Retrieval of the conductivity spectrum of tissuesin vitrowith novel multimodal tomography.

OBJECTIVE: Imaging of tissue engineered three-dimensional (3D) specimens is challenging due to their thickness. We propose a novel multimodal imaging technique to obtain multi-physical 3D images and the electrical conductivity spectrum of tissue engineered specimensin vitro. APPROACH: We combine simultaneous recording of rotational multifrequency electrical impedance tomography (R-mfEIT) with optical projection tomography (OPT). Structural details of the specimen provided by OPT are used here as geometrical priors for R-mfEIT. MAIN RESULTS: This data fusion enables accurate retrieval of the conductivity spectrum of the specimen. We demonstrate experimentally the feasibility of the proposed technique using a potato phantom, adipose and liver tissues, and stem cells in biomaterial spheroids. The results indicate that the proposed technique can distinguish between viable and dead tissues and detect the presence of stem cells. SIGNIFICANCE: This technique is expected to become a valuable tool for monitoring tissue engineered specimens' growth and viabilityin vitro.

Effects of a 6-month exercise program on patients with multiple sclerosis: a randomized study.

OBJECTIVE: To improve walking and other aspects of physical function with a progressive 6-month exercise program in patients with multiple sclerosis (MS). METHODS: MS patients with mild to moderate disability (Expanded Disability Status Scale scores 1.0 to 5.5) were randomly assigned to an exercise or control group. The intervention consisted of strength and aerobic training initiated during 3-week inpatient rehabilitation and continued for 23 weeks at home. The groups were evaluated at baseline and at 6 months. The primary outcome was walking speed, measured by 7.62 m and 500 m walk tests. Secondary outcomes included lower extremity strength, upper extremity endurance and dexterity, peak oxygen uptake, and static balance. An intention-to-treat analysis was used. RESULTS: Ninety-one (96%) of the 95 patients entering the study completed it. Change between groups was significant in the 7.62 m (p = 0.04) and 500 m walk tests (p = 0.01). In the 7.62 m walk test, 22% of the exercising patients showed clinically meaningful improvements. The exercise group also showed increased upper extremity endurance as compared to controls. No other noteworthy exercise-induced changes were observed. Exercise adherence varied considerably among the exercisers. CONCLUSIONS: Walking speed improved in this randomized study. The results confirm that exercise is safe for multiple sclerosis patients and should be recommended for those with mild to moderate disability.

Prevalence, predisposing factors, and prognostic importance of postural hypotension.

OBJECTIVES: To determine the prevalence and predisposing factors of postural hypotension and to evaluate the effect of postural hypotension on 10-year vascular mortality in an elderly population. METHODS: A random sample of 480 subjects aged 65 years or older was obtained in 1982. The participation rate of the subjects in the study was 72%, for a total of 347 subjects. Orthostatic testing and continuous ambulatory electrocardiographic recording, as well as comprehensive clinical evaluation, including medical history, physical examination, standard electrocardiography, chest radiography, blood pressure measurement, routine biochemical analysis, and determination of body mass index, were performed. In 1992, the 10-year mortality of subjects and causes of death were recorded from the mortality statistics. Of the participants, 184 (53%) had died and 163 were still alive. To determine the effect of postural hypotension on the 10-year mortality, the subjects who were alive and those who had died of vascular or nonvascular causes were compared. All of the examinations had been completed in 156 subjects who were still alive, in 109 subjects who had since died of vascular causes, and in 64 subjects who had died of nonvascular causes. RESULTS: An abnormal postural systolic blood pressure drop (-20 mm Hg or less) after standing for 3 minutes was demonstrated in 28.0% of subjects. There were no sex or age differences between the subjects with and without postural hypotension. No predisposing factors for postural hypotension other than elevated blood pressure were found. Chronic cardiovascular diseases, disability, body mass index, medication, and abnormal findings in ambulatory electrocardiographic monitoring were not associated with postural hypotension. In the univariate analysis, the extent of systolic or mean blood pressure change predicted neither vascular nor nonvascular death during the 10-year follow-up. On the other hand, diastolic blood pressure drop, in particular after standing for 1 minute, was associated with increased vascular mortality (odds ratio, 2.7; 95% confidence interval, 1.3 to 5.6). In the multivariate analysis, however, this association disappeared. CONCLUSIONS: Postural hypotension was common in an unselected elderly population. No predisposing factors for postural hypotension other than elevated blood pressure were found. The 10-year follow-up showed that postural diastolic, but not systolic, blood pressure drop predicted excess vascular mortality. However, this association disappeared in the multivariate analysis, thus being related to background factors such as cardiovascular diseases.

Predictive value of continuous ambulatory electrocardiographic monitoring in elderly people.

OBJECTIVE: To determine the predictive value of findings on continuous ambulatory electrocardiographic monitoring in elderly subjects. DESIGN: Retrospective cohort study. Ten year follow up of randomly selected elderly subjects who participated in ambulatory electrocardiography study in 1982. Mortality data derived from official registers. SETTING: Turku, Finland. SUBJECTS: 480 people aged 65 or older in 1982 who were living in the community, of whom 72% agreed to participate. MAIN OUTCOME MEASURES: Mortality from cardiac and non-cardiac causes during 10 year follow up. RESULTS: In the univariate analysis adjusted for age, risk of death from cardiac causes was increased among those with ventricular ectopy of more than 100 beats during the day (odds ratio 2.6; 99% confidence interval 1.4 to 6.1) or at night (3.3; 1.1 to 9.8) and in those with multifocal ventricular ectopic beats during the day (2.3; 1.0 to 5.0) or night (3.0; 1.3 to 7.1) compared with those with no ventricular ectopy. Sinoatrial pauses exceeding 1.5 seconds during the day (4.5; 1.8 to 11.1) were also associated with excess mortality from cardiac causes. None of the findings on ambulatory electrocardiography predicted death from non-cardiac causes. A further study of explanatory variables in the stepwise logistic regression analysis showed that sinoatrial pauses exceeding 1.5 seconds (4.0; 95% confidence interval 1.8 to 8.9) and night time multifocal ventricular ectopy (2.7; 1.2 to 5.9) predicted excess mortality from cardiac causes independently of age or clinically evident heart disease. CONCLUSION: Daytime sinoatrial pauses exceeding 1.5 seconds and night time multifocal ventricular ectopy in the ambulatory electrocardiogram predict increased mortality from cardiac causes independently of clinically evident cardiac diseases in unselected elderly subjects.

Does thermal stress decrease uterine blood flow in hypertensive pregnancies?

The aim of the study was to determine the acute effects of thermal stress on maternal and fetal circulatory responses in normal and hypertensive patients. Therefore we studied 14 healthy pregnant women and 12 women with compromised pregnancies during short-term heat stress using color Doppler ultrasound in addition to conventional follow-up methods. The uterine vascular resistance increased significantly during the exposure in the high-risk pregnancy group without change in the control group. The results of the present study give strong support to our earlier studies that short-term heat stress seems to be safe in uncomplicated pregnancies but may be detrimental in high-risk pregnancies.

Attenuated Valsalva heart rate response in subjects with smoking history: possible role of autonomic dysfunction.

The effects of smoking habits on autonomic cardiovascular heart rate reflexes were studied in 143 healthy subjects by using the Valsalva manoeuvre and deep breathing tests. Smoking seemed to cause attenuation of the Valsalva heart rate response. This attenuation was present also after adjustment for possible confounding factors including alcohol consumption. Our findings show that in subjects with smoking history there may occur dysfunction in some part of the autonomic reflex arch mediating the Valsalva heart rate response.

Effects of short-term thermal stress on plasma catecholamine concentrations and plasma renin activity in pregnant and nonpregnant women.

OBJECTIVE: The purpose of this study was to find out whether the effects of thermal stress on plasma catecholamines and plasma renin activity are altered by pregnancy. STUDY DESIGN: Nonpregnant (n = 15) and pregnant (13 to 14 weeks, n = 23; 36 to 37 weeks, n = 23) healthy women were examined. Samples were taken before the exposure, in the heat chamber (70 degrees C), and during the recovery. The BMDP statistical software was used. RESULTS: The concentration of epinephrine in plasma increased significantly only in the nonpregnant group. The epinephrine concentrations in the pregnancy groups increased most in the subjects who felt discomfort during or after the exposure. Plasma norepinephrine concentrations increased without significant differences between the groups. Plasma renin activity increased in each group, but the increases were significantly lower in the pregnancy groups as compared with the nonpregnant group. CONCLUSIONS: Pregnancy does not alter the thermally induced increase in norepinephrine release. The adrenaline response is mostly dependent on the mental discomfort. The plasma renin activity response to thermal stress is blunted during pregnancy.

Observations based on 10-years' experience of non-invasive cardiovascular reflex testing of autonomic function from a rehabilitation research centre.

Observations on 1,282 measurements of non-invasive cardiovascular reflex testing of autonomic function in 1,023 control subjects and patients with different disorders are presented. It is suggested that the Valsalva manoeuvre be performed three times rather than once and the highest Valsalva ratio should be used instead of the mean or first of the three ratios. The deep breathing test gives equally reliable information when three breathing cycles are used instead of six. Symptoms were detected in up to 15% of the subjects depending on the test, although the majority of these were minor and transient. The frequency of ventricular/supraventricular extrasystoles increased especially during the Valsalva manoeuvre (+67%/+40%) and post-strain (+49%/+25%) phases and early recovery phase of the orthostatic test (+69%/+156%) and to a lesser degree during deep breathing (+18%/+50%) and handgrip (+36%/-11%) phases compared with the resting phase. However, severe cardiac rhythm disturbances were very rare. 1-2% of the younger (less than 50 years) and 10% of the older subjects were not able to perform the tests adequately. The R-R intervals on which the results are based should be selected carefully, and use of a continuous non-invasive method of blood pressure monitoring should provide further useful information.

Doppler flow measurement of uterine and umbilical arteries in heat stress during late pregnancy.

The effect of a moderate heat stress (20 minutes 70 degrees C) on uterine and umbilical artery blood flow was studied by continuous-wave Doppler ultrasound in 17 women 36 to 37 weeks pregnant. Maternal heart rate increased on average by 26 beats/minute. Maternal arterial blood pressure did not change during the heat stress but declined slightly immediately after. The fetal heart rate increased on average by 14 beats/minute by the end of the exposure. The variability of fetal heart rate was normal in each subject during the whole experiment and only one subject had a nonreactive tracing during the heat stress, which returned to normal during the recovery period. The ratio of the systolic to diastolic velocity in the uterine artery did not change significantly. Only two subjects had a marked increase in uterine artery vascular resistance; they had concomitantly a significant fall in the arterial blood pressure. Still, there was no change in umbilical artery blood flow. The fetuses of healthy pregnant women are not compromised during or after moderate thermal stress.

Children in sauna: hormonal adjustments to intensive short thermal stress.

Hormonal response to Finnish sauna bath was investigated in 20 prepubertal children (age 5-10 years). Blood leukocyte count, plasma potassium, serum aldosterone, growth hormone and prolactin concentrations increased; plasma volume, plasma sodium, catecholamines, serum antidiuretic hormone, atrial natriuretic peptide (ANP), cortisol, and thyrotropin concentrations remained unchanged during sauna bath. One hour after sauna, serum thyrotropin, atrial natriuretic peptide and blood glucose concentrations decreased, whereas the rest of the hormones remained unchanged. Our results implicate that maintenance of homeothermia resulted in moderate hormonal changes in children during Finnish sauna bath which indicate similar adequate hormonal thermoregulatory adjustment as previously documented in adults.

Short- and long-term reproducibility of cardiovascular tests of autonomic function in normal subjects.

Ten healthy normal subjects participated in a follow-up study in which the reproducibility of noninvasive cardiovascular autonomic function testing was studied. The tests used were the Valsalva manoeuvre, deep and quiet breathing, standing upright and isometric handgrip exercise. These tests were performed six times within a 2-year period. The reproducibility of these autonomic function tests within a day was evaluated in a separate study involving nine healthy subjects. In this study the tests were performed three times between 08.00 and 15.00. The results indicate that indices based on R-R interval ratios during testing were highly reproducible; that the indices remain reproducible over a 2-year follow up period and that reproducibility within a day was similar to that within longer time periods. The reproducibility of pressor responses to isometric exercise was poor. It is concluded that indices based on R-R ratios are suitable for use in follow up studies of autonomic function.

Is the heat dissipating ability enhanced during pregnancy?

The effect of short-term heat stress on rectal and skin temperatures was measured in three groups: group I consisted of 15 non-pregnant, healthy women; group II of 23 women 13-14 weeks pregnant; and group III of 23 women 36-37 weeks pregnant. Rectal and skin temperatures were recorded every 5 min during a resting period (20 min, 21-23 degrees C) followed by thermal stress (20 min, 70 degrees C) and a recovery period (45 min, 21-23 degrees C). The rectal temperature decreased significantly in each group at the beginning of the stress. The total increase from pre-stress levels to the end of the heat stress was from 37.1 to 37.5 degrees C in group I, 37.2 to 37.6 degrees C in group II and 37.0 to 37.3 degrees C in group III (P less than 0.05). During the recovery period, the rectal temperature was significantly lower in the late-pregnancy group as compared to non-pregnant subjects. The skin temperature increased from the resting period to the end of the stress from 34.0 to 39.1 degrees C in group I, from 33.7 to 39.3 degrees C in group II and from 33.5 to 39.0 degrees C in group III (P less than 0.001). During the recovery period, the skin temperature declined significantly faster, and to lower levels in the late-pregnancy group as compared to both other groups. We conclude that the heat-dissipating ability is slightly enhanced during late pregnancy.

Haemodynamic response to moderate thermal stress in pregnancy.

The effect of a moderate heat stress on cardiovascular responses was studied: group I consisted of 15 healthy non-pregnant women, group II of 23 women 13-14 weeks pregnant and group III of 23 women 36-37 weeks pregnant. Heart rate, stroke volume, cardiac output, arterial blood pressure and peripheral vascular resistance were recorded every 5-10 minutes during a resting period (20 min, 21-23 degrees C) followed by heat stress (20 min, 70 degrees C, 15% relative humidity) and a recovery period (45 min, 21--23 degrees C). The rectal temperature increased 0.3-0.4 degrees C in each group during thermal stress. The heart rate before stress was highest in the advanced pregnancy group but increased almost identically in each group by 36--37 beats per minute during stress and approached starting values during recovery. There were no major changes in stroke volume during the experiment in any group nor were there any differences between the three groups. Arterial blood pressure did not change significantly in any group during the experiment; the differences between the groups were minimal. Peripheral vascular resistance began to fall at the start of the thermal stress and returned to prestress levels at the end of the recovery period. There were no differences between the groups in proportional changes of peripheral resistance. We conclude that pregnancy does not alter the cardiovascular responses to moderate thermal stress.

Serum lipids and lipoproteins in children, adolescents and young adults in 1980-1986.

A multicentre study on atherosclerosis precursors in young Finns aged three to 18 years was started in 1980 (3596 subjects) serum lipid concentrations (cholesterol, HDL (high density lipoprotein) cholesterol and triglycerides) were determined (n = 3554) and the apolipoproteins A-I and B measured (n = 1355). Two follow-up studies were carried out in 1983 (n = 2851) and 1986 (n = 2489), when HDL-subfractions (HDL-2-cholesterol and HDL-3-cholesterol) were also determined. Apolipoproteins A-I and B were measured again in 1986 (n = 1202). Serum total cholesterol concentration has fallen by about 1% annually during the 1980's from 5.07 mmol/l (1980) to 4.79 mmol/l (1986) in 9- to 18-year old children and adolescents. Mean values of serum triglycerides have slightly increased during the follow-up from 0.79 mmol/l to 0.84 mmol/l, respectively. In children and young adults (3-24 years) the mean cholesterol concentration was highest at the age of six and lowest during puberty. Concentrations of serum cholesterol, LDL (low density lipoprotein) cholesterol apoprotein B and triglycerides were higher in eastern than in western Finland in 1980 and 1983, but these differences were smaller in 1986, with the exception of serum triglycerides. Both in 1983 and in 1986 HDL-2-cholesterol was lower in the west than in the east, whereas HDL-3-cholesterol was higher in the former. The favourable changes in lipid levels should be reflected in future morbidity and mortality rates from coronary heart disease in Finland.

Children in sauna: cardiovascular adjustment.

Children's circulatory adjustment to a 10-minute heat stress in a climatic chamber was studied in 61 children and 20 adolescents and young adults. The thermal conditions corresponded to those of an ordinary Finnish sauna bath. In all subjects the rectal temperature and heart rate increased during the heat exposure (P less than .001). Systolic and diastolic blood pressures remained unchanged in sauna, but the systolic and especially the diastolic blood pressure decreased (P less than .001) in children less than 10 years of age immediately after the heat exposure; two vasovagal collapses developed. Cardiac output increased in all but the less than 5-year-old children (P less than .001). This was due to a significant decrease in stroke volume (32.9%) (P less than .001) in children less than 5 years old. Stroke volume declined slightly even in the older subjects. These changes indicate that the Finnish sauna bath puts great demands on a child's circulatory regulation. To avoid possible cardiovascular side effects, particularly small children should be supervised carefully during sauna bathing.

Long-term effects on lipid metabolism of weight reduction on lactovegetarian and mixed diet.

The effects of two dietary weight reduction programmes (1200 kcal/day) on lipid metabolism were followed for one year in moderately obese subjects. The groups consisted of lactovegetarian (n = 31), mixed diet (n = 37) and control (n = 42) groups. Serum triglyceride levels decreased rapidly during the first two weeks (46 per cent on average) especially in the mixed diet group, and this change was still statistically significant at 6 and 12 months after the beginning of the study. Serum total cholesterol levels also decreased rapidly in the beginning, but at 6 and 12 months the change was no longer statistically significant. After a small initial decrease HDL cholesterol levels appeared to increase towards the end of the study year. This increase was more marked in men (18.6 per cent at 6 months) than in women, and in the mixed diet group than in the lactovegetarian group (P less than 0.05 between the groups). The HDL/total cholesterol ratio increased rapidly in the beginning of the weight reduction and practically remained at the elevated (12-16 per cent) level during the whole follow-up. This increase was also more apparent in men than in women, and in the mixed diet group than in the lactovegetarian group. The changes in HDL subfractions, HDL2 and HDL3, paralleled those seen in the HDL cholesterol levels. Similarly the alterations in apolipoproteins A-I and B resembled those of the HDL and total cholesterol levels. The activity of adipose tissue lipoprotein lipase decreased drastically (about 50 per cent) at the beginning of the weight reduction, while at 6 and 12 months the mean activities were higher than the initial levels. This was also seen in the LPL activity when measured in post-heparin plasma. The activity of post-heparin plasma hepatic lipase decreased clearly at both 6 (P less than 0.001) and 12 months (P less than 0.01) in the mixed diet group, whereas no change was found in the lactovegetarian group. The ratio of subscapular to triceps skinfold reduced significantly (P less than 0.01) in women but not in men during the intervention period. Our study shows that in moderately overweight subjects weight reduction with the aid of a low-calorie dietary programme results in favourable responses in lipid metabolism many months after the cessation of the weight reduction programme. These responses appear to be stronger in subjects following mixed diet than in those attempting to follow a lactovegetarian diet.

Fatty acid composition of serum lipids in patients with a coronary bypass operation.

The fatty acid composition of serum phospholipids and cholesteryl esters was analysed in 71 male patients with angiographically defined three-vessel coronary artery disease (CAD) selected for a coronary bypass operation. Their 71 control subjects were matched according to age, sex, smoking, relative weight, and absence of CAD. The concentrations of fatty acids, 14:0, 16:0 and 16:1 of the serum phospholipids, were significantly (P less than 0.01, P less than 0.05 and P less than 0.01, respectively) higher in CAD patients than in the controls. On the other hand, linoleic (18:2 omega 6), linolenic (18:3 omega 3) and arachidonic (20:4 omega 6) acids were at a significantly lower level in the patients when compared to the controls. The polyunsaturated/saturated fatty acids (P/S) ratio in serum phospholipids was significantly (P less than 0.01) lower in the patients than in the controls. In the cholesteryl ester fraction the results paralleled those of the phospholipids. Significant correlations were obtained between the polyunsaturated fatty acids and the high density lipoprotein cholesterol or apolipoprotein A-I in the control subjects but most of these correlations were absent in the patients. Our present results further support the importance of linoleic acid in the protection against atherosclerosis. However, no unequivocal evidence on the possible beneficial effect of long-chain omega 3-fatty acids in comparison with omega 6-acids was obtained.

The effect of the short-term administration of fish oil on serum lipoproteins in old people.

The effect of large-dose short-term administration of Max-Epa fish oil on serum lipoproteins in elderly people was studied. 17 elderly (aged 61-96 years) hospital patients were given an isocaloric diet which contained 70-80 ml (14-16 g of eicosapentaenoate) of Max-Epa fish oil for 3 weeks. The concentration of plasma total cholesterol and LDL cholesterol decreased significantly during the diet with fish oil. The levels of plasma VLDL cholesterol, HDL cholesterol and triglycerides decreased slightly (p less than 0.05). The concentration of apoprotein A decreased significantly (p less than 0.001) during the fish oil diet but the plasma level of apoprotein B did not change significantly. The ratio of apoprotein B to LDL cholesterol increased significantly (p less than 0.01) during the period with Max-Epa fish oil. The results show that marked changes in the lipoproteins of the elderly people occur when diet contains large doses of fish oil.