Effect of nedocromil sodium on exercise-induced bronchoconstriction exacerbated by inhalation of cold air.

This double-blind placebo-crossover study examined the effect of nedocromil sodium, 4 mg aerosol 30 min before challenge, on exercise-induced bronchoconstriction (EIB) in cold air conditions. Twenty-one asthmatic patients (15-28 years), with methacholine PC20 < or = 8 mg/ml in the absence of significant allergen exposure, were randomized to active and placebo therapy on separate study days. Pulmonary function, measured up to 20 min after exercise, showed significantly less deterioration with nedocromil sodium, which effectively halved the maximum percentage decline in forced expiratory volume in the first second. EIB was increased by cold air, whereas an ancillary study in 15 healthy volunteers (18-19 years) showed no such effects. We conclude that prior inhalation of nedocromil sodium diminished cold air-exacerbated EIB in young adult asthmatic patients.

[Asthma and mountain air]. / Astma og fjelluft.

Geilomo hospital for children with asthma and allergy is situated 800 m above sea level in a non-polluted area in the central part of Norway. 31 children who were admitted to this hospital from different parts of Norway (mostly from the main cities) were studied for six weeks. They underwent physical training and daily measurements were taken of lung function and the effect of bronchodilators. The bronchial responsiveness of the children improved significantly from week 1 to week 6, as measured by reduction in lung function after sub-maximal running on a treadmill. There was significant improvement in daily symptom score, and in degree of obstruction as shown by physical examination. The children's improvement was probably the result of a stay in a mountainous area with very little air pollution or allergens, combined with regular planned physical activity, and regular medication and surveillance.

Doping and athletes--prevention and counseling.

Doping in sports is an old problem. Development of modern techniques has made doping control possible for all drugs listed on the International Olympic Committee's list. A survey is given of the preventive measures ( antidoping ) that have been carried out in Norway since 1976. This comprises regular doping control (during competition and at random in the training period) and extensive information programs to change attitudes toward the use and misuse of drugs in sports. The basic principles of the antidoping campaign include upholding the ethics of sports, protection of athletes' health, and preservation of equal chances for all. The campaign is directed to the athletes, their coaches, and trainers as well as to the team physicians, the different sports federations , and the public. The decision to intensify the random controls for anabolic steroids in loaded sports has increased the number of positive results substantially. The concepts of the antidoping campaign are now widely acknowledged at the national level. Recommendations are given that the results of the Norwegian antidoping work should be distributed internationally.

Menstrual dysfunction in Norwegian top athletes.

Of 301 Norwegian female top athletes, all members of the national team in 27 different sports, who were approached with a questionnaire about menstrual function, 278 (92.4%) responded. Ninety-nine of the respondents who used oral contraceptives were excluded. Of the remaining 179, 18 (10.1%) reported secondary amenorrhea (greater than 4 months since the last period) and were chosen for further studies. Blood samples were drawn for hormonal analyses between 10 and 12 a.m. and at least 12 hours after the last training session. Their mean age was 20.8 years (range 18-27), mean height 169.8 cm (160-180), mean weight 58.5 kg (51-67), and their mean age at menarche 14.6 years (13-16.5), significantly older than that of the other top athletes: 13.5 years (p less than 0.05). Their mean number of training hours per week was 16.1 (12-24). Hormonal changes were consistent with simple normoprolactinemic hypothalamic suppression, characterized by low values of FSH, estradiol-17 beta and prolactin. The androgen hormones demonstrated high levels of dihydrotestosterone. Testosterone levels were within normal limits, but in the upper part of the range, whereas sex hormone-binding globulin was in the lower normal range.

Physical activity in children and adolescents in relation to growth and development.

Physical activity during the growth period appears to be necessary for normal growth and development of the skeleton, musculature and oxygen-carrying organs. Compared with the adult, the child (in relation to body size) has poor maximal strength and low anaerobic capacity. Muscular endurance and aerobic performance are more comparable to what is found in adults, but even as regards these qualities the child is immature and not on the same level as the adult. The growth period appears to be particularly favourable for learning new movement patterns. In arranging training and competitive sport for children or growing adolescents, attention must be paid to their special physical qualifications and also to the need for versatility in the choice of exercise.

Asthma and physical activity.

Physical activity regularly leads to a decline in lung function in children and adolescents with asthma. This decline is a consequence of what is known as exercise-induced asthma (EIA), and can be determined and graded with the help of lung function tests before and after submaximal workloads on the ergometer cycle or the treadmill. Typical EIA appears in asthmatic individuals with entirely normal lung function before the effort, but EIA may also become clinically manifest with exercise in patients who have a subclinical degree of obstruction. The grade of EIA is essentially dependent on the duration and intensity of effort but also on the type of exercise. For example, free running causes much greater bronchoconstriction than swimming. The temperature and humidity of the inspired air may partially explain this difference. At the Voksentoppen Allergy Institute we find that about 85% of children develop a fall in lung function of 15% or more after a six minute ergometer cycle test. With typical EIA the fall may be totally or partially abolished by prophylactic medication 10 minutes before the start of the test. Disodium cromoglycate (Intal) and/or beta-adrenergic drugs are regularly used before all physical activity. Training programmes must be based on the interval principle. Swimming, ball games, relay races and dancing are examples of useful activities in the training and rehabilitation of children and adolescents with asthma. Through prophylactic medication and physical training, the aerobic work capacity, muscle strength and lung function in asthmatic children is improved. Training also leads to a significant mobilisation of mental resources and an increase in social integration.

Fat cell size and lipid content of subcutaneous tissue in congenital generalized lipodystrophy.

Fat cell size and lipid composition of subcutaneous tissue from 3 patients with congenital generalized lipodystrophy have been measured before and after treatment with either pimozide, fenfluramine or hypophysectomy. The fat cell volume before treatment ranged between 9.8 x 10(4) and 17.7 x 10(4) micron 3, compared to 9.0 x 10(4) and 85.3 x 10(4) micron 3 in 15 controls. The amount of lipids was only 1/10 to 1/50 of normal, triglycerides being the most heavily reduced lipid component. Neither the fat cell size nor the lipid content were affected by treatment with hypophysectomy, pimozide or fenfluramine.

Decreased binding of insulin to its receptor in patients with congenital generalized lipodystrophy.

Patients with congenital generalized lipodystrophy are extremely insulin resistant. To ascertain whether this resistance is due to an insulin receptor defect, we tested four young patients with congenital generalized lipodystrophy and seven healthy persons of comparable age for the binding of 125I insulin to mononuclear leukocytes isolated from peripheral blood. Mononuclear leukocytes from patients with congenital generalized lipodystrophy bound significantly less insulin than cells from normal subjects (P less than 0.01). When patients with lipodystrophy fasted for 60 hours, the insulin binding increased. Altered insulin receptors may be responsible for the pronounced insulin resistance and the decreased synthesis of triglycerides in congenital generalized lipodystrophy.

Lipodystrophic diabetes treated with fenfluramine.

Congenital generalized lipodystrophy is considered to be a diencephalic syndrome with disturbance of hypothalamic transmitters. After puberty and arrest of growth the patients develop a serious untreatable diabetes mellitus. One of our patients, a girl 15 years of age, developed a lipodystrophic diabetes with fasting blood glucose levels above 300 mg/100 ml, increased serum insulin with insulin resistance, and hyperlipidaemia. Daily administration of fenfluramine gave a dramatic improvement. The voracious hunger and profuse perspiration were reduced, the patient's serum lipids became normal, her blood glucose fell, and her sensitivity to exogenous insulin increased. A normalization of the urinary excretion of the serotonin metabolite, 5-OH-indole acetic acid, was observed.

A new well-characterized, purified allergen preparation from timothy pollen. I. Chemical properties.

A purified allergen preparation, Timothy N, from timothy pollen (Phleum pratense) was characterized with respect to chemical properties in comparison with a commercially available crude extract, Timothy O, from the same pollen material. In Timothy N about 94% of the protein and 99% of both hexoses and pentoses were removed during the purification. Timothy N contains a limited number of proteins with molecular weights of about 15,000 and 30,000. A Timothy N solution of 0.010 mg/ml will have an allergenic activity of 1 HEP.

Studies in congenital generalized lipodystrophy. IV. Effect of muscular exercise on carbohydrate and fat metabolism including plasma levels of IRI and HGH.

Two patients with congenital generalized lipodystrophy have been studied at rest, and during and after long-term exercise at different carefully measured work loads. The two patients represented different stages of diabetes development. Both patients derived most of their energy used during muscular exercise from carbohydrate, and comparatively little from fat. FFA levels remained low throughout the period of observation in contrast to normal individuals and patients with juvinile diabetes. The data presented seem to show that deposition of glucose and free fatty acids (FFA) as triglyceride, must be impaired and are not compatible with the concept of increased triglyceride turnover in the adipocytes. The fall in blood glucose concentration (BCG) was less than in normal individuals and juvenile diabetes during exercise, and the glucose tolerance remained unchanged following work stop in both patients (k-values unchanged), in contrast to normal persons and patients with juvenile diabetes. Both patients showed significant falls in circulating immuno-reactive insulin (IRI) levels during exercise irrespective of a rise or fall in BGC. Thus, the exercise itself might activate endogenous mechanisms which could, on the one hand increase the circulating BGC, and at the same time force circulating IRI to decrease, thus disturbing the well-known relationship between circulating glucose and IRI levels as has been exhibited in normal subjects. The high IRI levels, also during exercise in these patients, indicate a relative insulin resistance in the muscles, but less marked than the insulin resistance in the adipose tissue. The IRI response after glucose infusion did not change significantly with increasing work loads with one exception. Exercose did not alter significantly the human growth hormone (HGH) levels in either the diabetic or the non-diabetic patient indicating an abnormal regulation of the HGH secretion in congenital lipodystrophy.

Studies in congenital generalized lipodystrophy. VI. Suppressible and non-suppressible insulin-like activities of plasma.

1. Suppressible and non-suppressible insulin-like activities (ILA) of plasma from 3 patients with congenital generalized lipodystrophy have been studied, employing isolated fat cells from rat epididymal adipose tissue. 2. In all 3 patients the fasting ILA was markedly increased compared with the normal controls. In one of the patients (I.T.) total ILA rose to about 800 muU per ml during an iv glucose tolerance test. 3. The observed total ILA was in all cases (controls included) equal to or slightly higher than the previously determined immunoreactive plasma insulin (IRI). The exact determination of ILA was, however, hampered by a dilution effect, which was present even at high plasma dilutions. 4. In 2 of the patients addition of insulin antiserum inhibited plasma ILA by about 50%. In the third patient (I.T.), who exhibited the highest insulin level, at least 85% of the activity was suppressed by insulin antibodies. The levels of non-suppressible ILA were higher than in the controls in terms of muU per ml, but lower than in the controls when related to total ILA. 5. These findings strongly support our previous conclusion that the elevated plasma insulin seen in congenital generalized lipodystrophy is mainly due to true pancreatic insulin. 6. Since the effect of plasma insulin on isolated fat cells were freely expressed, i.e. suppressible ILA was equal to or slightly lower than IRI, the presence of a circulating insulin antagonist in this disease may be excluded.