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Biomedical subjects

P Koskinen

Publications and source records attributed to P Koskinen.

At least 19 recordsLinked to original sources
PubMed1992

Comparison of the cardiotoxicity of ethanol in women versus men.

Subclinical left ventricular (LV) dysfunction is a common occurrence in alcoholic men but has been claimed to be absent or very rare in alcoholic women. M-mode echocardiography was performed to study LV size, mass and systolic function, and Doppler ultrasound to study LV filling in 14 chronic female alcoholics aged 24 to 48 years and in 2 age-matched control groups consisting of 17 healthy women and 22 alcoholic men. Compared with healthy women, female alcoholics had no differences in heart rate or blood pressure but a shorter LV end-diastolic diameter (mean +/- standard deviation, 46 +/- 4 vs 48 +/- 3 mm, p less than 0.05), lower fractional shortening (31 +/- 6 vs 34 +/- 3%, p less than 0.05), increased wall thickness to radius ratio (0.43 +/- 0.08 vs 0.37 +/- 0.05, p less than 0.05), reduced peak early diastolic transmitral velocity (45 +/- 11 vs 68 +/- 7 cm/s, p less than 0.001), reduced deceleration of the early diastolic velocity (-274 +/- 69 vs -572 +/- 107 cm/s2, p less than 0.001), and an increased atrial filling fraction (35 +/- 12 vs 27 +/- 5%, p less than 0.05). Although alcoholic men had a longer duration of heavy drinking than alcoholic women (median 19 vs 5 years, p less than 0.001), and a higher systolic blood pressure (140 +/- 17 vs 120 +/- 17 mm Hg, p less than 0.001), there were no statistically significant differences between the sexes either in LV diameters, wall thickness or mass normalized to body area, or in indexes of systolic or diastolic LV function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

A novel polymorphism of apolipoprotein A-IV is the result of an asparagine to serine substitution at residue 127.

We have identified a hitherto unknown genetic polymorphism of apolipoprotein A-IV (apoA-IV). The molecular basis for this polymorphism is an A to G substitution at nucleotide 1687 resulting in an Asn to Ser change of amino acid 127. The frequencies of the two apoA-IV alleles (designated apoA-IV127Asn and apoA-IV127Ser), determined by Hin c II restriction analysis of PCR amplified exon three of the apoA-IV gene, were 0.788 and 0.212, respectively, in a Finnish population sample. Allele frequencies of another polymorphism due to a Thr to Ser substitution at amino acid 347 were determined using Hinf I restriction analysis. The allele frequencies were 0.823 for apoA-IV347Thr and 0.177 for apoA-IV347Ser. None of the apoA-IV polymorphisms (apoA-IV127:Asn----Ser, apoA-IV347:Thr----Ser and apoA-IV360:Gln----His) had any effect on plasma lipid and lipoprotein concentrations in cohorts of dyslipidemic men and in a population sample of normolipidemic controls. There was also no association between the history of previous myocardial infarction and any of the apoA-IV alleles.

Alleles↗
PubMed1992

Leukocytes as a coronary risk factor in a dyslipidemic male population.

The role of an elevated serum leukocyte count (WBC) as a coronary risk factor was investigated using a nested case-control design in dyslipidemic middle-aged men (n = 420) participating in the Helsinki Heart Study, a coronary primary prevention trial. Baseline WBC was significantly higher, 6.93 (2.11) x 10(9)/L in subjects with cardiac events, than in controls, 6.26 (1.88) x 10(9)/L; p less than 0.002. This association was time-dependent, however, since the difference was not significant for events occurring during the second half of the 5-year study. Using nonsmokers in the lowest WBC tertile as the reference sample, the relative risks in the highest WBC tertile were 1.86 (95% confidence intervals [CI] 0.81 to 4.28) for nonsmokers and 3.07 (95% CI 2.23 to 8.19) for smokers. Logistic regression analysis including smoking in the model disclosed an independent contribution of elevated WBC to coronary heart disease. We conclude that elevated leukocyte count was a coronary risk factor even in this dyslipidemic population.

Case-Control Studies↗
PubMed1992

Serum androgen and gonadotropin levels decline after progestogen-induced withdrawal bleeding in oligomenorrheic women with or without polycystic ovaries.

OBJECTIVE: To examine the effect of short-term progestogen treatment on androgen, gonadotropin, and sex hormone-binding globulin (SHBG) levels in oligomenorrheic women. DESIGN: Comparative study of changes in hormonal parameters in patients with or without ultrasonographically diagnosed polycystic ovarian disease (PCOD). SETTING: Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. PATIENTS: Seventy-five oligomenorrheic women with (n = 51) or without (n = 24) PCOD. MAIN OUTCOME MEASURES: Serum concentrations of testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and SHBG. RESULTS: The levels of T, A, LH, and the LH:FSH ratios decreased significantly after oral treatment with medroxyprogesterone acetate (10 mg/d for 10 days) in non-PCOD women and in women with PCOD decreasing the frequencies of pathological laboratory findings, in particular elevated levels of LH:FSH ratio and A in PCOD women and of LH:FSH ratio in non-PCOD women. The levels of T, A, and LH as well as the LH:FSH ratio were significantly higher in women with PCOD. Obesity was associated with high free androgen indices, low LH:FSH ratios, and low concentrations of LH, A, and SHBG. CONCLUSIONS: The serum samples for hormonal analyses used as an aid in diagnosing PCOD should be obtained without pretreatment with progestogen because it masks the biochemical findings of PCOD.

Adolescent↗
PubMed1992

Alcohol and sauna bathing: effects on cardiac rhythm, blood pressure, and serum electrolyte and cortisol concentrations.

The effect of heavy drinking and sauna bathing on cardiac rhythm, blood pressure, and serum electrolyte and cortisol concentrations was studied in 10 healthy male volunteers. Sauna bathing induced a comparable, significant increase in heart rate with and without alcohol consumption. During sauna bathing without alcohol, systolic blood pressure remained at the baseline level, whereas sauna and alcohol together decreased systolic blood pressure markedly from 136 +/- 4 to 113 +/- 3 mmHg (P less than 0.01). Neither sauna alone, nor sauna combined with alcohol intake, increased the frequency of premature ventricular complexes. Serum potassium, calcium and cortisol concentrations changed slightly during sauna, but alcohol consumption did not contribute further to this. In conclusion, sauna bathing, even in combination with heavy drinking, does not appear to provoke cardiac arrhythmias in healthy young men. However, the risk of hypotension is increased when sauna bathing is combined with alcohol consumption.

Adult↗
PubMed1992

Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study. Implications for treatment.

BACKGROUND: We studied the joint effect of baseline triglyceride and lipoprotein cholesterol levels on the incidence of cardiac end points in the trial group (n = 4,081) of the Helsinki Heart Study, a 5-year randomized coronary primary prevention trial among dyslipidemic middle-aged men. The relative risks (RR) were calculated using Cox proportional hazards models with a dummy variable technique that allows simultaneous study of subgroup combinations from the placebo and treatment groups. METHODS AND RESULTS: In the placebo group (n = 2,045), the low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) ratio was the best single predictor of cardiac events. This ratio in combination with the serum triglyceride level revealed a high-risk subgroup: subjects with LDL-C/HDL-C ratio greater than 5 and triglycerides greater than 2.3 mmol/l had a RR of 3.8 (95% CI, 2.2-6.6) compared with those with LDL-C/HDL-C ratio less than or equal to 5 and triglyceride concentration less than or equal to 2.3 mmol/l. In subjects with triglyceride concentration greater than 2.3 mmol/l and LDL-C/HDL-C ratio less than or equal to 5, RR was close to unity (1.1), whereas in those with triglyceride level less than or equal to 2.3 mmol/l and LDL-C/HDL-C ratio greater than 5, RR was 1.2. The high-risk group with LDL-C/HDL-C ratio greater than 5 and triglyceride level greater than 2.3 mmol/l profited most from treatment with gemfibrozil, with a 71% lower incidence of coronary heart disease events than the corresponding placebo subgroup. In all other subgroups, the reduction in CHD incidence was substantially smaller. CONCLUSIONS: Serum triglyceride concentration has prognostic value, both for assessing coronary heart disease risk and in predicting the effect of gemfibrozil treatment, especially when used in combination with HDL-C and LDL-C.

Adult↗
PubMed1992

Coronary heart disease incidence in NIDDM patients in the Helsinki Heart Study.

OBJECTIVE: To determine coronary heart disease (CHD) incidence among dyslipidemic subjects with non-insulin-dependent diabetes mellitus (NIDDM) and to assess the effect of lipid-modifying treatment on serum and lipoprotein lipids and the CHD incidence in these patients. RESEARCH DESIGN AND METHODS: Of the 4081 men participating in the Helsinki Heart Study, a coronary primary prevention trial with gemfibrozil in middle-aged men with high non-high-density lipoprotein (HDL) cholesterol (greater than 5.2 mM; 200 mg/dL), 135 had NIDDM at entry. The incidence of definite myocardial infarction and cardiac death and changes in serum and lipoprotein lipids were determined during the 5-yr trial in the NIDDM patients and compared with those observed in nondiabetic trial participants. RESULTS: Compared with nondiabetic subjects, NIDDM patients had lower HDL cholesterol (P less than 0.001), higher triglyceride concentration (P less than 0.0001), and greater body mass index (P less than 0.001), there were more hypertensive patients (P less than 0.001) among them. The incidence of myocardial infarction and cardiac death was significantly higher among diabetic than nondiabetic participants (7.4 vs. 3.3%, respectively, P less than 0.02). CHD incidence in the gemfibrozil-treated diabetic men (n = 59) was 3.4% compared with 10.5% in the placebo group (NS). In multivariate analysis, diabetes (P less than 0.05), age (P less than 0.0001), smoking (P less than 0.0001), low HDL cholesterol (P less than 0.05), and high low-density lipoprotein cholesterol (P less than 0.005) were independently related to CHD incidence. Gemfibrozil-induced serum and lipoprotein lipid changes in diabetic patients were similar to those observed in nondiabetic subjects. CONCLUSIONS: Compared with similarly dyslipidemic nondiabetic subjects, patients with NIDDM are at markedly increased risk of CHD. This elevated risk can be somewhat reduced by gemfibrozil.

Blood Glucose↗
PubMed1992

Blood glycated haemoglobin, serum fructosamine, serum glycated albumin and serum glycated total protein as measures of glycaemia in diabetes mellitus.

Blood glycated haemoglobin (HbAlc), serum fructosamine (FA), serum glycated albumin (GA), and serum glycated total protein (GTP) were determined in 61 subjects (19 pregnant women with gestational diabetes, 24 pregnant women with insulin-dependent diabetes mellitus [IDDM] and 18 nonpregnant subjects with IDDM). FA, GA, and GTP correlated with HbAlc similarly (r = 0.791, 0.816, and 0.794, respectively, p < 0.001). In a subgroup of 22 subjects data on blood glucose home monitoring was recorded and used for calculating mean blood glucose as an index of average glycaemia preceding sampling of the glycation products. Mean blood glucose levels preceding sampling of HbAlc by 2 months and FA, GA, or GTP by three weeks correlated significantly with HbAlc (r = 0.668, p < 0.001) and GA (r = 0.441, p < 0.05) whereas no significant correlation was found between mean blood glucose and FA (r = 0.003) or GTP (r = 0.252). In conclusion, such methods which measure specifically the non-enzymatic glycation of a single species of protein (i.e. FPLC for HbAlc and affinity chromatography for GA) are to be preferred for assessing glycaemia.

Adult↗
PubMed1992

A chimeric EGFR/neu receptor in functional analysis of the neu oncoprotein.

As the factor binding to the neu protein has been unknown, it has not been possible to confirm experimentally the proposed growth-factor receptor like functions of the neu protein. To approach this problem we constructed a recombinant receptor which enabled ligand regulation of the neu tyrosine kinase. The hybrid receptor consisted of the extracellular ligand binding, transmembrane and protein kinase C-substrate domains joined to the intracellular tyrosine kinase and carboxyl-terminal domains of the neu protein. Several properties of NIH3T3 cells carrying this construct were tested. We obtained the first experimental evidence that the neu proto-oncogene has mitogenic and transforming activities only in the presence of a ligand stimulating its tyrosine kinase activity. Various cellular and molecular biological parameters indicated that the chimeric receptor behaved very similarly to the EGFR. Also, this chimeric receptor has allowed us to compare the constitutive oncogenic and the ligand-activated non-oncogenic activities of the neu tyrosine kinase. In the future we plan to focus on characterization of possible differences between EGFR and neu signalling in more differentiated cellular backgrounds.

3T3 Cells↗
PubMed1992

Plasma atrial natriuretic factor during ethanol ingestion in volume-loaded subjects.

The present study was designed to test whether ethanol ingestion affects plasma atrial natriuretic factor (ANF) concentration in healthy volunteers. On the basis of previous studies showing that ethanol induces a diuretic response and a decrease in atrial size (atrial distension), it was hypothesized that ethanol intake might be associated with a decrease in plasma ANF level. To somewhat increase plasma ANF level, the subjects were slightly loaded with water before the trial. As compared with juice, ethanol, 1 g/kg within 1 hr, increased urine output [405 +/- 37 (mean +/- SEM) ml/hr vs. 197 +/- 20 ml/hr, P less than 0.001]. Left atrial size decreased similarly (P less than 0.001) with both drinks. Plasma ANF concentration did not change with either ethanol or juice during the 3-hr study period. No changes were observed in plasma arginine vasopressin concentration and plasma renin activity. Our results are in conflict with previous reports in fasted subjects showing significant changes in plasma concentrations of the same hormones. Thus, the basal fluid balance seems to be crucial to the hormonal response to ethanol. The plasma concentrations of the hormones measured in this study do not directly explain the diuretic response to ethanol observed in slightly volume-loaded subjects.

Adult↗
PubMed1992

Reference intervals for 24-h urinary normetanephrine, metanephrine, and 3-methoxy-4-hydroxymandelic acid in hypertensive patients.

The urinary excretion of normetanephrine, metanephrine, and 3-methoxy-4-hydroxymandelic acid was quantified by HPLC in hypertensive patients who were being routinely investigated for the exclusion of pheochromocytoma. The data were used to calculate reference intervals for these analytes. Age- and sex-specific 95% reference intervals for 24-h urinary excretion were as follows (mumol/24 h): normetanephrine in men ages 16-35 years (n = 17) 0.7-3.4, in men older than 35 years (n = 121) 0.8-5.1, in women ages 16-35 years (n = 41) 0.5-2.1, and in women older than 35 years (n = 144) 0.6-3.3 mumol/24 h; metanephrine in men (n = 138) 0.3-2.0, and in women (n = 185) 0.2-1.3; and 3-methoxy-4-hydroxymandelic acid in men (n = 142) 10-54, and in women (n = 184) 9-38. Normetanephrine or metanephrine excretion rates or both exceeded the proposed reference intervals in seven of the eight patients with pheochromocytoma. Determination of 3-methoxy-4-hydroxymandelic acid excretion did not yield any additional diagnostic information.

Adolescent↗
PubMed1992

Gemfibrozil also corrects dyslipidemia in postmenopausal women and smokers.

We compared the efficacy of three formulations and two dosage regimens of gemfibrozil in 322 dyslipidemic (non-high-density lipoprotein [HDL] cholesterol level, greater than or equal to 5.2 mmol/L [greater than or equal to 200 mg/dL]) middle-aged male and postmenopausal female patients in a 1-year open-label trial. Of the patients studied, 109 received the standard 1200-mg dose of gemfibrozil, ie, two 300-mg capsules twice daily; 107 received one 600-mg tablet twice daily; and 106 received a single dose of 900 mg of gemfibrozil in two 450-mg tablets in the evening. The three treatment groups showed equal changes in each lipoprotein measure studied, ie, in serum levels of triglycerides, total cholesterol, low-density lipoprotein and HDL cholesterol, HDL subfractions HDL2 and HDL3, and apolipoproteins A-I, A-II, and B. When the therapeutic responses were analyzed separately in men (n = 219) and women (n = 103), significantly greater decreases in serum levels of total triglycerides, low-density lipoprotein cholesterol, and apolipoprotein B, and a significantly greater increase in HDL3 cholesterol level and apolipoprotein A-I/B ratio, were seen in the women. When the study population was divided into smokers (n = 80) and nonsmokers (n = 242), the changes were similar in all lipoprotein measures except HDL3 cholesterol level, in which a significantly greater increase was seen in the non-smokers. This study showed that gemfibrozil is as effective, or more so, in dyslipidemic postmenopausal women as in dyslipidemic middle-aged men, and that smoking does not abolish its lipid-regulating effects. Importantly, a daily dose of 900 mg was found to be as effective as the standard dose of 1200 mg.

Apolipoproteins B↗
PubMed1991

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↗
PubMed1991

Time of onset of supraventricular tachyarrhythmia in relation to alcohol consumption.

It is widely believed but has never been proved that idiopathic supraventricular tachyarrhythmias beginning during or after weekends or winter holidays are frequently alcohol-related ("holiday heart" syndrome). The time of arrhythmia onset was therefore studied in relation to self-reported ethanol consumption and results of a screening test for alcoholism (CAGE questionnaire) in 289 patients aged less than 65 years admitted for supraventricular tachyarrhythmias. There were 102 patients having an etiologically idiopathic arrhythmia with a known time of onset. Among them, but not among those with disease-related arrhythmias, patients with arrhythmic episodes beginning on Saturdays or on Sundays were more often chronic alcohol abusers (9 of 19, 47%) than either patients with episodes beginning from Mondays through Fridays (18 of 83, 22%; p = 0.040) or control subjects from the out-of-hospital population (8 of 66, 12%; p = 0.002). In multivariate analysis, the time of arrhythmia onset was related to the CAGE response (G2 = 6.0, p = 0.014) but not to the most recent ethanol use. However, the increased frequency of problem drinkers among patients with weekend-onset idiopathic arrhythmias was only relative, and resulted from a decreased number of abstainers and non-problem drinkers. No conspicuous clustering of alcohol-related arrhythmias was seen after New Year's or May Day. Thus, although the present study confirms an association between heavy drinking and idiopathic arrhythmias beginning during weekends, it shows that the question may be of a relative rather than an absolute overrepresentation. The term holiday heart may also be somewhat misleading since no postholiday accumulation of alcohol-related arrhythmias was found.

Alcohol Drinking↗
PubMed1991

Characterization of the enzyme activity of human plasma lipoprotein (a) using synthetic peptide substrates.

The plasma concentration of lipoprotein (a) [Lp(a)] is correlated with the risk of atherosclerosis. It is a lipoprotein particle consisting of apoprotein (a) [Lp(a)] is correlated with the risk of atherosclerosis. It is a lipoprotein particle consisting of apoprotein (a) [apo(a)], a protein showing considerable amino acid sequence identity with plasminogen. bound to low-density lipoprotein. The apo(a) portion of Lp(a) was recently shown to have serine-proteinase-type amidolytic activity and to be able to degrade the adhesive glycoprotein fibronectin. To characterize this enzyme activity further, we used chromogenic peptide substrates and inhibitors. Of the substrates tested, those with arginine at the scissile bond [N-alpha-benzoyl-L-Arg p-nitroanilide (pNA), N-alpha-benzoyl-Ile-Glu-Gly-Arg-pNA, N-alpha-benzyloxycarbonyl-Arg-Gly-Arg-pNA] gave the highest hydrolysis rates. Synthetic substrates with plasmin specificity (Val-Leu-L-Lys-pNA and Val-Phe-L-Lys-pNA) were not hydrolysed by Lp(a). Neither tissue plasminogen activator nor urokinase had any effect on the enzyme activity. The addition of antibodies to these plasminogen activators did not inhibit the enzyme activity of Lp(a). Inhibition experiments with phenylmethanesulphonyl fluoride, carbodi-imide, dichloroisocoumarin and competitive peptide inhibitors demonstrated that Lp(a) has enzyme activity that closely resembles that of serine proteinases. Whether this serine-proteinase activity of Lp(a) plays any role in the genesis of atherosclerosis remains to be established.

Amino Acid Sequence↗
PubMed1991

Left ventricular size, mass and function in relation to the duration and quantity of heavy drinking in alcoholics.

Left ventricular (LV) hypertrophy and mild dysfunction are frequently observed in alcoholics but little is known about how they relate to the duration and severity of alcohol abuse. LV size, mass and function were studied using echocardiography and systolic time intervals in 78 middle-aged male alcoholics who also gave detailed accounts of the duration of heavy drinking, the quantity of recent ethanol consumption and the duration of abstinence. Compared with 34 healthy nonalcoholics, alcoholics had a higher LV mass index (85 +/- 2 [mean +/- standard error] vs 77 +/- 2 g/m2, p = 0.001), a thicker posterior wall (11 +/- 0.2 vs 10 +/- 0.2 mm, p = 0.02), a longer end-systolic diameter index (18 +/- 0.3 vs 17 +/- 0.3 mm/m2, p = 0.02), and a higher preejection period/ejection time ratio (0.36 +/- 0.01 vs 0.33 +/- 0.01, p = 0.002). In multivariate linear regression models, these abnormalities proved independent of the drinking history, except that posterior wall thickness was weakly related to the duration of heavy drinking (standardized correlation coefficient 0.36, p = 0.01). Univariate analyses suggested that the LV mass index and systolic time interval ratio had, if anything, a curvilinear relation to the total duration of heavy alcohol consumption. It is concluded that the LV hypertrophy and dysfunction found in alcoholics are poorly related to the duration and severity of self-reported alcohol abuse. Together with other data, this suggests that there is no simple linear dose-injury relation in the long-term cardiotoxicity of ethanol. Factors modifying the myocardial effects of ethanol need to be studies more in the future.

Adult↗