Detection of chromosomal abnormalities, congenital abnormalities and transfusion syndrome in twins.

OBJECTIVE: To evaluate the outcome of screening for structural malformations in twins and the outcome of screening for twin-twin transfusion syndrome (TTTS) among monochorionic twins through a number of ultrasound scans from 12 weeks' gestation. METHODS: Enrolled into this prospective multicenter observational study were women with twin pregnancies diagnosed before 14 + 6 gestational weeks. The monochorionic pregnancies were scanned every second week until 23 weeks in order to rule out early TTTS. All pregnancies had an anomaly scan in week 19 and fetal echocardiography in week 21 that was performed by specialists in fetal echocardiography. Zygosity was determined by DNA analysis in all twin pairs with the same sex. RESULTS: Among the 495 pregnancies the prenatal detection rate for severe structural abnormalities including chromosomal aneuploidies was 83% by the combination of a first-trimester nuchal translucency scan and the anomaly scan in week 19. The incidence of severe structural abnormalities was 2.6% and two-thirds of these anomalies were cardiac. There was no significant difference between the incidence in monozygotic and dizygotic twins, nor between twins conceived naturally or those conceived by assisted reproduction. The incidence of TTTS was 23% from 12 weeks until delivery, and all those monochorionic twin pregnancies that miscarried had signs of TTTS. CONCLUSION: Twin pregnancies have an increased risk of congenital malformations and one out of four monochorionic pregnancies develops TTTS. Ultrasound screening to assess chorionicity and follow-up of monochorionic pregnancies to detect signs of TTTS, as well as malformation screening, are therefore essential in the antenatal care of twin pregnancies.

Strain rate and tissue tracking imaging in quantitation of left ventricular systolic function in endurance and strength athletes.

AIM: The aim of this study was to assess the impact of long-term physical training on left ventricular longitudinal contraction by strain rate analysis and tissue tracking imaging. METHODS AND RESULTS: The study population comprised 17 male elite endurance and 15 male elite strength athletes and 12 male control subjects of similar age. Tissue Doppler imaging was recorded in the apical views and used for analysis of the longitudinal systolic myocardial velocity, annular diastolic velocities, strain rate and tissue tracking. Left ventricular mass index was significantly increased in both endurance athletes (209+/-40 g/m(2)) and strength athletes (138+/-38 g/m(2)) compared with normal subjects (96+/-20 g/m(2), P<0.001). Tissue tracking score index and mean strain rate of the 16 segments were significantly increased in strength athletes (7.9+/-1.1 mm and -1.4+/-0.3 s(-1), respectively) compared with endurance athletes (7.5+/-0.9 mm and -1.0+/-0.4 s(-1), P<0.01 for both) and normal subjects (7.4+/-1.0 mm and -1.0+/-0.3 s(-1), P<0.01 for both). CONCLUSION: Despite significant left ventricular hypertrophy and extensive training in elite athletes, we found normal longitudinal left ventricular systolic function, and in strength athletes performing isometric exercise even increased function.

[Transcatheter occlusion of patent ductus arteriosus]. / Kateterbaseret lukning af persisterende ductus arteriosus.

Percutaneous closure of a patent arterial duct was performed in 58 patients. A Rashkind double umbrella was inserted in 20 patients. A supplementary double umbrella or coils were implanted in four who had residual leaks after 12 months. Three complications: embolization, haemolysis and late bacteriaemia were managed successfully without surgery. A detachable PDA coil was inserted in 38 patients. Three coils embolized and one could not be retrieved. At complete follow-up of 28 patients the duct was closed in all. Median procedure duration and fluoroscopy time was 60 min. and 12 min. respectively for double umbrella implantation, and 20 min. and 5 min. for coil insertion. Transcatheter occlusion of the patent duct is effective and carries little morbidity.

Short-term changes in the immune system of elite swimmers under competition conditions. Different immunomodulation induced by various types of sport.

This study was designed to investigate changes in the immune system of elite swimmers compared with well-conditioned age- and sex-matched controls in relation to a competition swim (field study). Furthermore, the aim was to reveal possible differences in immune system changes depending on the type of sport performed by comparing with an earlier study of similar design, from the same laboratory that tested elite runners in relation to a competition run. The swimmers were tested before, immediately after and 2 h and 24 h after a competition swim. Lymphocyte subsets (CD5, CD3, HLA-DR, CD4, CD8, CD19, CD3/CD16+56, CD57, CD18, CD16/CD122) all increased after the run, decreased to normal or subnormal levels after 2 h, and returned to normal after 24 h (absolute numbers). The findings were identical for the swimmers and the age- and sex-matched control group. No change in polymorphonuclear granulocyte migration was found. The lymphocyte proliferative responses decreased 2 h after the exercise. No changes were seen in plasma cytokine levels (interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) in relation to exercise, but significantly lower baseline values for IL-6 were observed in the swimmers. An increase in total natural killer cell activity immediately after exercise, followed after 2 h by a decrease, was seen in both swimmers and controls. Finally, no complement activation was detected. Compared with an earlier study of elite runners, differences were seen in granulocyte chemotactic response, TNF-alpha plasma activity and the lymphocyte proliferative response to mitogen. These differences might be explained by the degree of immune system activation following muscle damage during exercise, inducing an increase in cytokines, which are known to activate and modulate both lymphocytes and granulocyte function. Our findings demonstrate identical exercise-induced, immune system changes in elite swimmers and well conditioned controls, and furthermore, the findings suggest that different types of sport performed at maximum intensity induce different immune system changes.

Lymphocyte redistribution in connection with physical activity in the rat.

Previous studies have demonstrated numerous immunobiological changes in connection with exercise. A decrease in peripheral blood mononuclear white cells (PBMC) 2 h after intense exercise has been shown. This lymphocytopenia in humans after exercise is thought to be of great importance regarding the morbidity to viral infection. We constructed an animal experimental set-up, previously published, to investigate the exercise-induced lymphocyte redistribution. The experimental set-up allowed us to draw blood from catheters implanted in the right carotid artery in rats. PBMC were isolated and labelled with In111 and reinfused before the exercise run on a treadmill to exhaustion. The runner and control rats were killed and dissection performed 1 h after the exercise. Tissue samples were weighed and measured in a gamma counter. Furthermore, blind microscopic examinations of selected tissues were performed to study a hypothesized accumulation of blood mononuclear cells in relation to muscle fibre lesions. We found that the total number of PBMC in the running rats was decreased (P = 0.018) and granulocytes increased, 1 h after the exercise (P = 0.028). Similar findings in humans in connection with physical activity have been observed. The percentage of total injected counts per minute per gram tissue (% c.p.m. g-1) showed significantly lower values in the liver and kidney from runners than from controls (P = 0.032 and P = 0.028). These findings might be the result of a visceral hypoflow in connection with exercise. Furthermore, a tendency to decreased % c.p.m. g-1 in the lungs were seen in the exercised rats (P = 0.083) indicating a possible redistribution from the lungs during the run. Light microscopy demonstrated an accumulation of PBMC around muscle fibre lesions, but there was no significant difference between runners and controls. Furthermore, no significant difference in % c.p.m. g-1 was found between working muscle groups in runner and control rats. In conclusion, the demonstration of the redistribution of PBMC from the liver and kidney in the exercised rats and the absence of any significant accumulation of PBMC in working muscles or other organs, do not explain the lymphocytopenia demonstrated here.

Cytokine plasma levels and lymphocyte subsets in patients with newly diagnosed insulin-dependent (type 1) diabetes mellitus before and following initial insulin treatment.

Changes in the plasma concentrations of interleukin-1 beta (IL-1 beta), tumour necrosis factor alpha (TNF alpha), interleukin 2 (IL-2), and lymphocyte subsets were investigated in 19 persons with newly diagnosed (type 1) insulin-dependent diabetes mellitus (IDDM) from admission to hospital prior to insulin treatment and following 1 week and 1 month of treatment. Furthermore, the cytokines were measured 16-28 months after the presentation of IDDM. The mean TNF alpha values were all within the normal range, but demonstrated a slight increase in all the samples taken (Friedman 0.06). The mean plasma IL-1 beta value was initially at the upper normal limit, but gradually increased significantly from admission to hospital to 1 week, 1 month, and 16-28 months afterwards (Friedman 0.031). No IL-2 activity was detectable in the majority of the samples. No significant changes in total leukocyte and lymphocyte counts were found. The lymphocyte subsets (CD5+, CD8+, CD4+, CD16+, CD20+, HLA-DR+) did not show any significant changes from admission to after the start of insulin treatment. It is concluded that the gradual increase in IL-1 beta and TNF alpha plasma levels may reflect an ongoing autoimmune inflammatory reaction at the onset of IDDM.

Decreased interleukin-1 beta levels in plasma from rheumatoid arthritis patients after dietary supplementation with n-3 polyunsaturated fatty acids.

The effects of dietary supplementation with n-3 fatty acids on the level of cytokines and complement activation in plasma from patients with rheumatoid arthritis were examined. Thirty-two patients with active rheumatoid arthritis were included in a 12-week double-blind, randomized study of dietary supplementation with n-3 fatty acids (3.6 g per day) or placebo. The cytokines were measured in plasma before and after treatment with fish oil or placebo. In general, cytokine values at the upper limits of the calculated normal areas were found. The Interleukin-1 beta concentration in plasma was reduced significantly after 12 weeks of dietary supplementation with fish oil (p < 0.03). No significant difference was observed in the placebo group. The tumour necrosis factor alpha activity in plasma did not change significantly (p = 0.167). No significant changes were observed in the degree of complement activation. The clinical status of the patients was improved in the fish oil group, but not in the placebo group, judged by Ritchie's articular index (p < 0.02). We conclude that dietary supplementation with n-3 fatty acids results in significantly reduced plasma IL-1 beta levels in patients with rheumatoid arthritis. Even though the cytokine levels were low, the anti-inflammatory effect of n-3 fatty acids could in part be explained by their ability to decrease cytokine production.

Tumour necrosis factor alpha and interleukin-2 in plasma from rheumatoid arthritis patients in relation to disease activity.

Tumour necrosis factor alpha (TNF alpha) and interleukin-2 (IL-2) are potential immunological mediators of pathogenetic changes in rheumatoid arthritis. We measured the concentrations of TNF alpha and IL-2 in plasma from 2 groups of patients suffering from rheumatoid arthritis (RA). One group had high and one had low disease activity. In addition, in connection with steroid treatment in the high disease activity group, TNF alpha was significantly increased in plasma from RA patients with high disease activity compared with those of low disease activity (p = 0.0009). Furthermore, TNF alpha decreased significantly in relation to steroid medication, parallel to clinical improvement (p = 0.016). All IL-2 concentration measurements were within the estimated normal range. The increased TNF alpha plasma levels in patients with rheumatoid arthritis with high disease activity, might result from activated white mononuclear cells in the inflamed joints. This might, in part, support the theory that TNF alpha is a possible mediator of pathogenetic changes known to occur in rheumatoid arthritis.

Plasma atrial natriuretic peptide in elite runners.

Plasma atrial natriuretic peptide (ANP) was measured in relation to a 5-km race in 11 elite mid- and long-distance runners. Plasma ANP, measured in relation to the race, was compared with the relative changes in plasma volume and the physical fitness of the runners. Relative changes in plasma volume were estimated by changes in hemoglobin and hematocrit, and physical fitness was evaluated by a cycle ergometer test, running time, and resting heart-rate. In connection with the race, plasma ANP increased in all the runners. Median plasma ANP was 4.7 pmol.l-1 before the race and 12.9 pmol.l-1 immediately after the race. No correlation was found between the changes in ANP and the relative changes in plasma volume or the measurements of physical fitness. A volume expansion of the red blood cells was found immediately after the race. We conclude that well-conditioned subjects have a prominent rise in plasma ANP, in spite of a high maximal cardiac output.

Comparative study of assays detecting complement activation. Complement-split product C3d (rocket immuno-electrophoresis) and C3d neodeterminants (ELISA).

The aim of the study was to investigate the correlation between two types of assay measuring specific products of complement C3 activation and their clinical application. Complement C3d split product was estimated using double-decker rocket immunoelectrophoresis (DD-RIE) and measurements of C3d neodeterminants exposed after C3 activation was carried out with an enzyme-linked immunosorbent assay (ELISA). A total of 595 blood samples were measured in parallel in the DD-RIE and the ELISA test systems. The samples originated from blood donors (44), uraemic patients undergoing dialysis (135), serial samples from rheumatoid arthritis (RA) patients during steroid treatment (88) and 328 randomly collected patient samples. The mean values for DD-RIE and ELISA (+/- 1 SD) for the 595 samples were 48 (+/- 20) mU/l and 48 (+/- 28) mU/l respectively. The interassay coefficient of variation (CV) in the ELISA was 18%. The Spearman rho-correlation coefficient between the two assays was 0.63 for all 595 samples. The mean values using ELISA and DD-RIE were practically identical for the 328 successively incoming samples, the samples from the 135 dialysis patients and the 44 donors. In RA patients a higher mean value was found for the 88 samples using DD-RIE than ELISA. In the majority of patient samples there was a good correlation between the two assays. However, the ELISA appears to be more sensitive in detecting acute complement activation and to give lower levels in RA patients with chronic complement activation.

Effect of physical exercise on cytokines and lymphocyte subpopulations in human peripheral blood.

To examine the effect of intensive physical exercise on interleukin 2 (IL-2), tumor necrosis factor alpha (TNF alpha) and lymphocyte subsets, eleven elite and well-conditioned runners were tested in relation to a five-kilometer race. IL-2 was significantly decreased (p less than 0.01) immediately after the exercise and significantly increased after 24 hours (p less than 0.05), compared to the pre-exercise values taken at steady state. TNF alpha was significantly increased after 2 hours (p less than 0.05), and returned to habitual values after 24 hours. In the steady state at rest, elevation of HLA-DR+ cells was observed in all runners compared with control subjects (p less than 0.05), indicating a persistent activation of lymphoid cells. In connection with exercise a significant increase in NK cells (CD16+) was observed (p less than 0.01). The T-helper/T-suppressor (CD4+/CD8+) ratio was significantly reduced in connection with physical activity (p less than 0.01). In seven runners the ratio was reduced to a value of less than one. This decrease was observed immediately after the exercise, followed by increased ratios 2 hours later (p less than 0.01), due to oppositely directed quantitative changes of the CD4+ and CD8+ cell populations. After 24 hours the ratios returned to habitual levels. Furthermore, we confirmed an increase in the total number of granulocytes in connection with exercise (p less than 0.01), and observed a decrease in absolute numbers of lymphocytes two hours after exercise (p less than 0.01). We emphasize the importance of obtaining information about physical activity within the previous 24 hours before measuring white blood cell parameters.

Reduction of complement activation in rheumatoid arthritis by steroid treatment.

Patients with severe active active rheumatoid arthritis (RA) have higher than normal plasma concentrations of the complement C3 split-product C3d, indicating increased complement activation. Treatment with steroids reduced plasma C3d levels in these patients. Ten patients with classic or definite RA and high disease activity were studied during six days of treatment with steroids. The C3d plasma concentrations declined in a dose-related manner with an increase in daily prednisolone dosage. However the statistical significance of this relationship did not seem to be high enough to validate the use of serial C3d estimations to monitor changes in disease activity in RA patients during short-term steroid treatment.

[Polyglandular autoimmune syndrome type II]. / Polyglandulaert autoimmunt syndrom type II.

The polyglandular autoimmune syndrome type II, (Schmidts syndrome), is defined as coexistence of two of the diseases: Addison's disease, insulin dependent diabetes mellitus and autoimmune thyroid disease. The first endocrine deficiency state typically develops after the age of twenty and in most cases it is Addison's disease. The prevalence is approximately 5 per 100,000. The syndrome occurs within families in half of the cases. The immunological mechanism is not finally determined, but both the humoral and cellular systems seem to be involved and furthermore there is an association with the major histocompatibility complex. Whereas treatment of the components in polyglandular autoimmune syndrome is straightforward, diagnosis may be troublesome: Patients with Addison's disease may be biochemically hypothyroid the first months of corticosteroid treatment. Patients with myxedema show decreased urine excretion of 17-ketosteroids until thyroid substitution treatment is sufficient. A decreased insulin requirement or increased frequency of hypoglycaemic attacks may be the first sign of an adrenocortical hypofunction in diabetic patients. Patients with one autoimmune disease and their relatives are predisposed to (other) autoimmune diseases.

[Lipids in the plasma of voluntary blood donors. A 2-year retrospective study (1985-1987)]. / Fedt i plasma hos frivillige bloddonorer. En 2 års retrospektiv undersøgelse (1985-1987).

In a regional blood transfusion centre, we observed 45 episodes of hyperlipidemic plasma among the 45,000 units produced from 12,000 unpaid volunteer blood donors during a two year period. Analysis of fasting serum cholesterol and serum triglycerides showed that 26 of the 45 were raised in either one or both of the values. Dietary instructions were given, in most cases through their general practitioners, who were informed of the results. Control of serum lipids taken in average 9.5 weeks later by the general practitioner showed a remarkable decrease in triglyceride and a slight decrease in serum cholesterol. Among the 26 we found one case of non insulin dependent diabetes mellitus, three possible and three chronic alcohol abusers. Based on these findings, fasting serum cholesterol and serum triglyceride are now analysed in donors, who repeatedly show hyperlipemic plasma.

Passive tension of the ankle before and after stretching.

The passive tension resulting from dorsiflexion of the ankle was measured in relation to stretching in six handball players and six soccer players. Corresponding values of ankle angle and passive tension were measured by a strain gauge and a potentiometer connected to a pedal system. The passive tension versus ankle angle was measured before and 90 minutes after a single contract-relax stretching program of the plantar flexors. Stretching lowered the passive tension by up to 18%. Contract-relax stretching performed twice a day for 3 weeks lowered the passive tension in the plantar flexors by up to 36%. Before the last measurements, no stretching was performed for 20 hours or more. Stretching thus had both a short-term effect, matching the length of a training session, and a long-term effect, shown in a reduction of passive tension after 3 weeks. The relative decrease in passive tension after stretching exercises was constant from a neutral position of the ankle to maximal dorsiflexion. There was no correlation between 1) flexibility and the short-term effect of stretching, 2) flexibility and the long-term effect of stretching, or 3) the short-term and long-term effects of stretching. This indicates that passive tension was decreased in all subjects irrespective of their flexibility, and that subjects who had short-term effects after stretching did not necessarily demonstrate a long-term effect.

Quantitation of the stretch reflex. Technical procedures and clinical applications.

The stretch reflex should ideally be quantitated for better clinical use by standardizing the muscle stretch and measuring the resulting muscle contraction. Quantitation of muscle contraction can be done by force measurements or electromyographic recordings. The electromyographic response to stretch consists of one component (short latency response) for short stretches (less than 15 ms) and of 2 or 3 components (short and long latency responses) for longer stretches (greater than 40-50 ms). The magnitude of the phasic stretch reflex is reflected by the short latency response, whereas the magnitude of the tonic stretch reflex is reflected by both the short and the long latency responses. In clinical studies of upper motor neuron syndromes, the knee jerk and the muscle tone correlated with the magnitude of the short latency response. In patients with paralysis agitans an increased long latency response, which correlated to the rigidity, was found.

Pyomyositis: a report on two cases from a region with a temperate climate.

Two cases of pyomyositis in Caucasians, from a region with temperate coastal climate is reported. The identification of staphylococci as an aetiological factor in both temperate and tropical regions is mentioned, and so are other possible identical aetiological factors.

[Stretching in relation to sports and prevention of injuries]. / Straekøvelser (stretching) i relation til idraet og skadeforebyggelse.

Stretching is a regular item in training programmes and it is employed to increase flexibility, to prevent muscle tenderness, overuse injuries and strains. Stretching is carried out by stretching muscles and connective tissue to the extreme positions of joints. A review of stretching exercises based on the literature is presented in relation to prevention of injuries. The various techniques employed are reviewed.

Changes in PMN leukocyte migration activity and complement C3d levels in RA patients with high disease activity during steroid treatment.

We have investigated chemotaxis of polymorphonuclear granulocytes (PMN) from 7 well characterized RA patients with intense disease activity, before and after steroid treatment. Increased spontaneous and directed granulocyte migration was observed in 6 out of 7 patients before steroid treatment. In 5 patients these parameters were reduced after treatment. In contrast to this, decreased chemotaxis of polymorphonuclear granulocytes (PMN) from patients with Rheumatoid Arthritis (RA), have been reported earlier. This has been suggested as a partial explanation of the increased morbidity of these patients. Plasma levels of Complement C3d were initially increased in all patients and were slightly reduced following treatment. PMN migration in highly active RA cases is increased and responds markedly to steroid treatment, in contrast to the complement activation. The mainly unaffected, increased levels of plasma C3d might, in part, explain the early recurrence of symptoms often seen when steroid medication is withdrawn. Our results contrast with earlier findings and need to be confirmed in further studies.