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Biomedical subjects

T Laitinen

Publications and source records attributed to T Laitinen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cardiac adrenergic denervation in patients with non-Q-wave versus Q-wave myocardial infarction.

In spite of smaller infarct size and better preserved left ventricular function the long-term prognosis after a non-Q-wave infarction is not better than after a Q-wave infarction. In fact, the risk of sudden cardiac death is higher in patients with a non-Q-wave infarction than in patients with a Q-wave infarction. One possible reason for postinfarction arrhythmias is cardiac adrenergic denervation resulting from myocardial infarction. In this study we compared cardiac adrenergic innervation after non-Q-wave and Q-wave infarctions. Single-photon emission tomography using iodine-123 metaiodobentzylguanidine (MIBG) and technetium-99m sestamibi (MIBI) tracers were conducted in order to compare cardiac adrenergic denervation and myocardial perfusion in 12 patients with a non-Q-wave infarction and 15 patients with a Q-wave infarction. MIBG and MIBI defects were determined as regional uptake < or = 30% of maximal myocardial activity. The size of MIBI defects calculated as a percentage of left ventricular mass was significantly smaller in patients with a non-Q-wave infarction than in patients with a Q-wave infarction (4%+/-3% vs 9%+/-7%, P<0.05, respectively). According to the maximal serum creatine kinase activity, less myocardium was damaged in patients with a non-Q-wave infarction than in patients with a Q-wave infarction (502+/-436 IU/l vs 1878+/-1265 IU/l, P<0.001). In spite of this, the extent of MIBG defects was similar in patients with a non-Q-wave and patients with a Q-wave infarction (21%+/-18% vs 23%+/-12%, respectively). In addition, the size of MIBG defect correlated with the infarct size (maximal creatine kinase activity) (r=0.52, P<0.05) after a Q-wave infarction but not after a non-Q-wave infarction. In conclusion, despite a smaller infarct size in non-Q-wave infarct patients, the extent of cardiac adrenergic denervation was similar in patients with a non-Q-wave and patients with a Q-wave infarction. In addition, the extent of cardiac adrenergic denervation was related to the infarct size in patients with a Q-wave infarction but not in patients with a non-Q-wave infarction.

3-Iodobenzylguanidine↗
PubMed2000

Juxtaposed regions of extensive and minimal linkage disequilibrium in human Xq25 and Xq28.

Linkage disequilibrium (LD), or the non-random association of alleles, is poorly understood in the human genome. Population genetic theory suggests that LD is determined by the age of the markers, population history, recombination rate, selection and genetic drift. Despite the uncertainties in determining the relative contributions of these factors, some groups have argued that LD is a simple function of distance between markers. Disease-gene mapping studies and a simulation study gave differing predictions on the degree of LD in isolated and general populations. In view of the discrepancies between theory and experimental observations, we constructed a high-density SNP map of the Xq25-Xq28 region and analysed the male genotypes and haplotypes across this region for LD in three populations. The populations included an outbred European sample (CEPH males) and isolated population samples from Finland and Sardinia. We found two extended regions of strong LD bracketed by regions with no evidence for LD in all three samples. Haplotype analysis showed a paucity of haplotypes in regions of strong LD. Our results suggest that, in this region of the X chromosome, LD is not a monotonic function of the distance between markers, but is more a property of the particular location in the human genome.

Finland↗
PubMed2000

The IL9R region contribution in asthma is supported by genetic association in an isolated population.

Interleukin 9 (IL9) is involved in mast cell maturation and the enhancement of IgE production by B cells. Furthermore, linkage data in human and mice have suggested that IL9 may contribute to asthma. Since our genetic analysis of the 5q cytokine cluster did not support a genetic role for the IL9 gene, we became interested in the IL9 receptor gene (IL9R) in the pseudoautosomal region. We genotyped markers sDF2 and sDF1 close to the IL9R gene among 289 affected and 368 family-based controls. The results were studied by using linkage, transmission disequilibrium, association and homozygosity analyses. Linkage analyses remained negative, presumably because of our low power for linkage study. However, all the other analyses yielded evidence that the IL9R gene region may have a role in the development of asthma. The sDF2*10 allele was more frequently transmitted than untransmitted to asthmatic offspring (34 vs 16, pchi2 < or = 0.01), and it was found homozygotic among asthma patients more often than expected (Psimul2 = 0.009). Also, a specific X chromosomal haplotype, sDF2*10-sDF1*6 associated with asthma (40 vs 7, Pchi2 < 0.005, Psimul1 = 0.04).

Alleles↗
PubMed2000

Cardiac adrenergic innervation within the first 3 months after acute myocardial infarction.

It is widely accepted that myocardial infarction results in adrenergic denervation of the infarcted and peri-infarcted myocardium. On the contrary, the concept of re-innervation of adrenergic nerve fibres is less well established. Although there is evidence of partial re-innervation occuring several months after myocardial infarction, the extent and time scale of re-innervation are only poorly known. In this study we investigated changes in cardiac adrenergic innervation and myocardial perfusion during the early convalescence period (the first 3 months) after an acute myocardial infarction. Single-photon emission computed tomographic imaging was conducted in 15 men 1 week and 3 months after an acute myocardial infarction with I123-metaiodobentzylguanidine (MIBG) and Tc99m-sestamibi (MIBI) to determine the extent of adrenergic denervation and impaired perfusion, respectively. A MIBG and MIBI defect was determined as regional uptake </=30% of maximal myocardial activity. The size of the MIBG defect calculated as a percentage of left ventricular mass remained unchanged between 1 week and 3 months after myocardial infarction (31.1 +/- 17.3% vs. 30. 5 +/- 16.8%, respectively). Accordingly, MIBG activity of the infarct and peri-infarct zones (expressed as a percentage of MIBG activity of the myocardium with normal perfusion) showed no significant change (23.7 +/- 10.0% vs. 25.3 +/- 11.0% and 39.0 +/- 11.3% vs. 40.8 +/- 12.8%, respectively) during the follow-up. On the other hand, the size of MIBI defect decreased significantly during the follow-up (14.2 +/- 11.5% vs. 11.4 +/- 9.7%, P<0.05, respectively) indicating improved myocardial perfusion. The results demonstrate that cardiac adrenergic re-innervation is a slow process; despite a significant increase in myocardial perfusion we found no evidence of adrenergic re-innervation during the first 3 months after acute myocardial infarction.

3-Iodobenzylguanidine↗
PubMed2000

Conscious sedation and cardiorespiratory safety during colonoscopy.

BACKGROUND: Cardiorespiratory events during colonoscopy are common. The effect of sedative premedication on cardiorespiratory parameters during colonoscopy has not been studied in controlled, prospective trials. METHODS: One hundred eighty patients undergoing colonoscopy were divided into 3 groups: (1) sedation with intravenous midazolam (midazolam group); (2) sedation with intravenous saline (placebo group); and (3) no intravenous cannula (control group). Arterial oxygen saturation (SaO(2)), systolic and diastolic blood pressure and continuous electrocardiogram were recorded prior to, during and after the endoscopic procedure. RESULTS: Midazolam produced lower SaO(2) values during colonoscopy compared with placebo or control groups (p < 0.001, repeated measures analysis of variance). Systolic and diastolic blood pressure during colonoscopy were lower in the midazolam group than in the placebo group (p < 0.01 and p < 0.05, respectively), but no difference was found between the midazolam and the control groups. Hypotension (systolic blood pressure less than 100 mm Hg) occurred more frequently in the midazolam group (19%) than in the placebo (3%; p < 0.01) or control groups (7%; p < 0.05). ST-segment depression developed in 7% of patients during the recording with no difference between the groups. In 75% of cases ST-depression appeared prior to the endoscopic procedure. CONCLUSIONS: Premedication with midazolam induced a statistically significant decrease in arterial oxygen saturation and increased the risk for hypotension. However, colonoscopy proved to be a safe procedure both with and without sedation.

Adult↗
PubMed2000

Effect of conscious sedation on cardiac autonomic regulation during colonoscopy.

BACKGROUND: Colonoscopy is associated with cardiovascular events including hypotension, hypertension, and myocardial ischemia. The pathogenetic mechanisms of these cardiovascular events are unknown, but there is evidence that the autonomic nervous system may play a role. Conscious sedation is often used to relieve the inconvenience caused by the procedure. In this study, we evaluated the effects of sedation on cardiac autonomic regulation during colonoscopy. METHODS: One hundred and eighty patients undergoing elective colonoscopy were prospectively randomized into three groups: (i) sedation with intravenous midazolam (midazolam group); (ii) sedation with intravenous saline (placebo group); and (iii) no intravenous cannula (control group). Continuous electrocardiogram was recorded prior to, during, and after the colonoscopic procedure. Heart rate variability (HRV) was assessed by means of the power spectral analysis; the powers of low-frequency (LF 0.04-0.15 Hz) and high-frequency (HF 0.15-0.40 Hz) components were calculated. RESULTS: Intubation of the colonoscope increased the LF component of HRV and decreased HF power in all study groups compared to baseline recording. Furthermore, compared to baseline, the LF/HF ratio--a marker of cardiac sympathetic regulation--increased during intubation in the midazolam (P < 0.001) and placebo (P < 0.05) groups, with no change in the control group. During intubation the midazolam group presented with higher LF and lower HF power than placebo (P < 0.001) and control groups (P < 0.01). Accordingly, the LF/HF ratio was higher in the midazolam group than in the placebo (P < 0.05) or control groups (P < 0.05). CONCLUSIONS: Midazolam potentiates the dominance of the sympathetic nervous system induced by colonoscopy. Therefore, conscious sedation with midazolam may contribute to the occurrence of cardiovascular events during colonoscopy.

Colonoscopy↗
PubMed2000

Inversion of the roles of the nucleophile and acid/base catalysts in the covalent binding of epoxyalkyl xyloside inhibitor to the catalytic glutamates of endo-1,4-beta-xylanase (XYNII): a molecular dynamics study.

X-Ray crystal structures have revealed that 2, 3-epoxypropyl-beta-D-xyloside reacts with endo-1,4-beta-xylanase (XYNII) by forming a covalent bond with Glu86. In contrast, 3, 4-epoxybutyl-beta-D-xyloside forms a covalent bond with Glu177. In the normal enzyme reaction Glu86 acts as the catalytic nucleophile and Glu177 as the acid/base catalyst. To rationalize the observed reactivity of the two mechanism-based inhibitors, we carried out eight 300 ps molecular dynamics simulations for different enzyme-inhibitor complexes. Simulations were done for both stereo isomers (R and S) of the inhibitors and for enzyme in which the protonation state of the nucleophile and acid/base catalyst was normal (Glu86 charged, Glu177 neutral) and in which the roles of the catalytic residues were reversed (Glu86 neutral, Glu177 charged). The number of reactive conformations found in each simulation was used to predict the reactivity of epoxy inhibitors. The conformation was considered to be a reactive one when at the same time (i) the proton of the catalytic acid was close (<2.9/3.4/3.9 A) to the oxirane oxygen of the inhibitor, (ii) the nucleophile was close to the terminal carbon of the oxirane group (<3.4/3.9/4.4 A) and (iii) the nucleophile approached the terminal carbon from a reactive angle (<30/45/60 degrees from an ideal attack angle). On the basis of the number of reactive conformations, 2,3-epoxypropyl-beta-D-xyloside was predicted to form a covalent bond with Glu86 and 3, 4-epoxybutyl-beta-D-xyloside with Glu177, both in agreement with the experiment. Thus, the MD simulations and the X-ray structures indicate that in the covalent binding of 3, 4-epoxybutyl-beta-D-xyloside the roles of the catalytic glutamates of XYNII are reversed from that of the normal enzyme reaction.

Acids↗
PubMed2000

Late correlative imaging findings of previous acute infective spondylitis.

PURPOSE: To evaluate late correlative imaging findings in relation to clinical outcome in persons with previous acute infective spondylitis, the authors performed bone and leukocyte scintigraphy (planar and SPECT imaging) and magnetic resonance imaging of the spine in nine patients (two men, seven women; mean age, 66 years; age range, 57 to 84 years) 3.1 years (range, 0.9 to 6.2 years) after the acute disease. METHODS: All images were evaluated visually. The relevant uptake on SPECT images was also quantitated using an adjacent normal vertebral body as the reference area. RESULTS: Except for one patient, all other patients had increased uptake in the affected vertebra on bone scintigraphy [corrected]. In leukocyte scintigraphy, clearly decreased uptake was noted quantitatively in six of the seven patients who underwent SPECT. On the magnetic resonance and computed tomographic scans, the typical findings were destruction of intervertebral disks and compression deformities of vertebral bodies, but there was high interindividual variance of other findings, such as osteophytes, spondylolisthesis, increased vertebral fat content, and postoperative changes. These data show that nearly all patients with previously acute infective spondylitis have gross abnormal anatomic and functional imaging findings years after the acute disease, despite good clinical outcome [corrected]. CONCLUSIONS: The utility of bone and leukocyte scans in the diagnosis of reactivated spondylitis is limited, and incidentally observed abnormal imaging findings in asymptomatic patients with known previous spondylitis should be interpreted with caution.

Aged↗
PubMed2000

Perinatal risk factors for asthma in Finnish adolescent twins.

BACKGROUND: Previous studies have suggested that, in addition to genetic liability and environment in early childhood, intrauterine life also influences the risk for asthma beyond childhood. Low birth weight, prematurity, young maternal age, and maternal smoking have all shown an association with asthma. The effect of perinatal factors on the risk for asthma in relation to familial and social risk factors was studied in a nationwide population-based sample of adolescent twins. In addition to a distribution of birth characteristics among twins which differs from that of singletons, data on twins enable a distinction to be made between genetic and environmental sources of variation. METHODS: Questionnaires were sent to five consecutive birth cohorts of Finnish 16 year old twins born in 1975-9 and to their parents (3065 families). The outcome measure was life time prevalence of doctor-diagnosed asthma in these adolescents. The association between asthma and potential risk factors was assessed by multiple logistic regression and discordant twin pair analysis. RESULTS: Risk for asthma increased with increasing ponderal index (p for trend <0.01) and decreasing maternal age (p for trend <0.05). Among the 25% of twins with the highest ponderal index, the odds ratio for asthma was 1.82 (95% confidence interval 1.18 to 2.79) compared with those in the lowest 25%. Neither birth weight, gestational age, nor Apgar score was associated with asthma. When perinatal risk factors were combined with familial and social risk factors, ponderal index, maternal smoking, parental asthma, and sibship size were all significant independent determinants of asthma in these adolescents. CONCLUSIONS: The risk for asthma in adolescent twins increases with increasing ponderal index when adjusted for familial and social factors.

Adolescent↗
PubMed2000

Association study of the chromosomal region containing the FCER2 gene suggests it has a regulatory role in atopic disorders.

On the basis of studies with animal models, the gene for the low-affinity receptor for immunoglobulin E (IgE) (FCER2, CD23) has been implicated as a candidate for IgE-mediated allergic diseases and bronchial hyperreactivity, or related traits. Given evidence for genetic complexity in atopic disorders, we sought to study two European subpopulations, Finnish and Catalonian. We studied three phenotypic markers: (1) total serum IgE level; (2) asthma; and (3) specific IgE level for a mixture of the most common aeroallergens in Finland. Altogether, eight polymorphic markers spanning a region of 10 cM around the FCER2 gene on chromosome 19p13 were analyzed in 124 families. The physical order of the markers and the location of the FCER2 gene were confirmed by using radiation hybrids. The allele and haplotype association study showed a suggestive haplotype association (significance of p </= 0.03 based on a permutation test) for a high serum IgE response. In a subset of chromosomes segregating with asthma in families with two or more affected members, a single haplotype was found to be highly enriched (p = 8.3 x 10(-6)). However, sequence polymorphisms, which would verify structural differences in the FCER2 gene, were not detected in the coding region of the receptor. Our results suggest that chromosome 19p13 might harbor a genetic determinant of IgE-related traits. Studies in other population samples are needed to verify this finding.

Adult↗
PubMed1999

Sympathovagal balance is major determinant of short-term blood pressure variability in healthy subjects.

Short-term blood pressure variability (BPV) has been suggested to provide important information about cardiovascular regulation. However, the background of BPV, its determinants, and physiological correlates have remained obscure. The aim of this study was to characterize physiological correlates of BPV and to investigate associations between BPV and neural and hormonal regulatory systems at rest in healthy subjects. We studied 117 healthy, normal-weight, nonsmoking male and female subjects aged 23-77 yr. Spectral analysis of BPV and heart rate variability (HRV) was performed from 5-min blood pressure (Finapres) and electrocardiogram recordings during controlled breathing. Baroreflex sensitivity (BRS) was measured using the phenylephrine method. In addition, plasma concentrations of norepinephrine, epinephrine, and arginine vasopressin and plasma renin activity were measured. We found that the ratio between the low- and high-frequency components of HRV, an index of cardiac sympathovagal balance, correlated positively with total power and very low- and low-frequency components of systolic and diastolic BPV and inversely with high-frequency components of systolic and diastolic BPV. BRS, predominantly a measure of cardiac vagal regulation, correlated inversely with BPV. Furthermore, age, gender, body mass index, and systolic blood pressure contributed to BPV. Vasoactive hormones were not significant correlates of BPV. We conclude that sympathovagal balance of cardiovascular regulation is the major determinant of BPV. Other factors associated with BPV are age, gender, body mass index, blood pressure, and BRS.

Adult↗
PubMed1999

Power spectral analysis of heart rate variability during hyperinsulinemia in nondiabetic offspring of type 2 diabetic patients: evidence for possible early autonomic dysfunction in insulin-resistant subjects.

Sympathetic activation has been considered as a link between insulin resistance, hyperinsulinemia, and hypertension. However, little is known about the association between insulin sensitivity and autonomic regulation or about the effect of acute hyperinsulinemia on cardiac sympathovagal balance. The aim of this study was to investigate heart rate variability (HRV) during the euglycemic-hyperinsulinemic clamp in nondiabetic offspring of patients with type 2 diabetes. We studied 35 nondiabetic offspring of patients with type 2 diabetes and 19 control subjects. Probands were chosen from a 10-year follow-up study of patients with well-characterized type 2 diabetes according to their fasting C-peptide level (selected from both ends of the distribution) and from control subjects to form three groups: 1) a group including subjects who were offspring of type 2 diabetic patients with low C-peptide levels (deficient insulin secretion group [IS group], n = 17), 2) a group including subjects who were offspring of type 2 diabetic patients with high C-peptide levels (insulin-resistant group [IR group], n = 18), and 3) a control group without a history of type 2 diabetes in first-degree relatives (n = 19). HRV was assessed at baseline and at the steady state during the euglycemic-hyperinsulinemic clamp. Rates of whole-body glucose uptake (M value) were lower in the IR group than in the IS group and the control group (41+/-3 vs. 54+/-2 vs. 60+/-4 micromol x kg(-1) x min(-1), P < 0.01 and P < 0.01, respectively). In all groups, heart rate increased significantly during hyperinsulinemia. In the IR group, insulin infusion increased total power of HRV [from 7.70+/-0.15 to 8.05+/-0.15 ln(ms2), P < 0.01] and the low frequency-to-high frequency ratio (from 0.62+/-0.14 to 1.14+/-0.18, P < 0.01) and decreased power of the high frequency spectral component (from 5.73+/-0.17 to 5.43+/-0.16 ln(ms2), P < 0.05), whereas in other groups, changes in HRV were not significant. We conclude that the HRV response to acute hyperinsulinemia in the offspring of type 2 diabetic probands was likely to be modulated by the type 2 diabetic phenotype of the parent. In insulin-resistant subjects, autonomic dysfunction may be an earlier defect than hitherto acknowledged.

Adult↗
PubMed1998

Pharmacokinetics and dosimetry of iodine-123 labelled PE2I in humans, a radioligand for dopamine transporter imaging.

The iodine-123 labelled selective ligand N-(3-iodoprop-2E-enyl)-2-beta-carbomethoxy-3beta-(4-methylphenyl) nortropane ([123I]PE2I) was evaluated as a probe for in vivo dopamine transporter imaging in the human brain. Six healthy subjects were imaged with a high-resolution single-photon emission tomography scanner. Striatal radioactivity peaked at 1 h after injection. The background radioactivity was low. The volume of distribution in the striatum was 94+/-24 ml/ml. The results were compared with those of [123I]beta-CIT imaging. There was no significant uptake of [123I]PE2I in serotonin-rich regions such as the midbrain, hypothalamus and anterior gingulus, suggesting that in vivo binding is specific for the dopamine transporter. One main polar metabolite of [123I]PE2I was found in plasma, and the parent plasma concentration decayed rapidly. Radiation exposure to the study subject is 0.022+/-0.004 mSv/MBq (effective dose). The preliminary results suggest that [123I]PE2I is a selective SPET ligand for imaging striatal dopamine transporter density.

Adult↗
PubMed1998

Verification of self-reported asthma and allergy in subjects and their family members volunteering for gene mapping studies.

Studies which aim at mapping genes contributing to the development of asthma and atopy demand that hundreds of patients and their family members be assessed. In Finland, the Social Insurance Institution (SII) grants substantial reimbursement for medication to all patients who meet diagnostic criteria of asthma, which include a history of asthmatic symptoms and a measured reversibility of bronchial obstruction. To recruit a large number of asthma patients efficiently in a short period of time, we took advantage of the national reimbursement procedure and retrospectively collective data on patients' medical history and lung function test results at the time of diagnosis. First, we wanted to investigate if the reimbursements could be regarded as objective verification for self-reported asthma. Altogether 335 adult self-reported asthma patients were evaluated, 87% of them were verified as having chronic asthma. Reimbursement for medication showed a sensitivity of 95% and a specificity of 76% for verified asthma. Second, we were interested to see if self-reported nasal allergic symptoms or self-reported physician diagnosed allergic rhinitis were sensitive and specific measures of allergy. The self-reported allergic nasal symptoms had a poor specificity (31% in the proband group and 59% in the family members group) when compared to the allergy screening test (Phadiatop). The best verification for self-reported asthma was achieved by combining the information on self-reported disease, granted reimbursement by the SII and the medical records. For allergies, the specificity of self-reporting was far too low to be used alone, and a positive allergy screening test together with relevant symptoms was chosen as a marker of allergy.

Adolescent↗
PubMed1998

Analogue and digital electrocardiogram recordings in the assessment of heart rate variability.

We compared analogue and digital 24-h electrocardiogram (ECG) recordings in the assessment of heart rate variability (HRV) in 41 patients with suspected coronary artery disease. The patients underwent ambulatory ECG recordings simultaneously with analogue (A) (Marquette 8500) and digital (D) (Oxford Medilog FD-3) recorders. Digital ECG recordings were analysed with the Excel Medilog II system (DE) and analogue recordings were analysed with both Marquette (AM) and Excel Medilog II (AE) systems. SDNN, SDANN, rMSSD and pNN50 were calculated for the assessment of time domain measures of HRV, and powers of low (0.04-0.15 Hz) and high (0.15-0.40 Hz) spectral components of HRV for the assessment of frequency domain measures of HRV. Correlations between time domain measures of HRV derived from AM, AE and DE recording and analysis techniques were high (r = 0.803-0.999, P < 0.001). SDANN and pNN50 assessed with AM and DE were equal, whereas SDNN and rMSSD values differed slightly but significantly from each other (P < 0.01 for both). All time domain measures of HRV assessed with AE differed significantly from AM (P < 0.001) and from DE (P < 0.01). Correlations between frequency domain measures of HRV derived from AM, AE and DE were also high (r = 0.973-0.992, P < 0.001). Despite this, frequency domain measures of HRV assessed with AM, AE and DE differed significantly from each other (P < 0.001). In conclusion, when analysed with their own analysis systems, analogue and digital recordings provided almost identical time domain, but not frequency domain, measures of HRV. In addition, analysis of an ECG recording with an analysis system of different manufacturer should be avoided.

Aged↗
PubMed1998

Imaging the structure of the striatum: a fractal approach to SPECT image interpretation.

The spatial pattern of striatal dopamine transporter density in the living human brain was tested by duplicate SPECT scans with [123I]PE2I, [123I]beta-CIT or [123I]beta-CIT-FP and striatal phantom measurements. The resolution-dependent spatial variation was calculated by the fractal analysis of SPECT images. This variation, which depends on the size of the region of interest, was described by the spatial dispersion i.e. the standard deviation of the count densities divided by the mean density. In each sub-region, the observed and methodological dispersions were computed, and the resulting spatial dispersion was calculated. The methodological dispersion is caused by the imaging resolution, flood field non-uniformity, count density, scatter, reconstruction errors and partial volume effects, whereas the spatial dispersion is based on the cerebral heterogeneity of the dopamine transporter density. Recognition of the normal variation in heterogeneity is important in evaluation of the striatal dopamine transporter density between controls and patients suffering from various neuropsychiatric disorders.

Adult↗