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Biomedical subjects

I Kantola

Publications and source records attributed to I Kantola.

At least 19 recordsLinked to original sources
PubMed2006

The effect of 12-month enzyme replacement therapy on myocardial perfusion in patients with Fabry disease.

Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder secondary to deficient alpha-galactosidase A activity which leads to the widespread accumulation of globotriaosylceramide (Gb(3)) and related glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. We have recently shown that the myocardial perfusion reserve of Fabry patients is significantly decreased. Thus, in the present study we investigated, whether it can be improved with enzyme replacement therapy (ERT). Ten patients (7 male, 3 female; mean age 34, range 19-49 years) with confirmed Fabry disease were approved for this uncontrolled, open-label study. Myocardial perfusion was measured at rest and during dipyridamole-induced hyperaemia by positron emission tomography and radiowater. Myocardial perfusion reserve was calculated as the ratio between maximal and resting perfusion. Perfusion measurements were performed before and after 6 and 12 months of ERT by recombinant human alpha-galactosidase A (Fabrazyme, Genzyme). Plasma Gb(3) concentration decreased significantly and the patients reported that they felt better and suffered less pain after the ERT. However, neither resting or dipyridamole-stimulated myocardial perfusion nor myocardial perfusion reserve changed during the ERT. Pretreatment relative wall thickness correlated negatively with posttreatment changes in flow reserve (r = -0.76, p = 0.05) and positively with posttreatment changes in minimal coronary resistance (r = 0.80, p = 0.03). This study shows that 12 months of ERT does not improve myocardial perfusion reserve, although the plasma Gb(3) concentration decreases. However, individual variation in the response to therapy was large and the results suggest that the success of the therapy may depend on the degree of cardiac hypertrophy.

Adult↗
PubMed2005

Impaired myocardial perfusion reserve but preserved peripheral endothelial function in patients with Fabry disease.

Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder due to deficient alpha-galactosidase A activity, which leads to accumulation of glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. The effect of this accumulation on peripheral and cardiac vascular function is poorly known. We studied 15 Fabry patients (mean age 35 years and mean BMI 24.8 kg/m2) and 30 age- and BMI-matched healthy controls to examine whether myocardial perfusion reserve and peripheral artery endothelial function are altered. Myocardial perfusion was measured at rest and during dipyridamole-induced hyperaemia by positron emission tomography and H2(15)O. Myocardial blood flow reserve was calculated as the ratio between the dipyridamole-induced maximal blood flow and resting blood flow. Peripheral artery endothelial function was assessed by measuring the brachial artery flow-mediated dilatation using ultrasound at rest and during reactive hyperaemia. The myocardial perfusion reserve was significantly lower in Fabry patients than in controls (3.3+/-1.2 vs 4.4+/-1.6, p=0.02), while the brachial artery flow-mediated dilatation was similar (5.9%+/-3.9% vs 4.5%+/-3.6%, p=0.27). Thus, inFabry disease, myocardial perfusion reserve is reduced while the peripheral artery endothelial function is preserved.

Adult↗
PubMed2001

ACE-inhibitor therapy with spirapril increases nocturnal hypotensive episodes in elderly hypertensive patients.

The purpose of this double-blind, randomised trial with a 4-week placebo run-in period followed by an active treatment period using either spirapril 3 mg or 6 mg once a day was to clarify the existence of hypotensive episodes in elderly hypertensive patients treated by an ACE-inhibitor. Forty hypertensive patients aged 60-76 years underwent 24-h ABPM at the end of the run-in (week 4) and active treatment (week 9) periods. The mean 24-h systolic blood pressure (SBP) decreased from 161.9 (26.7) mm Hg to 150.6 (29.9) mm Hg (P < 0.001) and diastolic blood pressure (DBP) from 91.70 (14.7) mm Hg to 84.2 (17.3) mm Hg (P < 0.001). No episodes of mean arterial pressure (MAP) <50 mm Hg were seen during the placebo period. Instead 11 episodes were observed during the antihypertensive treatment (one in the 3 mg group and 10 in the 6 mg group, P < 0.01 between the two treatment groups). Fifty-four episodes of MAP <70 mm Hg were observed during the placebo period and 117 during the treatment period (P < 0.001). During the placebo period low MAPs were observed only during night time. During the treatment period they were seen also from 11 am to 4 pm. In conclusion, ACE-inhibitor therapy with spirapril significantly increased hypotensive episodes in elderly hypertensive patients which may worsen their cerebral and myocardial circulation.

Aged↗
PubMed1999

Myocardial oxygen consumption is unchanged but efficiency is reduced in patients with essential hypertension and left ventricular hypertrophy.

BACKGROUND: Patients with hypertension and left ventricular hypertrophy (LVH) are prone to develop heart failure. We tested the hypothesis that compensatory LVH is associated with normalization of myocardial oxygen consumption and that this occurs at the expense of a decrease in the ratio between cardiac work and oxygen consumption (efficiency). METHODS AND RESULTS: Nine hypertensive men with LVH (LVH+) (age 42+/-2 years), left ventricular mass index (LVMI) 161+/-8 g/m(2), blood pressure (BP) 145+/-16/88+/-10 mm Hg (mean+/-SD); 8 hypertensive men without LVH (LVH-) (age 39+/-5 years, LVMI 107+/-15 g/m(2), BP 140+/-15/90+/-11 mm Hg); and 10 normotensive men (CONT) were studied. Myocardial blood flow, oxygen consumption, and glucose uptake were measured during euglycemic hyperinsulinemia using PET techniques. LV dimensions, volumes, and workload were determined by echocardiography, and efficiency was calculated. Myocardial workload (2.5+/-0.8 versus 3.0+/-0.6 versus 2. 3+/-0.5 mm Hg. mL. min(-1). g(-1) for CONT versus LVH- versus LVH+; P<0.05, LVH- versus LVH+), myocardial blood flow (0.84+/-0.16 versus 1.06+/-0.22 versus 0.81+/-0.09 mL. g(-1). min, respectively; P<0.05, LVH- versus other groups) and oxygen consumption (0.09+/-0.02 versus 0.14+/-0.03 versus 0.11+/-0.01 ml. g(-1). min(-1), respectively; P<0. 05, LVH- versus other groups) were increased in the LVH- group. Myocardial efficiency was reduced in the LVH+ group (18.1+/-4.1% versus 15.1+/-2.3% versus 13.5+/-1.9%, respectively; P<0.05, LVH+ versus CONT). CONCLUSIONS: Myocardial oxygen consumption per unit weight is increased in hypertensive patients without LVH but is normal in those with LVH. The normalization of oxygen consumption via hypertrophy occurs at the expense of efficiency, which may predispose hypertensive patients with LVH to heart failure.

Adult↗
PubMed1999

The effect of four different antihypertensive medications on cardiovascular regulation in hypertensive sleep apneic patients--assessment by spectral analysis of heart rate and blood pressure variability.

OBJECTIVE: To study the effect of antihypertensive medications on autonomic nervous system in patients with hypertension and sleep apnea syndrome using frequency domain measures of heart rate and blood pressure variabilities. METHODS: The beta-receptor blocking agent atenolol (50 mg), the calcium antagonist isradipine SRO (2.5 mg), the diuretic hydrochlorothiazide (25 mg) and the ACE inhibitor spirapril (6 mg) once daily were given in a double-blind crossover schedule for 8 weeks. Cardiovascular autonomic control was assessed using frequency domain measures of heart rate variability during the spontaneous and controlled breathing tests. During orthostatic maneuver and cold pressor test the blood pressure variability analysis also was performed. RESULTS: In general, the responses of heart rate and blood pressure variabilities were abnormal in the patients with arterial hypertension and sleep apnea syndrome compared to reference data. Of the four drugs, only atenolol effected heart rate and blood pressure variabilities as it shifted the autonomic regulation to the vagal direction. Other antihypertensive drugs did not change any parameter of heart rate or blood pressure variabilities. CONCLUSION: The short-term treatment with atenolol in patients with arterial hypertension and sleep apnea syndrome is associated with normalization of autonomic nervous control judged by heart rate and blood pressure variability. Thus, beta-receptor blockade may have adjunctive beneficial effects beyond blood pressure reduction in these patients. However, the long-term effects of blood pressure reduction on autonomic nervous control remain to be studied.

Adrenergic beta-Antagonists↗
PubMed1999

Reproducibility of abnormal heart rate variability indices: the case of hypertensive sleep apnoea syndrome.

Before heart rate variability can be used as an investigational tool in the clinical setting, its reproducibility must be known. We studied heart rate variability four times during 44 weeks in 15 hypertensive patients with sleep apnoea syndrome. Time and frequency domain analytical approaches were used during the spontaneous and controlled breathing tests, orthostatic manoeuvre and the cold pressor test. Alterations in resting heart rate were taken into account using the coefficient of component variance. In general, the response of heart rate variability was abnormal and variability was reduced in the hypertensive patients with sleep apnoea syndrome compared with reference data. Time domain measures of heart rate variability demonstrated generally better reproducibility over four recordings than frequency domain measures in these hypertensive patients with sleep apnoea syndrome. On the other hand, the reproducibility of frequency domain measures depended on the specific conditions: during orthostatic manoeuvre and cold pressor test the best reproducibility was found using normalized units. In the reference data set, there were no significant differences between the two heart rate variability recordings during any of the autonomic nervous function tests. In this follow-up study we found that simple procedures such as the controlled breathing test show good reproducibility. More complex tests such as the orthostatic manoeuvre require special attention in order to obtain acceptable reproducibility of heart rate variability measurements. Quantitatively minor changes in the variability indices when the overall variability is reduced exert major effects on the results. Therefore we suggest that reproducibility data obtained in healthy volunteers are not valid for the interpretation of data in patients with damaged cardiovascular autonomic control.

Adult↗
PubMed1998

Molecular genetic study of Finns with hypoalphalipoproteinemia and hyperalphalipoproteinemia: a novel Gly230 Arg mutation (LCAT[Fin]) of lecithin:cholesterol acyltransferase (LCAT) accounts for 5% of cases with very low serum HDL cholesterol levels.

In an attempt to identify genetic factors underlying extreme alterations of serum HDL cholesterol (HDL-C) concentrations, we examined two probands with HDL-C levels <0.2 mmol/L and subsequently screened two large cohorts of smoking men, one with very low (0.2 to 0.7 mmol/L, n=156) and the other with elevated (1.9 to 3.6 mmol/L, n=160) HDL-C levels, for the newly detected mutations as well as some other mutations proposed to affect HDL-C levels. One of the probands had corneal opacities, microalbuminuria, hypertriglyceridemia, and reduced LDL apoprotein B concentration; the other had anemia and presented with stomatocytosis in his peripheral blood. The first proband was found to be homozygous for a novel LCAT Gly230Arg (LCAT[Fin]) mutation, and the second was homozygous for an Arg399Cys mutation we described previously. Transient expression of the mutant LCAT(Fin) cDNA in COS cells disclosed markedly diminished LCAT enzyme activity. In the low-HDL-C group of men (n=156), 8 carriers of LCAT(Fin) and 1 carrier of the LCAT Arg399Cys were identified. In addition, the frequency of the lipoprotein lipase (LPL) Asn291Ser mutation was significantly (P<.05) higher in the low-HDL-C group (4.8%) than in the high-HDL-C group (1.6%). In addition, we identified 1 carrier of the intron 14G-->A mutation of cholesterol ester transfer protein (CETP) in the high-HDL-C group and subsequently demonstrated cosegregation of the mutant allele with elevated HDL-C levels in the proband's family. In conclusion, we have identified a novel LCAT gene Gly230Arg mutation (LCAT[Fin]), which, together with the LPL Asn291Ser mutation, represents a relatively common genetic cause of diminishing HDL-C levels, at least among Finns. This article also reports occurrence of a CETP mutation in subjects having non-Japanese roots.

Adult↗
PubMed1997

Identification of mutations in the CACNL1A3 gene in 13 families of Scandinavian origin having hypokalemic periodic paralysis and evidence of a founder effect in Danish families.

Familial hypokalemic periodic paralysis (hypoPP) is an autosomal dominant disorder characterised by episodic attacks of paralysis of varying severity. Recently, linkage was found to markers in 1q31-32 and to the gene encoding the muscle DHP-sensitive calcium channel alpha 1-subunit (CACNL1A3). Subsequently, three mutations in this gene were identified in patients with hypoPP: Arg528His, Arg1239His and Arg1239Gly. In this study, two different mutations were found in the CACNL1A3 gene in 13 Scandinavian families, 10 of whom have the Arg528His mutation while 3 families have the Arg1239His. Furthermore, there is evidence of a founder effect in 8 of the 9 Danish hypoPP families investigated, consisting of haplotypes of microsatellite markers close to and within the CACNL1A3 gene and of the geographic origin of the families. For the first time, reduced penetrance in males with the Arg528His mutation was found in several cases.

Adolescent↗
PubMed1996

Efficacy and safety of spirapril, a new ace-inhibitor, in elderly hypertensive patients.

OBJECTIVE: To compare the safety, efficacy, tolerability and duration of the antihypertensive effect of an ACE-inhibitor spirapril 3 mg or 6 mg in elderly (> or = 60 y) hypertensive patients in a multicentre, observational, double-blind randomised study. METHODS: After a four-week placebo period, 39 patients were randomised to six weeks of treatment with spirapril 3 mg and 47 patients with spirapril 6 mg. RESULTS: In the sitting position the mean (SD) decrease in systolic blood pressure (SBP) was 12(15) mmHg (95% confidence interval 7 to 17 mmHg) and in diastolic blood pressure (DBP) 10(7) mmHg (8 to 12 mmHg) in the 3-mg group and 10(13) mmHg (6 to 14 mmHg) and 9(7) mmHg (7 to 11 mmHg), respectively, in the 6-mg group (P < 0.001 compared to placebo period in both groups). Spirapril 3 mg and 6 mg produced DBP < or = 90 mmHg or a fall > or = 10 mmHg in 53% and 51% of the patients, respectively. DBP was < or = 90 mmHg in 36% and SBP < or = 160 mmHg in 67% of the patients taking 3 mg and in 26% and 63% of the patients taking 6 mg spirapril. The most commonly reported adverse effects were cough (13-17%), dizziness, headache and insomnia. A trend to a more frequent adverse effects was observed in patients receiving spirapril 6 mg. Spirapril was both cholesterol- and glucose-neutral. CONCLUSIONS: According to our study, spirapril 3mg seems to be a suitable starting dose for the treatment of hypertension in the elderly patients.

Aged↗
PubMed1996

beta-blockade, atrial natriuretic peptide and exercise.

Changes in the release of atrial natriuretic peptide (ANP) and vasopressin (VP) may contribute to the final outcome of beta-adrenoceptor blocking therapy. Therefore, we administered 2 hours before a bicycle exercise test (a 30-minute exercise with 100 W work load) in a randomized, double-blind, placebo-controlled crossover study orally 50 mg atenolol, 80 mg propranolol or 10 mg pindolol to 15 healthy volunteers. Hormone release and sympathoadrenal activation were estimated by measuring plasma ANP-, VP-, adrenaline and noradrenaline concentrations. beta-blockade and -antagonism were estimated by measuring the reduction of exercise-induced tachycardia and the extent to which the drugs occupied rabbit lung beta 1- and rat reticulocyte beta 2-adrenoceptors in the circulating plasma. We noticed clear differences in the animal beta 1- and beta 2-receptor occupancy between these agents. The agents and placebo during the exercise augmented plasma ANP level similarly, on average by 34-72%. Pindolol administration enhanced the decline of plasma ANP level after exercise (ANCOVA rep meas, pindolol vs placebo, p < 0.05). Although pindolol increased the mean plasma VP level by 25% (ANCOVA rep meas for the increase, pindolol vs placebo, p < 0.05), drug effects on plasma VP-level were generally negligible. In conclusion, in healthy volunteers beta 1- and beta 2-antagonism by pindolol, atenolol and propranolol do not markedly potentiate plasma ANP- and VP-responses to physical exercise. The responses are, however, slightly influenced presumably by the beta-agonist activity of pindolol.

Adrenergic alpha-Agonists↗
PubMed1994

Intestinal flora in early rheumatoid arthritis.

To study the role of intestinal flora in the pathogenesis of RA, we have applied computerized gas-liquid chromatography (GLC) for bacterial cellular fatty acids (CFAs) present in the stool. The CFA spectra represents the total composition of bacterial CFAs in a faecal sample. Correlation and cluster analysis of CFA spectra gathers samples with quantitatively and qualitatively similar bacterial flora into clusters, which then reveal the relationship of samples to each other. Stool samples were collected at the time of hospital admission from patients with early RA before any specific treatment. The CFA spectra in stool samples of RA patients were significantly different from those of non-RA controls. Patients with erosive RA formed a group most clearly different from the controls. Analyses based on the CFA composition of reference bacteria revealed that anaerobic bacteria are primarily responsible for the differences observed. These results suggest that intestinal bacteria play a role in the development of RA.

Arthritis, Rheumatoid↗
PubMed1994

Upper airway obstruction in hypothyroidism.

OBJECTIVES: To determine the occurrence and frequency of nocturnal upper airway obstruction in hypothyroidism. DESIGN: A case-control study of patients with newly diagnosed hypothyreosis and euthyroid subjects who had been selected from the population register. The subjects underwent sleep recordings with a static-charge-sensitive bed (SCSB). SETTING: Turku University Hospital and Research and Development Unit, Social Insurance Institution, Turku, Finland. SUBJECTS: Twenty six consecutive patients underwent sleep recordings with SCSB and a pulse oximeter. One hundred and eighty-eight euthyroid subjects who were previously studied with the SCSB were used as controls. MAIN OUTCOME MEASURES: In a multivariate analysis, hypothyroidism, gender, age, and body mass index (BMI) were considered as predictors for the occurrence of nocturnal breathing abnormalities. RESULTS: Nocturnal breathing abnormalities were frequent in both groups. Fifty per cent of the hypothyroid patients and 29.3% of the control subjects had at least some episodes of partial or complete upper airway obstruction (P = 0.04). Severe obstruction with episodes of repetitive apnoea was present in 7.7% of the patients and in 1.5% of the controls. The multivariate analysis revealed that the presence of hypothyroidism did not significantly (P = 0.06), and independently of age, BMI or gender, predict nocturnal breathing abnormalities, whereas obesity (P < 0.0001) and male gender (P = 0.0001) were independent and significant predictors. CONCLUSIONS: The incidence of nocturnal upper airway obstruction is increased in hypothyroidism, but is related to obesity and male gender rather than to hypothyroidism per se.

Adult↗
PubMed1994

Effects of antihypertensive medication on hypertension in patients with sleep apnoea.

The present study was to investigate the effect of four different antihypertensive medications [atenolol, hydrochlorothiazide (HCTZ), isradipine and spirapril] on the blood pressure and metabolic state of 18 patients with obstructive sleep apnoea. All patients received each of the drugs for a period of 8 weeks according to a randomized crossover design. Although all of the medications decreased systolic blood pressure (SBP), only spirapril decreased SBP significantly (17 +/- 15 mmHg; p < 0.001). All of the medications decreased diastolic blood pressure (DBP) significantly, but spirapril produced the greatest reduction (5-8 vs 10 mmHg, respectively). Both HCTZ and isradipine increased fasting serum total cholesterol concentration (0.3 +/- 0.5 and 0.3 +/- 0.4 mmol/l, respectively; p < 0.05). Atenolol decreased fasting serum high-density lipoprotein (HDL)-cholesterol concentration significantly (0.12 +/- 0.15 mmol/l; p < 0.01). Both HCTZ and isradipine increased fasting serum glucose concentration significantly (0.7 +/- 0.8 mmol/l and 0.6 +/- 0.7 mmol/l, respectively; p < 0.01). No significant effect on serum lipid and glucose levels was observed with spirapril. On the basis of these results, spirapril was the best medication for hypertensive patients with obstructive sleep apnoea.

Adult↗
PubMed1994

Acute exercise- and drug-induced potassium shifts during pregnancy.

The exercise- and drug-induced potassium shifts in pregnant women was studied. Six healthy nonpregnant women, six healthy pregnant women and four hypertensive, pregnant women on labetalol performed a bicycle exercise test. Blood samples for plasma potassium concentrations were drawn before, during and after the exercise. The exercise-induced plasma potassium increase was 0.9 +/- 0.2 mmol/l in healthy control women and 0.8 +/- 0.1 mmol/l in healthy pregnant women. In hypertensive pregnant women on labetalol the increase was 0.3 +/- 0.3 mmol/l (P < 0.01). There was a negative correlation (r = 0.941, P = 0.05) between the plasma potassium and labetalol concentration. Our results suggest that the potassium exchange during normal pregnancy is not changed. Labetalol reduced the exercise-induced plasma potassium increase which contrasts to other beta-blocking agents which usually augment the plasma potassium increase caused by exercise.

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↗