Follow-up study of the early, randomised paracetamol trial to preterm infants, found no adverse reactions at the two-years corrected age.

AIM: We examined the long-term outcomes and safety of early intravenous paracetamol for ductus arteriosus closure at a corrected age of two years. METHODS: This was a follow-up of the 2013-2014 randomised, double-blind Preterm Infant's Paracetamol Study at Oulu University Hospital, Finland, which recruited 48 very preterm infants within 24 hours of birth. They received intravenous paracetamol or a placebo for four days. In 2015-2017, we followed up 44 infants (92%) at two years of corrected age. This included clinical and neurodevelopmental assessments and a parental medical history questionnaire. RESULTS: The 44 infants (55% boys) were born at 235 -316 weeks of gestation. No differences in the cardiac parameters, including blood pressures and ultrasound scan results, were found. Neurodevelopmental stages, as quantified by the Griffiths test, were similar. No signs of autism were reported. Asthma medication was more common in the control group, but the difference was not significant. Atopy scores, numbers of infections and the use of public health services were similar between the two groups. CONCLUSION: No long-term adverse reactions of early intravenous paracetamol were detected two years later. Larger trials are needed on the safety and efficacy of paracetamol prophylaxis for early ductal closure in very preterm infants.

Trends in health status and the use of services among the 80-84-year-old Finnish war veterans during 1992 and 2004.

AIM: The aim of this study was to compare the differences in health state, functional capacity and the use of social and health services among the 80-84-year-old Finnish Second World War veterans in 1992 and 2004 and to describe the possible effects of the improvements made based on the results after 1992. METHODS: The Veteran Projects were conducted among the veterans using a postal questionnaire. In 1992, the questionnaire was sent to all veterans (n = 242,720) living in Finland, and in 2004 to 5750 veterans who had participated in the study in 1992. The comparable age groups of veterans aged 80-84 years were used. The data were analysed by descriptive statistics and binary logistic regression analysis. Analyses were conducted separately for men with and without disability and for all women. RESULTS: The proportion of men with good self-reported health, painlessness, normal memory and vision and who were able to walk 500 m without difficulties, significantly increased, as did the proportion of women with normal memory and vision. The prevalence of many diseases increased, but diseases appeared to be less disabling in 2004 than 1992. The need for hospital care decreased and the use of rehabilitation services increased, but the increased use of rehabilitation services was not indicative of the ability to walk 500 m. CONCLUSIONS: Self-rated health and functional capacity improved and the need for hospital care decreased among veterans, although the prevalence of many diseases increased during the follow-up. Rehabilitation was not associated with the ability to walk 500 m without difficulties.

Spin-asymmetric Josephson effect.

We propose that with ultracold Fermi gases one can realize a spin-asymmetric Josephson effect in which the two spin components of a Cooper pair are driven asymmetrically--corresponding to driving a Josephson junction of two superconductors with different voltages V(↑) and V(↓) for spin up and down electrons, respectively. We predict that the spin up and down components oscillate at the same frequency but with different amplitudes. Furthermore our results reveal that the standard interpretation of the Josephson supercurrent in terms of coherent bosonic pair tunneling is insufficient. We provide an intuitive interpretation of the Josephson supercurrent as interference in Rabi oscillations of pairs and single particles, the latter causing the asymmetry.

Cardiac troponin-I as a screening tool for myocarditis in children hospitalized for viral infection.

AIM: The incidence of myocarditis in children is uncertain because patients with minor symptoms can remain undiagnosed. We hypothesized that screening all children who are hospitalized for an acute infection with troponin-I (TnI) would reveal myocarditis cases and performed a prospective screening study. METHODS: Between October 2005 and July 2008, a blood sample for TnI measurement was taken every time a sample for C-reactive protein measurement was drawn. If TnI value was above the screening limit (0.06 microg/L), electrocardiogram (ECG) and cardiac ultrasound were performed. TnI measurements were repeated until at normal level. RESULTS: Altogether, 1009 children were screened during the 33 months. TnI was above the screening limit (0.06 microg/L) in six children. None of them had any signs of myocarditis in ECG or cardiac ultrasound. Five of those six children were younger than 30 days. All had a respiratory infection as a cause for hospitalization, three of which was caused by RSV. In four children, all younger than 30 days, TnI levels remained high (>0.37 microg/L) for two months, but decreased after that to normal levels. CONCLUSION: The incidence of myocarditis during viral infections is low and a routine TnI screening for asymptomatic myocarditis is not useful.

Spectral signatures of the Fulde-Ferrell-Larkin-Ovchinnikov order parameter in one-dimensional optical lattices.

We address an imbalanced two-component atomic Fermi gas restricted by a one-dimensional (1D) optical lattice and an external harmonic potential, within the mean-field Bogoliubov-de Gennes formalism. We show that characteristic features of the Fulde-Ferrell-Larkin-Ovchinnikov state are visible in the rf spectra and in the momentum-resolved photoemission spectra of the gas. Specially, Andreev states or midgap states can be clearly resolved, which gives a direct experimentally observable signature of the oscillating order parameter.

Serum fatty acids in postinfarction middle-aged men.

There is a multitude of data showing that coronary heart disease is affected by the quality of dietary fat. The fatty acid composition of serum lipids has been shown to reflect that of the diet. It is likely that, after myocardial infarction, both the health-care professionals and the patients themselves pay more attention to dietary guidelines. In order to assess the correctness of this assumption, we compared the composition of serum fatty acids in 40 male subjects with a history of myocardial infarction (MI) with that of 40 age-matched controls, both from the FINRISK study. The percentage composition of fatty acids of total serum lipids was analysed by gas chromatography. In comparison with the control group, the MI group had higher body mass index (BMI), a higher prevalence of diabetes, higher level of serum triglycerides and a lower level of serum high-density lipoprotein (HDL) cholesterol, all indicators of the metabolic syndrome. The MI group had higher proportions of serum palmitic (16:0) and oleic acids (18:1), and a lower proportion of linoleic (18:2 n-6) acid than the control group. The metabolic syndrome is accompanied by an elevated level of serum insulin, which is known to enhance the synthesis of saturated and monounsaturated fatty acids, such as 16:0 and 18:1, and to stimulate the activity delta-6 desaturase, decreasing the concentration of linoleic acid. Our results suggest that the observed serum fatty acid composition in subjects with coronary heart disease is dependent on metabolic factors in addition to dietary fatty acid composition.

Inhibition of c-kit tyrosine kinase by imatinib mesylate induces apoptosis in mast cells in rheumatoid synovia: a potential approach to the treatment of arthritis.

BACKGROUND: Mast cells have been implicated in the pathogenesis of arthritis, but elucidation of their precise role has been hampered by a lack of efficient and selective inhibitors of their function. OBJECTIVE: To elucidate the role of mast cells in the pathogenesis of rheumatoid arthritis (RA) and to assess whether apoptosis of cultured and synovial tissue mast cells can be induced by inhibiting mast cell growth factor receptor, c-kit tyrosine kinase. METHODS AND RESULTS: Double staining with tumour necrosis factor (TNF) alpha and tryptase antibodies showed the presence of TNFalpha positive mast cells in human rheumatoid synovial tissue. Selective activation of mast cells by anti-IgE resulted in production of TNFalpha in synovial tissue cultures. Inhibition of the c-kit tyrosine kinase with imatinib mesylate (1.0-10 micromol/l) induced profound apoptosis in cultured mast cells as judged by typical apoptotic morphology, increased number of apoptotic nucleosomes, and activation of caspases 8 and 9. Importantly, imatinib also induced apoptosis of mast cells in explant cultures of synovial tissue obtained from patients with RA as judged by a TUNEL assay. Inhibition of c-kit tyrosine kinase was accompanied by significant reduction of TNFalpha production in synovial tissue cultures. CONCLUSION: Mast cells may have a role in the pathogenesis of RA, and inhibition of c-kit may be a new means of inhibiting mast cell activity and of abrogating the contribution of mast cells to synovial inflammation in RA.

The Finnish version of The National Institutes Of Health Chronic Prostatitis Symptom Index correlates well with the visual pain scale: translation and results of a modified linguistic validation study.

UNLABELLED: Authors from Finland have assessed a version in their language of the National Institutes of Health-Chronic Prostatitis Symptom Index; they found that their translated version was valid and easily understandable in the management of the symptoms of chronic pelvic pain syndrome. They felt it should be used as a primary outcome measure in studies with these patients. There are three papers in this issue relating to the effect of drugs on LUTS; the first of these is a pooled analysis of three double-blind placebo-controlled studies into the safety and efficacy of the 10 mg dose of alfuzosin. The second evaluates the effect on quality-of-life issues of treatment with dutasteride. Finally, authors from Australia compare the effect of a Serenoa repens extract with placebo for LUTS. OBJECTIVES: To provide a fluent and easily comprehensible Finnish version of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and to study its linguistic validity and correlation with a visual pain scale (VAS). PATIENTS AND METHODS: The double-back translation method with two interim modifications was used to produce the Finnish version of the NIH-CPSI. The validity was tested by presenting the questionnaire to 155 men with clinically confirmed chronic pelvic pain syndrome (CPPS) and 12 controls with no previous urological symptoms. Convergent validity of the NIH-CPSI was tested by determining the correlation between the Finnish NIH-CPSI and VAS. Patients' and urologists' opinions about the utility of the Finnish NIH-CPSI were also reviewed. RESULTS: The total Finnish NIH-CPSI scores and the pain domain and voiding symptom domain scores differed significantly (P < 0.001) between the groups, suggesting good discriminant validity of the symptom index. The NIH-CPSI scores correlated well with the VAS (Pearson's correlation 0.76). The preciseness and comprehensibility of the questionnaire were consistently evaluated to be 'good' or 'excellent' both by patients and urologists. CONCLUSIONS: The Finnish version of the NIH-CPSI is valid and easily comprehensible for measuring CPPS symptoms. In addition, it provides good discriminant and convergent validity in distinguishing CPPS symptoms and should be used as primary outcome measure in CPPS studies.

Mast cell chymase inhibits smooth muscle cell growth and collagen expression in vitro: transforming growth factor-beta1-dependent and -independent effects.

In the vulnerable areas of fibrous caps of advanced atherosclerotic lesions, chymase-containing mast cells are present. In such areas, the numbers of smooth muscle cells (SMCs) and the content of collagen are reduced. In this in vitro study, we found that the addition of chymase, isolated and purified from rat serosal mast cells, to cultured rat aortic SMCs of the synthetic phenotype (s-SMCs) inhibited their proliferation by blocking the G(0)/G(1)-->S transition in the cell cycle. Rat chymase and recombinant human chymase inhibited the expression of collagen type I and type III mRNA in s-SMCs and in human coronary arterial SMCs. The growth-inhibitory effect of chymase was partially reversed by addition to the culture medium of an antibody capable of neutralizing the activity of transforming growth factor-beta1 (TGF-beta1). Immunocytochemistry showed that the s-SMCs expressed and synthesized extracellular matrix-associated TGF-beta1. On exposure to mast cell chymase, the extracellular matrix-associated latent TGF-beta1 was released and activated, as demonstrated by immunoblotting and by an ELISA with TGF-beta1 type II receptor for capture. When added to s-SMCs, such chymase-released TGF-beta1 was capable of inhibiting their growth. In contrast, the inhibitory effect of chymase on collagen synthesis by s-SMCs did not depend on TGF-beta1. Taken together, the findings support the hypothesis that chymase released from activated mast cells in atherosclerotic plaques contributes to cap remodeling.

Mast cell chymase induces apoptosis of vascular smooth muscle cells.

In human coronary atheromas, the numbers of degranulated mast cells and of apoptotic smooth muscle cells (SMCs) are increased. Accordingly, the possibility exists that mast cells participate in the regulation of SMC apoptosis in the lesions. Mast cells isolated from the serosal cavities of rats were stimulated to release their secretory granules. The neutral protease chymase, present in the exocytosed granules, was found to induce apoptosis when added to rat aortic SMCs in culture. The chymase-induced apoptosis of SMCs was detected by flow cytometry, microscopic analysis of cellular morphology, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), and electrophoretic demonstration of DNA laddering. Chymase induced SMC apoptosis in a dose- and time- dependent manner, and its proteolytic activity was essential for the proapoptotic effect. In addition to rat chymase, recombinant human chymase was also found to induce apoptosis of human coronary artery SMCs in culture. These results suggest that mast cells may participate in the apoptotic regulation of SMCs in atherosclerotic lesions.

Doppler radar detection of exceptional mass-migration of aphids into Finland.

Our objective was to detect mass migrations of insects of economic significance by insect traps and a Doppler weather radar. Migrants were sampled by suction traps, tow nets and light traps in the Helsinki region. We used radar to observe the migrating insects, and trajectories to backtrack mass migrations of aphids (Homoptera, Aphididae) in spring 1988. The aphid migrations were clearly observed in trap catches and by radar. The first migration, mainly involving Euceraphis betulae, occurred on 18 May and was tracked back to northern Poland. The second migration, mainly of Rhopalosiphum padi (a serious pest of small-grain cereals), occurred 3 days later and was tracked back to a large area covering Latvia and western Russia south of St Petersburg. The third migration included both E. betulae and R. padi, and took place on 30 May. It originated from Estonia. Neither trap nor radar data provide exact quantitative information on migrations. Trapping efficiency depends strongly on wind speed and insect size. Radar echo intensity is very strongly related to the sizes of insects in the large volume of air measured, and the sizes are not known accurately. Weather data, especially temperature, can be used in predicting the development of aphids, and air-parcel trajectories in estimating the source areas of migrants. These methods for forecasting aphid migrations, combined with radar observations, are useful for warning purposes and to intensify insect trapping. This would contribute to more efficient agricultural pest management.

Effects of finasteride in patients with inflammatory chronic pelvic pain syndrome: a double-blind, placebo-controlled, pilot study.

OBJECTIVES: To investigate whether treatment of inflammatory chronic pelvic pain syndrome (ICPPS) with finasteride has any influence on symptoms associated with ICPPS. METHODS: Forty-one patients with ICPPS were randomized (1:3) to treatment with either placebo (25%, n = 10) or finasteride 5 mg daily (75%, n = 31 ) for 1 2 months. Efficacy was evaluated by analysis of symptomatic improvement through responses to symptom questionnaires, pain evaluation on an analytical visual scale, analgesic use as reported in patient diaries, urine flow and residual volume, and prostate volume. RESULTS: Prostatitis Symptom Severity Index and prostatism scores dropped significantly in patients in the finasteride group (P < 0.001 and P < 0.05, respectively). There were no statistically significant differences in pain between the groups. There were significant differences in the changes of prostate volume and in serum prostate-specific antigen concentrations between the finasteride and placebo groups (P < 0.03 and P < 0.02, respectively). The groups did not differ with regard to side effects. CONCLUSIONS: Our results indicate that finasteride has an effect in ICPPS. The mechanisms by which finasteride works in these patients are unclear and could not be solved in this pilot study, which had relatively few patients. A further trial with larger numbers is required to confirm these results.

Effects of surface-induced hypothermia and rewarming on canine cardiac contraction-relaxation cycle.

The aims of this study were to elucidate the effects of cooling and rewarming on cardiac contraction-relaxation cycle. Cardiac catheterization was carried out on eleven anaesthetized beagle dogs. The dogs were cooled between icebags until the temperature of the blood in the ascending aorta was 25 degrees C and then rewarmed. Heart rate increased transiently at the beginning of cooling down to 33 degrees C (P < 0.05). Cardiac output first tended to increase until a body temperature of 33 degrees C was achieved but then decreased (P < 0.05). The systolic period lengthened significantly (P < 0.001) when the body temperature decreased from 37 degrees C to 25 degrees C. Cardiac relaxation slowed down linearly with temperature during cooling. The peak value of the first order derivative of the ventricular pressure curve (dP/dtmax) increased at the beginning of cooling down to 33 degrees C, indicating enhanced systolic pressure rise in left ventricle but returned to baseline values at lower temperatures. However the ejection fraction, systolic period and the systemic vascular resistance increased at the temperatures below 33 degrees C despite the unaltered peak dP/dt and thus we conclude that the contraction force is augmented in the hypothermia. All the parameters measured recovered to normal during rewarming and no signs of heart failure were noted during the experiments.

Reversibility of hypertensive vascular changes after coarctation repair in dogs.

A silk ligature was tied around the aorta at the site of the ligamentum arteriosum in beagle puppies aged 8 wk, and the aortic coarctation was corrected 8 mo later, when the aortic peak-to-peak systolic pressure gradient was 6.0 (SD 0.7) kPa. Similar thoracotomy was performed as a sham operation on the control animals on both occasions. One y after the coarctation repair, there was practically no systolic pressure gradient across the aortoplasty site at rest [0.5 (1.0) kPa]. Histologic examination 12 mo after the correction operation showed the medial and intimal layers of the aortic arch in the aortoplasty group (n = 8) were significantly thicker than those in the control group (n = 7) [media 1.86 (0.06) versus 1.78 (0.08) mm and intima 53.2 (13.3) versus 38.3 (10.9) microns, respectively, p less than 0.05 for both]. The thicknesses of both intima and media of the left anterior descending and circumflexing coronary arteries and descending aorta distal to the aortoplasty site were similar in both groups. The increased vascular wall thickness may cause reduced compliance of the vascular bed above the coarctation site and hypertension after correction of the coarctation. Our results support the finding that patients with repaired aortic coarctation have an increased risk of permanent vascular changes.

Left ventricular function in dogs 1 year after coarctectomy.

Juxtaductal aortic coarctation was surgically created in beagle puppies at the age of 2 months and resected at the age of 10 months, after the development of good collateral circulation. Control dogs undergoing sham operations on each occasion were studied in the same environment. Cardiac catheterization was performed 1 year after the coarctectomy to evaluate the recovery of the heart. Cardiac output, heart rate, end-diastolic pressure, and Vmax were similar in both groups of seven dogs, but the systolic pressure gradient (SPG) over the operated area during isoproterenol infusion was significantly higher in the coarctectomized group, with a mean of 8.9 +/- 6.3 (SD) vs. 0.1 +/- 0.3 mmHg (p less than 0.05). The preejection period [PEP, 58 +/- 8 vs. 47 +/- 5 ms (p less than 0.01)], electromechanical delay [EMD, 18 +/- 3 vs. 13 +/- 3 ms (p less than 0.05)], and isometric contraction time [ICT, 39 +/- 7 vs. 32 +/- 4 ms (p less than 0.05)], were all significantly longer in the coarctation group after isoproterenol infusion. The results demonstrate that, even though cardiac output increased adequately during loading and mechanical pumping efficiency was preserved, excitation-contraction coupling was still prolonged. Thus, an anatomical successful coarctectomy, even at the age of 10 months, does not fully restore left ventricular function in dogs after chronic experimental coarctation.

Left ventricular responses to experimental aortic coarctation in growing puppies.

The haemodynamic status of 8 coarctated and 7 sham-operated beagle puppies was studied by a catheterization technique at rest and during isoproterenol and volume loading at the ages of 7 (I) and 9 (II) months (5 and 7 months after the experimental coarctation). Proximal aortic systolic and pulse pressures were constantly higher in the coarctation group than in the control group (P less than 0.05), and the systolic pressure gradient across the coarctation was always significantly higher in the coarctation group [I at rest mean 45 +/- 5 (SD) vs 5 +/- 4 mmHg, P less than 0.001, and after I isoproterenol infusion 56 +/- 9 vs 10 +/- 6 mmHg, P less than 0.001, and after I dextran infusion 58 +/- 10 vs 8 +/- 7 mmHg, P less than 0.001]. The time constant of exponential isovolumic left ventricular pressure fall after the isoproterenol tests was longer in the coarctation group (I 28 +/- 8 ms and II, 30 +/- 4 ms) than in the control group (I, 21 +/- 2, P less than 0.05 and II, 19 +/- 3 ms, P less than 0.005), indicating impaired relaxation. The tension time index during the volume loading tests increased in the coarctation dogs (I, 4150 +/- 660 and II, 4080 +/- 810 mmHg s min-1) to higher levels than in the control group (I, 3550 +/- 220, II, 2540 +/- 1140 mmHg s min-1, P less than 0.05 both). Cardiac output, left ventricular end diastolic pressure, inotropic parameters and heart rate were similar in both groups during the infusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Venous patch aortoplasty for correction of experimental coarctation.

Experimental chronic aortic coarctation in eight beagle dogs was repaired with a free autogenous vein patch graft. Seven sham-operated dogs were controls. One year later the aortic resting blood pressure proximal to the aortoplasty was 122/77 (SD 10/8) mmHg in the aortoplasty group and 112/76 (SD 11/10) in the control group. The strength of the venous patch was tested with intravenous infusion of phenylephrine 0.01 mg/kg/min for 10 min (total dose 0.1 mg/kg). The aortic blood pressure after this infusion was 240/167 (38/26) and 271/179 (27/19) mmHg, respectively. The systolic gradient across the aortoplasty site was 3.9 (6.9) mmHg at rest and 7.7 (16.6) after the phenylephrine infusion. The aortic cross-sectional area at the aortoplasty site was 46.8 (2.7) mm2 in the aortoplasty group and 43.7 (3.7) in the control group. Focal intimal smooth muscle cell hyperplasia was found in the venous patch and in the aortic wall beside the sutures, and the medial layer of the patch was fibrotic. A venous patch may be an option for treatment of coarctation.