Impaired gallbladder function in patients after total gastrectomy.

BACKGROUND AND AIMS: The incidence of gallstones and gallbladder sludge is higher in patients after total gastrectomy than in general population. Formation of gallstones after gastrectomy is multifactorial. Here, we investigate the changes in gallbladder and biliary tract functions by cholescintygraphy and monitored changes in cholecystokinin (CCK) release in long-term survivors after total gastrectomy for gastric carcinoma. MATERIAL AND METHODS: Patients had undergone total gastrectomy for gastric carcinoma at least five years ago. The final study population consisted of 25 patients. RESULTS: Eight patients had undergone cholecystectomy before or at the time of gastrectomy. Gallstone formation was observed in seven of the remaining 17 patients during follow-up (41%). Maximum uptake of radioactivity and gallbladder maximum uptake was significantly delayed in the gastrectomy group than in the control group. There was no significant difference in CCK levels after the overnight fasting and at 60 minutes after stimulation among patients with or without stones in situ compared with healthy volunteers, but 30 minutes after the energy-rich drink patients had higher CCK levels than the control group. CONCLUSIONS: In gastrectomy patients, technetium isotope visualisation of the gallbladder and time for maximum activity was significantly delayed. This may indicate impaired gallbladder function. On the contrary, CCK release was not impaired.

Reference values for pulmonary diffusing capacity for adult native Finns.

Measurement standards for pulmonary diffusing capacity were updated in 2005 by the ATS/ERS Task Force. However, in Finland reference values published in 1982 by Viljanen et al. have been used to date. The main aim of this study was to produce updated reference models for single-breath diffusing capacity for carbon monoxide for Finnish adults. Single-breath diffusing capacity for carbon monoxide was measured in 631 healthy non-smoking volunteers (41.5% male). Reference values for diffusing capacity (DLCO), alveolar volume (VA), diffusing capacity per unit of lung volume (DLCO/VA), and lung volumes were calculated using a linear regression model. Previously used Finnish reference values were found to produce too low predicted values, with mean predicted DLCO 111.0 and 104.4%, and DLCO/VA of 103.5 and 102.7% in males and females, respectively. With the European Coalition for Steel and Coal (ECSC) reference values there was a significant sex difference in DLCO/VA with mean predicted 105.4% in males and 92.8% in females (p < .001). New reference values for DLCO, DLCO/VA, VA, vital capacity (VC), inspiratory vital capacity (IVC), and inspiratory capacity (IC) are suggested for clinical use to replace technically outdated reference values for clinical applications.

Following up infant bronchiolitis patients provided new evidence for and against the united airway disease hypothesis.

AIM: The united airway disease (UAD) hypothesis suggests that allergic rhinitis and asthma develop together. We evaluated the evidence for and against the UAD hypothesis at five to seven years of age after hospitalisation for bronchiolitis at less than six months. METHODS: This study used prospective follow-up data for 102 children hospitalised for bronchiolitis under the age of six months. We included the presence of previous and current asthma, prolonged rhinitis and skin prick tests (SPT) to common inhaled allergens and lung function by impulse oscillometry (IOS) at five to seven years of age. Bronchial hyper-reactivity (BHR) was assessed using the exercise challenge test and bronchodilation test. RESULTS: Current asthma, but not previous transient asthma, was associated with prolonged rhinitis and a positive SPT. BHR, which reflected reactive airways, but not lung function, was associated with respiratory allergy, namely the combination of current asthma, prolonged rhinitis and a positive SPT. CONCLUSION: This post-bronchiolitis follow-up study suggested an association between respiratory allergy and reactive airways at five to seven years of age, which supported the UAD hypothesis. However, previous transient asthma and a reduction in lung function reduction did not support the hypothesis.

[The effect of public defense of a doctoral thesis on the heart rate of the doctoral candidate]. / Väitöstilaisuuden vaikutus väittelijän sydämen syketaajuuteen.

The effect of public defense of a doctoral thesis on the heart rate of the doctoral candidate Most doctoral candidates find the public defense of a doctoral thesis an exciting and stressful experience. In this study, Holter recording during the defense was made for four doctoral candidates of the Faculty of Medicine. Maximum heart rate among the subjects was on the average 172 beats/min with a median heart rate of 116 beats/min. Sympathicotonia and release of stress hormones associated with the defense raise the heart rate to levels that may be very high for several hours. This is a risk factor for a coronary event and should be considered, if the doctoral candidate has coronary heart disease, carries risk factors for coronary heart disease, or is an elderly person.

High dose of red wine elicits enhanced inhibition of fibrinolysis.

BACKGROUND AND DESIGN: The purpose of this randomized controlled cross-over study was to determine the acute effects of high doses of alcoholic beverages on circulating markers related to atherosclerosis and fibrinolysis. METHODS: Twenty-two healthy men consumed a high dose (8.1+/-0.9 dl) of alcohol-containing red wine and dealcoholized red wine, and an equal ethanol dose of cognac (2.4+/-0.3 dl). Blood samples were taken before and shortly after interventions. RESULTS: Red wine, unlike dealcoholized red wine and cognac, increased tissue plasminogen activator inhibitor-1 levels significantly, indicating an acute inhibition of fibrinolysis after a high dose. CONCLUSION: Findings may explain the increased risk of cardiovascular mortality among binge drinkers.

Effects of cognac on coronary flow reserve and plasma antioxidant status in healthy young men.

BACKGROUND: The cardioprotective effects of certain alcoholic beverages are partly related to their polyphenol content, which may improve the vasodilatory reactivity of arteries. Effect of cognac on coronary circulation, however, remains unknown. The purpose of this randomized controlled cross-over study was to determine whether moderate doses of cognac improve coronary reactivity as assessed with cold pressor testing (CPT) and coronary flow reserve (CFR) measurement. METHODS: Study group consisted of 23 subjects. Coronary flow velocity and epicardial diameter was assessed using transthoracic echocardiography at rest, during CPT and adenosine infusion-derived CFR measurements before drinking, after a moderate (1.2 +/- 0.1 dl) and an escalating high dose (total amount 2.4 +/- 0.3 dl) of cognac. To explore the bioavailability of antioxidants, the antioxidant contents of cognac was measured and the absorption from the digestive tract was verified by plasma antioxidant capacity determination. RESULTS: Serum alcohol levels increased to 1.2 +/- 0.2 per thousand and plasma antioxidant capacity from 301 +/- 43.9 micromol/l to 320 +/- 25.0 micromol/l by 7.6 +/- 11.8%, (p = 0.01) after high doses of cognac. There was no significant change in flow velocity during CPT after cognac ingestion compared to control day. CFR was 4.4 +/- 0.8, 4.1 +/- 0.9 (p = NS), and 4.5 +/- 1.2 (p = NS) before drinking and after moderate and high doses on cognac day, and 4.5 +/- 1.4, and 4.0 +/- 1.2 (p = NS) on control day. CONCLUSION: Cognac increased plasma antioxidant capacity, but it had no effect on coronary circulation in healthy young men. TRIAL REGISTRATION: NCT00330213.

Impulse oscillometry at preschool age is a strong predictor of lung function by flow-volume spirometry in adolescence.

BACKGROUND: The transition from early childhood wheezing to persistent asthma is linked to lung function impairment over time. Little is known how the methods used to study lung function at different ages correlate longitudinally. METHODS: Sixty-four children with a history of hospitalization for bronchiolitis before 6 months of age were prospectively studied with impulse oscillometry (IOS) at the mean age of 6.3 years and these preschool IOS results were compared with flow-volume spirometry (FVS) measurements at mean age of 11.4 years. RESULTS: The baseline respiratory system resistance at 5 Hz (Rrs5) showed a modest statistically significant correlation with all baseline FVS parameters except FVC. The post-bronchodilator (post-BD) Rrs5 showed a modest statistically significant correlation with post-BD FEV1 and FEV1 /FVC. The bronchodilator-induced decrease in Rrs5 showed a modest statistically significant correlation with the percent increase in FEV1 . Baseline and post-BD respiratory reactance at 5 Hz (Xrs5) showed a modest statistically significant correlation with baseline and post-BD FVS parameters except post-BD FEV1 /FVC, respectively, and post-BD Xrs5 showed a strong correlation with post-BD FVC (ρ = 0.61) and post-BD FEV1 (ρ = 0.59). In adjusted linear regression, preschool Xrs5 remained as a statistically significant independent predictor of FVS parameters in adolescence; the one-unit decrease in the Z-score of preschool post-BD Xrs5 predicted 9.6% lower post-BD FEV1 , 9.3% lower post-BD FVC, and 9.7% lower post-BD MEF50 when expressed as %-predicted parameters. CONCLUSION: Persistent post-BD small airway impairment in children with a history of bronchiolitis detected with IOS at preschool age predicted FVS results measured in early adolescence.

Insulin improves myocardial blood flow in patients with type 2 diabetes and coronary artery disease.

Insulin infusion improves myocardial blood flow (MBF) in healthy subjects. Until now, the effect of insulin on myocardial perfusion in type 2 diabetic subjects with coronary artery disease (CAD) has been unknown. We studied the effects of insulin on MBF in ischemic regions evaluated by single-photon emission-computed tomography and coronary angiography and in nonischemic regions in 43 subjects (ages 63 +/- 7 years) with type 2 diabetes (HbA(1c) 7.1 +/- 0.9%). MBF was measured at fasting and during a euglycemic-hyperinsulinemic clamp at rest (n = 43) and during adenosine-induced (140 mug . kg(-1) . min(-1) for 7 min) hyperemia (n = 26) using positron emission tomography and (15)O-labeled water. MBF was significantly attenuated in ischemic regions as compared with in nonischemic regions (P < 0.0001) and was increased by insulin as compared with in the fasting state (P < 0.0001). At rest, insulin infusion increased MBF by 13% in ischemic regions (P = 0.043) and 22% in nonischemic regions (P = 0.003). During adenosine infusion, insulin enhanced MBF by 20% (P = 0.018) in ischemic regions and 18% (P = 0.045) in nonischemic regions. In conclusion, insulin infusion improved MBF similarly in ischemic and nonischemic regions in type 2 diabetic subjects with CAD. Consequently, in addition to its metabolic effects, insulin infusion may improve endothelial function and thus increase the threshold for ischemia and partly contribute to the beneficial effects found in clinical trials in these subjects.

Myocardial perfusion, oxidative metabolism, and free fatty acid uptake in patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the alpha-tropomyosin gene: a positron emission tomography study.

BACKGROUND: The relationship between myocardial metabolic changes and the severity of left ventricular (LV) hypertrophy in patients with hypertrophic cardiomyopathy (HCM) is largely unknown. We characterized metabolic abnormalities in patients with a genetically identical cause for HCM but with variable LV hypertrophy. METHODS AND RESULTS: Eight patients with HCM attributable to the Asp175Asn mutation in the alpha-tropomyosin gene underwent myocardial perfusion, oxidative, and free fatty acid (FFA) metabolism measurements via positron emission tomography and oxygen 15-labeled water, carbon 11 acetate, and fluorine 14(R,S)-[18F] Fluoro-6-thia-heptadecanoic acid (18 FTHA). LV mass, work, and efficiency were assessed by echocardiography. Thirty-six healthy volunteers served as control subjects. Compared with control subjects, HCM patients had increased myocardial oxidative metabolism and FFA uptake (P < .05). However, in patients, LV mass was inversely related to global myocardial perfusion, oxidative metabolism, and FFA uptake (all P < .03), and regional wall thickness was inversely related to regional perfusion (P < .01), oxidative metabolism (P < .001), and FFA uptake (P < .01). Therefore patients with mild (LV mass less than median of 177 g) but not advanced LV hypertrophy were characterized by increased perfusion, oxidative metabolism, and LV efficiency as compared with control subjects (P < .05). CONCLUSIONS: In HCM attributable to the Asp175Asn mutation in the alpha-tropomyosin gene, myocardial oxidative metabolism and FFA metabolism are increased and inversely related to LV hypertrophy at both the whole heart and regional level. Increased metabolism and efficiency characterize patients with mild myocardial hypertrophy. These hypermetabolic alterations regress with advanced hypertrophy.

Vasodilation of epicardial coronary artery can be measured with transthoracic echocardiography.

Transthoracic Doppler echocardiography (TTE) has been introduced as a noninvasive tool to measure coronary flow velocity reserve (CFVR). Velocity measurement, however, fails to take into account epicardial coronary artery vasodilation during hyperemia and this may cause underestimation of CFVR measurements. Therefore, we sought to determine whether the vasodilation of epicardial coronary artery can be measured during cold pressor test (CPT) and adenosine infusion simultaneously with the flow velocity measurement using TTE. We studied 41 healthy nonsmoking men with a linear high-frequency 8.0-MHz transducer. The CPT and adenosine infusion dilated the diameter of the distal left anterior descending coronary artery (LAD) from 1.4 +/- 0.4 mm to 1.5 +/- 0.4 mm (14 +/- 13%, p < 0.01) and from 1.4 +/- 0.4 mm to 1.8 +/- 0.5 mm (31 +/- 19%, p < 0.01), respectively. The CPT increased flow velocity and calculated coronary blood flow rate (velocity time integral x cross-sectional area) from 0.23 +/- 0.05 m/s to 0.36 +/- 0.13 m/s (31 +/- 34%, p < 0.01) and from 8.1 +/- 4.2 mL/min to 11.4 +/- 6.0 mL/min (47 +/- 51%, p < 0.01). CFVR and calculated coronary blood flow rate reserve were 3.9 +/- 1.0 and 6.0 +/- 1.9, respectively. In Bland-Altman analysis, velocity measurements underestimated the vasodilation response of the CPT and adenosine compared with the measurements where epicardial diameter dilation was taken into account. Intra- and interobserver variability of diameter measurements was low (coefficient of variation [CV] 2.6 to 6.5%). Day-to-day, within-day and intersonographer variabilities were of similar magnitude (CV 4.6 to 8.2%), suggesting good reproducibility. This study demonstrates that TTE can be used to assess changes in both epicardial coronary artery diameter and flow velocity simultaneously in the distal LAD artery.

Rosiglitazone improves myocardial glucose uptake in patients with type 2 diabetes and coronary artery disease: a 16-week randomized, double-blind, placebo-controlled study.

Rosiglitazone therapy improves insulin sensitivity and glucose uptake in patients with uncomplicated type 2 diabetes. In coronary artery disease (CAD), glucose is an important source of energy and preserved myocardial glucose uptake is essential for the viability of jeopardized myocardium. The aim was to test whether rosiglitazone changes myocardial metabolism in type 2 diabetic patients with CAD. We studied 54 patients (38 men and 16 women) with type 2 diabetes (HbA(1c) 7.2 + 0.9%) and CAD. Myocardial glucose uptake was measured with [(18)F]fluoro-2-deoxy-d-glucose positron emission tomography in ischemic (evaluated by single-photon emission tomography and coronary angiography) and nonischemic regions during euglycemic-hyperinsulinemic clamp before and after a 16-week intervention period with rosiglitazone (n = 27) or placebo (n = 27). Rosiglitazone significantly improved glycemic control (P < 0.0001) and whole-body insulin sensitivity (P < 0.0001). Rosiglitazone increased myocardial glucose uptake from 20.6 +/- 11.8 to 25.5 +/- 12.4 micromol . 100 g(-1) . min(-1) (P = 0.038 vs. baseline, P = 0.023 vs. placebo) in ischemic regions and from 21.7 +/- 12.1 to 28.0 +/- 12.7 micromol . 100 g(-1) . min(-1) (P = 0.014 vs. baseline, P = 0.003 vs. placebo) in nonischemic regions. The increase in myocardial glucose uptake was partly explained by the suppression of free fatty acid levels during clamp. Rosiglitazone therapy significantly increased insulin sensitivity and improved myocardial glucose uptake in type 2 diabetic patients with CAD. These results suggest that rosiglitazone therapy may facilitate myocardial glucose storage and utilization in these patients.

Gene Polymorphism of Toll-Like Receptors and Lung Function at Five to Seven Years of Age after Infant Bronchiolitis.

AIM: Toll-like receptors (TLR) play a crucial role in innate immunity, protecting the host from pathogens such as viruses. Genetic variations in TLRs have been associated with the severity of viral bronchiolitis in infancy and with the later occurrence of post-bronchiolitis asthma. The aim of the present study was to evaluate if there are any exploratory associations between TLR gene polymorphisms and lung function at 5 to 7 years of age in former bronchiolitis patients. METHODS: We performed impulse oscillometry (IOS) at the median age of 6.3 years for 103 children who had been hospitalized for bronchiolitis at less than six months of age. The main parameters evaluated were airway resistance and reactance at 5Hz in baseline and post-exercise measurements. Data on single nucleotide polymorphisms (SNP) of TLR1 rs5743618, TLR2 rs5743708, TLR6 rs5743810 and TLR10 rs4129009 (TLR2 subfamily) and TLR3 rs3775291, TLR4 rs4986790, TLR7 rs179008, TLR8 rs2407992 and TLR 9 rs187084 were available for analyses. RESULTS: The TLR4 rs4986790 wild genotype A/A was associated with a greater Rrs5 response (0.72 vs. -0.42, p = 0.03) to exercise. In TLR6 rs5743810, the minor allele T was associated with greater Rrs5 response (0.80 vs. -0.03, p = 0.04) to exercise. In TLR7 rs179008, the major allele A was associated with baseline decline in dRrs/df (-1.03 vs 0.61, p = 0.01) and increased Fres (2.28 vs. 0.89, p = 0.01) in girls. CONCLUSION: Among the nine studied TLRs, only TLR7 rs179008 showed some exploratory associations with post-bronchiolitis lung function deficiency, and polymorphisms of TLR4 rs4986790, and TLR6 rs5743810 in particular, with airway reactivity. These findings call for further confirmatory studies.

Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes.

BACKGROUND: Endothelial dysfunction may play a pathophysiological role in the development of atherosclerosis in subjects with type 1 diabetes. We examined whether alterations in vascular endothelial function exist in children with type 1 diabetes and tested the hypothesis that endothelial dysfunction is associated with early structural atherosclerotic vascular changes in these children. METHODS AND RESULTS: Noninvasive ultrasound was used to measure brachial artery flow-mediated dilation (FMD) responses and carotid artery intima-media thickness (IMT) in 75 children (mean age 11+/-2 years), 45 with type 1 diabetes (diabetes duration 4.4+/-2.9 years) and 30 healthy control children. Children with diabetes had lower peak FMD response (4.4+/-3.4% versus 8.7+/-3.6%, P<0.001) and increased IMT (P<0.001) compared with controls. Sixteen children with diabetes (36%) had endothelial dysfunction defined as total FMD response in the lowest decile for normal children. These children had increased carotid IMT (0.58+/-0.05 versus 0.54+/-0.04 mm, P=0.01) and higher LDL cholesterol concentration (2.63+/-0.76 versus 2.16+/-0.60 mmol/L, P=0.03) compared with diabetic children without endothelial dysfunction. Multivariate correlates of increased IMT included diabetes group (P=0.03), low FMD (P=0.03), and high LDL cholesterol (P=0.08). CONCLUSIONS: Impaired FMD response is a common manifestation in children with type 1 diabetes and is associated with increased carotid artery IMT. These data suggest that endothelial dysfunction in children with type 1 diabetes may predispose them to the development of early atherosclerosis.

Cardiac structure and function in monozygotic twin pairs discordant for physical fitness.

Cross-sectional studies in athletes and untrained subjects suggest that exercise training induces adaptations in cardiac structure and function. However, the role of genetic variation on the results has largely been ignored in these studies. The purpose of this study was to investigate the effects of long-term volitionally increased physical activity on electrocardiographic and echocardiographic parameters in male monozygotic twin pairs discordant for physical activity and fitness. On the basis of the mailed questionnaires, a telephone interview, and the inclusion criteria, 12 pairs of young adult male monozygotic twins were recruited from a Finnish twin cohort. All subjects completed a maximal oxygen uptake (.VO2 (max)) test and electrocardiography and echocardiography studies. Nine pairs had at least 9% difference in .VO2(max) and were selected for further analysis and for a second echocardiography study. Twins were divided into the more (MAG) and less active group (LAG), according to their VO2(max). On average, MAG had 18% higher VO2(max) compared with LAG. In electrocardiography, MAG had 29% (P = 0.02) higher Cornell voltage and 37% (P = 0.01) higher right-side hypertrophy index. In echocardiography, no significant differences were observed between the groups, and left ventricular mass index was only 7% (P = 0.16) higher in MAG. These results show that the volitionally increased physical activity that has led to an 18% increase in cardiorespiratory fitness induces greater changes in electro- than echocardiographic parameters. Electrocardiographic changes were suggestive of left ventricular hypertrophy, and echocardiography showed a similar but statistically nonsignificant trend.

Effect of pravastatin on low-density lipoprotein oxidation and myocardial perfusion in young adults with type 1 diabetes.

OBJECTIVE: Diabetes has been associated with increased oxidative stress and impaired vascular function. Statins have been shown to reduce low-density lipoprotein (LDL) oxidizability and improve myocardial perfusion in hypercholesterolemic nondiabetic subjects. We studied whether pravastatin decreases LDL oxidation and improves myocardial perfusion in normocholesterolemic subjects with type 1 diabetes. METHODS AND RESULTS: In this randomized, double-blind study, myocardial perfusion was measured at rest and during dipyridamole stimulation with positron emission tomography and [15O]H2O during hyperinsulinemic euglycemia in 42 patients (age 30+/-6 years; LDL cholesterol 2.48+/-0.57 mmol/L) before and after 4-month treatment with pravastatin 40 mg/d or placebo. In addition, 12 healthy nondiabetic subjects were studied. LDL oxidation was measured by determining the level of baseline diene conjugation in lipids extracted from LDL. The level of LDL oxidation was similar in the pravastatin and placebo groups before treatment (23.9+/-4.6 versus 25.6+/-9.5 micromol/L, respectively) and decreased significantly during pravastatin treatment to 19.5+/-5.0 micromol/L (P<0.005). Myocardial perfusion reserve was significantly lower in diabetic patients compared with controls (4.15+/-1.29 versus 5.31+/-1.86, P<0.05) and did not change after treatment. Glycemic control and insulin sensitivity remained unchanged during treatment. CONCLUSIONS: Pravastatin treatment, resulting in decreased LDL oxidation, did not improve myocardial perfusion reserve in subjects with type 1 diabetes.

Obesity and bronchial obstruction in impulse oscillometry at age 5-7 years in a prospective post-bronchiolitis cohort.

BACKGROUND AND AIMS: Obesity has been linked with asthma symptoms, need for asthma treatment and reduced lung function but not with increased bronchial reactivity in children. The aim of this study was to evaluate the association between previous or current weight status and current lung function and bronchial reactivity to exercise at early school age. METHODS: Ninety-nine children hospitalized for bronchiolitis at the age of less than 6 months were studied with impulse oscillometry (IOS) at the mean age of 6.3 years. Data on birth weight and weight gain in infancy before hospitalization were collected during hospitalization. Current weight and height data were transformed into age- and sex-specific height-related body mass index z scores (zBMI) using the Finnish national population-based weight and height data as reference. RESULTS: Some significant though only low or modest correlations were found between current zBMI and baseline, post-exercise and post-bronchodilator IOS values in adjusted linear regression analysis. Seven obese children by zBMI had higher post-bronchodilator airway impedance (Zrs) and resistance (Rrs) at 5 Hz and lower post-bronchodilator frequency dependency of resistance (dRrs/df) than normal weight children. There were no significant differences in responses to exercise or to bronchodilators between currently obese or overweight children and normal weight children. Birth weight less than 3,000 g was associated with larger exercise-induced changes in Zrs and Rrs at 5 Hz, and in reactance (Xrs) at 5 Hz, than those with birth weight more than 3,000 g. CONCLUSIONS: Preliminary evidence was found that obesity may be associated with airway obstruction, but not with bronchial hyper-reactivity.

Lung function by impulse oscillometry at age 5-7 years after bronchiolitis at age 0-6 months.

BACKGROUND: Viral bronchiolitis in infancy has been associated with increased bronchial reactivity and reduced lung function in later childhood and even in adulthood. However, lung function at preschool age is less studied, mainly due to technical difficulties. The purpose of the study was to evaluate lung function and bronchial reactivity at preschool age in children who were hospitalized for bronchiolitis in early infancy. SUBJECTS AND METHODS: Airway resistance and reactance, and bronchial reactivity to exercise were studied with impulse oscillometry (IOS) at the mean age of 6.3 years in 103 children hospitalized for bronchiolitis at less than 6 months of age. RESULTS: In baseline lung-function measurement, resistance (n = 8; 7.8%) or reactance (19; 18.4%) at 5 Hz were pathological in 20% of children compared to Finnish population-based height-adjusted reference values. Increased bronchial reactivity by exercise challenge (5; 4.9%) or bronchodilatation (11; 10.7%) tests was present in 16%. Irreversible changes were revealed in only one case. CONCLUSIONS: Though reduced lung function and increased airway reactivity were rather common, evidence for persistent lung function reduction was rare, less than 1%, at preschool age in children hospitalized for bronchiolitis caused mainly by respiratory syncytial virus at age less than 6 months.

IL-10 Gene Polymorphisms Are Associated with Post-Bronchiolitis Lung Function Abnormalities at Six Years of Age.

AIM: Interleukin-10 (IL-10) has been associated with wheezing and asthma in children and the genetic variation of the IL-10 cytokine production may be linked to post-bronchiolitis lung function. We used impulse oscillometry (IOS) to evaluate the associations of IL10 polymorphisms with lung function at a median age of 6.3 years in children hospitalised for bronchiolitis before six months of age. METHODS: We performed baseline and post-exercise IOS on 103 former bronchiolitis patients. Data on single nucleotide polymorphisms (SNP) of IL10 rs1800896 (-1082G/A), rs1800871 (-819C/T), rs1800872 (-592C/A) were available for 99 children and of IL10 rs1800890 (-3575T/A) for 98 children. RESULTS: IL10 rs1800896, rs1800871 and rs1800872 combined genotype AA+CT+CA and carriage of haplotype ATA, respectively, were associated with higher resistance and lower reactance in baseline IOS in adjusted analyses. At IL10 rs1800890, the A/A-genotype and carriers of A-allele were associated with lower reactance in baseline IOS. There were no significant associations between the studied SNPs and airway hyper-reactivity to exercise. CONCLUSION: Low-IL-10-producing polymorphisms in the IL-10 encoding gene were associated with obstructive lung function parameters, suggesting an important role for IL-10 in development of lung function deficit in early bronchiolitis patients.

Myocardial perfusion reserve and peripheral endothelial function in patients with idiopathic dilated cardiomyopathy.

The aim of this study was to assess the relation between peripheral endothelial function and myocardial perfusion reserve in patients with mild heart failure due to idiopathic dilated cardiomyopathy (IDC). Myocardial perfusion and brachial artery flow mediated dilation (FMD) were measured in 20 clinically stable patients with IDC (New York Heart Association classes I to III, ejection fraction 35 +/- 9%) and 13 apparently healthy subjects who were matched for age and lipid profile. Resting and hyperemic (dipyridamole; 0.56 mg/kg/min) perfusion were measured using oxygen-15-labeled water and positron emission tomography (PET). Perfusion reserve was calculated as the ratio of hyperemic to resting perfusion. FMD was assessed by measuring the change in brachial artery diameter in response to reactive hyperemia. Patients with IDC had lower hyperemic perfusion (1.73 +/- 0.83 vs 3.01 +/- 1.20 ml/min/g, p <0.001) and perfusion reserve (2.01 +/- 0.91 vs 3.08 +/- 1.35, p <0.01) compared with healthy subjects. Brachial artery FMD, however, was not different from that of the healthy subjects. Furthermore, neither hyperemic perfusion nor perfusion reserve was correlated with FMD in the patients with IDC, whereas the healthy subjects demonstrated a positive correlation between FMD and perfusion reserve (r = 0.57; p = 0.04). Thus, abnormal myocardial perfusion characterizes patients with IDC. Myocardial perfusion reserve and peripheral endothelial function do not parallel each other in patients with IDC.

Pravastatin-induced improvement in coronary reactivity and circulating ATP and ADP levels in young adults with type 1 diabetes.

AIMS: Extracellular ATP and ADP regulate diverse inflammatory, prothrombotic and vasoactive responses in the vasculature. Statins have been shown to modulate their signaling pathways in vitro. We hypothesized that altered intravascular nucleotide turnover modulates vasodilation in patients with type 1 diabetes (T1DM), and this can be partly restored with pravastatin therapy. METHODS: In this randomized double blind study, plasma ATP and ADP levels and echocardiography-derived coronary flow velocity response to cold pressor test (CPT) were concurrently assessed in 42 normocholesterolemic patients with T1DM (age 30 ± 6 years, LDL cholesterol 2.5 ± 0.6 mmol/L) before and after four-month treatment with pravastatin 40 mg/day or placebo (n = 22 and n = 20, respectively), and in 41 healthy control subjects. RESULTS: Compared to controls, T1DM patients had significantly higher concentrations of ATP (p < 0.01) and ADP (p < 0.01) and these levels were partly restored after treatment with pravastatin (p = 0.002 and p = 0.007, respectively), but not after placebo (p = 0.06 and p = 0.14, respectively). Coronary flow velocity acceleration was significantly lower in T1DM patients compared to control subjects, and it increased from pre- to post-intervention in the pravastatin (p = 0.02), but not in placebo group (p = 0.15). CONCLUSIONS: Pravastatin treatment significantly reduces circulating ATP and ADP levels of T1DM patients, and concurrently improves coronary flow response to CPT. This study provides a novel insight in purinergic mechanisms involved in pleiotropic effects of pravastatin.