Somatic effects of AAS abuse: A 30-years follow-up study of male former power sports athletes.

OBJECTIVES: The aim of the present study was to investigate the association between somatic health and former abuse of AAS in former elite male athletes 30 years after the end of their active sports career. DESIGN: Retrospective follow-up study. METHODS: N=996 former elite male athletes were sent a questionnaire concerning sociodemographic variables, previous and past sport activity and lifetime prevalence of seeking professional help for health problems. N=683 (68.6%) answered the questionnaire. The lifetime prevalence of AAS-abuse was 21% (n=143), while 79% (n=540) did not admit having ever used AAS. RESULTS: Former AAS-abuse was associated with tendon ruptures (p=0.01), depression (p=0.001), anxiety (p=0.01) and lower prevalence of prostate hypertrophy (p=0.01) and decreased libido (p=0.01). Former advanced AAS-abusers had higher anxiety (p=0.004) compared to the former less advanced AAS-abusers. Moreover, former advanced AAS-abusers, compared to AAS-naïves, reported more psychiatric problems (p=0.002), depression (p=0.003) and anxiety (p=0.00). CONCLUSIONS: A former AAS-abuse seems to be associated with some somatic and mental health problem, although a former less advanced AAS-abuse is related to lower incidence of prostate hypertrophy. The results raise the question whether some of these associations might be dose- and frequency dependent. These findings should however be seen as hypothesis generating and further studies are needed.

Increased mortality rate and suicide in Swedish former elite male athletes in power sports.

Physical training has been shown to reduce mortality in normal subjects, and athletes have a healthier lifestyle after their active career as compared with normal subjects. Since the 1950s, the use of anabolic androgenic steroids (AAS) has been frequent, especially in power sports. The aim of the present study was to investigate mortality, including causes of death, in former Swedish male elite athletes, active 1960-1979, in wrestling, powerlifting, Olympic lifting, and the throwing events in track and field when the suspicion of former AAS use was high. Results indicate that, during the age period of 20-50 years, there was an excess mortality of around 45%. However, when analyzing the total study period, the mortality was not increased. Mortality from suicide was increased 2-4 times among the former athletes during the period of 30-50 years of age compared with the general population of men. Mortality rate from malignancy was lower among the athletes. As the use of AAS was marked between 1960 and 1979 and was not doping-listed until 1975, it seems probable that the effect of AAS use might play a part in the observed increased mortality and suicide rate. The otherwise healthy lifestyle among the athletes might explain the low malignancy rates.

A retrospective 30-year follow-up study of former Swedish-elite male athletes in power sports with a past anabolic androgenic steroids use: a focus on mental health.

BACKGROUND: The knowledge concerning the long-term effect of former anabolic androgenic steroids (AAS)-use on mental health is sparse. AIM: This study aims to investigate whether previous AAS-use affects mental health, present sociodemographic data, sport activity and substance abuse in a retrospective 30-year follow-up study of former elite athletes. METHODS: Swedish male-elite power sport athletes (n=683) on the top 10 national ranking lists during any of the years 1960-1979 in wrestling, Olympic lifting, powerlifting and the throwing events in track and field answered a questionnaire. RESULTS: At least 20% of the former athletes admitted previous AAS-use. They had more often sought professional expertise for mental problems and had used illicit drugs compared to those not having used AAS. The AAS-users also differed in former sport activity pattern compared to non AAS-users. CONCLUSIONS: It is clear that a relationship exists between use of AAS and mental-health problems. Further studies need to be done in order to clarify this relationship.

Cardiomyopathy in children with mitochondrial disease; clinical course and cardiological findings.

AIMS: To determine the frequency of cardiomyopathy in children with mitochondrial disease and describe their clinical course, prognosis and cardiological manifestations. METHODS AND RESULTS: Of 301 children with CNS and neuromuscular disease referred to our institution in 1984 to 1999, 101 had mitochondrial disease. Seventeen patients had cardiomyopathy, diagnosed by echo-Doppler investigations, all of the hypertrophic, non-obstructive type. The onset of symptomatic mitochondrial disease ranged from birth to 10 years of age. Eight children had cytochrome-c oxidase deficiency, while the remaining nine had various defects. Cardiomyopathy was diagnosed from birth to 27 years. Left ventricular posterior wall and septal thickness were both increased: z-scores +4.6+/-2.6 and +4.3+/-1.6 (mean+/-SD), respectively. The left ventricular diastolic diameter z-score, +1.3+/-3.4, and fractional shortening, 24+/-13%, displayed marked variations. Nine patients developed heart failure. Eleven patients with cardiomyopathy died, including all eight with cytochrome-c oxidase deficiency, and one patient underwent a heart transplantation. Mortality in children with mitochondrial disease was higher in those with cardiomyopathy (71%) than those without (26%) (P<0.001). CONCLUSIONS: In children with mitochondrial disease, cardiomyopathy was common (17%) and was associated with increased mortality. The prognosis for children with cytochrome-c oxidase deficiency and cardiomyopathy appeared to be particularly unfavorable.

Health equity in transition from planned to market economy in China.

This paper examines the impact of economic transition and health sector reform on health equities in the urban and rural populations of China in the 1990s. Since 1980, China has experienced a rapid economic development and fundamental transformation of its society. Three secondary data sources were used as the basis for the analysis and discussion: mortality data from the National Death Notification System; infant mortality from the National Maternal and Child Health Surveillance System; and morbidity, health care utilization and financing data from the National Health Household Interview Surveys. The analysis revealed a very complex picture with: general mortality rates decreasing in both urban and rural populations, but the differences between urban and rural increasing; declining infant mortality rates with narrowing of the urban-rural gap; health care needs declining in both urban and rural populations, but more rapidly in the urban areas; health service payments increasing in both urban and rural areas, while, at the same time, health insurance coverage decreased. The analysis suggests that despite overall improvements in the population's health status, the economic and health system policy reforms are leading to increased inequities in health care. The lowest income quintiles in both urban and rural areas are receiving less health care compared with their needs in 1998 than in 1993, and the urban-rural divide, in particular with regard to receiving inpatient health care, is widening appreciably. The reform of the health insurance system, combined with the market setting of prices for care, have had profound implications for all population groups, in particular the lower income segments and the rural populations. During the period 1993-98 the proportion of the urban population that had to cover the increasing cost of medical care themselves doubled.

Bubble contrast echocardiography in detecting pulmonary arteriovenous malformations after modified Fontan operations.

The development of pulmonary arteriovenous malformations is a well-known complication after Fontan operations, and may result in significant morbidity due to increasing arterial desaturation. We compared the use of bubble contrast echocardiography and pulmonary angiography in detecting such malformations. We also examined which anatomical and haemodynamic variables were associated with their development. Our study includes 20 patients who had undergone modified Fontan procedures, 10 with atriopulmonary and 10 with total cavopulmonary connections, in Gothenburg between 1980 and 1991. All patients underwent cardiac catheterisation and pulmonary angiography. Bubble contrast echocardiography was performed at the same time, with injection of agitated polygelin colloid solution (Haemaccel, Hoechst) into the right and left pulmonary arteries, respectively. Transoesophageal echocardiography was used to detect the appearance of bubble contrast in the pulmonary venous atrium. The aim was also to evaluate the role of hepatic venous blood. Of the 20 patients, 9 (45%) had a positive contrast echocardiography study, compared with only 2 (10%) detected by pulmonary angiography. Patients with positive contrast echocardiography had a significantly lower arterial oxygen saturation than those with negative studies, both at rest (88% vs 95%, p < 0.01) and during exercise testing (78% vs 89%, p = 0.01). Bubble contrast echocardiography is much more sensitive in detecting pulmonary arteriovenous malformations than pulmonary angiography. By injecting echo contrast into the right and left pulmonary arteries, the method can be made highly selective. Pulmonary arteriovenous malformations develop much more frequently in patients with the Fontan circulation than previously reported.

Skeletal muscle characteristics, muscle strength and thigh muscle area in patients before and after cardiac transplantation.

BACKGROUND: Patients with chronic heart failure demonstrate several skeletal muscle abnormalities. The underlying mechanisms are unclear. After cardiac transplantation, cardiac function is restored, but exercise capacity is still impaired. AIM: To evaluate the influence of cardiac transplantation on skeletal muscle fibre composition, fibre area and capillarization as well as muscle enzymes, lactate, thigh muscle area and strength. METHODS: Ten patients were longitudinally investigated before, 1-3 and 6-9 months after transplantation. Ten healthy individuals served as controls. A biopsy from the lateral vastus muscle was obtained and the thigh muscle area was measured with computed tomography. Muscle strength in the knee extensors and exercise capacity were also evaluated. RESULTS: Muscle lactate was elevated in patients vs. controls (3.6+/-3.0 vs. 1.5+/-0.7 mmol/kg wet wt., P=0.037), and decreased to normal (1.4+/-0.3 mmol/kg wet wt., P=0.038) after transplantation. Citrate synthase activity was decreased in patients (5.6+/-1.5 micromol/g wet wt./min) vs. controls (8.1+/-1.6 micromol/g wet wt./min, P=0.0018), and did not change post transplantation. Patients had decreased number of capillaries in contact with each fibre vs. controls (2.6+/-0.5 vs. 3.5+/-1.0, P=0.039) which persisted post transplantation. Exercise capacity increased after transplantation (74+/-22 vs. 118+/-26 W, P=0.0002), whereas muscle strength did not improve significantly. CONCLUSION: The persisting intrinsic abnormalities in skeletal muscle after cardiac transplantation may contribute to the impaired exercise capacity observed in cardiac transplant recipients.

Thoracic organ transplantation in children. The Sahlgrenska University Hospital experience.

On the basis of the experience acquired from more than 350 thoracic organ transplantations in adults, the outcome of thoracic organ transplantations in the paediatric age group (0-17 years of age) performed consecutively from 1989 to 1998 at our centre was reviewed. Heart transplantation was performed in 27 patients, heart-lung in 6 and bilateral lung transplantation in 2 patients. The preoperative diagnosis included dilated cardiomyopathy in 17 patients, congenital heart defects in 8, hypertrophic cardiomyopathy in 2, cystic fibrosis in 1 and secondary and primary pulmonary hypertension in 5 and 2 patients, respectively. The median age at transplantation and the follow-up period were 12.7, range 0.3-18.2, and 4, range 0.1-9.2 years, respectively. No early deaths occurred after heart transplantation, but one patient died of coronary artery disease 4.8 years after transplantation. One early death occurred one week after heart-lung transplantation as a result of bleeding complications, and another patient died of obliterative bronchiolitis and pulmonary infection 2.5 years after surgery. The remaining patients are alive and have been functionally rehabilitated. In conclusion, despite a relatively small centre volume, paediatric thoracic organ transplantations can be performed with good short- and medium-term survival and good functional status can be achieved by deriving knowledge and experience from transplantations in adults and by collaboration between the various professionals involved in the caring process.

[CATCH22 or 22q11 deletion syndrome. An underdiagnosed and misunderstood disease category with a variable clinical picture]. / CATCH 22-syndrom/22q11-deletionssyndrom. Underdiagnostiserad och missförstådd sjukdomsgrupp med skiftande klinisk bild.

Patients with CATCH 22 or 22q11 deletion syndrome constitute a fast growing category in Sweden as it is still underdiagnosed. In a series of 54 patients the predominant features were found to be speech and language difficulties, cardiac malformations, susceptibility to infection, learning and behavioural problems, hypoparathyroidism, minor motor deficits, and characteristic facies. The severity of these problems varied individually, but as the patients had numerous symptoms and disabilities the overall degree of handicap was considerable. Thus, regular evaluation of the patient's condition and overall need of care is important.

Plasma metabolites after a lipid load in infants with congenital heart disease.

Growth retardation is common in infants with congenital heart defects. The aim of this study was to investigate whether growth retardation or type of heart defect in infants with congenital heart defects is related to disturbances in lipid metabolism. Sixteen infants with ventricular septal defects and six infants with transposition of the great arteries were given an intravenous load of lipid emulsion (Intralipid 20 mg/ml) corresponding to 0.5 g fat/kg body weight for 5 min after fasting for 8 h. Blood samples were drawn immediately before the infusion and 3, 20, 60, 120 and 240 min after the infusion was completed. Plasma concentrations of triglycerides (TG), free fatty acids (FFA), ketones, lactate, pyruvate, alanine, glycerol and glucose were determined. The fatty acid patterns in the TG and FFA fractions were measured using gas chromatography. Severe growth retardation in infants with defects of these kinds was correlated to higher fasting and maximum levels of linoleic acid in plasma FFA. The maximum levels of linoleic acid in the TG fraction were positively correlated to weight SD score, and maximum glycerol levels were higher in the most growth-retarded infants, indicating faster intravascular lipolysis. Linoleic acid in the TG fraction was still elevated at 120 and 240 min after the lipid load. Some differences between the cyanotic and VSD groups could be noted. These indicate decreased metabolic capacity to utilize released FFA in the cyanotic group. Infants with cyanotic heart defects also had higher lactate and alanine levels compared to infants with VSD. Our results support the hypothesis that lipid metabolism is disturbed in infants with congenital heart defects.

The heart and pericardial effusions in CDGS-I (carbohydrate-deficient glycoprotein syndrome type I).

Pericardial effusions were found in 6 of 10 children with carbohydrate-deficient glycoprotein syndrome type I (CDGS-I). In three cases pericardectomy was necessary. Blood concentrations of several glycoproteins and albumin were low. Similar abnormal isoforms of four glycoproteins were found in blood (B) and pericardial fluid (PF). There was a significant negative correlation between the mean concentration ratio PF/B and the molecular mass (MW) of 11 proteins. For proteins with MW < 100 kDa there were significant correlations in the controls, but not in the patients, between the PF/B ratio and both the MW and the sialic acid contents in the (glyco-)proteins. The pericardium exhibited focal mixed inflammatory changes with mesothelial proliferation, with widened endoplasmic reticulum and flocculent and/or lamellated material. Damage to a pericardial protein barrier is suggested to be involved in pericardial effusion in CDGS-I.

Cardiac output and pulmonary gas exchange at maximal exercise after atrial redirection for complete transposition.

AIMS: To assess the determinants of exercise capacity and exercise oxygenation after atrial redirection for complete transposition. METHODS AND RESULTS: At graded bicycle ergometry, including respiratory and arterial blood gas analyses, intra-arterial blood pressure recording, and cardiac output determination (dye-dilution technique), we tested 17 post-Mustard/Senning patients, 8.9-22.0 years old (mean 14.5, SD 4.0). Reference data were obtained by similar methods. At maximal exercise, oxygen uptake (29.6 ml x kg(-1) x min(-1)) and heart rate (167 beats x min(-1)) were low (P<0.001). Right-to-left shunts were detected in five patients. Arterial oxygen partial pressure and saturation fell in all subjects (P<0.0001). In 15/16 (94%) the alveolar-arterial oxygen partial pressure difference was > +2 SD. In 13/15 (87%) stroke volumes fell during exercise. Cardiac output per oxygen uptake was low (P<0.0001), which implies a high arteriovenous oxygen difference and a low mixed venous oxygen content at peak exercise. CONCLUSION: The low exercise capacity was caused by a combination of low maximally attained heart rate and falling stroke volumes. The impaired arterial oxygenation may be caused by a combination of pulmonary ventilation/perfusion mismatch, a low mixed venous content and atrial shunting in some patients.

Glucose metabolism and insulin secretion in children with cyanotic congenital heart disease.

The aim of the study was to reveal differences in carbohydrate metabolism in children with cyanotic congenital heart diseases (CHD). Thirteen children with diseases of these kinds were investigated with regard to glucose tolerance and insulin secretion and comparisons were made with healthy controls of the same age. Investigations included an intravenous glucose tolerance test, insulin response to the glucose load in plasma and insulin secretion rate. The results reveal lower fasting glucose levels and signs of a higher insulin secretion rate in the relatively few patients in the CHD group where C-peptide measurements were performed, but no differences in glucose tolerance. The reasons for the differences are unclear, but the chronic increases in circulating catecholamines in combination with the impaired nutritional status of these children with CHD are probably the most important factors. We conclude that these divergences in carbohydrate metabolism should be emphasized in the care of children with CHD.

Endomyocardial biopsy in heart-transplanted children: comparison of sheaths to guide biopsy forceps.

The risk of perforation during 65 endomyocardial biopsies (380 specimens) was investigated using two different sheaths to guide the biopsy forceps in five heart-transplanted children aged 1.6-12.9 years. One of the sheaths guided the biopsy forceps simply into the right ventricle (prefabricated 110 degrees curved tip); the other (specially curved sheath) had two curves, the distal one of which guided the forceps posteriorly toward the interventricular septum. The position of the sheath was evaluated by biplane fluoroscopy and, in children

Skeletal muscle alterations in patients with chronic heart failure.

AIMS: To investigate skeletal muscle in patients with chronic heart failure and controls, and relate skeletal muscle variables to functional class, exercise capacity, central haemodynamics, muscle strength and medical treatment. METHODS: Biopsy from the lateral vastus muscle was obtained in 43 patients and 20 controls. Right sided heart catheterization was performed in 19 patients and maximal exercise testing in 26 patients. In nine patients muscle strength was measured. Patients had higher lactate levels, higher lactate dehydrogenase activity, and lower oxidative enzymes activity than controls. In patients, the percentage of type I fibres and capillarization were decreased while the percentage of type II B fibres were increased. Lactate dehydrogenase activity correlated with exercise capacity, muscle strength and right atrial pressure. Digoxin-treated patients had significantly lower oxidative enzyme activity than patients without digoxin treatment. CONCLUSION: Patients with chronic heart failure have several skeletal muscle abnormalities. Central haemodynamics and medical treatment may, in addition to inactivity, be important in skeletal muscle changes.

Pivalic acid-induced carnitine deficiency and physical exercise in humans.

To study the effect of carnitine depletion on physical working capacity, healthy subjects were administered pivaloyl-conjugated antibiotics for 54 days. The mean carnitine concentration in serum decreased from 35.0 to 3.5 mmicromol/L, and in muscle from 10 to 4.3 micromol/g noncollagen protein (NCP). Exercise tests were performed before and after 54 days' administration of the drug. At submaximal exercise, there was a slight increase in the concentration of 3-hydroxybutyrate in serum, presumably caused by decreased fatty acid oxidation in the liver. There was also a decreased consumption of muscle glycogen, indicating decreased glycolysis in the skeletal muscle. The muscle presumably had enough energy available, since there was no significant decrease in the concentration of adenosine triphosphate (ATP) and creatine phosphate during exercise. The work at maximal oxygen uptake (VO2max) and the maximal heart rate were reduced. Since VO2max is considered dependent on heart function, carnitine depletion seemed to affect cardiac function.

Skeletal muscle changes in patients with chronic heart failure before and after treatment with enalapril.

To evaluate if enalapril treatment can influence skeletal muscle metabolism and histology we investigated 26 patients with congestive heart failure and 20 normal subjects. The patients were treated with enalapril for 3 months in addition to diuretics and digitalis. Biopsies from the lateral vastus muscle were taken before and after treatment. Citrate synthetase, 3-hydroxyacyl-CoA dehydrogenase and phosphorylase activities were significantly decreased in the patients compared with controls. The number of capillaries per fibre and the number of capillaries surrounding each fibre were significantly decreased among patients. After 3 months of enalapril treatment functional class improved significantly. The lactate dehydrogenase activity increased whereas the oxidative enzymes did not change significantly. The type I, II and II A fibre areas increased significantly after enalapril treatment. We conclude that patients with chronic heart failure have decreased activity of oxidative enzymes and of phosphorylase in skeletal muscle. They also have decreased capillarization in skeletal muscle. These changes were not influenced by enalapril treatment. The increase in muscle fibre area seen after enalapril treatment could be due to increased physical activity. The cause of increased muscle lactate dehydrogenase activity after enalapril treatment needs further investigation.

Skeletal muscle energy substrates, metabolic products and enzyme activity in infants with symptomatic ventricular septal defect.

Muscle biopsy studies were performed on 26 infants with symptomatic ventricular septal defect (VSD) (mean age 4.7 months) and 10 healthy infants (mean age 7.8 months). Analyses were made of muscle energy substrates, metabolic products, muscle enzyme activity, fibre types and fibre sizes. Relatively few differences were noted between the groups. The most important difference was a reduced ATP level in the VSD group. Glucose 6-phosphate concentrations were also lower in the VSD group. These differences could indicate a low metabolic activity in skeletal muscle in infants with heart failure. Most muscle enzyme activity was comparable with the exception of lactate dehydrogenase (LD), which was lower in the VSD group. Within the VSD group, no differences were revealed in muscle substrate concentrations for muscle enzyme activity in terms of the degree of heart failure. We conclude that low energy levels are probably explained by undernourishment and/or reduced blood flow to skeletal muscle and that the lack of other discrepancies in muscle metabolism indicates a desirable relatively normal motor activity in these infants with symptomatic VSD.

Skeletal muscle metabolism during exercise in patients with chronic heart failure.

OBJECTIVE: To investigate the metabolic response of skeletal muscle to exercise in patients with chronic heart failure and determine its relation to central haemodynamic variables. SETTING: University hospital in Sweden. PARTICIPANTS: 16 patients in New York Heart Association class II-III and 10 healthy controls. MAIN OUTCOME MEASURES: Skeletal muscle biopsies were obtained from the quadriceps muscle at rest and at submaximal and maximal exercise. Right sided heart catheterisation was performed in eight patients. RESULTS: The patients had lower maximal oxygen consumption than the control group (13.2 (2.9) v 26.8 (4.4) ml/kg/min, P < 0.001). They had reduced activities of citrate synthetase (P < 0.05) and 3-hydroxyacyl-CoA dehydrogenase (P < 0.05) compared with the controls. At maximal exercise adenosine triphosphate (P < 0.05), creatine phosphate (P < 0.01), and glycogen (P < 0.01) were higher whereas glucose (P < 0.001) and lactate (P < 0.06) were lower in the patients than in the controls. Citrate synthetase correlated inversely with skeletal muscle lactate at submaximal exercise (r = -0.90, P < 0.003). No correlations between haemodynamic variables and skeletal muscle glycogen, glycolytic intermediates, and adenosine nucleotides during exercise were found. CONCLUSION: Neither skeletal muscle energy compounds nor lactate accumulation were limiting factors for exercise capacity in patients with chronic heart failure. The decreased activity of oxidative enzymes may have contributed to the earlier onset of anaerobic metabolism, but haemodynamic variables seemed to be of lesser importance for skeletal muscle metabolism during exercise.

Status of survivors after atrial redirection for transposition of the great arteries: a complete long-term follow-up.

All 32 survivors with transposition of the great arteries, born in 1964-83 and operated on at our institution using atrial redirection, were evaluated by cardiac catheterization, echocardiography and Holter monitoring. There were 17 Mustard patients, age 17.1 years (+/-3.5, 12.0-22.0) and 15 Senning patients, age 9.4 years (+/-1.6, 7.2-12.1). All but one had simple transposition. Six had caval obstruction, one had pulmonary venous obstruction, three had large atrial shunts, four had considerable pulmonary hypertension, seven had mild ventricular outflow tract obstruction, four had significant tricuspid regurgitation, 11 had systemic ventricle dysfunction (one severe), 14 had sinus node dysfunction (three symptomatic) and two had atrioventricular block (one with pacemaker). Eight Mustard patients (47%) and one Senning patient (7%) had symptomatic cardiac sequelae, and only one patient (Senning) was free from sequelae, illustrating that these patient groups will need continuing medical attention.