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Biomedical subjects

T Heinonen

Publications and source records attributed to T Heinonen.

At least 19 recordsLinked to original sources

Efficacy and short-term safety of a new ACAT inhibitor, avasimibe, on lipids, lipoproteins, and apolipoproteins, in patients with combined hyperlipidemia.

Although acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors have been shown to reduce lipid levels in several animal models, the safety and lipid modifying activity of any single agent in this class has not been demonstrated in humans. The safety and efficacy of avasimibe (CI-1011), a new, unique, wholly synthetic ACAT inhibitor, was evaluated in the treatment of 130 men and women with combined hyperlipidemia and hypoalphalipoproteinemia (low levels of high-density lipoprotein cholesterol [HDL-C]). Following an 8-week placebo and dietary-controlled baseline period, patients were randomly assigned to double-blind treatment with placebo, 50, 125, 250, or 500 mg avasimibe administered as capsules once daily for 8 weeks. At all evaluated doses, avasimibe treatment resulted in prompt and significant reductions (P<0.05) in plasma levels of total triglycerides (TG) and very low-density lipoprotein cholesterol (VLDL-C) with mean reductions of up to 23% and 30% respectively, apparently independent of dose. No statistically significant changes in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), HDL-C or apolipoprotein (apo) B were detected. ApoAI levels were also unchanged on all doses of avasimibe apart from the 500 mg dosage, which was associated with a significant decrease in plasma apoAI. The relevance of this latter finding in only one dosage group is not known. All doses of avasimibe were well tolerated with no resulting significant abnormalities of biochemical, hematological, or clinical parameters.

Acetamides↗

Magnetic resonance imaging based volume estimation of ovarian tumours: use of a segmentation and 3D reformation software.

The application of a new segmentation software, Anatomatic in the evaluation of volumetric measurements of ovarian tumours and the new Medimag three-dimensional (3D) software in the evaluation of 3D image representation of ovarian tumours with 1.5 T magnetic resonance imaging (MRI) is described. Our goal was to compare MRI based volumetry with operative findings at laparotomy for six consecutive patients with suspected ovarian tumours. Volumetric analysis and three dimensional image reconstructions of the tumours were obtained. At laparotomy, the tumour sizes were measured in situ, and the volumes were calculated. Using Anatomatic, reproducible tumour volumes were achieved with ease and within a reasonably fast time in patients with ovarian tumours without ascites. Medimag helped achieve realistic 3D representations of the tumours. For the four solitary tumours segmentation based volumetry and laparotomy findings agreed in three cases. In one patient with an oval shaped tumour, the segmented volume was double as compared to that estimated at laparotomy. Of the two patients with multiple tumours, both patients had significant ascites, and volumetry misinterpreted the fluid as tumour cyst fluid and markedly overestimated the tumour size. In conclusion, the MRI based segmentation volumetry and 3D image reconstructions are rapid, and reproducible methods of measuring ovarian tumours in patients without significant ascites.

Adult↗

Volumetric measurements of right cerebral hemisphere infarction: use of a semiautomatic MRI segmentation technique.

The applications of a new segmentation software, Anatomatic, in the evaluation of volumetric measurements of brain infarctions and the new Medimag 3D software in the evaluation of 3D image representation of infarctions are described. These programs are applied to magnetic resonance imaging. The aim of this study is to evaluate the use of these software packages in making accurate volumetric measurements in 40 patients with right cerebral infarctions, in determining the correlations between the quantitated lesions and neurological/neuropsychological dysfunctions and in creating realistic 3D views of the infarctions. Using Anatomatic, reproducible infarction volumes were achieved with ease and within a reasonably fast time. Medimag helped achieve realistic 3D representations of the infarctions. When compared, the semiautomatic segmentation proved to be much faster and yielded higher infarction volumes than the manual segmentation technique. Significantly positive correlations between the infarction volumes and neurological dysfunctions and neuropsychological deficit (neglect) helped to explain the effect of volumes on the clinical status of the patients.

Adult↗

Conceptualizing and applying a minimum basic needs approach in southern Philippines.

This study, a collaboration between Canadian and Filipino researchers, focuses on how the national government's Minimum Basic Needs (MBN) Approach has been implemented at the local level in some selected sites in Region XI on the Philippine island of Mindanao. This case study of MBN implementation focuses on the experiences of three municipalities and three barangays (villages) within them. The research explores, through interviews and group discussions, what the mayors, technical working groups and volunteer health workers in these areas thought about MBN and how they participated in the initiative. The objectives of the study were: to explore models of MBN data utilization at the municipal and barangay levels; to understand how the MBN data guided decision-making about community priorities and resource allocation; to examine the role that community volunteers played in promoting the use of MBN data, and in community health and development activities which ensued; and to determine what factors challenged or encouraged the use of MBN data for social development at the barangay level. In all the sites, MBN had some impact, most often due to methods of concentrating information on unmet basic needs locally and making use of it in planning and project development processes. The findings show that although there is still some way to go before MBN is effectively integrated into local planning and project development, some responses to problems have been implemented and innovative projects were undertaken or being considered.

Community Health Planning↗

Magnetic resonance imaging compared to ultrasonography in fetal weight and volume estimation in diabetic and normal pregnancy.

OBJECTIVE: To estimate fetal volume and weight in diabetic and normal pregnancy using high-resolution magnetic resonance imaging. METHODS: T1-weighted magnetic resonance imaging was combined with semiautomatic segmentation technique. The accuracy of fetal volume estimations thus obtained was compared with conventional ultrasound-based weight estimations in ten pregnant women with insulin-dependent diabetes mellitus and ten women with normal pregnancy. Examinations were made within 48 hours before delivery. RESULTS: Ultrasound-based estimations of fetal weight showed a correlation rate of r=0.77 with the actual birth weights in the whole material, while volume determinations based on magnetic resonance imaging showed a significantly better correlation rate of r=0.95. Diabetic women did not differ from the normal pregnancy group with regard to birth weight or the accuracy of weight estimations. CONCLUSIONS: High-resolution magnetic resonance imaging combined with semiautomatic segmentation software was found to be accurate in determining fetal volume and, consequently, better than conventional ultrasound-based techniques in estimating fetal weight. The use of magnetic resonance imaging in fetal weight estimation may be recommended for clinical situations where an accurate weight estimate is considered essential.

Adult↗

Volumes of brain atrophy and plaques correlated with neurological disability in secondary progressive multiple sclerosis.

The objectives of the present study was to correlate the segmented magnetic resonance imaging (MRI) volumes of intracranial cerebrospinal fluid (CSF) spaces (expressing the extent of brain atrophy) and cerebral plaques with the neurological disability in secondary progressive multiple sclerosis (MS). Earlier studies have mainly correlated MS plaques and neurological disability measured by expanded disability status scale (EDSS). The data on the association between brain atrophy and EDSS or regional functional scoring scale (RFSS) are very limited. We measured the volumes of intracranial CSF spaces in 28 patients with secondary progressive MS using MRI, and semiautomatic segmentation software. The volumes of T1-weighted hypointense and T2-weighted hyperintense MS plaques were also measured. In multiple regression analysis, increasing volumes of total (P=0.006) and relative (P=0.005) intracranial CSF spaces were significantly associated with worsening neurological disability as expressed by EDSS. No associations were found between these intracranial CSF space volumes and total RFSS scores. The mean volume of T2-weighted plaques showed a tendency to associate with total RFSS score (r=0.40, P=0.03), but no correlations were detected between T1- or T2-weighted plaque volumes and EDSS. The application of a new segmentation technique in quantifying intracranial cerebrospinal fluid spaces allowed an exact and sensitive way of assessing brain atrophy. The associations between brain atrophy and neurological disability expressed by EDSS suggests that the effect of MS therapies should be evaluated by measurement of brain atrophy.

Adult↗

Implementation of three-dimensional EEG brain mapping.

The electroencephalogram (EEG) visualization software was developed containing two-dimensional (2D) and three-dimensional (3D) brain mapping modules. The input to the program is standard clinical individual patient data recorded using digital EEG and magnetic resonance imaging (MRI). The software utilizes several techniques, such as heuristic triangulation, ray casting, Gouraud shading, and image fusion to form multimodal 3D images. The program has been applied to the 3D visualization of various EEG signals, "cortical" EEG signals, and potential fields generated by a computer model. The developed program appears to operate efficiently and intuitively in PC/Windows environment.

Algorithms↗

Computerised volumetric analysis of lesions in multiple sclerosis using new semi-automatic segmentation software.

The paper describes the application of new semi-automatic segmentation software to the task of detection of anatomical structures and lesion and their three-dimensional (3D) visualisation in 23 patients with secondary progressive multiple sclerosis (MS). The purpose is to study the correlation between magnetic resonance imaging (MRI) parameters (volumes of plaques and cerebrospinal fluid spaces) and clinical deficits (neurological deficits in the form of EDSS and RFSS scores, and neuropsychological deficits). The software operates in PC/Windows and PC/NeXTstep environments and utilises graphical user interfaces. Quantitative accuracy is measured by performing segmentation of fluid-filled syringes (relative error of 1.5%), and reproducibility is measured by intra- and inter-observer studies (3% and 7% variability, respectively). The mean volumes of MS plaques show significant correlations with the total RFSS scores (p = 0.04). Relative intracranial cerebrospinal fluid (CSF) space volumes show statistically significant correlation with EDSS scores (p = 0.01). The mean volume of MS plaques shows a significant correlation with the overall neuropsychological deficits (p = 0.03). 3D visualisation helps to understand the relationship of lesions to the surrounding brain structures. The use of semiautomatic segmentation techniques is recommended in the clinical diagnosis of MS patients.

Brain↗

Semi-automatic segmentation of computed tomographic images in volumetric estimation of nasal airway.

The objective of this study was to determine nasal cavity volumes and cross-sectional profiles from segmented coronal high-resolution computed tomography (HRCT) images. Pathological mucosal changes and congenital sinonasal variants were quantitated and three-dimensional (3D) images for determining sinonasal airway diseases evaluated by using the new semiautomatic segmentation software, Anatomatic. Anterior to posterior cross-sectional profiles of the sinonasal airway were obtained from acoustic rhinometry and segmented coronal HRCT images and compared in five patients having complaints of nasal obstruction and chronic sinusitis. Results showed that accurate volumes of air spaces in the nasal cavity and paranasal sinuses were obtained. When compared, the cross-sectional profiles of the nasal cavities obtained from acoustic rhinometry and the segmentation technique were similar in the anterior portion, but differed in the posterior portion. The results obtained by coronal HRCT and segmentation were more reliable than those produced with acoustic rhinometry. 3D images acquired from segmented images were found to help make a good pre-operative assessment of the whole sinonasal compartment. Segmentation and volumetric analysis using the Anatomatic technique also proved to be well suited to the evaluation of the nasal cavity and paranasal sinus geometry in patients with sinonasal diseases.

Acoustics↗

Semi-automatic tool for segmentation and volumetric analysis of medical images.

Segmentation software is described, developed for medical image processing and run on Windows. The software applies basic image processing techniques through a graphical user interface. For particular applications, such as brain lesion segmentation, the software enables the combination of different segmentation techniques to improve its efficiency. The program is applied for magnetic resonance imaging, computed tomography and optical images of cryosections. The software can be utilised in numerous applications, including pre-processing for three-dimensional presentations, volumetric analysis and construction of volume conductor models.

Brain Ischemia↗

Effect of a new HMG-CoA reductase inhibitor, atorvastatin, on lipids, apolipoproteins and lipoprotein particles in patients with elevated serum cholesterol and triglyceride levels.

The effects of atorvastatin (lipitor) on cholesterol-rich and triglyceride-rich lipoproteins were evaluated in this multicenter trial. Following a 6-week baseline period, 47 patients with elevated cholesterol and triglyceride levels were treated with atorvastatin 10 mg once daily (QD) for the initial 12 weeks (Period 1) increasing to 20 mg QD for the following 12 weeks (Period 2). At both the 10 and 20 mg doses, atorvastatin treatment resulted in significant reductions compared to pretreatment levels in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), very low-density lipoprotein cholesterol (VLDL-C), apolipoprotein (apo) B, apoB in LDL (LDL-apo B), apo B in VLDL (VLDL-apo B), lipoprotein (Lp)B, lipoprotein B-complex (LpBc), triglycerides (TG), low-density lipoprotein triglycerides (LDL-TG), very low-density lipoprotein triglyceride (VLDL-TG), high-density lipoprotein triglycerides (HDL-TG), and apo C-III. Atorvastatin 10 and 20 mg QD also resulted in significant increases in high-density lipoprotein cholesterol (HDL-C), apo AI, and LpAII:B:C:D:E. Due to its unique ability to normalize both cholesterol-rich and triglyceride-rich particles, atorvastatin is a promising candidate for monotherapy in a broad range of patients including those with varying degrees of hypercholesterolemia and hypertriglyceridemia.

Adolescent↗

Segmentation of T1 MR scans for reconstruction of resistive head models.

This paper describes a segmentation method primarily developed for reconstructing resistive head models for electroencephalographic modelling purposes. The method was implemented by combining several image processing techniques, such as amplitude segmentation, region growing, and image fusion. Also a graphical user interface was developed to enable semiautomatic approach to the segmentation process. This method was developed especially for segmentation of the brain and skull from T1-weighted magnetic resonance images, but can also be applied in any segmentation procedure. The entire project was implemented successfully in a PC-based computer running the Unix/NeXTstep operating system.

Algorithms↗

Efficacy and safety of a new hydroxymethylglutaryl-coenzyme A reductase inhibitor, atorvastatin, in patients with combined hyperlipidemia: comparison with fenofibrate.

This 24-week, randomized, open-label multicenter study evaluated the efficacy and safety of atorvastatin compared with fenofibrate in the treatment of patients with combined hyperlipidemia (CHL). Following a 6-week baseline period, 84 patients with CHL were randomly assigned to either atorvastatin treatment, 10 mg QD for 12 weeks increasing to 20 mg QD for 12 weeks, or fenofibrate treatment, 100 mg TID for 24 weeks. Changes from baseline in lipid parameters were evaluated at weeks 12 and 24. At both 10- and 20-mg doses, atorvastatin treatment resulted in significantly greater reductions in LDL cholesterol, apolipoprotein (apo) B, total cholesterol, LDL-apoB, and lipoprotein-B compared to 300-mg fenofibrate treatment (P < .05). While atorvastatin also resulted in clinically significant reductions in triglyceride, VLDL cholesterol, apoB in VLDL, triglyceride in VLDL, and apoC-III and significant increases in HDL cholesterol and apoA-I levels, fenofibrate was more effective than atorvastatin in altering all these parameters. However, by significantly affecting both the cholesterol-rich and triglyceride-rich particles, atorvastatin holds promise as a lipid-regulator able to adequately treat a broad range of patients that includes those with CHL.

Adult↗

Strenuous physical activity, aspirin and heat stress increase urinary dolichols: evidence for lysosomal origin of urinary dolichols.

Strenuous physical activity, aspirin and heat stress (Finnish sauna) were all found to significantly increase urinary dolichol excretion. In contrast, serum dolichol concentration studied before and after aspirin and sauna, was not affected. A similar aspirin-induced increase, as seen in urinary dolichol concentration, was also observed in the urinary excretion of two lysosomal enzymes--beta-hexosaminidase and beta-glucuronidase. In contrast, the excretion of two non-lysosomal enzymes--lactate dehydrogenase and leucine aminopeptidase--was not affected. The lack of correlation between serum and urinary dolichols, and the parallel increase in urinary dolichols and the activities of the lysosomal enzymes suggest that urinary dolichols may be derived from the lysosomes of the renal cells. We conclude that the finding of increased urinary dolichol concentrations in some relatively common conditions limits the clinical use of urinary dolichols as a diagnostic tool in neuronal ceroid lipofuscinosis or alcoholism.

Adult↗

Interleukin-1 beta prevents the stimulatory effect of transforming growth factor-beta on collagen gene expression in human skin fibroblasts.

Transforming growth factors beta 1 and beta 2 (TGF-beta 1 and TGF-beta 2) are well-characterized strong inducers of collagen gene expression. A 100 pM concentration of TGF-beta 1 or TGF-beta 2 increases pro alpha 1(I) collagen mRNA levels in human skin fibroblasts 6.6-fold and 7.0-fold respectively, and also increases the accumulation of procollagens in the cell culture medium. Interleukin-1 beta (IL-1 beta) is an inflammatory mediator which also regulates connective tissue metabolism. A small concentration of IL-1 beta (0.01-1.0 unit/ml) slightly increases pro alpha 1(I) collagen mRNA levels (2.2-fold). Here we provide evidence that IL-1 beta prevents the stimulatory effect of TGFs-beta on collagen synthesis in human skin fibroblasts. An IL-1 beta concentration of 1 unit/ml is enough to keep pro alpha 1(I) collagen mRNA levels at control values in cells stimulated by 100 pM-TGF-beta 1. Thus the results indicate that IL-1 beta inhibits collagen synthesis in cells activated by TGFs-beta, whereas it does not significantly change or might even stimulate collagen gene expression in non-activated cells.

Cells, Cultured↗

Enhanced peroxisomal beta-oxidation of fatty acids and glutathione metabolism in rats exposed to phenoxyacetic acids.

Peroxisomal beta-oxidation of fatty acids and the activities of glutathione-metabolizing enzymes in rat liver were measured after administration of 2,4-dichlorophenoxyacetic acid (2,4-D), 4-chloro-2-methylphenoxyacetic acid (MCPA), clofibrate [ethyl], 2-(p-chlorophenoxy)-2-methylpropionate], glyphosate (N-phosphonomethyl glycine, a herbicide not structurally related to phenoxy acids) or saline for 14 days. beta-Oxidation increased by 6-fold in the group given clofibrate, 3-fold in the 2,4-D-treated group, and 2-fold in the MCPA-treated group over the level in the controls (saline-treated). Glyphosate did not increase beta-oxidation. No significant change in reduced glutathione content from that in controls was found in any of the treated groups. Glutathione reductase activity increased by about 40% after administration of either 2,4-D or MCPA, and glutathione peroxidase activity increased by 30% in animals given MCPA. A slight decrease in glutathione S-transferase activity was found in the group treated with clofibrate. The marked increases in peroxisomal beta-oxidation of fatty acids were accompanied by only minor changes in the activities of enzymes involved in glutathione-dependent inactivation of organic hydroperoxides and other oxygen-centred reactive agents.

2,4-Dichlorophenoxyacetic Acid↗

DNA binding of [14C]styrene in isolated rat hepatocytes.

Incubation of hepatocytes from phenobarbital-pretreated rats with diethylmaleate (DEM) and 1 mM [14C]styrene for 3 to 5 hours did not result in binding of styrene 7,8-oxide (SO) to DNA as determined by ion exchange chromatography of enzymatic digests of DNA. The elution of substantial amounts of radioactivity together with natural nucleosides and bases suggests that styrene is partly metabolized via splitting of the vinyl bond and that incorporation of C1 fragments into DNA is most likely the result of repair DNA synthesis following DNA damage by styrene itself or one of its metabolites.

Animals↗