Clinical and socioeconomic impact of moderate-to-severe versus mild influenza in children

Some studies have assessed the efficacy of influenza vaccination in children separately for moderate-to-severe and any influenza, but the definition used for identifying children with moderate-to-severe illness has not been validated. We analyzed clinical and socioeconomic data from two prospective cohort studies of respiratory infections among children aged ≤13 years (four influenza seasons, 3,416 child-seasons of follow-up). We categorized children with laboratory-confirmed influenza into two mutually exclusive groups of moderate-to-severe and mild influenza using the previously proposed criteria. We obtained the data for the analyses from structured medical records filled out by the study physicians and from daily symptom cards filled out by the parents. Of 434 cases of influenza, 217 (50 %) were classified as moderate-to-severe and 217 (50 %) as mild. The mean duration of fever was 4.0 days in children with moderate-to-severe influenza and 3.1 days in those with milder illness (P?<?0.0001). Antibiotics were prescribed to 111 (51 %) children with moderate-to-severe and to ten (5 %) children with mild influenza (P?<?0.0001). The rates of parental work absenteeism were 184 days per 100 children with moderate-to-severe influenza and 135 days per 100 children with mild influenza (P?=?0.02). The corresponding rates of children’s own absenteeism from day care or school were 297 and 233 days respectively per 100 children (P?=?0.006). Categorization of children into groups with moderate-to-severe and mild influenza is meaningful, and it identifies children in whom the clinical and socioeconomic impact of influenza is highest. Illness severity should be considered when assessing influenza vaccine effectiveness in children.     

Effects of furazolidone, PCB77, PCB126, Aroclor 1248, paraquat and p,p'-DDE on transketolase activity in embryonal chicken brain

The effect of in ovo exposure to PCBs, DDE and paraquat on transketolase activity was measured in 19-day-old chicken embryos. Furazolidone was used as a positive control for decreased activity of the enzyme. The potency of contaminants to interact with transketolase was also tested in an in vitro system, using control brain 7000xg supernatants containing the enzyme. No effects were found on transketolase activity after in ovo or in vitro exposure to PCB126, Aroclor, DDE or paraquat. PCB77 decreased transketolase activity in vitro, but only at concentrations that, extrapolated to in ovo exposure, would be lethal to the embryo. Furazolidone decreased transketolase activity both in ovo and in vitro. For this contaminant, thiamine residues were analysed in the yolk sacs, but no differences were found between exposed and non-exposed eggs. Transketolase is dependent on thiamine pyrophosphate as a cofactor, and therefore, the decreased enzyme activity could be the result of an interaction between furazolidone and thiamine metabolism. Since thiamine residues were not affected by furazolidone and transketolase inhibition in vitro was similar to the inhibition after in ovo exposure, it was concluded that furazolidone interacted with transketolase on the enzymatic level rather than by a depletion of thiamine.     

Second derivative of developed tension in classifying cardiotonics with respect to their mechanisms of action: drugs affecting cAMP metabolism.

The second derivative of developed tension (T", d2T/dt2) has not come into common use in the analysis of cardiac contractility, although it has been shown to give additional information on the myocardial contraction-relaxation cycle (CRC). In the present study a new way to use T" in the analysis of myocardial mechanics, including the time course of T", is described. Profiles of the T" of the some drugs with established cardiotonic effects are presented. Experiments were carried out in spontaneously beating whole rat atria preparations. The effects of changing contraction frequency on the measured parameters were studied with electrically paced left atria. Qualitative inotropic effects of 1-methyl-3-isobutylxanthine (MIX), theophylline, caffeine, milrinone, isoprenaline and forskolin were studied. Concentrations equieffective with respect to the force of contraction were tested. Inotropic profiles were evaluated at the time of maximal force of contraction. We found that methylxanthines have a mechanical behaviour quite distinct from other inotropic agents acting via cAMP. The effects of MIX were similar to those of theophylline in all respects. A tendency to increase the active relaxation phase of T" was a property common to methylxanthines. Caffeine also prolonged the phases of contraction, whereas MIX and theophylline have opposite effects. Milrinone in turn mimics the effects of isoprenaline and forskolin; abbreviation of the relaxation phase of T" was the feature most typical of them. Caffeine was the only agent which did not shorten the duration of CRC. The method proved valuable in basic research on drug effects on cardiac contractility.     

Atrial Natriuretic Peptide and Cyclic Guanosine-3′5′-monophosphate in Hypertensive Pregnancy and During Nifedipine Treatment

Atrial natriuretic peptide exhibits natriuretic. diuretic and vasodilatory properties. We compared plasma concentrations of atrial natriuretic peptide, cyclic guanosine-3′,5′-monophosphate (cGMP), electrolytes and urinary excretion of cGMP and electrolytes in hypertensive pregnant women to those in normotensive pregnant and normotensive non-pregnant women. Plasma atrial natriuretic peptide concentrations in hypertensive pregnant and normotensive nonpregnant women were equal, whereas in normotensive pregnant women it was lower (P<0.05), than in non-pregnant. Urinary cGMP excretion was higher in both normotensive and hypertensive pregnant than in non-pregnant women (P<0.01). whereas plasma cGMP levels were similar. A five-day nifedipine treatment (10 mg t.i.d.) had no effects on any of the variables. In hypertensive pregnancy, a reduction of systolic blood pressure by nifedipine correlated with the initial plasma atrial natriuretic peptide (P<0.05) and a decrease in diastolic blood pressure with the initial plasma cGMP concentration (P<0.05). The results of this small material suggest that plasma atrial natriuretic peptide concentration predicts the response to nifedipine in hypertensive pregnancy. However, the atrial natriuretic peptide-cGMP system does not seem to mediate the antihypertensive effect of nifedipine, while plasma atrial natriuretic peptide remained unaltered. Increased urinary cGMP excretion in both pregnant groups but lowered plasma atrial natriuretic peptide in normotensive pregnancy suggest other factors than circulating atrial natriuretic peptide to promote renal cGMP excretion during pregnancy.     

Effects of P1 and P2Y purinoceptor antagonists on endothelium-dependent and -independent relaxations of rat mesenteric artery to GTP and guanosine.

1. Guanosine 5'-triphosphate (GTP) and guanosine can relax both endothelium-intact and -denuded arterial preparations. In the present work the P1 and P2Y purinoceptor antagonists, 8-phenyltheophylline and reactive blue 2, respectively, were used to study the mechanisms of relaxation responses induced by GTP, guanosine, adenosine 5'-triphosphate (ATP) and adenosine in noradrenaline-precontracted rat mesenteric artery rings. 2. GTP (10 microM-1mM) dose-dependently relaxed endothelium-intact mesenteric artery rings and also induced moderate relaxation responses in endothelium-denuded preparations. Pretreatment of the rings with 8-phenyltheophylline (10 microM) or reactive blue 2 (10 microM) did not attenuate the relaxant effect of GTP. 3. Guanosine (10 microM-1mM) relaxed both endothelium-intact and -denuded artery rings in a dose-dependent manner. The presence of 8-phenyltheophylline or reactive blue 2 had no effects on guanosine-induced relaxations. 4. ATP-induced (0.1 microM-0.1 mM) relaxation of endothelium-intact artery rings was attenuated by reactive blue 2 while 8-phenyltheophylline was ineffective. ATP also relaxed endothelium-denuded artery rings and this relaxation was inhibited by 8-phenyltheophylline, but not by reactive blue 2. 5. Adenosine-induced (10 microM-1 mM) relaxation of endothelium-intact and -denuded artery rings was attenuated by the presence of 8-phenyltheophylline, but not of reactive blue 2. 6. In conclusion, the endothelium-dependent and -independent relaxations of rat mesenteric arteries to GTP and guanosine are not mediated via P1 and P2Y purinoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of toremifene and tamoxifen in post-menopausal patients with advanced breast cancer: a randomized double-blind, the 'nordic' phase III study.

The study was planned to compare, in a prospective double-blind randomized trial, the efficacy and safety of toremifene (TOR) and tamoxifen (TAM) in post-menopausal patients with advanced breast cancer who have not had prior systemic therapy for advanced disease. Four hundred and fifteen post-menopausal patients with oestrogen receptor (ER)-positive or ER-unknown advanced breast cancer were randomly assigned to receive daily either 60 mg TOR or 40 mg TAM. The patients were stratified to measurable and non-measurable but evaluable groups. They were assessed for response to therapy, time to progression (TTP), time to treatment failure (TTF), response duration, overall survival and drug toxicity. Two hundred and fourteen patients were randomized into TOR and 201 into TAM treatment. The response rate (complete + partial) was 31.3% for TOR and 37.3% for TAM (P = 0.215). The 95% confidence interval (CI) for the 6% difference was -15.1% to 3.1%. The median TTP was 7.3 months for TOR and 10.2 months for TAM (P = 0.047). The 95% CI for the hazard ratio of 0.80 was 0.64-1.00. A percentage of the TOR patients (9.8%) and the TAM patients (18.9%) discontinued the treatment prematurely (P = 0.011) for various reasons. Consequently, the median TTF of 6.3 vs 8.5 months did not differ significantly (P = 0.271). The hazard ratio was 0.89 and the subsequent 95% CI 0.73-1.09. The median overall survival was 33.0 months for TOR and 38.7 months for TAM (P = 0.645). The hazard ratio was 0.94 with 95% CI of 0.73-1.22. The transient difference in TTP may be related to an imbalance in ER content of the tumours. When only patients with ER-positive tumours were considered (n = 238), no difference between two treatments was seen (P = 0.578). TAM was associated with an overall slightly higher frequency of adverse drug reactions than TOR (44.3 vs 39.3%) and a higher discontinuation rate due to these events (3.5% vs 0.9%). Treatment-emerged moderate dizziness (P = 0.026) and cataracts (P = 0.026) were more frequent among TAM than among TOR patients. In conclusion, TOR (60 mg day(-1)) and TAM (40 mg day(-1)) are equally effective and safe in the treatment of advanced post-menopausal ER-positive or ER-unknown breast cancer.     

Comparison of nutrient intake data calculated on the basis of two different databases. Results and experiences from a Swedish-Finnish study

BACKGROUND AND OBJECTIVE: In international surveys of food consumption and nutrient intake, it is essential that the dietary data are comparable when different databases and calculation programs are used. The aim of the present analysis was to examine the comparability of nutrient intake data calculated on the basis of the Swedish food composition database PC-kost and the Finnish food composition database Nutrica. SUBJECTS AND METHODS: A total of 20 male adults currently living in Sweden were selected from a group of Finnish twins of the Finnish Twin Cohort Study. Food consumption data were collected by means of diet history interviews. The estimated intakes of 30 nutrients calculated on the basis of PC-kost were compared to the corresponding estimates calculated on the basis of Nutrica. The calculation procedures were standardised. RESULTS: No statistically significant differences were observed in the mean intakes of energy, total fat, saturated fat, carbohydrates, dietary fibre, alcohol, cholesterol, vitamin A, retinol, beta-carotene, vitamin D, alpha-tocopherol, riboflavin, niacin, vitamin B(12), vitamin C or phosphorus. PC-kost yielded a 20% higher intake (NS) for vitamin D and 23% higher intake (P<0.001) for thiamine than Nutrica, which is mainly attributed to the differences in the enrichment of foodstuffs between Sweden and Finland. Conversely, PC-kost yielded 53% lower values (P<0.001) for selenium than Nutrica, owing to the increased selenium content in many Finnish foodstuffs as a result of the addition of selenium to fertilisers. Statistically significant differences were found for protein, monounsaturated fatty acids, vitamin B(6), iron and sodium (5-9% higher values from PC-kost) and for polyunsaturated fatty acids, folate, zinc, calcium, magnesium and potassium (4-10% lower values from PC-kost). The variation in the intake of these nutrients between the two methods may be explained by the differences in foodstuff-specific nutrient values (eg product formulations), or differences in the sources of data, recipes or calculation procedures.The correlation coefficient was > or =0.81 for most nutrients. At least 85% of the subjects in each PC-kost quintile were classified into the same or adjacent Nutrica quintile for all nutrients. CONCLUSIONS: Our results indicate that, for a dominant part of the examined nutrients, the estimated intakes calculated by means of standardised procedures using the PC-kost and Nutrica databases are comparable between Sweden and Finland. Differences observed for some nutrients reflect either actual differences in foods between the two countries or methodological differences in the assessment of nutrient intakes.