Biomedical subjects

P Pajunen

Publications and source records attributed to P Pajunen.

12 recordsLinked to original sources

PubMed2006

Level A in vitro-in vivo correlation (IVIVC) model with Bayesian approach to formulation series.

In vitro-in vivo correlation (IVIVC) models for formulation series are useful in drug development, but the current models are limited by their inability to include data variability in the predictions. Our goal was to develop a level A IVIVC model that provides predictions with probabilities. The Bayesian approach was used to describe uncertainty related to the model and the data. Three bioavailability studies of levosimendan were used to develop IVIVC model. Dissolution was tested at pH 5.8 with basket. The IVIVC model with Bayesian approach consisted of prior and observed data. All observed data were fitted to the one-compartment model together with prior data. Probability distributions of pharmacokinetic parameters and concentration time profiles were obtained. To test the external predictability of IVIVC model, only dissolution data of formulations E and F were used. The external predictability was good. The possibility to utilize all observed data when constructing IVIVC model, can be considered as a major strength of Bayesian approach. For levosimendan capsule data traditional IVIVC model was not predictable. The usefulness of IVIVC model with Bayesian approach was shown with our data, but the same approach can be used more widely for formulation optimization and for dissolution based biowaivers.

Anti-Arrhythmia Agents↗

PubMed2005

Myocardial infarction in diabetic and non-diabetic persons with and without prior myocardial infarction: the FINAMI Study.

AIMS/HYPOTHESIS: We compared the risk of acute coronary events in diabetic and non-diabetic persons with and without prior myocardial infarction (MI), stratified by age and sex. METHODS: A Finnish MI-register study known as FINAMI recorded incident MIs and coronary deaths (n=6988) among people aged 45 to 74 years in four areas of Finland between 1993 and 2002. The population-based FINRISK surveys were used to estimate the numbers of persons with prior diabetes and prior MI in the population. RESULTS: Persons with diabetes but no prior MI and persons with prior MI but no diabetes had a markedly greater risk of a coronary event than persons without diabetes and without prior MI. The rate of recurrent MI among non-diabetic men with prior MI was higher than the incidence of first MI among diabetic men aged 45 to 54 years. The rate ratio was 2.14 (95% CI 1.40-3.27) among men aged 50. Among elderly men, diabetes conferred a higher risk than prior MI. Diabetic women had a similar risk of suffering a first MI as non-diabetic women with a prior MI had for suffering a recurrent MI. CONCLUSIONS/INTERPRETATION: Both persons with diabetes but no prior MI, and persons with a prior MI but no diabetes are high-risk individuals. Among men, a prior MI conferred a higher risk of a coronary event than diabetes in the 45-54 year age group, but the situation was reversed in the elderly. Among diabetic women, the risk of suffering a first MI was similar to the risk that non-diabetic women with prior MI had of suffering a recurrent MI.

Age Factors↗

PubMed2005

Five-year risk of developing clinical diabetes after first myocardial infarction; the FINAMI study.

AIM: To investigate the incidence of clinical diabetes as determined by the incidence of diabetes drug reimbursements within a 5-year period after the first myocardial infarction (MI) in patients who were non-diabetic at the time of their first MI. RESEARCH DESIGN AND METHODS: A population-based MI register, FINMONICA/FINAMI, recorded all coronary events in persons of 35-64 years of age between 1988 and 2002 in four study areas in Finland. These records were used to identify subjects sustaining their first MI (n = 2632). Participants of the population-based risk factor survey FINRISK (surveys 1987, 1992, 1997 and 2002), who did not have diabetes or a history of MI, served as the control group (n = 7774). The FINMONICA/FINAMI study records were linked with the National Social Security Institute's drug reimbursement records, which include diabetes medications, using personal identification codes. The records were used to identify subjects who developed diabetes during the 5-year follow-up period (n = 98 in the MI group and n = 79 in the control group). RESULTS: Sixteen per cent of men and 20% of women sustaining their first MI were known to have diabetes and thus were excluded from this analysis. Non-diabetic men having a first MI were at more than twofold {hazard ratio (HR) 2.3 [95% confidence interval (CI) 1.6-3.4]}, and women fourfold [HR 4.3 (95% CI 2.4-7.5)], risk of developing diabetes mellitus during the next 5 years compared with the control population without MI. CONCLUSIONS: Many patients who do not have diabetes at the time of their first MI develop diabetes in the following 5 years.

Adult↗

PubMed2002

Serum homocysteine, creatinine, and glucose as predictors of the severity and extent of coronary artery disease in asymptomatic members of high-risk families.

BACKGROUND: There has been no previous study to determine the severity and extent of coronary artery disease (CAD) in subjects with no diagnosis or symptoms of CAD at the time of the angiography. METHODS: Fifty-three subjects, who were siblings of patients with early onset CAD, underwent coronary angiography. Indices to describe per-patient characteristics of CAD were calculated, based on computer-aided quantitative coronary angiography. Clinical and laboratory characteristics were correlated to the angiographic parameters. RESULTS: Serum total homocysteine (rho = 0.29, P < 0.05) and creatinine (rho = 0.47, P = 0.001) levels were related to the global atheroma burden index. The median of the atheroma burden index was two times higher in the top homocysteine quartile compared to the lowest quartile. The overall atheroma burden index correlated significantly with the fasting blood glucose level in all subjects. Diabetes, especially when albuminuria was present, was a powerful risk factor. In a multivariate analysis, only age and sex were independent predictors of atheroma burden. CONCLUSIONS: Serum homocysteine and creatinine concentrations, and diabetes with albuminuria were found to be markers of the severity and extent of CAD in subjects of high-risk families without symptoms of CAD.

Biomarkers↗

PubMed2001

Neurologic sequelae after caesarean section.

BACKGROUND: Because pregnancy increases the sensitivity of nervous tissue to local anaesthetics, pregnant patients may be at higher risk of developing neurologic deficits after spinal block than non-pregnant patients. Therefore, we evaluated prospectively the incidence and type of neurologic symptoms after spinal anaesthesia with hyperbaric bupivacaine for caesarean section. METHODS: In this prospective follow-up study we recorded neurologic complications during anaesthesia and postoperatively until discharge from the hospital of 219 patients, who underwent caesarean section under spinal anaesthesia with hyperbaric bupivacaine (5 mg/ml, mean 13 mg). The patients filled in a questionnaire on the first and fifth postoperative days. In the case of complaints typical of neurologic symptoms they were checked first by the anaesthesiologist and, in the case of persistent symptoms, afterwards additionally by a neurologist. RESULTS: Twenty-six of 219 patients were not included in the further evaluation because of incomplete return of their questionnaires. Seventeen mothers (8.8%) complained of transient neurologic symptoms (TNSs), lasting mostly 1-2 days, in the buttocks and/or legs during the first three postoperative days. Eleven patients (5.7%) complained of postdural puncture headache. Two patients (emergency caesarean section because of protracted labour in one and elective caesarean section because of previous caesarean section in the other) complained of persisting pain or sensory abnormalities. Neither of them felt paraesthesia during lumbar puncture. CONCLUSION: Women after caesarean section under a spinal block seem to suffer more often from TNSs than non-pregnant women. The conclusions are, however, uncertain since we had no control group operated on under other than spinal anaesthesia. The persisting neurologic symptoms in two patients might also be due to the obstetric procedure itself. To find out about the validity and possible underlying causes of our results, we need randomised studies with control groups receiving epidural or general anaesthesia.

Adolescent↗

PubMed2001

Cholesterol efflux capacity in vitro predicts the severity and extent of coronary artery disease in patients with and without type 2 diabetes.

OBJECTIVE: To investigate the relation between severity and extent of coronary artery disease (CAD) and in vitro cholesterol efflux capacity. DESIGN: This study consisted of 46 type 2 diabetic, and 42 nondiabetic men undergoing coronary angiography. Quantitative coronary angiography was used to estimate the severity, extent, and overall "atheroma burden" of CAD. The capacity of patient plasma to induce cholesterol efflux from cultured Fu5AH rat hepatoma cells was measured in vitro. RESULTS: In the combined study population (n = 88), there was a significant inverse correlation between efflux and global atheroma burden (r = -0.23, p < 0.05). In the diabetic group, the global atheroma burden index was independently associated both with cholesterol efflux and with LpA-I levels. However, in the nondiabetic CAD group this association was lost when efflux and LpA-I levels were included in the same model. CONCLUSION: The present study demonstrated that efflux capacity was inversely associated with the severity and extent of CAD. In the diabetic group this association was independent of LpA-I levels, suggesting impaired antiatherogenic potential of these particles in type 2 diabetic patients.

Aged↗

PubMed2001

Determinants of the severity and extent of coronary artery disease in patients with type-2 diabetes and in nondiabetic subjects.

BACKGROUND: Factors predicting the anatomic distribution and the severity and extent of coronary atherosclerosis in patients with clinically manifest coronary artery disease (CAD) for type-2 diabetic patients could be different than those for nondiabetic patients. OBJECTIVE: To study the determinants of severity and extent of CAD in consecutive patients with type 2 diabetes mellitus, compared with those for matched nondiabetic patients, undergoing clinically indicated coronary angiography. METHODS: Coronary angiograms of 48 men and seven women with type-2 diabetes and an equal number of nondiabetic subjects were analyzed quantitatively. Scores reflecting severity and extent of CAD were compared with potential risk factors using univariate correlation analyses and multivariate regression models. RESULTS: For the diabetics, a global coronary atheroma burden index was independently and directly related to age (P = 0.022) and to level of intermediate-density lipoprotein cholesterol (P = 0.055), and inversely to level of particles of a subtype of high-density lipoprotein (P = 0.022). Several angiographic indexes were related to the duration of diabetes and control of glycemia. For the nondiabetic group, global atheroma burden was independently related to age (P = 0.028), a history of hypertension (P = 0.028), and concentration of low-density lipoprotein (P = 0.013), and inversely to level of apolipoprotein A-I (P = 0.008). The duration of coronary disease and a history of smoking were also predictive of severe coronary atherosclerosis among nondiabetic patients. CONCLUSIONS: Classical risk factors are strong predictors of the severity and extent of coronary atherosclerosis in nondiabetic patients, but the most important determinants for type-2 diabetic patients are levels of triglyceride-rich lipoproteins and apolipoprotein A-I-containing particles of high-density lipoprotein, and factors directly related to diabetes.

Aged↗

PubMed2000

Angiographic severity and extent of coronary artery disease in patients with type 1 diabetes mellitus.

Studies of the characteristics of coronary artery disease (CAD) in diabetic patients have shown conflicting results. Only 2 studies exploring the severity of CAD, specifically in type 1 diabetes, have been published, and neither of them has used computer-aided quantitative coronary angiography. This retrospective study comprised 64 (24 women and 40 men) type 1 diabetic patients and nondiabetic control subjects. To estimate the severity, extent, and overall "atheroma burden" of CAD, we used quantitative coronary angiographic-based segmental analysis of coronary angiograms. Type 1 diabetic patients had greater global severity (p < 0.001), global extent (p < 0.001), and global atheroma burden (p < 0.001) indexes than nondiabetic control subjects. Quantitative coronary angiographic-derived indexes of CAD were, on average, 1.4- to 4.3-fold higher in diabetic than in nondiabetic patients. These differences were particularly marked in women. We found that type 1 diabetic patients with a clinical indication for coronary angiography, especially women, have more severe, extensive, and distal type of CAD than individually matched nondiabetic control patients. Our findings, including a loss of sex difference for CAD among type 1 diabetic patients and a marked impact of type 1 diabetes in women, are not explained by established risk factors.

Adult↗

PubMed1999

Ursodeoxycholic acid and endothelial-dependent, nitric oxide-independent vasodilatation of forearm resistance arteries in patients with coronary heart disease.

AIMS: Ursodeoxycholic acid (UDCA) has cholesterol lowering and anti-inflammatory effects and bile acids are reported to exert vasodilator effects; all of these properties might be considered desirable in a drug used in the treatment of patients with coronary heart disease. We investigated a hypothesis that UDCA may dilate arteries and the mechanism of action. METHODS: We evaluated effects of a 6-week treatment with UDCA in 11 coronary heart disease patients on endothelium-dependent (acetylcholine-induced) and -independent (nitroprusside-induced) vasodilatations in forearm vasculature by strain-gauge plethysmography. Healthy individuals (n=14) served as baseline controls. RESULTS: The percentage increase by acetylcholine in the flow of the infused arm relative to the non-infused arm of coronary heart disease patients during the trial remained unaltered, but vasodilatation to NG-monomethyl-l-arginine+acetylcholine was improved by 161+/-27% with UDCA vs 83+/-22% with placebo (mean difference 91% [95% CI 35%, 147%], P=0.016). CONCLUSIONS: Six weeks' UDCA therapy improved endothelium-dependent nitric oxide-independent vasodilatation, which might maintain arterial flow in coronary heart disease patients under conditions of impaired nitric oxide production.

Acetylcholine↗

PubMed1997

Quantitative comparison of angiographic characteristics of coronary artery disease in patients with noninsulin-dependent diabetes mellitus compared with matched nondiabetic control subjects.

The angiographic characteristics of coronary artery disease (CAD) in noninsulin-dependent diabetes mellitus (NIDDM) patients were studied by quantitative coronary angiography (QCA). Fifty-seven consecutive NIDDM patients undergoing clinically indicated elective coronary angiography and 57 nondiabetic coronary artery disease (CAD) patients were individually matched for sex, age, and body mass index. Technically adequate coronary angiograms, available for 55 subjects in each group, were analyzed with third-generation QCA software. To evaluate the anatomic severity and extent of CAD, several QCA-derived parameters were incorporated into indexes describing various per-patient features of CAD. These measures reflect CAD severity, extent, and overall "atheroma burden," and were calculated separately for different coronary segments (i.e., left main, proximal, mid, and distal segments), for the different coronary arterial territories (i.e., left main, left anterior descending, left circumflex, and right), and for the entire coronary tree. No significant differences were found between the NIDDM and nondiabetic groups (global severity index, 51 +/- 14 vs 54 +/- 13, p = NS; global extent index, 34 +/- 13 vs 32 +/- 12, p = NS; global atheroma burden index, 27 +/- 16 vs 24 +/- 12, p = NS). We also found no between-group differences in proximal, mid, or distal segments, in separate vessel territories, or in left ventricular function. Our data suggest that CAD patients, with and without NIDDM, who have similar symptoms at a given age, have similar severity and extent of CAD.

Coronary Angiography↗

PubMed1997

On neural blind separation with noise suppression and redundancy reduction.

Noise is an unavoidable factor in real sensor signals. We study how additive and convolutive noise can be reduced or even eliminated in the blind source separation (BSS) problem. Particular attention is paid to cases in which the number of sensors is larger than the number of sources. We propose various methods and associated adaptive learning algorithms for such an extended BSS problem. Performance and validity of the proposed approaches are demonstrated by extensive computer simulations.

Algorithms↗

PubMedDate not supplied

Least-squares methods for blind source separation based on nonlinear PCA.

In standard blind source separation, one tries to extract unknown source signals from their instantaneous linear mixtures by using a minimum of a priori information. We have recently shown that certain nonlinear extensions of principal component type neural algorithms can be successfully applied to this problem. In this paper, we show that a nonlinear PCA criterion can be minimized using least-squares approaches, leading to computationally efficient and fast converging algorithms. Several versions of this approach are developed and studied, some of which can be regarded as neural learning algorithms. A connection to the nonlinear PCA subspace rule is also shown. Experimental results are given, showing that the least-squares methods usually converge clearly faster than stochastic gradient algorithms in blind separation problems.

Algorithms↗