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Biomedical subjects

M Laakso

Publications and source records attributed to M Laakso.

At least 109 records · Page 6Linked to original sources
PubMed1999

Antiplatelet treatment does not reduce the severity of subsequent stroke. European Stroke Prevention Study 2 Working Group.

OBJECTIVE: To assess the the effect of antiplatelet therapy on the severity of subsequent stroke in patients with stroke and TIA. BACKGROUND: The Second European Stroke Prevention Study (ESPS2) recruited 6,602 patients in four treatment groups: placebo, 2 x 25 mg acetylsalicylic acid (ASA), 2 x 200 mg dipyridamole (DP), and the combination of 50 mg ASA and 400 mg DP per day. Seventy-six percent of the patients had had a stroke as the qualifying event, whereas 24% had a TIA. All patients were followed at 3-month intervals for 2 years. ESPS2 showed a benefit from antiplatelet treatment compared with placebo and an additional benefit using ASA and DP together compared with either of these antiplatelet agents alone. METHODS: In the ESPS2, the study protocol included assessment of severity of end point stroke with the modified Rankin scale once the stroke had clinically stabilized, and no further impairment was observed. There were 824 new stroke events during follow-up. In 701 of them, the initial Rankin scale was known, and this was also evaluated after each nonfatal recurrent stroke. The difference in Rankin scale between treatment groups was analyzed after recurrent stroke, and the progress in Rankin scale between entry and recurrent stroke was quantified by calculating the number of patients with a change of one or more degrees in the scale. RESULTS: There were no significant differences in these changes in Rankin scale between the treatment groups. The mean time to reach an end point of stroke was longest in patients who used ASA + DP (p = 0.057). However, there was no difference among the treatment groups in the time to death during follow-up. CONCLUSION: This study suggests that antiplatelet therapy does not influence the severity of recurrent stroke as evaluated with the Rankin scale. However, antiplatelet therapy seems to lengthen the time the patient remains free from a recurrent stroke.

Aged↗
PubMed1999

Simultaneous hypertrophic cardiomyopathy and ventricular septal defect in children.

Our findings are based on clinical observations and not on a designed study. However, in our University Hospital area, all children with suspected or verified HC are sent to the same pediatric cardiologist (TT). Therefore, our patients are probably representative of children with HC, at least in East Finland. Although the number of patients was small, the prevalence of VSD in children with HC was so high, that it is improbable that the association between the 2 diseases is due to chance alone. Larger studies are needed to confirm our results and to show if muscular VSDs are typical of all HC cases or of specific subgroups only. We suggest that children with HC should undergo a thorough echocardiographic examination to detect possible muscular VSDs, which are usually readily detected by modern color flow mapping techniques. Importantly, in children with a muscular VSD, the possibility of HC as an underlying pathology should be kept in mind.

Adolescent↗
PubMed1999

Hexokinase II-deficient mice. Prenatal death of homozygotes without disturbances in glucose tolerance in heterozygotes.

Type 2 diabetes is characterized by decreased rates of insulin-stimulated glucose uptake and utilization, reduced hexokinase II mRNA and enzyme production, and low basal levels of glucose 6-phosphate in insulin-sensitive skeletal muscle and adipose tissues. Hexokinase II is primarily expressed in muscle and adipose tissues where it catalyzes the phosphorylation of glucose to glucose 6-phosphate, a possible rate-limiting step for glucose disposal. To investigate the role of hexokinase II in insulin action and in glucose homeostasis as well as in mouse development, we generated a hexokinase II knock-out mouse. Mice homozygous for hexokinase II deficiency (HKII(-/-)) died at approximately 7.5 days post-fertilization, indicating that hexokinase II is vital for mouse embryogenesis after implantation and before organogenesis. HKII(+/-) mice were viable, fertile, and grew normally. Surprisingly, even though HKII(+/-) mice had significantly reduced (by 50%) hexokinase II mRNA and activity levels in skeletal muscle, heart, and adipose tissue, they did not exhibit impaired insulin action or glucose tolerance even when challenged with a high-fat diet.

Adipose Tissue↗
PubMed1999

Insulin resistance syndrome predicts coronary heart disease events in elderly nondiabetic men.

BACKGROUND: The role of a cluster of risk factors characteristic for the insulin resistance syndrome as a predictor for coronary heart disease (CHD) has not been studied previously. METHODS AND RESULTS: Clustering of cardiovascular risk factors was analyzed by factor analysis to investigate whether these clusters (factors) predict CHD events (CHD death or nonfatal myocardial infarction) in a nondiabetic population of 1069 subjects 65 to 74 years old from eastern Finland followed up for 7 years. There were 151 CHD events (92 for men, 59 for women) during the follow-up period. In men, factor 1 (the insulin resistance factor, which reflected primarily body mass index, waist-to-hip ratio, triglycerides, fasting plasma glucose, and insulin) (hazards ratio [HR] with 95% CI, 1.33, CI 1.08, 1.65, P=0.008), factor 2 (alcohol consumption, high HDL cholesterol, low triglycerides) (HR 0.78, CI 0.63, 0.96, P=0.020), factor 3 (age, systolic blood pressure, urinary albumin/creatinine ratio, left ventricular hypertrophy) (HR 1.52, CI 1.26, 1.83, P<0.001), and factor 4 (high total cholesterol and triglycerides) (HR 1.42, CI 1. 15, 1.77, P=0.002) predicted CHD events in multivariate Cox regression analysis. In women, the insulin resistance factor did not predict CHD events (HR 1.06, CI 0.82, 1.36), but factor 2 (previous stroke, low HDL cholesterol and high triglycerides) (HR 1.34, CI 1. 06, 1.69, P=0.014) and factor 3 (age, systolic blood pressure, urinary albumin/creatinine ratio, left ventricular hypertrophy) (HR 1.44, CI 1.15, 1.82, P=0.002) predicted CHD events. CONCLUSIONS: Our study supports the notion that the insulin resistance syndrome is a risk factor for CHD in elderly men.

Aged↗
PubMed1999

Is leptin concentration associated with the insulin resistance syndrome in nondiabetic men?

OBJECTIVE: Insulin resistance has been strongly associated with cardiovascular risk. Recently, leptin, a hormone that regulates appetite, has been associated with both obesity and insulin resistance. However, the possible relation of leptin to the insulin resistance syndrome has been controversial. RESEARCH METHODS AND PROCEDURES: To explore this issue, we examined the relation of leptin to blood pressure, lipid levels, low density lipoprotein (LDL) size, and glucose levels in 87 normoglycemic men. RESULTS: Leptin levels were significantly correlated with body mass index (BMI) (r = 0.494), fasting insulin (r = 0.576), whole-body glucose disposal rate (GDR) (r = -0.566), fasting glucose (r = 0.510) total triglycerides (r = 0.294), apolipoprotein B (r = 0.223), systolic blood pressure (r = 0.223), and LDL size (r = -0.244). After adjustment for BMI and GDR, leptin levels remained significantly correlated with fasting insulin, fasting glucose, triglyceride, apolipoprotein B, and systolic blood pressure. Leptin levels were also correlated with the number of metabolic risk factors (dyslipidemia, systolic blood pressure, and fasting glucose). DISCUSSION: We conclude that leptin concentrations may be associated with several cardiovascular risk factors related to insulin resistance syndrome. These associations are only partly explained by leptin's relationship with BMI and GDR.

Apolipoproteins B↗
PubMed1999

The cardiac troponin I gene is not associated with hypertrophic cardiomyopathy in patients from eastern Finland.

Defects in seven genes encoding sarcomere proteins have been shown to cause hypertrophic cardiomyopathy. To date, only one study reporting defects in the cardiac troponin I gene associated with hypertrophic cardiomyopathy has been published, and the proportion of hypertrophic cardiomyopathy cases caused by defects in this gene is unknown. Therefore, the authors screened 37 unrelated Finnish patients with hypertrophic cardiomyopathy for variants in the cardiac troponin I gene. Exons 1-8 of the troponin I gene were screened with the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method. Five different variants (four intron variants and one silent exon variant) were found. Most variants were also present in control samples and none of the variants co-segregated with the disease in families. The results of the present study indicate that defects in the cardiac troponin I gene do not cause hypertrophic cardiomyopathy in patients from Eastern Finland.

Cardiomyopathy, Hypertrophic↗
PubMed1999

Prevention of Type II diabetes in subjects with impaired glucose tolerance: the Diabetes Prevention Study (DPS) in Finland. Study design and 1-year interim report on the feasibility of the lifestyle intervention programme.

UNLABELLED: AIMS/HYPOTHESIS; The aim of the Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying Type II (non-insulin-dependent) diabetes mellitus in subjects with impaired glucose tolerance, to evaluate the effects of the intervention programme on cardiovascular risk factors and to assess the determinants for the progression to diabetes in persons with impaired glucose tolerance. METHODS: A total of 523 overweight subjects with impaired glucose tolerance ascertained by two oral glucose tolerance tests were randomised to either a control or intervention group. The control subjects received general information at the start of the trial about the lifestyle changes necessary to prevent diabetes and about annual follow-up visits. The intervention subjects had seven sessions with a nutritionist during the first year and a visit every 3 months thereafter aimed at reducing weight, the intake of saturated fat and increasing the intake of dietary fibre. Intervention subjects were also guided individually to increase their physical activity. RESULTS: During the first year, weight loss in the first 212 study subjects was 4.7 +/- 5.5 vs 0.9 +/- 4.1 kg in the intervention and control group, respectively (p < 0.001). The plasma glucose concentrations (fasting: 5.9 +/- 0.7 vs 6.4 +/- 0.8 mmol/l, p < 0.001; and 2-h 7.8 +/- 1.8 vs 8.5 +/- 2.3 mmol/l, p < 0.05) were significantly lower in the intervention group after the first year of intervention. Favourable changes were also found in blood pressure, serum lipids and anthropometric indices in the intervention group. CONCLUSION/INTERPRETATION: The interim results show the efficacy and feasibility of the lifestyle intervention programme.

Blood Glucose↗
PubMed1999

Reactive microglia in aging and dementia: an immunohistochemical study of postmortem human brain tissue.

Significantly increased up-regulation of HLA DR (major histocompatibility complex class II antigen) was seen using immunohistochemistry in postmortem brain tissue from demented patients with Alzheimer's disease (AD) (73 cases, 61 females/12 males, mean age 84 +/- 9 years) compared to controls (22 cases, 10 females/12 males, mean age 78 +/- 9 years). The counts of HLA DR-expressing activated microglia were significantly higher in female AD patients compared to males, significantly higher in AD patients with the age at death greater than 75 years compared to those dying younger and higher, although not statistically significantly, in AD patients with the apolipoprotein E (ApoE) epsilon4 allele compared to those patients not carrying this allele. In contrast to the situation in AD patients, in the control cases the HLA DR expression was higher in males compared to females. Furthermore, in the very old non-demented patients (age at death > 80 years), a decrease in the up-regulation of HLA DR expression was observed. A significant correlation between activated microglia and neurofibrillary tangles was seen in female AD patients compared to males, in AD cases without ApoE epsilon4 allele compared to those with this allele, in sporadic cases compared to familial and in cases with senile rather than presenile onset of the disease. Our results indicate that there is an age- and/or sex-related variability in up-regulation of HLA DR expression of microglia and that the linkage between this up-regulation and AD lesions is significantly influenced by the ApoE epsilon4 allele, gender of subjects, age at onset and familiality of the disease.

Age Factors↗
PubMed1999

Cognitive load and detection thresholds in car following situations: safety implications for using mobile (cellular) telephones while driving.

This study was aimed at investigating drivers' ability to detect a car ahead decelerating, while doing mobile phone related tasks. Nineteen participants aged between 20 and 29 years, (2000-125000 km driving experience) drove at 80 km/h, 50 m behind a lead car, on a 30 km section of motorway in normal traffic. During each trial the lead car started to decelerate at an average of 0.47 m/s2 while the participant either looked at the car in front (control), continuously dialed series of three random integers on a numeric keypad (divided visual attention), or performed a memory and addition task (non-visual attention). The results indicated that drivers' detection ability was impaired by about 0.5 s in terms of brake reaction time and almost 1 s in terms of time-to-collision, when they were doing the non-visual task whilst driving. This impairment was similar to when the drivers were dividing their visual attention between the road ahead and dialing numbers on the keypad. It was concluded that neither a hands-free option nor a voice controlled interface removes the safety problems associated with the use of mobile phones in a car.

Adult↗
PubMed1999

The codon 64 polymorphism of the beta3-adrenergic receptor gene is not associated with coronary heart disease or insulin resistance in nondiabetic subjects and non-insulin-dependent diabetic patients.

Hyperinsulinemia has been shown to predict coronary heart disease (CHD) events in both nondiabetic subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). Therefore, defects in genes that regulate insulin action could be responsible for an increased risk of CHD. The Trp64Arg polymorphism of the beta3-adrenergic receptor gene has been linked with abdominal obesity, insulin resistance, and early-onset NIDDM. Therefore, we screened for this polymorphism among 185 unrelated nondiabetic subjects (101 men and 84 women; age, 56+/-1 years [mean +/- SEM]; body mass index [BMI], 27.8+/-0.3 kg/m2) with angiographically confirmed CHD (stenosis > 50% in > or = two coronary arteries), among 119 unrelated patients with NIDDM (90 men and 29 women; age, 62+/-1 years; BMI, 28.7+/-0.4 kg/m2; 95 had CHD by the same criteria and 24 had definite myocardial infarction [MI]), and among 82 healthy men (age, 54+/-1 years; BMI, 26.3+/-0.4 kg/m2) from our previous study. The frequency of the Trp64Arg allele of the beta3-adrenergic receptor gene was similar in nondiabetic patients with CHD (8%), NIDDM patients with CHD (7%), and nondiabetic subjects without CHD (7%). No association was found between cardiovascular risk factors and the codon 64 polymorphism of the beta3-adrenergic receptor gene in patients with CHD. Similarly, this polymorphism was not significantly related to insulin resistance in nondiabetic and NIDDM subjects with CHD evaluated by the euglycemic clamp technique. These results indicate that the Trp64Arg allele of the beta3-adrenergic receptor gene does not contribute to the risk of CHD in nondiabetic subjects and NIDDM patients.

Alleles↗
PubMed1999

Evidence of a state of increased insulin resistance in preeclampsia.

Similarities in certain biochemical variables between preeclampsia and the insulin resistance syndrome imply a possible link between insulin resistance and preeclampsia. We measured insulin sensitivity by the minimal model technique between 29 and 39 weeks of gestation in 22 preeclamptic and 16 control women, whose glucose tolerance was first confirmed as normal by an oral glucose tolerance test. In addition, we measured the fasting levels of serum C-peptide, uric acid, lipids, and lipoproteins. Preeclamptic women showed a higher insulin response (P = .001) during the oral glucose tolerance test than the controls. Insulin sensitivity in preeclamptic women (1.11+/-0.15 x 10(-4) x min(-1) x microU/mL) was 37% lower (P = .009) than in control women (1.77+/-0.19 x 10(-4) x min(-1) x microU/mL). The free fatty acid (FFA) concentration in preeclamptic women (0.17+/-0.01 g/L, P = .0004) was 70% higher than in control women (0.10+/-0.01 g/L). Also, baseline serum levels of C-peptide, uric acid, and triglyceride were higher in preeclamptic women. Insulin sensitivity increased fourfold to fivefold within the first 3 postpartum months, but insulin sensitivity in preeclamptic women was still 26% lower (P = .04) than in control women. Preeclampsia is a state of increased insulin resistance, and it persists for at least 3 months after pregnancy. This may be a pathogenetic factor in preeclampsia and may contribute to the excess cardiovascular morbidity among women with prior preeclampsia.

Adult↗
PubMed1999

Hyperglycemia as a risk factor for cardiovascular disease in type 2 diabetes.

According to several prospective population-based studies, glycemic control influences the risk for cardiovascular disease, including coronary heart disease, independently of conventional risk factors in patients with type 2 diabetes. Recent clinical trials, particularly the United Kingdom Prospective Diabetes Study, have shown that microvascular complications and macrovascular complications, although to a lesser extent, can be prevented in patients with type 2 diabetes with correction of glycemic control. However, in the treatment and prevention of cardiovascular disease in type 2 diabetes, all known cardiovascular risk factors should be attacked simultaneously.

Blood Glucose↗
PubMed1999

Prandial glucose regulation and cardiovascular disease in type 2 diabetes.

Type 2 diabetes is associated with an increased risk for cardiovascular disease. In recent years, prospective studies have indicated that, in addition to conventional risk factors, glycaemic control of diabetes predicts cardiovascular disease in both middle-aged and elderly patients with Type 2 diabetes. However, there are no consistent data from different studies to indicate that postprandial glucose is a better predictor for cardiovascular risk than fasting glucose level. Although no clinical trials are available to show that improving glycaemic control prevents cardiovascular mortality and morbidity, recent studies imply that hyperglycaemia in patients with Type 2 diabetes should be treated more intensively than recommended by current guidelines

Cardiovascular Diseases↗
PubMed1999

Genomewide scan for familial combined hyperlipidemia genes in finnish families, suggesting multiple susceptibility loci influencing triglyceride, cholesterol, and apolipoprotein B levels.

Familial combined hyperlipidemia (FCHL) is a common dyslipidemia predisposing to premature coronary heart disease (CHD). The disease is characterized by increased levels of serum total cholesterol (TC), triglycerides (TGs), or both. We recently localized the first locus for FCHL, on chromosome 1q21-q23. In the present study, a genomewide screen for additional FCHL loci was performed. In stage 1, we genotyped 368 polymorphic markers in 35 carefully characterized Finnish FCHL families. We identified six chromosomal regions with markers showing LOD score (Z) values >1.0, by using a dominant mode of inheritance for the FCHL trait. In addition, two more regions emerged showing Z>2.0 with a TG trait. In stage 2, we genotyped 26 more markers and seven additional FCHL families for these interesting regions. Two chromosomal regions revealed Z>2.0 in the linkage analysis: 10p11.2, Z=3.20 (theta=.00), with the TG trait; and 21q21, Z=2.24 (theta=.10), with the apoB trait. Furthermore, two more chromosomal regions produced Z>2.0 in the affected-sib-pair analysis: 10q11.2-10qter produced Z=2.59 with the TC trait and Z=2.29 with FCHL, and 2q31 produced Z=2.25 with the TG trait. Our results suggest additional putative loci influencing FCHL in Finnish families, some potentially affecting TG levels and some potentially affecting TC or apoB levels.

Adult↗
PubMed1999

Short-term metabolic effects of isradipine and metoprolol in pre-eclampsia.

OBJECTIVE: To study the effects of isradipine or metoprolol on insulin sensitivity and lipid profiles as well as on blood pressure and umbilical vascular resistance in pre-eclamptic women in the third trimester of pregnancy. DESIGN: A single-centre, prospective, randomized, double-blind, double-dummy and parallel-group study. SETTING: Helsinki University Central Hospital, a tertiary referral centre. PATIENTS: Twenty-four previously healthy pregnant women with normal findings in an oral glucose-tolerance test who were hospitalized for preeclampsia, of whom 17 completed the study. INTERVENTIONS: Between 29 and 39 weeks of gestation, measurements were made of insulin sensitivity (the minimal model), magnitude of proteinuria, and the fasting levels of serum uric acid, lipids and lipoproteins. Subsequently, treatment with isradipine 2.5 mg (n = 9) or metoprolol 50 mg (n = 8) twice daily was started, and these women were reinvestigated 5-7 days later. Blood pressure was recorded during 24 h by automated ambulatory blood pressure measurement. Umbilical artery resistance index was measured by Doppler ultrasound. MAIN OUTCOME MEASURES: Insulin sensitivity, uric acid, degree of proteinuria, lipids and lipoproteins, blood pressure, umbilical artery resistance index. sensitivity, degree of proteinuria, blood pressure, or the umbilical artery resistance index. Serum uric acid increased in both groups (P<0.05). High-density lipoprotein2 cholesterol increased 15.6% in the isradipine group (P<0.05), but no significant changes appeared in other lipids and lipoproteins in either group. CONCLUSIONS: In this study, short-term antihypertensive treatment with isradipine or metoprolol in preeclampsia had no detrimental effect on serum lipid and lipoprotein levels or insulin sensitivity.

Adrenergic beta-Antagonists↗
PubMed1999

Second European Stroke Prevention Study: antiplatelet therapy is effective regardless of age. ESPS2 Working Group.

BACKGROUND: The Second European Stroke Prevention Study (ESPS2) was a randomized, placebo-controlled trial that investigated the efficacy of low-dose acetylsalicylic acid (ASA) and modified-release dipyridamole (DP), alone or in combination, in the secondary prevention of ischemic stroke. The trial demonstrated that the combination was significantly more effective than either agent used alone. The aim of the present study was to evaluate the influence of age on the efficacy of ASA and DP, alone or in combination, in the secondary prevention of stroke in the ESPS2 population. METHODS AND RESULTS: A total of 6602 patients were recruited to the ESPS2 and there were 4 treatment groups: ASA (25 mg twice daily), DP (200 mg twice daily), ASA and DP in a combined formulation, or placebo. Primary endpoints were stroke, death, and stroke or death together. The endpoints evaluated in the present study were stroke, stroke and/or death, and vascular events. Stroke was the qualifying event in 76% of the patients, while 24% had a transient ischaemic attack. Patients were reviewed at 3-month intervals for 2 years. The study population consisted of 2565 (39%) patients aged less than 65 years, 2240 (34%) patients aged between 65 and 74 years, and 1797 (27%) patients aged 75 years and over. Advancing age was associated with an increased incidence of endpoints in all 4 treatment groups. The combination of ASA and DP significantly reduced the incidence of all endpoints, compared with placebo, in each age group. There was no influence of age on the efficacy of antiplatelet therapy for any of the evaluated endpoints. Relative risk reductions of treatment compared with placebo were 11.1-27.6% in the ASA group, 8.0-18.7% in the DP group, and 20.3-45.2% in patients receiving combination therapy. CONCLUSION: This study clearly demonstrates that combination therapy with DP and ASA is superior to either agent used alone in the secondary prevention of ischemic stroke, irrespective of the age of the patient.

Administration, Oral↗
PubMed1999

Type-2 diabetes and cognitive function in a non-demented population.

OBJECTIVES: To study if type-2 (non-insulin-dependent) diabetes mellitus (NIDDM) is associated with cognitive dysfunction independently of clinically diagnosed dementia in an elderly population. MATERIAL AND METHODS: Cognitive function was investigated with a brief neuropsychological test battery in a non-demented elderly population consisting of 183 NIDDM (World Health Organization, 1985) patients and 732 non-diabetic subjects. RESULTS: Patients with NIDDM were impaired in the Trail-Making Test parts A and C, which may be a reflection of mildly affected frontal lobe/executive functions. Women with NIDDM performed better than non-diabetic subjects in the Mini-Mental State Examination. CONCLUSIONS: We conclude that NIDDM per se is not associated with impaired memory in the elderly, and the minor defects observed in tests of frontal lobe/executive functions are unlikely to affect daily living. In the non-demented population aged 69 78 years, NIDDM does not carry a significant risk of cognitive dysfunction, when compared to the non-diabetic subjects.

Activities of Daily Living↗