Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “crossover frequency”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 775 records · Page 43Linked to original sources
PubMed1988

Transposon Tn21 encodes a RecA-independent site-specific integration system.

The IncW plasmid R388 and the DNA region of Tn21 containing the Smr and the Sur genes are capable of RecA-independent recombination. This recombination occurs at a relatively high frequency (up to 10(-4) recombinants per recipient molecule) and results in integration of the two plasmids. No detectable repeats are formed in the process. The crossover points have been confined to a 0.4-kb homologous segment in both plasmids which contains a 59-bp DNA sequence presumably involved in the acquisition of new genes by Tn21 and its relatives (Cameron et al. 1986). It is likely that the recombination occurs precisely at this point. At least one trans-acting function (an integrase) is required for the site-specific recombination. It has been localized to a 1456-bp BstEII-BamHI fragment of Tn21 and can efficiently complement the integration of plasmids containing the integration site.

DNA Transposable Elements↗
PubMed2003

Gene rearrangements in the glucocerebrosidase-metaxin region giving rise to disease-causing mutations and polymorphisms. Analysis of 25 Rec NciI alleles in Gaucher disease patients.

The glucocerebrosidase and metaxin genes lie in a gene-rich region that also includes two corresponding pseudogenes. This gives rise to recombinant alleles. We analysed two groups of patients from Argentina and Spain: 25 bearing the Rec NciI allele and 36 carrying L444P. The mutational mechanism is described and the crossover site precisely defined. Most of the Rec NciI alleles were generated by gene conversion. Rearranged alleles involving the metaxin gene were also identified. The high frequency of Rec NciI alleles associated with a polymorphic rearrangement at the metaxin level is probably due to a founder effect.

Alleles↗
PubMed1998

Dosage effects of methylphenidate on the social behavior of adolescents diagnosed with attention-deficit hyperactivity disorder.

Research participants were 46 adolescents (mean age = 13.8 years) who completed an intensive summer treatment program including a placebo-controlled, double-blind, crossover trial of 3 doses of methylphenidate (MPH) totaling 25, 50, or 75 mg per day. Dependent measures focused on social behavior and included observed behavior frequencies and ratings completed by counselors and parents, including side effects. Multiple data analytic methods were used with the goal of (a) describing the shape of the dose-response curves across multiple measures of social functioning, (b) determining the percentage of adolescents whose social behavior improved in response to MPH, and (c) assessing the incremental gains that result from increases in dose. The results show that (a) the shape of the dose-response curve is influenced by the measurement method, (b) the majority of adolescents exhibited improved social behavior when treated with MPH, (c) the bulk of the positive effects of MPH were achieved at the lowest dose, and (d) there appear to be diminishing positive effects and an increased risk of negative effects with successively higher doses.

Adolescent↗
PubMed1992

Pharmacokinetic-pharmacodynamic modeling of the central nervous system effects of midazolam and its main metabolite alpha-hydroxymidazolam in healthy volunteers.

The pharmacodynamics of midazolam and its main metabolite alpha-hydroxymidazolam were characterized in individual subjects by use of saccadic eye movement and electroencephalographic (EEG) effect measurements. Eight healthy volunteers received 0.1 mg/kg midazolam intravenously in 15 minutes, 0.15 mg/kg alpha-hydroxymidazolam intravenously in 15 minutes, 7.5 mg midazolam orally and placebo in a randomized, double-blind, four-way crossover experiment. Plasma concentrations of midazolam, alpha-hydroxymidazolam and 4-hydroxymidazolam were measured by gas chromatography. The amplitudes in the 11.5 to 30 Hz (beta) frequency band were used as EEG effect measure. The concentration-effect relationships were quantified by the sigmoid maximum effect model. The median effective concentrations of midazolam and alpha-hydroxymidazolam were (mean +/- SE) 77 +/- 15 and 98 +/- 17 ng/ml, respectively, for the EEG effect measure. For peak saccadic velocity the values were 40 +/- 7 ng/ml for midazolam and 49 +/- 10 ng/ml for alpha-hydroxymidazolam. The maximum effect values were similar for both compounds. The effects observed after oral administration of midazolam could not be predicted accurately by an additive and competitive interaction model. It seems that alpha-hydroxymidazolam is highly potent with respect to the measured effects and contributes significantly to those effects of midazolam after oral administration.

Administration, Oral↗
PubMed2006

Vibrational spectrum of the spin crossover complex [Fe(phen)(2)(NCS)(2)] studied by IR and Raman spectroscopy, nuclear inelastic scattering and DFT calculations.

The vibrational modes of the low-spin and high-spin isomers of the spin crossover complex [Fe(phen)(2)(NCS)(2)] (phen = 1,10-phenanthroline) have been measured by IR and Raman spectroscopy and by nuclear inelastic scattering. The vibrational frequencies and normal modes and the IR and Raman intensities have been calculated by density functional methods. The vibrational entropy difference between the two isomers, DeltaS(vib), which is--together with the electronic entropy difference DeltaS(el)--the driving force for the spin-transition, has been determined from the measured and from the calculated frequencies. The calculated difference (DeltaS(vib) = 57-70 J mol(-1) K(-1), depending on the method) is in qualitative agreement with experimental values (20-36 J mol(-1) K(-1)). Only the low energy vibrational modes (20% of the 147 modes of the free molecule) contribute to the entropy difference and about three quarters of the vibrational entropy difference are due to the 15 modes of the central FeN(6) octahedron.

Ferrous Compounds↗
PubMed2001

A comparison of the effect of loperamide in oral or suppository form vs placebo in patients with ileo-anal pouches.

OBJECTIVE: The effect of the anti-diarrhoeal drug, loperamide hydrochloride, on bowel function in patients with an ileo-anal pouch was studied by means of a blinded, three-tailed, case-controlled and randomized crossover trial, using a daily dose of 12 mg in either oral (4 mg t.d.s.) or suppository (6 mg b.d.) form. PATIENTS AND METHODS: Daily stool frequency was recorded in a diary and an objective measure of pouch motor function was obtained at the end of each treatment phase. Ten subjects (seven males, three females) aged 23-50 years (median 38 years) were studied 9-48 months (median 27 months) after ileostomy closure. Eight pouches had been constructed for ulcerative colitis and two for familial adenomatous polyposis (9J, 1W). RESULTS: Mean daily stool frequency during the oral loperamide phase was lower than during both the placebo (P=0.05) and suppository (P < 0.02) phases. Stool frequency did not differ significantly between placebo and suppository phases. There was a strong inverse correlation between mean daily stool frequency and pouch capacity (r=-0.82 after both oral and suppository phases). Large isolated pouch contractions were evident in five of eight subjects studied; suppression was observed in two of the five after oral loperamide and in three of the five after loperamide suppositories. Rhythmic pouch contractions were seen in four subjects and suppression was evident after loperamide suppositories (but not after oral loperamide) in three. A daily oral dose of 12 mg loperamide significantly lowered stool frequency in pouch patients and modified some aspects of pouch contraction. Loperamide suppositories produced more prominent suppression of pouch contractions but did not lower stool frequency. CONCLUSION: This suggests that the beneficial effect of oral loperamide is primarily due to its action on intestine proximal to the pouch itself.

Clinical Trial↗
PubMed1989

Sustained-release diltiazem versus metoprolol in stable angina pectoris.

The efficacy of sustained-release diltiazem (diltiazem-SR) 120 mg b.i.d. was compared with metoprolol 100 mg b.i.d. in 12 patients with stable angina. Following a 1-week placebo period, patients received diltiazem-SR or metoprolol in two 3-week treatment periods, in a randomized double-blind crossover design. Total exercise time was increased more with diltiazem-SR than with metoprolol (1.2 min vs 0.4 min, P = 0.02), although the reduction in frequency of weekly anginal attacks was equal with both drugs (5 +/- 3 with placebo to 1 +/- 1 with both drugs). The difference between diltiazem-SR and metoprolol may, in part, be due to the fact that the tests were performed 12 h after drug administration. The diltiazem plasma levels were in the therapeutic range; metoprolol plasma levels, in contrast, were all below the therapeutic range. In addition, the patients might be tired out earlier during beta-blockade therapy, because a greater increase in exercise time with diltiazem-SR compared with metoprolol was found in those patients in whom the exercise endpoint changed from angina to fatigue. Thus, diltiazem-SR effectively reduces the frequency of anginal attacks when given twice daily, and improves exercise capacity to a greater extent than metoprolol 12 h after last dose.

Adult↗
PubMed1979

Analysis of coliphage lambda mutations that affect Q gene activity: puq, byp, and nin5.

We describe in this paper the isolation and characterization of a class of mutations, designated puq, that allow phage lambda to grow better under conditions that limit the synthesis of the phage Q gene product. These mutations were located between phage genes P and Q, a region of the lambda chromosome containing two gene N-independent mutations, nin5 and byp, that we also show to be puq mutations. Whereas the puq-3 and puq-16 mutations probably map under the nin5 deletion, the byp mutation maps between this deletion and the Q lambda-Q phi 80 crossover point. These mutations likely act by increasing the synthesis of the Q gene product. We demonstrate that the clear-plaque phenotype and reduced lysogenization frequency of byp mutants depend on increased Q gene activity. The significance of these results in understanding how transcription proceeds through the P-Q region of the lambda genome is discussed.

Bacteriophage lambda↗
PubMed1998

Mutations in the N terminus of the brome mosaic virus polymerase affect genetic RNA-RNA recombination.

Previously, we have observed that mutations in proteins 1a and 2a, the two virally encoded components of the brome mosaic virus (BMV) replicase, can affect the frequency of recombination and the locations of RNA recombination sites (P. D. Nagy, A. Dzianott, P. Ahlquist, and J. J. Bujarski, J. Virol. 69:2547-2556, 1995; M. Figlerowicz, P. D. Nagy, and J. J. Bujarski, Proc. Natl. Acad. Sci. USA 94:2073-2078, 1997). Also, it was found before that the N-terminal domain of 2a, the putative RNA polymerase protein, participates in the interactions between 1a and 2a (C. C. Kao, R. Quadt, R. P. Hershberger, and P. Ahlquist, J. Virol. 66:6322-6329, 1992; E. O'Reilly, J. Paul, and C. C. Kao, J. Virol. 71:7526-7532, 1997). In this work, we examine how mutations within the N terminus of 2a influence RNA recombination in BMV. Because of the likely electrostatic character of 1a-2a interactions, five 2a mutants, MF1 to MF5, were generated by replacing clusters of acidic amino acids with their neutral counterparts. MF2 and MF5 retained nearly wild-type levels of 1a-2a interaction and were infectious in Chenopodium quinoa. However, compared to that in wild-type virus, the frequency of nonhomologous recombination in both MF2 and MF5 was markedly decreased. Only in MF2 was the frequency of homologous recombination reduced and the occurrence of imprecise homologous recombination increased. In MF5 there was also a 3' shift in the positions of homologous crossovers. The observed effects of MF2 and MF5 reveal that the 2a N-terminal domain participates in different ways in homologous and in nonhomologous BMV RNA recombination. This work maps specific locations within the N terminus involved in 1a-2a interaction and in recombination and further suggests that the mechanisms of the two types of crossovers in BMV are different.

Amino Acid Sequence↗
PubMed1999

Increased instability of human CTG repeat tracts on yeast artificial chromosomes during gametogenesis.

Expansion of trinucleotide repeat tracts has been shown to be associated with numerous human diseases. The mechanism and timing of the expansion events are poorly understood, however. We show that CTG repeats, associated with the human DMPK gene and implanted in two homologous yeast artificial chromosomes (YACs), are very unstable. The instability is 6 to 10 times more pronounced in meiosis than during mitotic division. The influence of meiosis on instability is 4.4 times greater when the second YAC with a repeat tract is not present. Most of the changes we observed in trinucleotide repeat tracts are large contractions of 21 to 50 repeats. The orientation of the insert with the repeats has no effect on the frequency and distribution of the contractions. In our experiments, expansions were found almost exclusively during gametogenesis. Genetic analysis of segregating markers among meiotic progeny excluded unequal crossover as the mechanism for instability. These unique patterns have novel implications for possible mechanisms of repeat instability.

Chromosomes, Artificial, Yeast↗
PubMedDate not supplied

Bowel function of long-term tube-fed patients consuming formulae with and without dietary fiber.

Diarrhea, constipation and subsequent laxative use are chronic problems in long-term enterally fed patients. We have conducted a double-blind randomized crossover study to evaluate the effects of two enteral formulae (Enrich, 12.8 g of dietary fiber per 1000 kcal and Ensure, fiber-free) on stool frequency, fecal weight, laxative use, gastrointestinal tolerance and bowel function in chronic care tube-fed patients. Twenty-eight subjects (24 male, 4 female) completed the study. Mean daily number of stools and mean daily fecal wet weight in Enrich-fed patients were not significantly different from those of patients receiving Ensure. Ensure-fed patients required significantly more laxatives (p = 0.02) than those receiving Enrich. There were 26 reports of diarrhea in the Ensure-fed group as compared to 6 in the Enrich-fed group, and this difference was significant (p = 0.006). Reporting rates for constipation were not significantly different in the two groups. At the end of the study, the bowel function of 57.1% of patients receiving Enrich was improved when compared with that of 14.3% of Ensure-fed patients, and this difference was significant (p = 0.005). These results suggest that the addition of dietary fiber to enteral formulae improves gastrointestinal tolerance and bowel function, and reduces laxative use in long-term enterally fed patients.

Adult↗
PubMed1997

Red snow: is it safe to eat? A pilot study.

The objective of this study was to determine if the ingestion of snow contaminated with Chlamydomonas nivalis causes diarrhea. The design was a single-blind crossover. Subjects were seven healthy volunteers, aged 24-56 who ingested 500 g of snow contaminated with C. nivalis. Outcome was measured by stool and diarrhea frequency. No differences in stool or diarrhea frequency were noted between treatment and placebo groups. The conclusion is that in this pilot study, there was no evidence supporting the concern that ingestion of "red snow" causes diarrhea.

Adult↗
PubMed1987

[Nicardipine in the treatment of Raynaud's phenomenon].

The efficacy of the calcium-channel blocker nicardipine in the treatment of Raynaud's phenomenon was assessed in a double-blind, randomised, crossover trial in 20 patients. Each patient received 2 weeks of nicardipine 20 mg three times daily and 2 weeks of placebo. Nicardipine significantly improved the frequency and severity of Raynaud's phenomenon. An open study during 2 months in 30 patients confirmed the effectiveness of nicardipine (20-40 mg 3 times daily). Side effects (headache, flushing, ankle oedema) were frequent but usually mild. We conclude that nicardipine is effective in the treatment of Raynaud's phenomenon.

Adult↗
PubMed1995

[Alcohol consumption and the diagnosis of alcoholic patients in primary care].

OBJECTIVE: To find the frequency of investigation of alcohol-related problems and how often alcoholic patients are identified in primary care. DESIGN: A descriptive cross-sectional [correction of crossover] study. SETTING: An urban health centre. PATIENTS: 219 patients over 15 who attended an appointment occasioned by a CAGE questionnaire validation study. 108 had answered affirmatively some of the questions in the test and 111 had answered the four questions negatively. MEASUREMENTS AND MAIN RESULTS: Diagnoses of alcoholism based on the fulfillment of the DSM-III criteria and/or on the presence of alcoholic consumption of > or = 60 grammes per day for men or 30 grammes per day for women were investigated. Additionally, each patient's medical records were checked to see whether their habitual alcohol consumption or a diagnosis of alcoholism were recorded. 54 patients were diagnosed as alcoholic. Previous inquiries into consumption of alcohol were recorded in the medical records of 167 patients (76.2%). A diagnosis of alcoholism was found to be recorded in 19 of the 54 patients who fulfilled the diagnostic criteria of our study (35.2%) and in 3 patients who did not fulfil those criteria. CONCLUSIONS: Although good records of patients' habits of alcohol consumption existed, 64.8% of those diagnosed as alcoholic in our study had not been previously identified as such. This must lead us to question the efficacy of our usual diagnostic methods.

Adult↗
PubMed1995

Intranasal insulin therapy: the clinical realities.

To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin was low, since intranasal insulin doses were approximately 20 times higher than subcutaneous doses. The frequency of hypoglycaemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosa physiology was unaffected after intranasal insulin. We conclude that due to low bioavailability and to a high rate of therapeutic failure, intranasal insulin treatment is not a realistic alternative to subcutaneous insulin injections at the present time.

Administration, Intranasal↗
PubMed1993

[Outbreak of rubella in Puerto de Santa María (Cádiz)].

OBJECTIVE: To find the frequency of cases of German measles and its spread according to the variables of age, gender, the position regarding vaccination and time; to identify groups at risk in line with the above variables and find out how efficacious vaccination is. DESIGN: Crossover, descriptive study. SETTING: Catchment area of the Pinillo Chico Health Centre in Puerto de Santa María (Cádiz). PATIENTS AND OTHER PARTICIPANTS: Between March and June, 1991, there was an outbreak of 175 cases of German measles in our catchment area. We included in the study 149 of these, for whom an epidemiological index card had been filled out. Cases were defined in line with the CDC criteria of a probable or confirmed case. The frequency of cases for the different groups were calculated and compared using the Chi squared test. MAIN MEASUREMENTS AND RESULTS: More than 95% of those affected were aged between 15 months and 26 years (average age 13). There were only significant gender differences, in proportion to the general population, for the 9 to 11 age-group for girls and 12 to 16 for boys. The frequency of cases was significantly greater in males than in females in the 12 to 16 and 17 to 21 age-groups (p < 0.05); and in females than males in the 9 to 11 group (p < 0.05). The frequency of cases between those vaccinated and those not vaccinated also showed significant differences for all the age and gender groups (p < 0.05). Efficacy of vaccination was 81.51%, being over 70% in all age groups. CONCLUSIONS: Studying outbreaks at the Primary Care level assists the identification of susceptible groups and planning of a course of action.

Adolescent↗
PubMed2000

Does heavy physical exertion trigger myocardial infarction? A case-crossover analysis nested in a population-based case-referent study.

To study possible triggering of first events of acute myocardial infarction by heavy physical exertion, the authors conducted a case-crossover analysis (1993-1994) within a population-based case-referent study in Stockholm County, Sweden (the Stockholm Heart Epidemiology Program). Interviews were carried out with 699 myocardial infarction patients after onset of the disease. These cases represented 47 percent of all cases in the study base, and 70 percent of all nonfatal cases. The relative risk from vigorous exertion was 6.1 (95% confidence interval: 4.2, 9.0). The rate difference was 1.5 per million person-hours, and the attributable proportion was 5.7 percent. The risk was modified by physical fitness, with an increased risk being seen among sedentary subjects as in earlier studies, but the data also suggested a U-shaped association. In addition, the trigger effect was modified by socioeconomic status. Premonitory symptoms were common, and this implies risks of reverse causation bias and misclassification of case exposure information that require methodological consideration. Different techniques (the use of the usual-frequency type of control information, a pair-matched analysis, and a standard case-referent analysis) were applied to overcome the threat of misclassification of control exposure information. A case-crossover analysis in a random sample of healthy subjects resulted in a relative risk close to unity, as expected.

Aged↗
PubMed2006

Efficacy and safety of enoxaparin compared with unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention in the Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial.

BACKGROUND: Enoxaparin reduces ischemic events more effectively than unfractionated heparin (UFH) in patients treated conservatively for non-ST-segment elevation acute coronary syndrome. The SYNERGY trial compared these agents in high-risk patients undergoing early invasive treatment. Enoxaparin was noninferior to UFH for the 30-day primary end point of death/myocardial infarction (MI), but modestly increased bleeding. METHODS AND RESULTS: This article compares the outcomes of the 4687 SYNERGY patients (47%) undergoing percutaneous coronary intervention, who were randomized to receive enoxaparin or UFH. Antithrombotic therapy was administered prerandomization in 78%. Crossover (usually in the catheterization laboratory) to the alternative antithrombotic occurred in 14.6% of enoxaparin patients and 2.9% of UFH-treated patients (P < .0001). Stenting was performed in 86.3%. Abrupt vessel closure occurred in 1.3% of enoxaparin patients and 1.7% of UFH-treated patients (P = .318). The rates of death/MI were similar at 30 days (13.1% with enoxaparin vs 14.2% with UFH, P = .289). GUSTO severe bleeding occurred with similar frequency in both groups (1.5% vs 1.6%, P = .688). TIMI major bleeding was more common with enoxaparin (3.7% vs 2.5% with UFH, P = .028). Transfusions were more frequent with enoxaparin than with UFH (6.8% vs 5.4%, P = .047). TIMI major bleeding increased with crossover from enoxaparin to UFH (from 3.7% to 7.8%) and from UFH to enoxaparin (from 2.5% to 8.6%). Statistical adjustment to model reasons for crossover did not affect the overall safety and efficacy outcomes. CONCLUSIONS: In high-risk patients undergoing early percutaneous coronary intervention for acute coronary syndrome, enoxaparin avoids the need for monitoring and achieves similar effectiveness to UFH but is associated with more bleeding.

Acute Disease↗