient then carried out dynamic handgrip work at 60 Hz. Pain or discomfort in the forearm was estimated continuously according to the Borg CR-10 scale. After the first test, theophylline was infused for 10 min intravenously at a dose of 5 mg/kg body weight. The ischaemic forearm test was then repeated. On a second occasion, the procedure was repeated with the opposite treatment (adenosine/placebo). Only six of 12 Syndrome X patients completed the protocol because of pain during the catheterization procedure or an inability to establish an intra-arterial line. The time to onset of pain in the working, ischaemic forearm was greater for subjects treated with adenosine than for those treated with placebo, both in those Syndrome X patients who tolerated catheterization (49+/-27 s compared with 32+/-18 s; P<0.03) and in healthy controls (40+/-19 s compared with 16+/-8 s; P<0.02). The time to maximum pain, limiting ischaemic work, was also greater with adenosine pretreatment both in Syndrome X patients (137+/-28 s compared with 106+/-28 s; P<0.03) and in healthy controls (109+/-31 compared with 82+/-18 s; P<0.01). After infusion of theophylline there was no difference between adenosine and placebo in either group. Intra-arterially infused adenosine had similar peripheral analgesic effects on experimentally induced muscular ischaemia in those female Syndrome X patients who tolerated intra-arterial catheterization and in healthy controls. Thus adenosine analgesia is counteracted by theophylline, suggesting that the effect is mediated by membrane-bound peripheral adenosine receptors.

Impaired exercise performance but normal skeletal muscle characteristics in female syndrome X patients.

Pathophysiologic mechanisms in syndrome X (anginal chest pain, positive exercise stress test, and angiographically normal coronary arteries) have been extensively studied. Recent reports suggest an ischemic origin of the pain to be less probable. Other contributing mechanisms that have been hypothesized are enhanced sympathetic drive or sensitivity or an abnormal muscle metabolism. Our aim in this study was to characterize exercise performance, skeletal muscle characteristics, and sympathetic control of blood flow in patients with syndrome X. Seven female patients aged 50 to 65 years and 5 matched controls were tested. Exercise test was performed according to clinical routine. Plasma catecholamine and blood lactate levels were measured before, during, and after exercise. Autonomic blood flow control was measured plethysmographically in the resting contralateral forearm during isometric handgrip. Muscle biopsy specimens were obtained at rest from the lateral part of Musculus vastus at midthigh. The biopsy samples were investigated for the relative number of different fiber types, phosphagen content, and energy charge, calculated as (adenosine triphosphate +/- 1/2 adenosine diphosphate)/[adenosine triphosphate +/- adenosine diphosphate +/- adenosine monophosphate]). Exercise capacity was markedly decreased in syndrome X compared with controls (85 +/- 14 vs 156 +/- 11 W, p <0.0005) and all patients discontinued exercise because of chest pain (Borg CR-10, 5 +/- 3). Peak heart rate was lower in syndrome X (150 +/- 18 vs 176 +/- 7 beats/min, p <0.01), whereas systolic blood pressure and double product did not differ. Peak norepinephrine plasma levels were lower than in controls (11 +/- 6 vs 24 +/- 13 nmol/L, p <0.04), whereas peak blood lactate levels did not differ. Blood flow increase in the resting forearm during isometric handgrip was similar to that in controls. The proportion of different fiber types, phosphagen content, and energy charge were normal. Thus, patients with syndrome X have a reduced physical exercise capacity but no skeletal muscle abnormalities. Catecholamine hypersensitivity may contribute to their condition.

SPIKEII: an integrate-and-fire AVLSI chip.

We present the SPIKEII chip, an integrate-and-fire neural network chip with programmable synapses implemented in analogue VLSI. It is the successor to the SPIKEI chip. We describe the circuitry, and show some results using networks of integrate-and-fire neurons.

Explaining different profiles in quality of life experiences in acute and chronic leukemia.

There is a need to understand and explain why quality of life (QOL) is experienced and viewed differently by those with acute and chronic leukemia. A total of 23 adults with either acute or chronic leukemia were interviewed about their experience of QOL. Adults with acute leukemia described QOL as a positive attitude to life, whereas those with chronic leukemia described QOL as life satisfaction. In order to elucidate why there are differences in their experience of QOL, a qualitative text analysis was used. The narrated interviews, tape-recorded and transcribed verbatim, were interpreted based on the following three questions: Why are there differences in these individuals' description of QOL? What are they talking about? Which phenomenon are they describing? The findings were interpreted, "a feeling of uncertainty," which made the difference to their experience of QOL. This uncertainty was expressed in different forms and could be seen in different degrees. Uncertainty is an important factor affecting the QOL of these adults. Nurses who work with these patients have a major role to play in minimizing uncertainty by offering coping skills to deal with feelings and improving QOL since QOL is one of the outcomes of nursing care.

A substantive theory of quality of life of adults with chronic leukaemia.

The person with chronic leukaemia is living with a chronic and life-threatening disease. The aims of this study were to gain a deeper understanding of what individuals with chronic leukaemia consider QOL to be and to give the concept of QOL a theoretical and empirical significance relevant to nursing care. Fifteen adults with different forms of diagnosed chronic leukaemia have been interviewed about their experience of QOL. Verbatim transcripts were analysed using constant comparative analysis. The emerging core category was life satisfaction. Under this construct there were four categories; self-esteem, interpersonal relationships, performance ability and social ability. Changed QOL was described in two ways. First, coping was the core category for living with chronic leukaemia. The strategies were action, denial and hope. Second, QOL was seen as individual perception, experience of a positive attitude to life and self-contemplation.

Isokinetic plantar flexion endurance. Reliability and validity of output/excitation measurements.

The reliability and validity of isokinetic measurement of plantar flexion endurance has been studied by a method previously described by us which utilizes simultaneous measurements of mechanical contractional work (CW) and integrated electromyogram (iEMG). The reliability was gauged by test/re-test with a two year's interval; while validity was assessed by myoelectric power spectrum analyses. The output/input balance (CW/iEMG) remained unchanged for the group as well as inter-individually. Changes in myoelectric power spectrum as function of number of contractions were clearly indicative of fatigue. Under the present conditions fatigue of fast twitch motor units may explain the rapid decreases in output and excitation followed by nearly steady state levels of all registered parameters. As is the case for non-fatigued isokinetic plantar flexions, the motor unit recruitment order appears quite stereotyped during plantar flexion fatigue. The findings of significantly lower mean power spectrum during the first part of each contraction than during the second part may support the size-principle described by Henneman.