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At least 757 records · Page 42Linked to original sources
PubMed1994

Effect of continuous positive airway pressure treatment on daytime function in sleep apnoea/hypopnoea syndrome.

Continuous positive airway pressure (CPAP) is the treatment of choice for the sleep apnoea/hypopnoea syndrome (SAHS); it is usually given with the aim of improving daytime cognitive function, mood, and sleepiness. However, its efficacy has not been validated by controlled trials. We have carried out a randomised, placebo-controlled, crossover study of objective daytime sleepiness, symptoms, cognitive function, and mood in a consecutive series of 32 SAHS patients with a median apnoea plus hypopnoea frequency of 28 (range 7-129) per hour slept. Patients were treated with 4 weeks each of CPAP and an oral placebo, which they were told might improve upper airway muscle function during sleep. Assessments on the last day of each treatment included a multiple sleep latency test and tests of symptom scores, mood profiles, and cognitive performance. The patients had significantly less daytime sleepiness on CPAP than during the placebo period (mean sleep latency 7.2 [SE 0.7] vs 6.1 [0.7] min, p = 0.03). There were also improvements with CPAP in symptom ratings (2.1 [0.2] vs 4.3 [0.3], p < 0.001), mood (p < 0.05 for several measures), and cognitive performance, which showed improved vigilance (obstacles hit in Steer Clear "driving" test 76 [5] vs 81 [6], p < 0.01), mental flexibility (trail-making B time 66 [5] vs 75 [5] s, p < 0.05), and attention (p < 0.05). Objectively monitored CPAP use averaged only 3.4 (0.4) hours per night, but this study provides evidence of improved cognitive performance even at this low level of CPAP compliance.

Affect↗
PubMed2002

DNA-dependent protein kinase suppresses double-strand break-induced and spontaneous homologous recombination.

DNA-dependent protein kinase (DNA-PK), composed of Ku70, Ku80, and the catalytic subunit (DNA-PKcs), is involved in repairing double-strand breaks (DSBs) by nonhomologous end-joining (NHEJ). Certain proteins involved in NHEJ are also involved in DSB repair by homologous recombination (HR). To test the effects of DNA-PKcs on DSB-induced HR, we integrated neo direct repeat HR substrates carrying the I-SceI recognition sequence into DNA-PKcs-defective Chinese hamster ovary (V3) cells. The DNA-PKcs defect was complemented with a human DNA-PKcs cDNA. DSB-induced HR frequencies were 1.5- to 3-fold lower with DNA-PKcs complementation. In complemented and uncomplemented strains, all products arose by gene conversion without associated crossover, and average conversion tract lengths were similar. Suppression of DSB-induced HR in complemented cells probably reflects restoration of NHEJ, consistent with competition between HR and NHEJ during DSB repair. Interestingly, spontaneous HR rates were 1.6- to >3.5-fold lower with DNA-PKcs complementation. DNA-PKcs may suppress spontaneous HR through NHEJ of spontaneous DSBs, perhaps at stalled or blocked replication forks. Because replication protein A (RPA) is involved in both replication and HR, and is phosphorylated by DNA-PKcs, it is possible that the suppression of spontaneous HR by DNA-PKcs reflects regulation of replication-dependent HR by DNA-PKcs, perhaps by means of phosphorylation of RPA.

Animals↗
PubMed1991

Flunarizine in migraine prophylaxis: an Indian trial.

Flunarizine, a calcium channel blocker is considered useful in migraine prophylaxis. We report the first Indian trial with this drug. Fifteen patients with migraine were studied in a 6 months double-blind, placebo-controlled crossover trial. Flunarizine was superior to placebo in reducing the severity and duration of the individual attacks though there was no statistically significant effect on frequency of migraine attacks. The side effects most frequently caused by flunarizine were weight gain and daytime sleepiness.

Adult↗
PubMed1993

Early experience with dobutamine stress testing and cardiac cine-tomographic imaging in the elderly: antianginal effects of nifedipine-GITS.

OBJECTIVE: To determine the effects of nifedipine-GITS (GITS = gastrointestinal transport system) on angina and cardiovascular responses to stress-dobutamine infusion, we used ultrafast cine-computed tomography (CT) to assess regional wall motion, myocardial perfusion, and indices of ventricular filling and emptying. DESIGN: Randomized, double-blind placebo-controlled efficacy study after an open-label dose titration phase. SETTING: University of California, San Francisco. PATIENTS: Elderly patients (> 60 years; n = 9:8 male, 1 female) with coronary artery disease by history and diagnostic treadmill or coronary angiography. INTERVENTION: After a 3-week open-label dose-titration phase, eight subjects were randomized to receive either placebo or nifedipine-GITS at the highest tolerated dose for 2 weeks, followed by a crossover to the alternate therapy for 2 weeks. One declined because of singulus in the open-label period. MAIN OUTCOME MEASURES: Symptomatic angina relief (frequency and nitroglycerin consumption), dobutamine stress responses (time to ischemia during dobutamine infusions, cardiac output, cardiac ejection fraction, ventricular segmental wall motion, and perfusion as measured by ultrafast cine-CT), and reported adverse effects. RESULTS: When compared with placebo, nifedipine-GITS administration was associated with less frequent angina and nitroglycerin consumption (NS) and significantly decreased systolic blood pressure. Nifedipine-GITS administration also increased resting supine heart rates. Dobutamine infusions increased heart rate, cardiac output, cardiac ejection fraction, and stroke volume and induced angina symptoms. Neither double product at angina nor systolic indices of cardiac function in response to dobutamine differed between nifedipine-GITS and placebo, although heart rate responses were greater during nifedipine. A trend toward increased peak filling rates was seen during dobutamine stress in the nifedipine-administration period. In most subjects (6/8), perfusion and regional wall motion abnormalities were not visualized on regional wall motion abnormalities were not visualized on either rest or stress cine-CT studies. Edema without congestive heart failure occurred frequently during nifedipine-GITS administration. CONCLUSIONS: These data suggest that (1) dobutamine stress can be used to induce cardiac ischemia in elderly patients with coronary artery disease, (2) nifedipine-GITS provides symptomatic angina relief in elderly patients, (3) peripheral edema is frequent in elderly patients on nifedipine-GITS, and (4) ultrafast computed cine-tomography testing can be used to assess ventricular performance, but current methodology may not detect perfusion or wall motion abnormalities during angina.

Age Factors↗
PubMed1978

Genetic and segregation analysis of Escherichia coli strains containing a tandem duplication of the trpD-purB region of the chromosome.

Genetic and segregation analysis of Escherichia coli strains containing a partial duplication of the trp operon reveal that the 2.5-min-long region trpD-purB is duplicated in tandem in the chromosome. The adjacent loci cysB and fabD are not duplicated. Although one copy of the duplicated region is longer than the maximum size of bacteriophage P1kc transducing fragments, the frequency at which the duplicated segment trpDCBA is transferred by transduction to tonB-trp deletion strains is equal to that observed for transfer of the normal trp operon. This suggests that three-point recombination events believed to account for transduction of long duplications occur as frequently as two-point recombination events believed to account for normal transduction. Cotransduction frequencies of trpDCBA with the duplicated loci tonB, galU, tyrT, and hemA are very similar to those for the trp operon with the same loci. This indicates that normal genetic linkage is maintained during the three-point recombination event. However, purB, which is normally unlinked to trp by transduction, is closely linked to trpDCBA and thus must be near the repeat point of the duplication. Transduction tests with point mutations in the trp operon indicated that the repeat point occurs near the normal boundary between trpE and trpD. Segregation analysis of heterogenotes constructed from tonB-trp deletion strains shows that the frequency at which a marker is lost is approximately proportional to its distance from the repeat point. This finding is consistent with a random, singlesite crossover event during segregation. Several observations indicate that non-reciprocal genetic exchange also occurs between copies of the duplication. Analysis of heterogenotes containing dadR1 and dadR(+) demonstrate that the mutant allele is transdominant.

Chromosome Aberrations↗
PubMed1988

Importance of ancillary properties of beta blockers in angina: a study of celiprolol and atenolol.

Celiprolol (400 mg) and atenolol (100 mg) were given once a day to 16 patients with stable angina pectoris in a double blind placebo controlled crossover study. Celiprolol produced less suppression of heart rate both at rest and during exercise than atenolol. Both drugs were equally effective in reducing the frequency of angina and in delaying the onset of ischaemia during exercise. Radionuclide ventriculography showed that atenolol but not celiprolol lowered cardiac output at rest and during exercise. Thus the ancillary properties of celiprolol, including partial beta 2 agonist activity and direct vasodilating activity, have detectable effects on cardiac function that may be beneficial in patients with angina.

Adrenergic beta-Antagonists↗
PubMed1999

Priming-induced shift in synaptic plasticity in the rat hippocampus.

The activity history of a given neuron has been suggested to influence its future responses to synaptic input in one prominent model of experience-dependent synaptic plasticity proposed by Bienenstock, Cooper, and Munro (BCM theory). Because plasticity of synaptic plasticity (i.e., metaplasticity) is similar in concept to aspects of the BCM proposal, we have tested the possibility that a form of metaplasticity induced by a priming stimulation protocol might exhibit BCM-like characteristics. CA1 field excitatory postsynaptic potentials (EPSPs) obtained from rat hippocampal slices were used to monitor synaptic responses before and after conditioning stimuli (3-100 Hz) of the Schaffer collateral inputs. A substantial rightward shift (>5-fold) in the frequency threshold between long-term depression (LTD) and long-term potentiation (LTP) was observed <1 h after priming. This change in the LTD/P crossover point occurred at both primed and unprimed synaptic pathways. These results provide new support for the existence of a rapid, heterosynaptic, experience-dependent mechanism that is capable of modifying the synaptic plasticity phenomena that are commonly proposed to be important for developmental and learning/memory processes in the brain.

2-Amino-5-phosphonovalerate↗
PubMed2005

Overdrive atrial pacing does not improve obstructive sleep apnoea syndrome.

The aim of this study was to assess the ability of overdrive atrial pacing to reduce sleep apnoea severity. A total of 17 unselected patients (12 males; mean+/-SD age 71+/-10 yrs; body mass index 27+/-3 kg x m(-2)) who had received permanent atrial-synchronous ventricular pacemakers for symptomatic bradyarrhythmias and not known to have central or obstructive sleep apnoea syndrome (OSAS) were studied. Using a crossover study design, patients were or were not in pacing mode with atrial overdrive (15 beats x min(-1) faster than mean baseline nocturnal cardiac frequency) for 1 month. Patients were paced only during sleep periods, identified by a specific algorithm included in the pacemaker. Patients underwent three overnight polysomnographic evaluations 1 month apart. The first was performed for baseline evaluation. The patients were then randomly assigned to either 1 night in spontaneous rhythm or to 1 night in pacing mode with atrial overdrive. Two patients refused to continue the study after the first polysomnographic evaluation. OSAS was highly prevalent in this population: 10 of the 15 (67%) patients exhibited an apnoea-hypopnoea index of >30 events x h(-1). The nocturnal spontaneous rhythm was 59+/-7 beats x min(-1) at baseline, compared to 75+/-10 beats x min(-1) with atrial overdrive pacing. The apnoea-hypopnoea index was 46+/-29 events x h(-1) in spontaneous rhythm, compared to 50+/-24 events x h(-1) with atrial overdrive pacing. Overdrive pacing changed none of the respiratory indices, or sleep fragmentation or sleep structure parameters. In conclusion, atrial overdrive pacing has no significant effect on obstructive sleep apnoea.

Aged↗
PubMed2003

Increased severity of murine lupus in female mice is due to enhanced expansion of pathogenic T cells.

A strong female predominance is a well-recognized feature of human lupus. The mechanism by which sex influences disease expression and severity is not fully understood. To address this question, we used the parent-into-F(1) (p-->F(1)) model of chronic graft-vs-host disease (cGVHD) in which lupus-like humoral autoimmunity and renal disease are induced in normal F(1) mice. An advantage of this model is that the pathogenic T cells driving disease (donor strain) can be studied separately from nonspecifically activated T cells (host strain). We observed that lupus-like disease using female donor and host mice (f-->F cGVHD) is characterized by more severe long-term disease (glomerulonephritis) than with male donor and host (m-->M cGVHD). Interestingly, differences in disease parameters could be seen at 2 wk after parental cell transfer, as evidenced by a 2- to 3-fold greater engraftment of donor CD4(+) T cells in f-->F cGVHD mice, which persisted throughout disease course. Enhanced engraftment of donor CD4(+) T cells in f-->F cGVHD mice was not due to differences in splenic homing, alloreactive precursor frequency, initial proliferation rates, or apoptotic rates, but rather to sustained high proliferation rates during wk 2 of disease compared with m-->M cGVHD mice. Crossover studies (m-->F, f-->M) demonstrated that enhanced donor CD4(+) T cell proliferation and engraftment segregate with the sex of the host. These results demonstrate that the sex of the recipient can influence the expansion of pathogenic T cells, thus increasing long-term the burden of autoreactive T cells and resulting in greater disease severity.

Animals↗
PubMed1985

A double blind placebo controlled crossover randomized trial of diltiazem in Raynaud's phenomenon.

We report the results of a double blind placebo controlled crossover randomized study of the calcium channel blocking agent diltiazem in the treatment of Raynaud's phenomenon. Our results showed a significant reduction in both frequency and duration of attacks of vasospasm in the hands. There was no detectable difference in response between patients with primary and those with secondary Raynaud's phenomenon. Our study supports the use of calcium channel blocking agents in the treatment of intermittent digital vasospasm.

Adolescent↗
PubMed1990

Effects of feeding frequency on ruminal parameters, plasma insulin, milk yield, and milk composition in Holstein cows.

Two experiments were conducted to determine the effects of frequency of feeding on ruminal fermentation, blood parameters, milk yield, and milk composition in cows fed a 60% pelleted concentrate and 40% chopped alfalfa hay (DM basis) diet. In Experiment 1, four ruminally cannulated cows were fed concentrates in 12 equal portions at 2-h intervals or in two equal portions at 0500 and 1500 h in a crossover design. In Experiment 2, treatments were as in Experiment 1 plus an additional treatment consisting of a total mixed diet fed at 2-h intervals in a 3 x 3 Latin square design. All treatment periods were 2 wk. In Experiment 1, increased frequency of concentrate feeding tended to result in elevated ruminal pH and increased acetate to propionate ratio. Plasma insulin concentration tended to be higher (1.54 vs. 1.04 ng/ml) and milk fat percentage increased from 2.21 to 2.60% for 2 and 12 times daily feeding, respectively. In Experiment 2, frequency of feeding concentrate or total mixed diet did not affect ruminal and blood parameters or milk yield. In both experiments, milk protein and lactose concentrations were not influenced by feeding frequency. Results suggest that where intake is kept constant, increased feeding frequency will not influence milk yield but could result in elevated milk fat percent in animals fed fat-depressing diets.

Animals↗
PubMed2000

Prevalence of methylenetetrahydrofolate reductase mutations in patients with venous thrombosis.

BACKGROUND: The objectives of this study are to examine the prevalence of combined methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298A-->C mutations in patients with venous thrombosis (VT) and healthy volunteers and to determine if these mutations are in Hardy-Weinberg equilibrium. METHODS AND RESULTS: Sixty-five patients with VT and 64 healthy volunteers were assessed for MTHFR 677T and 1298C alleles using polymerase chain reaction and restriction fragment length polymorphism. Observed MTHFR genotype frequencies were compared with expected genotype combinations, and their odds ratios were determined. MTHFR allele frequency did not differ between VT and control groups; however, differences were observed for MTHFR genotype distribution. MTHFR 677T and 1298C alleles occurred in cis in our population, and therefore mutation crossover has occurred. There was deviation from the Hardy-Weinberg equilibrium for combined MTHFR genotypes, although this may at least partly be attributable to linkage disequilibrium. MTHFR 677CT/1298CC and 677TT/1298CC genotypes (P<.05) were not observed in either group. CONCLUSIONS: The absence of MTHFR 677CT/1298CC and 677TT/1298CC genotypes in both groups suggests that certain MTHFR genotypes may carry a selective advantage. Our discovery of a substantial number of MTHFR mutations in cis configuration suggests that any MTHFR allele linkage disequilibrium present is incomplete.

Gene Frequency↗
PubMed2000

Should we use a case-crossover design?

The first decade of experience with case-crossover studies has shown that the design applies best if the exposure is intermittent, the effect on risk is immediate and transient, and the outcome is abrupt. However, this design has been used to study single changes in exposure level, gradual effects on risk, and outcomes with insidious onsets. To estimate relative risk, the exposure frequency during a window just before outcome onset is compared with exposure frequencies during control times rather than in control persons. One or more control times are supplied by each of the cases themselves, to control for confounding by constant characteristics and self-confounding between the trigger's acute and chronic effects. This review of published case-crossover studies is designed to help the reader prepare a better research proposal by understanding triggers and deterrents, target person times, alternative study bases, crossover cohorts, induction times, effect and hazard periods, exposure windows, the exposure opportunity fallacy, a general likelihood formula, and control crossover analysis.

Acute Disease↗
PubMed1996

High-frequency jet ventilation in the early management of respiratory distress syndrome is associated with a greater risk for adverse outcomes.

OBJECTIVE: The objective of this investigation was to determine if high-frequency jet ventilation (HFJV) used early in the treatment of premature infants with respiratory distress syndrome was effective in reducing pulmonary morbidity without increasing the occurrence of adverse neurologic outcomes. STUDY DESIGN: A total of 73 premature infants who met the inclusion criteria (gestational age of less than 33 weeks, birth weight of more than 500 g, age of less than 24 hours, need for assisted ventilation with peak inspiratory pressure of more than 16 and FIO2 more than 0.30, and roentgenographic evidence of respiratory distress syndrome) were randomized to either conventional (n = 36) or to high-frequency jet (n = 37) ventilation. Our goals were to maintain the infants on the assigned ventilator for at least 7 days unless they could either be extubated or meet crossover criteria. Univariate analyses were initially used to compare the two groups. Stepwise logistic regression was subsequently used to assess whether various factors independently influenced adverse outcomes. RESULTS: The two groups of infants were similar in all obstetrical, perinatal, and neonatal demographic characteristics. The mean birth weight and gestational age in the conventional group were 930 g and 26.6 weeks and in the HFJV group, 961 g and 26.9 weeks. The infants were randomized at similar ages (7.1 and 7.3 hours of life, respectively). Their prerandomization ventilator settings and arterial blood gases were nearly identical. There were no differences in pulmonary outcomes (occurrence of air leaks, need for oxygen or ventilation at 36 weeks postconception), and there were no differences in the mean number of days oxygen was required, number of days ventilated, or length of hospital stay. Infants ventilated with HFJV were significantly more likely to develop cystic periventricular leukomalacia (10 vs 2, P = .022) or to have a poor outcome (grade IV hemorrhage, cystic periventricular leukomalacia, or death) (17 vs 7, P = .016). Logistic regression analysis revealed HFJV to be a significant independent predictor of both cystic periventricular leukomalacia and a poor outcome. The presence of hypocarbia was not an independently significant predictor of adverse outcomes. CONCLUSIONS: With the HFJV treatment strategy that we used, use of the high-frequency jet ventilator in the early management of premature infants with respiratory distress syndrome resulted in significantly more adverse outcomes than in those treated with conventional mechanical ventilation.

Blood Pressure↗
PubMed2002

Predicting out-of-sequence reassembly in DNA shuffling.

We present an analysis for calculating the frequency of out-of-sequence reassembly in DNA shuffling experiments. Out-of-sequence annealing events are undesirable since they typically encode non-functional proteins with missing or repetitive regions. The approach builds on the e Shuffle framework for the prediction of crossover formation using equilibrium thermodynamics and complete sequence information to model the reassembly process. An in silico case study of a set of subtilases reveals that, as expected, the presence of significant sequence identity between distant portions of the parental sequences gives rise to out-of-sequence annealing events that upon reassembly generate sequences with missing or repetitive DNA segments. The frequency of these events increases as the fragment length decreases. Interestingly, out-of-sequence annealing events are at a minimum near the annealing temperature of 55 degrees C used in the original DNA shuffling protocol. Neither parental sequence identity nor number of shuffled parents significantly alter the extent of out-of-sequence reassembly

Amino Acid Motifs↗
PubMed1986

DNA inversion in bacteriophage Mu: characterization of the inversion site.

Gin-mediated site-specific recombination promotes inversion of the G segment of phage Mu. The crossover takes place between two 34 bp-long inverted repeat sequences flanking the G segment. We have characterized the inversion site, the target for the site-specific recombination mechanism. An artificial invertible segment was constructed which consists of parts of the invertible segments of Mu and phage P1, which in this respect are largely homologous. Upon inversion of this hybrid segment the crossover site could be located, by DNA sequencing, in the ACCT sequence of the centre of symmetry in the inverted repeat in Mu. The hybrid Mu-P1 segment inverts at a lower frequency than its parental invertible segments probably because of the mismatches between the inverted repeats of Mu and P1. This suggests that base pairing between the inverted repeats is an intermediate step in recombination. Plasmids with subcloned G segments lacking the adjacent beta region of Mu or the corresponding region in P7, a relative of P1, are deficient in inversion. By analysis through site-specific mutagenesis of Mu DNA, an enhancer element with multiple recognition sites was identified which is necessary for efficient inversion. This component of the inversion site was located in a 170 bp segment within the Mu beta region, 30 bp to the right of the inverted repeat sequence, but can be separated from the crossover site by a 1200 bp insertion without losing its effect.

Bacteriophage mu↗
PubMed1989

Nasal intermittent positive-pressure ventilation offers no advantages over nasal continuous positive airway pressure in apnea of prematurity.

A prospective, randomized, cross-over trial was performed to compare the efficacy of nasal intermittent positive-pressure ventilation with nasal continuous positive airway pressure in infants of less than 32 weeks of gestation. Continuous positive airway pressure was delivered at end-expiratory pressures of 4 cm H2O, while peak pressures of 20 cm H2O and end-expiratory pressures of 4 cm H2O were used during nasal intermittent positive-pressure ventilation at ventilatory rates of 20 breaths per minute. The frequency and extent of apnea and bradycardia during a 6-hour period in a patient receiving nasal continuous positive airway pressure were compared with a similar crossover period of nasal intermittent positive-pressure ventilation. Although the infants had slightly less frequent episodes of apnea per hour (0.6 +/- 0.7 vs 0.5 +/- 0.7) and bradycardia per hour (1.2 +/- 1.3 vs 0.9 +/- 1.0) during nasal intermittent positive-pressure ventilation, these differences were not significant. There were no significant differences in the severity of these events as assessed by the duration and fall in transcutaneous oxygen pressure during apnea and heart rate during bradycardia. There were no significant changes in blood gases throughout the study. Nasal intermittent positive-pressure ventilation appears to have no advantages over nasal continuous positive airway pressure in preventing apnea and does not alter gas exchange in infants of less than 32 weeks of gestation.

Apnea↗
PubMed1993

Theoretical analysis of the effects of mitotic crossover in large yeast populations.

In a diploid yeast population which is heterozygous for a given marker, A1A2, mitotic crossover (mit. c.o.) between the centromere and the marker will give rise to homozygous daughter cells, A1A1 and A2A2. Since this causes a decrease in the frequency of A1A2 cells, mit. c.o. is an important population genetic process in vegetatively propagated yeast cultures. The effect of mit. c.o. is counteracted by mutations and, in the case of heterosis, by selection. We present a mathematical analysis of these interactions.

Crossing Over, Genetic↗