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K Pulkki

Publications and source records attributed to K Pulkki.

At least 19 recordsLinked to original sources
PubMed2001

Cytokine levels in midtrimester amniotic fluid in normal pregnancy and in the prediction of pre-eclampsia.

Midtrimester amniotic fluid cytokines may reflect the function of the maternal immune system in the maternal-fetal interface and thus be predictive of pre-eclampsia. We determined the concentrations of interleukin (IL)-6, IL-8, IL-10, IL-11, IL-12, IL-15, tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta in amniotic fluid at 14-16 weeks of gestation from women with normal pregnancies and from those who subsequently developed severe pre-eclampsia. The concentrations of the cytokines in amniotic fluid did not significantly differ between patients and normal controls. The median concentration of IL-6 was 950 pg/ml in normal pregnant women and 578 pg/ml in the patient group. The median concentration of IL-8 was 606 pg/ml in normal controls and 294 pg/ml in the patient group. The levels of IL-6, IL-8 and TGF-beta correlated positively with each other. TNF-alpha concentrations were low and similar in both groups. IL-10 and IL-12 were detected at very low levels in 37 and 7% of the samples, respectively. No difference was found in IL-15 concentrations between the groups. IL-11 was found only at low levels in both groups. Although none of the cytokines measured was predictive of pre-eclampsia, this study provides information of cytokines in amniotic fluid during the period when the spiral arteries are remodelled.

Adult↗
PubMed2001

Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats.

We investigated the role of cardiomyocyte apoptosis in the remodeling of the left ventricle from 24 h to 12 wk after myocardial infarction in the rat. Infarct size planimetry, quantification of cardiomyocyte apoptosis, terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) methodology, and echocardiography (left ventricular diastolic diameter and ejection fraction) were performed. Sham-operated animals showed low rates of cardiomyocyte apoptosis (0.03%) and no change in diastolic diameter or ejection fraction during the study. Twenty-four hours after infarction, TUNEL positivity was high in the infarct areas (1.4%) and border zones (4.9%). It declined to 0.34% (P < 0.01 vs. sham) at 4 wk and 0.10% at 12 wk in the border zones. In the remote myocardium, cardiomyocyte apoptosis increased to 0.07% (P = 0.03 vs. sham) on day 1 and remained on the same level up to 4 wk. The increase in diastolic diameter 1-4 wk after infarction correlated (r = 0.60, P < 0.01) with cardiomyocyte apoptosis in the noninfarcted myocardium, which quantitatively contributed most (>50%) to the apoptotic cell loss by 4 wk.

Animals↗
PubMed2000

Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis.

Despite well-documented cardiotoxic effects, doxorubicin remains a major anticancer agent. To study the role of myocardial apoptosis following doxorubicin administration, male Wistar rats were exposed to 1.25, 2.5, and 5 mg/kg of i.p. doxorubicin and terminated on days 1-7 in groups of five. Doxorubicin caused a significant (P < 0.001) and dose-dependent induction of cardiomyocyte apoptosis at 24-48 h after the injection. Repeated injections of 2.5 mg/kg given every other day resulted in peaks of apoptosis at 24 h after each injection. However, no additive effect of repeated dosing was noted. In histological samples, alterations in the cytoskeletal apparatus with focal loss of contractile elements were seen after a single injection. Myocyte necrosis was absent. Thus, acute doxorubicin-induced cardiotoxicity involves cardiomyocyte apoptosis, a potentially preventable form of myocardial tissue loss.

Animals↗
PubMed2000

Bactericidal/permeability-increasing protein (BPI) in sepsis correlates with the severity of sepsis and the outcome.

OBJECTIVE: To compare the prognostic significance of bactericidal/permeability-increasing protein (BPI), group II phospholipase A2 (PLA2-II), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF), interleukin-8 (IL-8) and interferon-gamma (IFN) in terms of predicting severity of sepsis and outcome. DESIGN: A prospective study. SETTING: Medical intensive care unit (ICU) of a university hospital. PATIENTS: Thirty-four patients with severe sepsis requiring ICU treatment. MEASUREMENTS AND RESULTS: The levels of BPI, PLA2-II, CRP, TNF, IL-8 and IFN were measured in these 34 patients. High levels of BPI were associated particularly with Gram-negative sepsis. BPI and BPI/neutrophil ratios correlated positively with PLA2-II, CRP, TNF and IL-8 and negatively with blood pressure. At 24 h, BPI/neutrophil ratios, IL-8 and Simplified Acute Physiology Scores II (SAPS II) scores were higher in non-survivors than in survivors. No such associations were noted in the levels of CRP, PLA2-II, TNF or IFN. The areas under the curve (AUC(ROC)s) of SAPS II scores and IL-8 were higher than AUC(ROC) of BPI/neutrophil ratio. CONCLUSION: The BPI and BPI/neutrophil ratios may serve as adjunctive tools to illustrate the severity of sepsis. However, their predictive power for sepsis-related death was not comparable to that of SAPS II scores and IL-8.

Adult↗
PubMed2000

Level of circulating phospholipase A2 in prediction of the prognosis of patients with suspected myocardial infarction.

OBJECTIVES: Atherosclerotic lesions result from inflammatory-proliferative responses of the endothelium and smooth muscle of the arterial wall. Poor prognosis of acute myocardial infarction (AMI) patients has been associated with elevated levels of acute phase proteins including C-reactive protein. We investigated the significance of circulating phospholipase A2 in the long-term prognosis of suspected AMI patients. METHODS: The concentration of phospholipase A2 was measured by an immunoassay in sera of 100 suspected AMI patients. Admission phospholipase A2 95 % fractile outliers were excluded to eliminate the effect of acute infectious diseases. The total and atherosclerotic mortalities were followed for a 4-year period. RESULTS: The most powerful prognostic limit for both admission (p = 0.02, RR = 2.6 and 95% CI = 1.2 to 5.6) and maximal (p = 0.06, RR = 2.4 and 95% CI = 0.96 to 5.9) phospholipase A2 groups was > or =8 microg/l. The admission phospholipase A2 level had an independent prognostic significance for atherosclerotic mortality (p = 0.04, RR = 2.4 and CI = 1.02 to 5.8) in multivariate analysis with CK-MB and age. CONCLUSIONS: The elevated serum phospholipase A2 level at admission is an independent predictor of long-term atherosclerotic mortality in patients with suspected AMI. The prognostic significance of phospholipase A2 weakens during hospitalisation concomitant to the onset of the acute inflammatory response to myocardial injury.

Aged↗
PubMed2000

Morphologic and biochemical hallmarks of apoptosis.

Apoptosis is characterised by a series of typical morphological features, such as shrinkage of the cell, fragmentation into membrane-bound apoptotic bodies and rapid phagocytosis by neighbouring cells. This paper reviews the current knowledge on the molecular mechanisms of apoptosis as they relate to the morphologic hallmarks and their implications for the detection of apoptosis in cardiac tissue. Activation of cysteine proteases called caspases plays a major role in the execution of apoptosis. These proteases selectively cleave vital cellular substrates, which results in apoptotic morphology and internucleosomal fragmentation of DNA by selectively activated DNases. In response to several pro-apoptotic signals, mitochondria release caspase activating factors, that initiate an escalating caspase cascade and commit the cell to die. Members of the Bcl-2 oncoprotein family control mitochondrial events and are able to prevent, or induce, both apoptotic and non-apoptotic types of cell death. This suggests that different types of cell death share common mechanisms in the early phases, whereas activation of caspases determines the phenotype of cell death. Detection of apoptotic cells in tissue samples currently relies on the TUNEL assay. TUNEL-positive cardiomyocytes show morphological features of apoptosis and the typical ladder pattern in DNA electrophoresis. Thus, provided that the staining protocol is carefully standardised, this quantitative methodology provides reproducible results of the occurrence of cardiomyocyte apoptosis in cardiac samples. Recently, potentially more specific assays based on analysis of DNA fragmentation or demonstration of caspase activation have been developed. Applicability of these assays to demonstrate cardiomyocyte apoptosis should be tested.

Animals↗
PubMed2000

Cardiac decompensation during an ischemic event weakens the predictive power of myocardial injury markers.

Our objection was to find determinants of long-term outcome in routine data collected for differential diagnosis of suspected acute myocardial infarction. Study population consisted of 263 discharged patients who were initially hospitalized for differential diagnosis of suspected acute myocardial infarction between October 1992 and January 1993. Follow-up time for all cause and cardiac mortality was 5 years. The variables studied as predictors of outcome were computerized ECG, peak creatine kinase isoenzyme MB, peak troponin I, radiographic evidence of pulmonary congestion (cardiac decompensation), treatment for hyperlipidemia, hypertension or diabetes, smoking, previous myocardial infarction, age and gender. Total mortality was 32% at 5 years, of which 77% (64/83) was of cardiac origin. Pulmonary congestion in chest X-ray was the most powerful predictor of outcome (RR=3.3, 95% CI=2.0-5.2, P<0.001). In multivariate analysis congestion (RR=3.3, CI=2.0-5.2) was the only independent predictor of 5-year total mortality in addition to age (RR=1.06, CI=1.04-1.08). These two variables together with previous myocardial infarction (RR=1.9, CI=1.2-3.1) and hyperlipidemia (RR=2. 0, CI=1.1-3.5) were independent predictors of cardiac mortality. Radiographic evidence of cardiac decompensation during hospitalization is a strong and independent predictor of long-term outcome in unselected patients with suspected AMI. The predictive power of cardiac markers is confined to patients without pulmonary congestion.

Aged↗
PubMed2000

RT-PCR from eosinophil-depleted leukocytes without RNA extraction: cell selection using streptavidin PCR tubes.

OBJECTIVES: The major RNase activity of leukocytes has been attributed to eosinophil-derived neurotoxin EDN. Depletion of eosinophils enables RT-PCR from 10(5) leukocytes without RNA extraction. In this study we introduced streptavidin-coated PCR tube strips for the selection of eosinophil-free leukocytes for RT-PCR analysis. DESIGN AND METHODS: Polypropylene 0.2 ml PCR tube strips were coated with streptavidin and biotinylated antibodies against cell surface antigens were attached to the tubes. CD7-positive T-lymphocytes, CD19-positive B-lymphocytes and CD16-positive cells (mainly neutrophils and monocytes) were positively selected by incubating of 1-2 x 10(5) leukocytes in the antibody-coated PCR tubes for 30 min at 23 degrees C. RESULTS: The mean amount of cells bound into a tube was 31,500 (CV25%) T-cells and 8,600 (CV61%) B-cells from 12 blood samples, and 23,600 (CV22%) CD16+ cells from 17 samples. The influence of selected cell lysate on the RT-PCR analysis of Philadelphia chromosome (bcr/abl translocation) from 100 K562 cells was small: 78% (CV28%) of the leukocyte-free signal was obtained in the presence of CD16+ cells or 89% (CV15%) and 99% (CV11%) and in the presence of T-cells and B-cells, respectively. CONCLUSIONS: These results suggest that through the introduction of eosinophil-free cell population into RT-PCR a reproducible method with reasonable leukocyte yield and avoiding RNA extraction was developed.

Adolescent↗
PubMed2000

Plant stanol ester margarine lowers serum total and low-density lipoprotein cholesterol concentrations of healthy children: the STRIP project. Special Turku Coronary Risk Factors Intervention Project.

OBJECTIVE: To investigate cholesterol-lowering efficacy and safety of plant stanol ester margarine in healthy 6-year-old children already consuming a low-saturated-fat, low-cholesterol diet. STUDY DESIGN: Eighty-one intervention children from the STRIP project, a randomized prospective trial aimed at reducing exposure of young children to the known environmental atherosclerosis risk factors, were recruited to this double-blind crossover study at 6 years of age. In randomized order the families were advised to replace daily 20 g of the child's dietary fat intake with plant stanol ester margarine or control margarine for 3 months. The washout period lasted 6 weeks. Statistical analysis was performed according to intention-to-treat principle with analysis of variance for crossover design. RESULTS: The mean daily plant stanol ester margarine consumption was 18.2 g (1.5 g plant stanol). The well-tolerated plant stanol ester margarine reduced serum total and low-density lipoprotein cholesterol concentrations by 5.4% and 7.5%, respectively (P =.0001 for both). The serum high-density lipoprotein cholesterol and triglyceride concentrations and alpha-tocopherol to low-density lipoprotein cholesterol ratio remained unchanged. The serum beta-carotene to low-density lipoprotein cholesterol ratio decreased by 19% (P =.003). CONCLUSION: Plant stanol ester margarine significantly diminishes serum total and low-density lipoprotein cholesterol concentration without adverse clinical effects in healthy children who already consume a low-saturated-fat, low-cholesterol diet but decreases the serum beta-carotene to low-density lipoprotein cholesterol ratio.

Child↗
PubMed2000

Effect of lysine infusion on urea cycle in lysinuric protein intolerance.

Poor intestinal absorption and excessive renal loss of dibasic amino acids result in low plasma concentrations in patients with lysinuric protein intolerance (LPI). Arginine and ornithine deficiency impair the function of the urea cycle and cause hyperammonemia after protein intake, while chronic lysine deficiency may cause growth failure and lead to reduced bone density in such patients. Since high lysine concentrations inhibit several enzymes of the urea cycle in the liver, lysine supplementation may induce hyperammonemia in LPI. We thus studied how LPI patients tolerate high plasma lysine by intravenous (IV) infusion of 3.3 mmol/kg lysine hydrochloride over 90 minutes in 6 adult patients and 4 healthy controls. The plasma lysine concentration (mean +/- SD, range) peaked in the patients (9,114 +/- 1,864, 7,156 to 12,044 micromol/L) and controls (10,185 +/- 2,253, 7,714to 13,122 micromol/L) at 90 minutes. Urinary lysine excretion peaked in the second 2-hour urine collection in the patients (4,582 +/- 1,276, 3,018 to 6,315 micromol/m2 body surface area per hour) and in the first 2-hour collection in the controls (5,373 +/- 1,766, 3,551 to 7,286 micromol/m2/h). Two patients had mild nausea but no hyperammonemia and one patient had moderate hyperammonemia (peak, 112 micromol/L) at the end of the infusion. Orotic acid excretion increased in 2 subjects with a peak excretion rate of 33 and 251 micromol/m2/h in the third 2-hour collection after starting the load. All other subjects remained asymptomatic and showed no change in plasma ammonia or urinary orotic acid excretion. We thus conclude that an acute increase in plasma lysine caused minimal clinical or biochemical untoward effects in patients with LPI. Moderate increases in plasma lysine after low-dose oral supplementation with lysine or well-absorbed lysine derivatives are probably well tolerated in LPI.

Adult↗
PubMed2000

Celiprolol augments the effect of physical exercise on insulin sensitivity and serum lipid levels in chronic heart failure.

PURPOSE: Impaired insulin sensitivity has been linked with chronic heart failure (CHF). Exercise has a beneficial effect on insulin sensitivity in healthy subjects. It is used also as an adjunctive therapy in patients with CHF. We studied the effect of randomized treatment with celiprolol, a vasodilating beta(1)-adrenoceptor antagonist, 200 mg once daily (n=20) or placebo (n=11) on serum lipid levels and insulin sensitivity in patients with CHF. In addition, all subjects participated in a 6-month exercise training protocol. Thirteen subjects in the celiprolol and eight subjects in the control group were on additional beta(1)-adrenoceptor antagonist as part of their tailored CHF therapy. Insulin sensitivity was determined using the hyperinsulinemic euglycemic clamp test (diabetic subjects excluded, n=11 for the celiprolol group and n=8 for the placebo group). RESULTS: Insulin sensitivity index (ISI) increased by 33% (P<0.05) in the celiprolol group and by 17% (NS) in the control group. The mean increase in the whole group was 20% [from 68.2+/-11.5 to 81.7+/-10.7 ml/min/kg (mU/l), P<0.05]. No change was found in the total cholesterol level. HDL cholesterol levels increased by 12% (from 0.98+/-0.05 to 1.10+/-0.05 mmol/l, P<0. 005), and HDL/total cholesterol and HDL/LDL cholesterol ratios by 15% and 16%, respectively (P<0.005). The increase in serum fasting HDL cholesterol level was greater in the celiprolol-treated group (P<0.05). At baseline ISI correlated with maximal oxygen uptake (r=0. 65, P<0.0001) and body mass index (r=-0.55, P<0.001). The change in ISI correlated weakly with the improvement in muscle exercise capacity (r=0.53, P<0.05). CONCLUSIONS: Insulin sensitivity and serum lipid levels may be favorably affected by exercise training in subjects with mild-to-moderate CHF. Celiprolol, a vasodilating beta1- selective adrenoceptor antagonist, potentiates this effect.

Adrenergic beta-Antagonists↗
PubMed2000

Serum oncostatin M in multiple myeloma: impact on disease severity and prognosis.

Since high levels of serum IL-6 predict a poor prognosis of patients with multiple myeloma (MM), we investigated if a related cytokine, oncostatin M (OSM), correlates with clinical or biochemical findings or has prognostic significance in patients with MM. Among 82 newly diagnosed MM patients, OSM was detected in the sera in 45 (55%). Serum OSM had a borderline statistical correlation with serum IL-6 (r = 0.198, p = 0.074) and C-reactive protein (r = 0.199, p = 0.074) concentrations. However, OSM did not have prognostic significance alone or in combination with other factors. The median survival of patients with detectable serum OSM concentration was 41 months (range 2-124 months) and of OSM negative patients 35 months (1-75 months). Serum OSM concentration was not associated with clinical factors or severity of bone disease at diagnosis. We conclude that serum OSM concentration is not a prognostic factor in MM patients.

Adult↗
PubMed2000

Interferon-alpha treatment decreases serum cross-linked C-terminal telopeptide of type I collagen in haematological diseases.

Interferon-alpha (IFN-alpha) is used in the treatment of many haematological diseases and it is known that IFN-alpha may affect bone turnover. The effect of IFN-alpha on bone metabolism was studied in 10 haematological patients. The mean duration of the treatment was 4 (range: 2.8-7.2) months. Besides the usual markers of bone metabolism, levels of the cross-linked C-terminal telopeptide of type I collagen (ICTP), the N-terminal propeptide of type I procollagen (PINP) and the bone-specific alkaline phosphatase were measured. The bone mineral density was measured by computed tomography. During IFN-alpha treatment, serum ICTP decreased from a mean of 5.4 (range: 1.8-12.4) to 3.6 (range: 1.4-8.8) microg/l (P = 0.017). All other variables reflecting bone metabolism remained unaltered during IFN-alpha treatment. The bone mineral density remained unchanged. It was concluded that the observed decrease in ICTP may be an indicator of a beneficial therapeutic effect of IFN-alpha on bone turnover, resulting in decreased bone resorption. However, it is possible that elevated pretreatment ICTP values reflected disease of the bone marrow.

Adult↗
PubMed2000

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Journal Article↗
PubMed2000

Serum soluble tumor necrosis factor-alpha receptor 2 is elevated in obesity but is not related to insulin sensitivity: a study in identical twins discordant for obesity.

Tumor necrosis factor-alpha (TNFalpha) and its soluble receptor 2 (TNFR2) are expressed in adipose tissue and are possibly involved in the pathogenesis of insulin resistance. Information about serum levels of TNFR2 in human obesity, especially the possible role of genetic factors and body fat distribution, is scanty. We measured serum TNFalpha and soluble TNFR2 concentrations in 23 identical twin pairs who had an average 18-kg intrapair difference in body weight. The mean TNFalpha concentration was 44.1 ng/L in obese and 34.2 ng/L in lean cotwins (P = 0.051). The respective values for TNFR2 were 1,989 and 1,840 ng/L (P = 0.004). The intrapair difference in TNFR2 level correlated positively (r-value always > or = 0.56; P < or = 0.01) with intrapair differences in body mass index, percent body fat, and abdominal sc fat area (assessed by magnetic resonance imaging), but not with differences in visceral fat area, glucose or insulin areas under the curve, or insulin sensitivity index in the oral glucose tolerance test. The intraclass correlation for TNFR2 was 0.67, and the genetic variation in circulating TNFR2 level was almost 6-fold higher than the variation due to obesity. We conclude that the soluble TNFR2 concentration is determined by both genetic factors and adiposity, especially sc fat. Measurement of circulating TNFR2 does not seem to be useful in identifying obese individuals who are insulin resistant.

Aged↗
PubMed2000

Prediction of short-term outcome in patients with suspected myocardial infarction.

STUDY OBJECTIVE: Although specific cardiac injury markers have enhanced early patient classification, the ECG remains a necessary investigation in the acute phase of chest pain. Combined use of both tests could further improve the diagnostic and prognostic accuracy. METHODS: We studied 311 consecutive patients who came to the emergency department of a regional referral hospital for the differential diagnosis of acute chest discomfort. The admission ECG was classified using an automated interpretation program and tested together with elevated admission creatine kinase isoform MB (CK-MB) and cardiac troponin I (TnI) concentration for prediction of final myocardial injury (44%) and in-hospital mortality (14%). RESULTS: Combining the information from the admission ECG and cardiac markers, the sensitivity for becoming final myocardial injury (maximal CK-MB >/=11 microg/L) was 90% and specificity 61%. The proportion of false-negative results (10%) was independent of symptom duration. Age, positive ECG findings, and increased admission TnI levels were predictive for in-hospital mortality. CONCLUSION: The commonly available biochemical and ECG criteria allow risk stratification of patients with a suspected acute ischemic event. The data analysis can easily be automated and is independent of patient delay.

Adult↗