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Comparison of oral propranolol and verapamil for combined systemic hypertension and angina pectoris. A placebo-controlled double-blind randomized crossover trial.

The relative efficacies of oral verapamil, a calcium-entry blocking drug, and propranolol, a beta-adrenergic blocking drug, were compared in 12 patients who had both stable angina pectoris and mild to moderate systemic hypertension, using a placebo-controlled, double-blind, randomized crossover protocol. Compared with placebo, both propranolol and verapamil decreased the frequency of anginal attacks and the number of nitroglycerin tablets consumed, and increased exercise duration and total work; there were no significant differences in the antianginal effect of the two drugs. Both verapamil and propranolol reduced the supine and standing systolic and diastolic blood pressure measured at rest; compared with propranolol, however, verapamil had greater effects on standing diastolic blood pressure (p less than 0.002). Resting heart rate was reduced from placebo baseline with large doses of both drugs; compared with verapamil, however, propranolol exerted greater effects on resting heart rate and rate-pressure product. Plasma renin activity was increased from placebo baseline with verapamil (p less than 0.05), but was reduced with propranolol (p less than 0.05); no significant change in plasma aldosterone was seen with either drug. Verapamil appears to be a safe and effective treatment alternative to propranolol for relieving anginal symptoms, improving exercise tolerance, and reducing elevated systemic blood pressure in patients with both angina pectoris and mild to moderate systemic hypertension.

Adrenergic beta-Antagonists↗

Comparison of bepridil with nadolol for angina pectoris.

Bepridil hydrochloride is a unique calcium channel-blocking drug with anti-ischemic and type 1 antiarrhythmic properties. With a half-life of more than 40 hours, once-daily therapy is possible. Twenty-four patients (22 men, 2 women), mean age 58 years (range 43 to 72), with stable exertional angina were assigned to therapy with bepridil and nadolol in a randomized, double-blind, crossover trial. Antianginal efficacy was assessed by a diary of angina frequency and nitroglycerin consumption as well as by treadmill exercise testing. The effect of therapy on ventricular function was assessed by symptom-limited equilibrium gated exercise radionuclide angiography. During therapy with both nadolol and bepridil, the number of episodes of angina per week was significantly reduced and nitroglycerin consumption decreased compared with baseline evaluation. Exercise duration was prolonged by both therapies (baseline 281 +/- 122 seconds, nadolol 377 +/- 96 seconds, bepridil 400 +/- 109 seconds; p less than 0.005 for nadolol and bepridil vs baseline). Time to the onset of angina was similarly prolonged, 50% by nadolol and 65% by bepridil (p less than 0.005). Bepridil had no effect on PR and QRS durations, although QTc was significantly prolonged (baseline 0.43 +/- 0.03, nadolol 0.42 +/- 0.03, bepridil 0.45 +/- 0.04; p less than 0.005 for bepridil vs baseline and nadolol). By radionuclide angiography, neither nadolol nor bepridil had an adverse effect on left ventricular function at rest or during exercise. Bepridil therefore provides effective therapy for angina without adverse effects on left ventricular function, comparable to the effects of beta blockade with nadolol.

Adult↗

Frequent feeding delays the gastric emptying of a subsequent meal.

To assess the suitability of the 13C-octanoic acid breath test for measuring gastric emptying in circumstances other than the post-absorptive state, a preliminary study was performed where 6 hourly spaced isoenergetic meals preceded the determination of gastric emptying of a subsequent 2 MJ meal. Emptying was measured in three individuals on four separate occasions, with a reproducibility of 8%. A crossover study was then conducted to test the hypothesis that meal frequency can modulate the gastric emptying of a subsequent meal, with the potential to influence appetite regulation. Sixteen subjects were fed to energy balance, receiving food either as 2 isoenergetic meals 3 h apart or 6 isoenergetic meals fed hourly. Gastric emptying of a subsequent 2 MJ meal was investigated. Visual analogue scales were used throughout to assess appetite. The maximum rate of gastric emptying was unchanged but the onset of emptying was delayed by the more frequent feeding pattern. There was no significant difference in subjective appetite before or after the test meal. In conclusion, short-term increases in feeding frequency delayed the gastric emptying of a subsequent meal, but significant effects on post-meal appetite could not be demonstrated.

Adult↗

Signatures of the fast dynamics in glassy polystyrene: first evidence by high-field electron paramagnetic resonance of molecular guests.

The reorientation of one small paramagnetic molecule (spin probe) in glassy polystyrene (PS) is studied by high-field electron paramagnetic resonance spectroscopy at two different Larmor frequencies (190 and 285 GHz). Two different regimes separated by a crossover region are evidenced. Below 180 K the rotational times are nearly temperature independent with no apparent distribution. In the temperature range of 180-220 K a large increase of the rotational mobility is observed with the widening of the distribution of correlation times which exhibits two components: (i) a deltalike, temperature-independent component representing the fraction of spin probes w which persist in the low-temperature dynamics; (ii) a strongly temperature-dependent component, to be described by a power distribution, representing the fraction of spin probes 1-w undergoing activated motion over an exponential distribution of barrier heights g(E). Above 180 K a steep decrease of w is evidenced. The shape and the width of g(E) do not differ from the reported ones for PS within the errors. For the first time the large increase of the rotational mobility of the spin probe at 180 K is ascribed to the onset of the fast dynamics detected by neutron scattering at T(f)=175+/-25 K.

Journal Article↗

Quantum pump for spin and charge transport in a Luttinger liquid.

We study two different parametric pumps--one for pumping spin currents, the other for charge currents--in interacting quantum wires. We find that, as a function of pumping frequency, the spin or charge pumped per cycle has a nonuniversal crossover--depending on pumping details--between two universal fixed point values of 0 and twice the electronic spin or charge quantum number. The direction of flow between these two fixed points depends on whether the interactions are repulsive or attractive, while the quantization itself is a signature of interactions.

Journal Article↗

Half-integer Shapiro steps at the 0-pi crossover of a ferromagnetic Josephson junction.

We investigate the current-phase relation of S/F/S junctions near the crossover between the 0 and the pi ground states. We use Nb/CuNi/Nb junctions where this crossover is driven both by thickness and temperature. For a certain thickness a nonzero minimum of critical current is observed at the crossover temperature. We analyze this residual supercurrent by applying a high frequency excitation and observe the formation of half-integer Shapiro steps. We attribute these fractional steps to a doubling of the Josephson frequency due to a sin((2phi) current-phase relation. This phase dependence is explained by the splitting of the energy levels in the ferromagnetic exchange field.

Journal Article↗

Treatment of stable angina of effort with verapamil: a double-blind, placebo-controlled randomized crossover study.

The effects of verapamil were assessed in 26 patients with stable exertional angina pectoris in a double-blind, placebo-controlled, randomized crossover protocol using serial treadmill tests. Verapamil, 480 mg/day, reduced anginal frequency from 5.6 +/- 7.3 to 2.2 +/- 3.9 attacks per week (p less than 0.001) and nitroglycerin consumption from 3.4 +/- 4.9 to 1.2 +/- 2.5 tablets per week (p less than 0.05) compared with placebo. Treadmill time increased from 6.4 +/- 2.1 minutes during the placebo phase to 7.5 +/- 1.8 minutes during the verapamil phase (p less than 0.001). Verapamil's beneficial effect appeared to be related, in part, to a 10% reduction of the rate-pressure product at rest (p less than 0.05) and a 12% reduction during submaximal exercise (p less than 0.001). Verapamil also caused less marked ST-segment depressions at peak exercise (p less than 0.05) at a similar rate-pressure product, suggesting a favorable redistribution of coronary blood flow to the ischemic zone. Side effects from verapamil were minimal, consisting mainly of constipation (six patients). Verapamil appears to be a safe and effective drug for treating angina of effort.

Adult↗

Clomipramine treatment for stereotype and related repetitive movement disorders associated with mental retardation.

The efficacy of the serotonin uptake inhibitor clomipramine in the treatment of stereotyped and related repetitive behavior disorders was tested in individuals with severe and profound mental retardation. A double-blind, placebo-controlled crossover trial of clomipramine was associated with significant reductions in the frequency and intensity of stereotyped behavior and teacher ratings of stereotypy, hyperactivity, and irritability as well as increased adaptive engagement and decreased staff intervention for nontargeted behavior problems. Adverse effects occurred in 3 of the 10 subjects. Of the 7 subjects who tolerated the drug, 6 exhibited a clinically significant improvement in one or more repetitive behaviors. Our results provide support for the hypothesis that clomipramine is effective in treating stereotyped and related behaviors associated with mental retardation.

Adolescent↗

L-dopa therapy of uremic and idiopathic restless legs syndrome: a double-blind, crossover trial.

We report the effects of a single bedtime dose of L-dopa 100-200 mg on sleep quality, frequency of periodic leg movements (PLM) and daily living in patients with idiopathic and uremic restless legs syndrome (RLS). Seventeen patients with idiopathic and 11 with uremic (on continuous hemodialysis) RLS were evaluated comparatively by polysomnography, actigraphy and subjective ratings in a randomized, controlled and double-blind crossover trial with L-dopa and placebo for 4 weeks each. Neurophysiologic assessments showed significant reduction of the number of periodic leg movements (p = 0.003) and the PLM-index (p = 0.005) most pronounced during the first 4 hours of bedtime after L-dopa (p = 0.001). Subjective evaluation confirmed improvement of sleep quality (p = 0.002) and showed significantly higher quality of life during daytime (p = 0.030) while the patients received L-dopa therapy. We conclude that L-dopa 100-200 mg proved to be effective in idiopathic RLS and for the first time under controlled conditions in uremic RLS without any severe side effects.

Adult↗

Evidence for biased holliday junction cleavage and mismatch repair directed by junction cuts during double-strand-break repair in mammalian cells.

In mammalian cells, several features of the way homologous recombination occurs between transferred and chromosomal DNA are consistent with the double-strand-break repair (DSBR) model of recombination. In this study, we examined the segregation patterns of small palindrome markers, which frequently escape mismatch repair when encompassed within heteroduplex DNA formed in vivo during mammalian homologous recombination, to test predictions of the DSBR model, in particular as they relate to the mechanism of crossover resolution. According to the canonical DSBR model, crossover between the vector and chromosome results from cleavage of the joint molecule in two alternate sense modes. The two crossover modes lead to different predicted marker configurations in the recombinants, and assuming no bias in the mode of Holliday junction cleavage, the two types of recombinants are expected in equal frequency. However, we propose a revision to the canonical model, as our results suggest that the mode of crossover resolution is biased in favor of cutting the DNA strands upon which DNA synthesis is occurring during formation of the joint molecule. The bias in junction resolution permitted us to examine the potential consequences of mismatch repair acting on the DNA breaks generated by junction cutting. The combination of biased junction resolution with both early and late rounds of mismatch repair can explain the marker patterns in the recombinants.

Animals↗

The effect of montage on the analgesic response to percutaneous neuromodulation therapy.

The analgesic response to percutaneous neuromodulation therapy (PNT) is influenced by the location, frequency, and duration of electrical stimulation. We evaluated the effect of different patterns of stimulation (montages) on the acute analgesic response to PNT when applied at the same dermatomal levels in 72 consenting patients with low back pain. All of the patients received a standardized montage (I) and three alternative montage (II-IV) patterns according to a randomized, single-blinded, crossover study design. All of the PNT treatments were administered at identical alternating stimulation frequencies of 15 and 30 Hz for a period of 30 min, three times per week for two consecutive weeks, with 1 wk "off" between each modality. Pretreatment assessments included the health status survey short form (SF-36) questionnaire, as well as visual analog scale scores for pain, physical activity, and quality of sleep (with 0 = the best to 10 = the worst). The pain visual analog scale was repeated 5--10 min after each treatment session. The daily oral analgesic usage was recorded in a patient diary. All four montages produced significant improvements in pain (42%--64%), physical activity (35%--51%), and quality of sleep (28%--46%), as well as 23% to 47% reductions in the daily oral analgesic usage. However, Montage II was significantly more effective than the standard (Montage I) and the other two montages studied. These data suggest that the pattern of stimulation (i.e., montage) can influence the acute analgesic response to PNT.

Adult↗

A crossover study of naproxen, diclofenac and tolmetin in seronegative juvenile chronic arthritis.

Nonsteroidal anti-inflammatory drugs (NSAID) are useful in the management of juvenile chronic arthritis (JCA) and efficacy has usually been compared with aspirin. The disadvantages of aspirin include the frequency of dosage, monitoring of salicylate levels and concern about Reye's syndrome. We have performed a single blind crossover study comparing naproxen 10 mg/kg/day, tolmetin 25 mg/kg/day and diclofenac 2 mg/kg/day in 28 children with seronegative JCA over 12 weeks. Clinical and laboratory assessments were made after 4 weeks of treatment on each drug. Clinical improvement was seen with all three NSAID compared to baseline after a 24-hour washout period, but statistical significance was reached in only 2 or 3 of the clinical parameters for each drug. Side effects were mild and typical of NSAID, but occurred less frequently with naproxen (5) and tolmetin (5) than with diclofenac (7). Thus the anti-inflammatory effect of all three drugs was confirmed with no significant differences between them in terms of efficacy and tolerance. Tolmetin 200 mg tablets are now only available in France and N. America, therefore naproxen or diclofenac are recommended as the first line of treatment in children with chronic arthritis over the age of 5.

Adolescent↗

Frequency-dependent shear viscosity, sound velocity, and sound attenuation near the critical point in liquids. III. The shear viscosity.

We compare theoretical results for the shear viscosity calculated in one-loop order within the field-theoretical method of the renormalization-group theory with experiments. Our expressions describe the nonasymptotic crossover in both temperature and density, and allow us to consider effects of finite gravitation and finite frequency at which the experiments are performed. In doing so we treat the critical exponent x(eta) of the shear viscosity as an independent parameter, keeping the one-loop value of the Kawasaki amplitude fixed. Within our model we also consider the temperature and density dependence of the thermal diffusion including gravitational effects.

Journal Article↗

An insertion/deletion TEX28 polymorphism and its application to analysis of red/green visual pigment gene arrays.

TEX28 gene (fTEX) is present immediately downstream of the red/green visual pigment gene array on the human X chromosome. Its pseudogene (pTEX) that lacks exon 1 is present within the array between pigment genes. We found that both fTEX and pTEX genes had a 697 bp insertion/deletion polymorphism in their introns 3. In color-normal male subjects, the frequency of the 697 bp region was 43% (40/94) in pTEX and 97% (91/94) in fTEX in the array of Red-pTEX-Green-fTEX and 10% (9/94) in pTEX and 87% (41/47) in fTEX in the array of Red-pTEX-Green-pTEX-Green-fTEX. These results suggest that normal arrays with multiple green genes may have arisen through gene duplication rather than unequal homologous crossover. In color-vision-deficient male subjects with a single-gene array, the frequency of the 697 bp region was 83% (25/30) in the array of Green-fTEX and 66% (74/112) in the array of Red-fTEX. In color-vision-deficient male subjects with a 2-gene array, the frequency of the region was 44% (16/36) in pTEX and 97% (35/36) in fTEX in the array of Green-pTEX-Green-fTEX and 75% (18/24) in pTEX and 92% (22/24) in fTEX in the array of Red-pTEX-Red-fTEX. These results suggest that 2-green-gene arrays have arisen through unequal homologous crossover between a normal 2-gene array and a single-green-gene array. With data from a long-range PCR method using the insertion/deletion polymorphism, we proposed a structure of the second gene of 3-gene arrays, Green-pTEX-Green-pTEX-Green-fTEX and Red-pTEX-Red-pTEX-Red-fTEX, in color-vision-deficient subjects.

Base Sequence↗

Regular meal frequency creates more appropriate insulin sensitivity and lipid profiles compared with irregular meal frequency in healthy lean women.

OBJECTIVE: To investigate the impact of irregular meal frequency on circulating lipids, insulin, glucose and uric acid concentrations which are known cardiovascular risk factors. DESIGN: A randomised crossover dietary intervention study. SETTING: Nottingham, UK--Healthy free-living women. SUBJECTS: A total of nine lean healthy women aged 18-42 y recruited via advertisement. INTERVENTION: A randomised crossover trial with two phases of 14 days each. In Phase 1, subjects consumed their normal diet on either 6 occasions per day (regular) or by following a variable meal frequency (3-9 meals/day, irregular). In Phase 2, subjects followed the alternative meal pattern to that followed in Phase 1, after a 2-week (wash-out) period. Subjects were asked to come to the laboratory after an overnight fast at the start and end of each phase. Blood samples were taken for measurement of circulating glucose, lipids, insulin and uric acid concentrations before and for 3 h after consumption of a high-carbohydrate test meal. RESULTS: Fasting glucose and insulin values were not affected by meal frequency, but peak insulin and AUC of insulin responses to the test meal were higher after the irregular compared to the regular eating patterns (P < 0.01). The irregular meal frequency was associated with higher fasting total (P < 0.01) and LDL (P < 0.05) cholesterol. CONCLUSION: The irregular meal frequency appears to produce a degree of insulin resistance and higher fasting lipid profiles, which may indicate a deleterious effect on these cardiovascular risk factors. SPONSORSHIP: : The Ministry of Health and Medical Education, IR Iran.

Adolescent↗

Effect of particulate and gaseous pollutants on spontaneous arrhythmias in aged rats.

Epidemiology studies suggest that exposure to air pollution increases the frequency of cardiac arrhythmias. A limitation of these studies is that it is difficult to link an increased risk of arrhythmias to a specific air pollutant. Animal exposure studies offer the opportunity to examine the effects of concentrated ambient fine particulate matter (PM), ultrafine PM, and copollutant gases separately. Male Fischer 344 rats, aged 18 mo, with implanted electrocardiograph (ECG) transmitters were used to determine the effects of PM on the frequency of arrhythmias. We found that old F344 rats had many spontaneous arrhythmias. An arrhythmia classification system was developed to quantify arrhythmia frequency. Arrhythmias were broadly grouped into two categories: premature beats and delayed beats. The rats were exposed to concentrated ambient PM (CAPS) or air for 4 h. The rats were exposed twice with a crossover design so each rat could serve as its own control. The CAPS concentrations were 160 microg/m(3) and 200 microg/m(3) for the first and second exposures, respectively. There was a significant increase in the frequency of irregular and delayed beats after exposure to CAPS. The same rats were subsequently exposed to laboratory-generated ultrafine carbon particles, to SO(2), or to air with a repeated crossover design. In these experiments there was no significant change in the frequency of any category of spontaneous arrhythmia following exposure to ultrafine carbon or SO(2). Thus, this study adds supporting evidence that acute exposure to elevated levels of ambient PM increases the frequency of cardiac arrhythmias.

Aging↗

Effect of levetiracetam in patients with epilepsy and interictal epileptiform discharges.

The effect of acute treatment with the new antiepileptic drug (AED) levetiracetam (Keppra) on the frequency of interictal epileptiform discharges (IEDs) was evaluated in a double-blind, placebo-controlled, crossover study with therapeutic drug monitoring and serial electroencephalographic (EEG) observations. Acute (500 mg twice daily) and chronic (individualized, 500-1000 mg twice daily) doses of levetiracetam were administered as an add-on to current AED treatment. Efficacy was tested by measuring the frequency of IEDs in EEG recordings and the number of seizures. A single acute dose of levetiracetam induced a reduction of IEDs in eight out of ten patients. During the acute phase, an insufficient number of seizures occurred for analysis. During chronic treatment over 8 weeks, seven patients showed a reduction in seizure frequency (responder rate), and one patient remained seizure free. No correlation was seen between levetiracetam levels and IED frequency. Doses of levetiracetam of up to 2000 mg/day were well tolerated, and no interactions were seen with concomitant AEDs.

Adolescent↗

Cibenzoline for high-frequency ventricular arrhythmias: a short-term comparison with quinidine and a long-term follow-up.

Cibenzoline, a new class I antiarrhythmic drug, was compared with quinidine in an open crossover study of 20 patients with frequent (greater than 30/hr) premature ventricular depolarizations (PVDs). Eight patients treated with cibenzoline experienced more than 75% reduction in PVD frequency. Cibenzoline completely suppressed ventricular couplets in eight of 17 patients and inhibited ventricular tachycardia (VT) in four of 13 patients. Only four patients (20%) responded to quinidine with a similar reduction in PVDs. Quinidine completely suppressed ventricular couplets in eight of 17 patients and episodes of VT in six of 13 patients. Cibenzoline prolonged PR, QRS, and QTc intervals. Eight patients who had shown more than a 75% reduction of PVDs were treated with cibenzoline for an extended period. At the end of three months, only five of eight patients continued to have 75% or greater reduction of PVDs. At the end of six and 12 months, four of five patients continued to have 75% or greater reduction of PVDs. Cibenzoline was similarly effective in suppressing complex arrhythmias. Thus, cibenzoline was only slightly superior to quinidine in suppressing ventricular arrhythmias. With long-term use of cibenzoline, significant PVD suppression was noted at the end of three months but not afterward.

Adult↗