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PubMed1987

Adjuvant therapy of parkinsonian tremor.

The effect of long-acting propranolol hydrochloride (160 mg/d), primidone (250 mg at night), and clonazepam (4 mg/d) on the resting, postural, and kinetic component of tremor was investigated in ten parkinsonian patients in a double-blind crossover design. Tremor was assessed by patient opinion, clinical scoring, and accelerometer recordings. The amplitude and frequency of tremorgrams were determined by spectral analysis. Most patients preferred long-acting propranolol and chose to continue taking the drug. The mean clinical score for resting and postural tremor was significantly decreased by long-acting propranolol but not by primidone or clonazepam. Long-acting propranolol reduced the mean amplitude of resting tremor by 70% and the mean amplitude of postural tremor by 50%. Mean tremor amplitudes were not changed by primidone or clonazepam. Tremor frequency was unaltered by the drugs. No side effects occurred with long-acting propranolol but adverse reactions were common with primidone and clonazepam. Long-acting propranolol is a useful adjuvant therapy for the tremors associated with Parkinson's disease.

Aged↗

PubMed1988

Treatment of chronic Parkinson's disease with controlled-release carbidopa/levodopa.

Controlled-release carbidopa/levodopa 50/200 (SINEMET CR) and standard carbidopa/levodopa (SINEMET 25/100) were compared in a double-blind, six-month, crossover study involving 21 patients with chronic Parkinson's disease and motor response fluctuations. Daily dosage frequency was significantly reduced with SINEMET CR compared with SINEMET 25/100, while the daily amount of levodopa required with SINEMET CR was significantly greater. No significant differences in disability ratings, motor response fluctuations, or safety were detected during double-blind conditions. In the open-label, dose-finding phase of the study, SINEMET CR was superior to standard SINEMET 25/100 in patient ratings of percent "on" time (good motor function), clinical assessments of motor function, and activities of daily living. This finding resulted from a depreciation of the value of the "old drug" rather than an overestimation of the value of the experimental drug. This double-blind study also suggested that elderly male patients with Parkinson's disease derived the greatest benefit from SINEMET CR.

Aged↗

PubMed1990

A comparison of enteric coated microspheres with enteric coated tablet pancreatic enzyme preparations in cystic fibrosis. A controlled study.

A comparative study of the efficacy of pH sensitive enteric coated microspheres (ECM) with an enteric coated tablet (ECT) pancreatic enzyme preparation was carried out in 20 children with cystic fibrosis in a double-blind double-placebo crossover manner. Steatorrhoea was assessed by 3 day faecal fat analysis and dosage of medication, stool frequency and consistency; abdominal pain and appetite were documented by a patient-kept diary card. ECM controlled steatorrhoea (11.8 +/- 9.2 g vs 23.2 +/- 18.9 g, P less than 0.02), stool frequency (1.7 +/- 0.6 vs 2.1 +/- 0.9, P less than 0.01) and abdominal pain (8.8 +/- 13.8 vs 23.4 +/- 24.1, P less than 0.05) significantly better than ECT. Out of 20 patients 17 preferred ECM to ECT (P less than 0.00036). ECM preparations should allow more satisfactory dietary management of patients with cystic fibrosis with longterm beneficial effect.

Adolescent↗

PubMed1985

Comparison of diltiazem and nifedipine for both angina pectoris and systemic hypertension.

In a randomized, double-blind, placebo-controlled crossover trial, diltiazem and nifedipine were compared in 10 patients with stable angina pectoris and mild to moderate hypertension (supine diastolic blood pressure greater than or equal to 90 mm Hg). Patients received placebo for 2 weeks, then increasing doses of diltiazem (90 to 360 mg/day) or nifedipine (30 to 120 mg/day) in 3 daily divided doses over 2 weeks, followed by 1 week of therapy at the maximal dose, a 1-week placebo "washout," then crossover to the other drug. Heart rate and blood pressure at rest and during exercise, anginal frequency, nitroglycerin consumption and treadmill exercise tolerance were assessed. Compared with placebo, anginal frequency and nitroglycerin consumption were reduced with both diltiazem and nifedipine (p less than 0.01) and exercise tolerance was increased with both drugs (p less than 0.01). Standing blood pressure at rest was reduced by diltiazem and nifedipine (146.6 +/- 11.4/97.7 +/- 5.3 mm Hg at placebo, baseline reduced to 129.6 +/- 15.2/79.5 +/- 13.7 mm Hg with diltiazem, and to 122.2 +/- 9.9/82.0 +/- 7.1 with nifedipine, p less than 0.01 for both). Compared with placebo, diltiazem and nifedipine also reduced exercise diastolic blood pressure (p less than 0.01), but not systolic blood pressure. Diltiazem lowered the heart rate at rest from 88.5 +/- 14.4 beats/min at placebo baseline to 79.7 +/- 17.9 beats/min (p less than 0.01); the heart rate with diltiazem was 11 beats/min lower than that with nifedipine (p less than 0.05). Both diltiazem and nifedipine had similar effects on the heart rate-blood pressure product at rest and during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Atenolol and celiprolol for stable angina pectoris.

Once-daily atenolol and celiprolol were compared in a placebo-controlled crossover study of 16 patients with stable angina pectoris. Atenolol and celiprolol equally and significantly reduced frequency of angina and electrocardiographic evidence of cardiac ischemia. Celiprolol, however, produced less suppression of the double product at 1 mm of ST-segment depression than atenolol, suggesting that actions other than reduction of heart rate may contribute to its antianginal efficacy.

Adrenergic beta-Antagonists↗

PubMed1982

Controlled trial of nifedipine in the treatment of Raynaud's phenomenon.

17 patients with moderate to severe Raynaud's phenomenon were entered into a 6 week randomised double-blind crossover study to compare the efficacy of nifedipine with that of placebo. Nifedipine significantly reduced the frequency of attacks and also the severity of attacks, which was assessed by the patients on a linear analogue scale. Patients gave nifedipine a significantly higher drug-effectiveness score than placebo. Skin temperature recovery times were not affected by treatment with nifedipine. 12 of the patients regarded nifedipine as effective in reducing the frequency and severity of Raynaud's phenomenon.

Adolescent↗

PubMed1991

Influence of ultrasound on the percutaneous absorption of nicotinate esters.

The influence of ultrasound on the percutaneous absorption of three nicotinate esters was investigated in 10 healthy volunteers in a double-blind placebo controlled crossover clinical trial. Using a specially designed experimental protocol, the effect of continuous output ultrasound (at frequency 3.0 MHz and intensity 1.0 W/cm2 for 5 min) on the percutaneous absorption of methyl, ethyl, and hexyl nicotinates, from gel bases, was investigated. A placebo control, involving massage with each of the gels, without ultrasound for 5 min, was also incorporated. The pharmacodynamic parameter of vasodilation caused by the nicotinates was used to monitor the percutaneous absorption of the drugs. Laser Doppler velocimetry, a noninvasive optical technique, was used to measure vasodilation of the cutaneous vessels within the treatment site. Ultrasound treatment led to enhanced vasodilator response to the nicotinates, therefore indicating an enhancement of their percutaneous absorption. These agents may prove to be useful compounds in examination of the mechanism of action of phonophoresis.

Adult↗

PubMed1977

Three linked enzyme loci in fishes: implications in the evolution of vertebrate chromosomes.

A three-point linkage group comprised of loci coding for adenosine deaminase (ADA), glucose-6-phosphate dehydrogenase (G6PDH), and 6-phospho-gluconate dehydrogenase (6PGD) is described in fish of the genus Xiphophorus (Poeciliidae). The alleles at loci in this group were shown to assort independently from the alleles at three other loci--isocitrate dehydrogenase 1 and 2, and glyceraldehyde-3-phosphate dehydrogenase 1. Alleles at the latter three loci also assort independently from each other. Data were obtained by observing the segregation of electrophoretically variant alleles in reciprocal backcross hybrids derived from crosses between either X. helleri guentheri or X. h. strigatus and X. maculatus. The linkage component of chi2 was significant (less than 0.01) in all crosses, indicating that the linkage group is conserved in all populations of both species of Xiphophorus examined. While data from X. h. guentheri backcrosses indicate the linkage relationship ADA--6%--G6PDH--24%--6PGD, and ADA--29%--6PGD (30% when corrected for double crossovers), data from backcrosses involving strigatus, while supporting the same gene order, yielded significantly different recombination frequencies. The likelihood of the difference being due to an inversion could not be separated from the possibility of a sex effect on recombination in the present data. The linkage of 6PGD and G6PDH has been shown to exist in species of at least three classes of vertebrates, indicating the possibility of evolutionary conservation of this linkage.

Adenosine Deaminase↗

PubMed1998

Relationships between heart rate and heart rate variability: study in conscious rats.

Heart rate (HR) and heart rate variability (HRV) are risk markers in cardiac disease. HRV is also an index of the sympathovagal modulation of heart rate. Their relations have been rarely analyzed. We aimed to study such relations in normal adult conscious rats by using a novel bradycardic agent, a sinus node inhibitor, S-16257. Placebo-drug crossover designs were used while monitoring HR with telemetry and analyzing HRV in both time and frequency domains. S-16257 (2 mg/kg; n = 10) decreased HR by 29% and markedly increased HRV in parallel. By using various combinations of S-16257, atropine (2 mg/kg), and propranolol (4 mg/kg), a positive relation was shown between RR interval and various indexes of HRV: the slower the HR, the greater the HRV. Nevertheless, there is one exception to this correlation. When S-16257 was associated with both atropine and propranolol, the deep bradycardia was accompanied by a reduction of HRV, which indicates that the physiologic negative correlation between HR and HRV is not an intrinsic property of the pacemaker but is highly dependent on the two components of the autonomic system.

Animals↗

PubMed1992

Model misspecification and multipoint linkage analysis.

Pairwise linkage analysis is robust to genetic model misspecification provided dominance is correctly specified, the primary effect being inflation of the recombination fraction. By contrast, we show that multipoint analysis under misspecified models is not robust when a putative disease locus is placed between close flanking markers, with potentially spuriously negative multipoint lod scores being produced. The problem is due to incorrect attribution of segregation of a disease allele and the consequent conclusion of (unlikely) double crossovers between flanking markers. As a possible solution, we propose the use of high disease allele frequencies, as this allows probabilistically for nonsegregation (through parental homozygosity or dual matings). We show analytically and through analysis of pedigree data simulated under a two-locus heterogeneity model that using a disease allele frequency of 0.05 in the dominant case and 0.25 in the recessive case is quite robust in producing positive multipoint lod scores with close flanking markers across a broad range of conditions including varying allele frequencies, epistasis, genetic heterogeneity and phenocopies.

Animals↗

PubMed1998

Famciclovir for the suppression of symptomatic and asymptomatic herpes simplex virus reactivation in HIV-infected persons. A double-blind, placebo-controlled trial.

BACKGROUND: Herpes simplex virus (HSV) infection is one of the most common opportunistic infections in HIV-infected persons. However, most documentation of the effectiveness of antiviral therapy in reducing HSV reactivation is anecdotal. OBJECTIVE: To evaluate the quantitative effect of antiviral therapy on the frequency of HSV reactivation in HIV-infected persons. DESIGN: Double-blind, placebo-controlled, crossover trial. SETTING: Research clinic at a university hospital. PATIENTS: 48 persons (45 men and 3 women) who were HIV positive and HSV seropositive. INTERVENTION: Patients were randomly assigned to receive famciclovir, 500 mg orally twice daily, or placebo for 8 weeks. They then crossed over to receive the other regimen after a 1-week washout period. MEASUREMENTS: Patients obtained daily cultures of their perirectal, urethral, oral, and genital areas and kept dairy records of signs and symptoms of genital and oral-labial herpes. RESULTS: The median CD4 cell count at study entry was 384 cells/mm3. In the intention-to-treat analysis of the first study period, HSV was isolated on 122 of 1114 (11%) placebo days compared with 9 of 1071 (1%) famciclovir days (relative risk, 0.15; P < 0.001). For patients who completed the crossover, the median difference in days with symptoms between placebo and famciclovir was 13.8% of days and the median difference in days on which HSV was isolated was 5.4% of days (P < 0.001 for both). Percentage of days with HSV-2 shedding was reduced from 9.7% to 1.3%. Breakthrough reactivations that occurred while patients were receiving famciclovir were infrequent, short, and often asymptomatic, HSV-2 isolates from these reactivations were susceptible to penciclovir in vitro. CONCLUSIONS: Antiviral chemotherapy with famciclovir results in clinically and statistically significant reductions in the symptoms associated with HSV infection and the symptomatic and asymptomatic shedding of HSV among HIV-positive persons.

2-Aminopurine↗

PubMed2003

[Study on relationship between length of homologous sequences and chromosomic recombination rate in Saccharopolyspora erythraea].

In order to study the relationship between lengths of homologous fragments and chromsomic recombination rate in Saccharopolyspora erythraea, three homologous sequences, with mutant loci and different flanking sequences, (26bp + 27bp), (500bp + 576bp) and (1908bp + 1749bp), were synthesized by chemical reaction or PCR amplification, and cloned into pWHM3 to construct homologous recombination plasmids, pWHM1113, pWHM1116 and pWHM1119. When the plasmids were transformed into protoplast of Saccharopolyspora erythraea A226 under PEG mediated, on an average 30, 69 and 170 transformants grew on each plate for the three plasmids respectively, but chromosomic integration frequency were 0, 2% and 19% among corresponding transformants. Both pWHM1116 and pWHM1119 could take double crossover recombination, and exchange the mutant loci in the chromosome. It was concluded that when the flanking sequences were equal or more than (500bp + 576bp), they could take effective single and double recombination with Saccharopolyspora erythraea chromosome.

Chromosomes, Bacterial↗

PubMed2006

Prevention of migraine with olmesartan in patients with hypertension/prehypertension.

OBJECTIVE: To explore the effects of olmesartan on frequency and severity of migraine attacks in patients with comorbid hypertension and prehypertension. BACKGROUND: A randomized, double-blind, placebo-controlled, crossover study with a total of 60 patients has demonstrated the efficacy and safety of the angiotensin II receptor blocker candesartan in migraine prophylaxis. We study the potential efficacy and tolerability of olmesartan in preventing migraine in patients with hypertension and prehypertension. DESIGN/METHODS: Twenty-four adults, aged 27 through 76, with either hypertension or prehypertension, were included in this open-label study. Participants suffered from migraines (diagnosed according to International Headache Society classifications) for at least 3 months. Patients were treated with 10 to 40 mg of olmesartan per various observational periods of at least 3 months. Frequency and severity were recorded by office visits or by telephonic interview. RESULTS: Patients reported an 82.5% average reduction in the frequency of migraine attacks. Patients also experienced a 45% average reduction in the severity of migraine attacks measured on a numeric pain scale of 1 to 10. The only undesired effect was dizziness or presyncope. No serious adverse events occurred and no adverse event caused a premature termination. Two patients had no reduction in headache frequency, intensity, and blood pressure. CONCLUSIONS: The favorable results and low rate of adverse effects, in this open migraine prevention study in patients with hypertension or prehypertension, are similar to results of the randomized, double-blind, placebo-controlled, crossover study in patients taking candesartan. Olmesartan shows a potential as an effective and well-tolerated migraine prophylactic agent for patients with comorbid hypertension and prehypertension.

Adult↗

PubMed1985

Localized conversion in Streptococcus pneumoniae recombination: heteroduplex preference.

In pneumococcal transformation the frequency of recombinants between point mutations is generally proportional to distance. We have recently described an aberrant marker in the amiA locus that appeared to enhance recombination frequency when crossed with any other allele of this gene. The hyperrecombination that we have observed in two-point crosses could be explained by two hypotheses: the aberrant marker induces frequent crossovers in its vicinity or the mutant is converted to wild type. In this report we present evidence showing that, in suitable three-point crosses, this hyperrecombination does not modify the recombination frequency between outside markers, suggesting that a conversion occurs at the site of this mutation. To estimate the length over which this event occurs, we isolated very closely linked markers and used them in two-point crosses. It appears that the conversion system removes only a few base pairs (from three to 27) around the aberrant marker. This conversion process is quite different from the mismatch-repair system controlled by hex genes in pneumococcus, which involves several thousand base pairs. Moreover, we have constructed artificial heteroduplexes using separated DNA strands. It appears that only one of the two heteroduplexes is specifically converted. The conversion system acts upon 5'..ATTAAT..3'/3'.. TAAGTA..5'. A possible role of the palindrome resulting from the mutation is discussed.

Base Sequence↗

PubMed2006

Frequency-dependent reciprocal modulation of verbal fluency and motor functions in subthalamic deep brain stimulation.

BACKGROUND: High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor functions in those with Parkinson disease but may worsen frontal functions such as verbal fluency (VF). In contrast, low-frequency DBS leads to deterioration of motor functions. It is not known whether low-frequency STN DBS also has an effect on frontal functions. OBJECTIVE: To examine whether low-frequency STN DBS in contrast to high-frequency STN DBS has a positive effect on frontal functions on the basis of VF test results. DESIGN: A double-blind randomized crossover experiment to compare performance in 4 VF subtests and motor performance at 10 Hz, 130 Hz, and no stimulation. SETTING: University hospitals in Düsseldorf and Cologne, Germany. PATIENTS: Twelve patients with Parkinson disease 3 months or more after bilateral electrode implantation into the STN. MAIN OUTCOME MEASURE: Mean number of words in VF at different stimulation frequencies. RESULTS: The VF was significantly better at 10 Hz (48.3 words) compared with 130 Hz and showed a nonsignificant trend toward worsening at 130 Hz (42.3 words) compared with no stimulation (43.8 words). These results were consistent across all subtests. CONCLUSIONS: The study provides evidence of a beneficial effect of low-frequency (10 Hz) STN DBS on VF, which may be caused by activating neural pathways projecting to the frontal cortex. In addition, the study reproduces the negative effect of therapeutic high-frequency STN DBS on VF. The study results provide evidence for a frequency-dependent modulation of cognitive circuits involving the STN.

Aged↗

PubMed1984

The evolution of multigene families under intrachromosomal gene conversion.

A model for the evolution of the probabilities of genetic identity within and between loci of a multigene family in a finite population is formulated and investigated. Unbiased intrachromosomal gene conversion, equal crossing over between tandemly repeated genes, random genetic drift and mutation to new alleles are incorporated. Generations are discrete and nonoverlapping; the diploid, monoecious population mates at random. Formulas for the equilibrium values of the probabilities of identity and a cubic equation for the rate of convergence are deduced. Numerical examples indicate the following. The amount of homology at equilibrium generally decreases as the mutation rate, the population size and the number of repeats increase; it may increase or decrease with increasing crossover rate. The intralocus homology has an intermediate minimum, whereas the interlocus homology increases, as the rate of gene conversion increases. The intralocus homology decreases, whereas the interlocus homology increases, as the proportion of symmetric heteroduplexes increases. The characteristic convergence time can be sufficiently short to imply that intrachromosomal gene conversion may be an important mechanism for maintaining sequence homogeneity among repeated genes. The convergence time decreases as the conversion rate and the proportion of symmetric heteroduplexes increase; although exceptions occur, it generally increases as the population size and the number of repeats increase; it may increase or decrease with increasing crossover rate.

Animals↗

PubMed2005

Single-use plaque removal efficacy of three power toothbrushes.

OBJECTIVES: To compare the safety and plaque removal efficacy of two oscillating/rotating/pulsating toothbrushes (Oral-B ProfessionalCare 7000 [PC 7000] and Oral-B 3D Excel [3DE]) and a high-frequency toothbrush (Sonicare Advance, Philips Oral Healthcare; SA) in a single-use, examiner-blind, three period crossover study. METHODS: After refraining from all oral hygiene procedures for 23-25 hours, subjects received an oral tissue examination and those with pre-brushing whole mouth mean plaque scores > or = 0.6 based on the Rustogi et al. Modified Navy Plaque Index were randomly assigned to treatment sequence. After brushing with the assigned toothbrush and a commercially available dentifrice for 2 minutes, oral tissues were then re-examined and post-brushing plaque scores recorded. Following a brief washout period between two additional visits, the above procedures were repeated with the two alternate toothbrushes. One examiner, blinded to the treatment sequence, performed all clinical measurements. RESULTS: A total of 79 subjects (28 males and 51 females) were enrolled and completed the study. Each toothbrush was found to be safe and significantly reduced plaque levels after a single brushing. The PC 7000 and 3DE were equally more effective in plaque removal than the SA, at all tooth areas, reducing plaque by 59.0%, 59.7% and 51.8%, respectively on whole mouth surfaces, and by 67.5%, 67.8% and 59.4%, respectively on approximal surfaces. CONCLUSIONS: The action of the oscillating/rotating/pulsating toothbrushes (Oral-B ProfessionalCare 7000 and Oral-B 3D Excel) was more effective in plaque removal than the high-frequency toothbrush (Sonicare Advance).

Adolescent↗

PubMed1988

Recombinants in the H-2S/H-2D interval of mouse chromosome 17 define the map position of a gene for cleft palate susceptibility.

The H-2 region of mouse chromosome 17 is known to include one or more genes that affect susceptibility to cortisone-induced cleft palate. We have now studied congenic strains that possess crossovers in the interval between H-2S and H-2D and have observed significant differences in susceptibility among recombinants that had been believed to possess the same H-2 haplotypes. Pregnant mice were injected on days 11 through 14 of gestation with 100 mg of cortisone per kg of body weight. The frequency of cleft palate in B10.A(2R) was significantly greater than in B10.A(1R), despite the fact that both have H-2a/H-2b crossovers in the interval between the S and D loci and have the same alleles at all loci that have been previously characterized. Both B10.BAR5 and B10.BAR12 were significantly more susceptible than B10.A(18R), although these strains also share the same alleles at all loci that have been previously characterized. All three of these strains have H-2b/H-2a recombinant chromosomes, with crossovers in the S/D interval. Genetic linkage between H-2 and the high-susceptibility gene of B10.BAR5 was confirmed by testing H-2 homozygotes derived by intercrossing backcross animals. These data therefore suggest that a gene coding for susceptibility, which we designate Cps-1, maps in the 350-kb interval between H-2S and H-2D, and the congenic strains that we have found to be different have different crossover points within this interval. Alleles at the Cps-1 locus have embryonic effects, but no demonstrable effects on the maternal environment.

Alleles↗