Reversal of electrophysiologic effects of flecainide on the accessory pathway by isoproterenol in the Wolff-Parkinson-White syndrome

To determine the reversibility of the effects of flecainide on accessory pathways, electrophysiologic studies were performed in the drug-free control state, after flecainide loading and with isoproterenol infusion during flecainide treatment in 12 patients with symptomatic preexcitation syndrome. After the baseline drug-free evaluation, oral flecainide was given in dosages of 50 to 200 mg twice daily (mean daily dose 282 +/- 75) for at least 4 days before the repeat electrophysiologic study. Isoproterenol infusion was given in dosages of 1 to 4 micrograms/min to increase the heart rate at rest by 50%. Anterograde block in the accessory pathway was observed in 3 patients with flecainide therapy, whereas in the other patients the anterograde refractory period increased from 243 +/- 20 to 315 +/- 23 ms (p less than 0.05). The shortest preexcited RR interval during atrial fibrillation lengthened from 234 +/- 27 ms before flecainide to 313 +/- 38 ms (p less than 0.05). Retrograde block occurred in 2 patients after flecainide, whereas the retrograde refractory period of the accessory pathway increased from 247 +/- 26 to 337 +/- 45 ms in the other patients. Orthodromic atrioventricular reciprocating tachycardia, inducible in 10 patients before therapy, became noninducible in 3 patients. Its rate was significantly slowed in the other 7 patients (from 346 +/- 50 to 471 +/- 81 ms). In 2 patients the tachycardia was nonsustained during flecainide treatment. Atrial fibrillation, inducible in all patients at baseline, was rendered nonsustained and more difficult to induce in 7 patients with flecainide. When isoproterenol was infused during flecainide treatment, complete anterograde (3 patients) or retrograde block (2 patients) persisted in the accessory pathway.(ABSTRACT TRUNCATED AT 250 WORDS)     

Secular trends in fitness,moderate-to-vigorous physical activity,and TV-viewing among first grade school children of Crete,Greece between 1992/93 and 2006/07

ObjectivesTo assess secular changes in physical fitness (PF), moderate-to-vigorous-physical activity (MVPA) and TV-viewing in 1st-grade children from Crete, Greece.DesignCross-sectional cohorts examined in academic years 1992/93 and 2006/07.MethodsTwo representative samples of children, aged 5.9–7.8 years, were studied during 1992/93 (N = 606) and 2006/07 (N = 361). PF (sit-and-reach, standing-broad-jump, sit-ups and 20 m-shuttle-run-test) was assessed by the European-PF test battery and MVPA by a physical activity (PA) questionnaire. Data on the frequency of TV-viewing was also collected.ResultsBetween 1992/93 and 2006/07, there was a significant increase in all fitness tests in both genders (P < 0.001) and in MVPA in boys (76.5 min/week vs. 38.7 min/week, P < 0.001). Time spent watching TV on weekdays was significantly more in both genders in 2006/07, compared to 1992/93 (P < 0.001). In 2006/07, active boys and active girls spent more time in MVPA than active boys and girls in 1992/93 (P < 0.001). Significantly higher proportions of boys and girls engaged in vigorous activities in 2006/07, than 1992/93 (P < 0.001 and P = 0.027, respectively).ConclusionsA significant increase in physical and cardiorespiratory fitness in both genders and MVPA in boys was observed in children from Crete between 1992/93 and 2006/07. The increase in weekday TV-viewing, despite being parallel to an increase in leisure-time MVPA, could have an unfavorable effect on health and should be tackled in future interventions in this population. Dietary, anthropometric and biochemical indices should also be investigated to assess their impact on the secular changes in physical fitness and activity observed in this sample of children.     

Zofenopril Plus Hydrochlorothiazide and Irbesartan Plus Hydrochlorothiazide in Previously Treated and Uncontrolled Diabetic and Non-diabetic Essential Hypertensive Patients

Introduction

In most treated patients with hypertension, a two or more drug combination is required to achieve adequate blood pressure (BP) control. In our study we assessed whether the combination of zofenopril + hydrochlorothiazide (HCTZ) was at least as effective as irbesartan + HCTZ in essential hypertensives with at least one additional cardiovascular risk factor, uncontrolled by a previous monotherapy.

Methods

After a 2-week placebo washout, 361 treated hypertensive patients [office sitting diastolic BP (DBP), ≥90 mmHg], aged 18–75 years, were randomized double blind to 18-week treatment with zofenopril 30 mg plus HCTZ 12.5 mg or irbesartan 150 mg plus HCTZ 12.5 mg once daily, in an international, multicenter study. After the first 6 and 12 weeks, zofenopril and irbesartan doses could be doubled in non-normalized subjects. The primary study end point was the office sitting DBP reduction after 18 weeks of treatment. Secondary end points included office systolic BP (SBP), ambulatory BP and high sensitivity C-reactive protein (hs-CRP).

Results

The between-treatment difference for office DBP averaged to +1.0 (95% CI ?0.4, +0.8) mmHg (P = 0.150), the upper limit of the 95% confidence interval being inferior to the protocol-defined non-inferiority limit (3 mmHg). In the subset of patients with valid ambulatory BP, no difference in 24-h average DBP [n = 181; 6.7 (8.7, 4.6) zofenopril + HCTZ vs. 6.3 (8.8, 3.7) mmHg irbesartan + HCTZ, P = 0.810] and SBP reductions [11.7 (15.4, 8.0) vs. 12.6 (17.2, 8.0) mmHg, P = 0.758] were observed between the two treatment groups. hs-CRP was reduced by zofenopril + HCTZ [?0.52 (?1.05, 0.01) mg/L], while it was increased by irbesartan plus HCTZ [0.97 (0.29, 1.65) mg/L, P = 0.001 between treatments].

Conclusion

In previously monotherapy-treated, uncontrolled patients with hypertension, zofenopril 30–60 mg + HCTZ 12.5 mg is as effective as irbesartan 150–300 mg plus HCTZ 12.5 mg, with the added value of a potential protective effect against vascular inflammation.     

Prolactin and TSH responses to TRH and to haloreridol in schizophrenic patients before and after treatment

The prolactin (PRL) and the TSH responses to thyrotropin releasing hormone (TRH, 0.4 mg i.v.) and to haloperidol (5 mg i.m.) were studied in 11 male schizophrenic patients in a drug-free state and after treatment with haloperidol, 60 mg daily. The PRL responses observed after i.m. haloperidol in the drug-free state, on average 35.4 ng/ml, were abolished after treatment, indicating complete receptor blockade, while the PRL responses to TRH were preserved, although moderately reduced (from 19.4 to 14.8 ng/ml on average). The TSH responses to TRH were unaltered by the treatment (means 8.25 and 7.74 mIU/1). The results show that the TSH and partially the PRL releasing actions of TRH are not mediated via receptors that are effectively blocked by haloperidol.     

Torsades de Pointes as a Cause of Sudden Death in a Patient with Aortic Stenosis and Atrial Fibrillation

The occurrence of sudden cardiac death during Holter monitoring in patients with aortic stenosis has been reported previously. In the majority of the reported cases, the cause of death was a malignant ventricular tachyarrhythmia. The presence of a strong association between frequency and complexity of ventricular arrhythmias and sudden death in patients with aortic stenosis has been proposed. We report the case of a 77‐year‐old woman with aortic stenosis and atrial fibrillation who had an episode of torsades de pointes that degenerated into ventricular fibrillation during Holter monitoring. A short–long–short sequence, but not increased ventricular ectopics, precipitated torsades de pointes and sudden death in this case which is strongly indicative of triggered activity as the underlying mechanism of the lethal arrhythmia.     

Smoking habits of Greek preschool children's parents

Background  

Smoking is Greece's largest public health threat. Greece has the highest adult smoking prevalence among all E.U countries, which in turn possibly predisposes Greek children and adolescents to smoke. The purpose of our study was to research into the smoking habits of preschool children's parents since children of that age could be vulnerable to parental negative role modeling and to investigate into the necessity of conducting a public health awareness programme aimed at the general population.     

Effects of 4 weeks treatment with chlorpromazine and/or trihexyphenidyl on the pituitary-gonadal axis in male paranoid schizophrenics

Summary Serum prolactin (PRL), luteinizing hormone (LH) and testosterone (T) levels were estimated in a group of 30 male paranoid schizophrenics before and after 4 weeks treatment with chlorpromazine and/or trihexyphenidyl, and in a group of 14 healthy male individuals. After treatment with chlorpromazine (100 mg t.i.d., p. o.), 10 patients presented a significant increase in serum PRL values and a significant decrease in serum T values. A significant increase in serum PRL values was also found in 10 patients who were treated with chlorpromazine (100 mg t.i.d., p. o.) plus trihexyphenidyl (5 mg t.i.d., p. o.). No significant difference in any of the investigated endocrine parameters was detected in 10 patients after 4 weeks administration of trihexyphenidyl (5mg t.i.d., p.o.). Following chlorpromazine treatment with or without concomitant administration of trihexyphenidyl, 20 patients showed a significant increase in serum PRL levels and a significant decrease in serum LH and T levels.     

Therapeutic serum lidocaine and metabolite concentrations in patients undergoing electrophysiologic study after discontinuation of intravenous lidocaine infusion

Serum concentrations of lidocaine and its metabolites monoethylglycinexylidide (MEGX) and glycinexylidide (GX) were measured in seven patients after discontinuation of intravenous lidocaine necessary for control of spontaneous arrhythmias prior to electrophysiologic study. Standard loading doses of lidocaine were given intravenously followed by 2 mg/min infusions for 79.5 +/- 6.5 hours. Electrophysiologic studies all started more than 5 half-lives or 7.5 hours after discontinuation of intravenous lidocaine. Local anesthesia with subcutaneous lidocaine (mean 162 +/- 96 mg) was administered in six patients. Plasma concentrations of lidocaine and its metabolites were determined at the termination of the infusion, 2 and 4 hours afterwards, at the start of the electrophysiologic study prior to local anesthesia, and at the end of the study. Levels were also determined at 12 and 24 hours after discontinuation of the infusion. Mean plasma concentrations of lidocaine, MEGX, and GX at the start of the study were 1.02, 0.86, and 0.62 micrograms/ml, respectively. These had increased to 2.78, 0.92, and 0.68 by the end of the electrophysiologic study. One patient with coronary artery disease and prior out-of-hospital ventricular fibrillation had a therapeutic lidocaine level and no inducible arrhythmia at the time of the initial study. At a subsequent electrophysiologic study, no lidocaine or metabolites were detected in the serum and ventricular fibrillation was induced. Thus using the reported half-life of 90 minutes and discontinuing lidocaine 5 half-lives prior to electrophysiologic evaluation does not ensure lack of electrophysiologic effects of the parent compound or its metabolites. Lidocaine given for local anesthesia further increases lidocaine and metabolite levels.(ABSTRACT TRUNCATED AT 250 WORDS)