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PubMed1990

A clustering of RNA recombination sites adjacent to a hypervariable region of the peplomer gene of murine coronavirus.

Coronaviruses undergo RNA recombination at a very high frequency. To understand the mechanism of recombination in murine coronavirus, we have performed RNA sequencing of viral genomic RNA to determine the precise sites of recombination in a series of recombinants which have crossovers within the gene encoding the peplomer protein. We found that all of the recombination sites are clustered within a region of 278 nucleotides in the 5'-half of the gene. This region in which all of the crossovers occurred represents a small fraction of the distance between the two selection markers used for the isolation of these recombinant viruses. This result suggests that this region may be a preferred site for RNA recombination. The crossover sites are located within and immediately adjacent to a hypervariable area of the gene. This area has undergone deletions of varying sizes in several virus strains which have been passaged either in vivo or in vitro. These results suggest that a similar RNA structure may be involved in the occurrence of both recombination and deletion events.

Animals↗
PubMed1990

Botran and bleomycin induce crossing-over, and bleomycin also increases aneuploidy in diploid strains of Aspergillus.

Both bleomycin, an antineoplastic drug, and botran (2,6-dichloro-4-nitro-aniline), a fungicide, are known to inhibit growth and induce genetic segregation in diploid tester strains of Aspergillus nidulans when present in agar media. To identify primary effects, samples of induced apparent crossover types were analysed in detail. For both compounds, coincident and consecutive events of mitotic crossing-over were found to be very frequent and such events showed a random distribution among isolated colour sectors. In the case of botran, a thorough search for imbalanced precursor types was negative and recessive lethals were found only rarely. Such segregants are therefore unlikely the result of terminal deletions. For bleomycin, induction of reciprocal crossing-over was confirmed by treatments of germinating conidia. On plating to normal growth medium, crossover segregants showed up as coloured half- or quarter-colonies, including some "twin spots". Whole coloured colonies were also frequent and these increased with dose levels which caused decreasing survival and increasing frequencies of abnormal colonies. Analysis of large fractions of such "abnormals" identified aneuploids in all cases. While botran, in plate tests, also increased haploid segregants and disomic precursors could be found, tests of germinating conidia "in liquid" were inconclusive, because botran is insoluble in water. Some increases of aneuploids were observed, but only when botran and the solvent DMSO both were present at increased levels.

Aneuploidy↗
PubMed2006

Effects of thirty-minute mobile phone use on visuo-motor reaction time.

OBJECTIVE: To investigate whether exposure to pulsed high-frequency electromagnetic field (pulsed EMF) emitted by a mobile phone has short-term effects on the visuo-motor choice reaction time (RT) and movement time (MT). METHODS: A double blind, counterbalanced crossover design was employed. In 16 normal subjects, we studied the performance of a visuo-motor precued choice reaction time task (PCRT) before and after exposure to EMF emitted by a mobile phone for 30 minutes or sham exposure. RESULTS: The RTs and MTs under different conditions of precue information were not affected by exposure to pulsed EMF emitted by a mobile phone or by sham phone use. CONCLUSIONS: Thirty minutes of mobile phone use has no significant short-term effect on the cortical visuo-motor processing as studied by the present PCRT task. SIGNIFICANCE: This is the first study to investigate visuo-motor behavior in relation to mobile phone exposure. No significant effect of mobile phone use was demonstrated on the performance of the visuo-motor reaction time task.

Adult↗
PubMed1989

Synergistic adverse hemodynamic interaction between oral verapamil and propranolol.

The interaction between oral verapamil and propranolol may involve negative chronotropic, inotropic or dromotropic effects. The immediate effects of orally administered verapamil (120 mg) and propranolol (80 mg), alone and combined, on submaximal exercise hemodynamics and on pharmacokinetics were studied in eight healthy male volunteers in a randomized, double-blind, crossover manner. Maximum effects on heart rate, systolic blood pressure, PR interval and rate-adjusted PR prolongation were greatest with the combined administration of verapamil and propranolol. The combination caused a high frequency of adverse drug events, predominantly exercise fatigue. Verapamil increased the AUC and Cmax and shortened the tmax of propranolol. Propranolol decreased the AUC and Cmax of verapamil. The greater reduction of heart rate with the combination of verapamil and propranolol was only partially explained by higher plasma concentrations of propranolol. The combination of propranolol and verapamil produced clinically important synergistic adverse effects during exercise. Negative dromotropic effects occurred primarily by direct AV node inhibition and were more important than previously recognized.

Administration, Oral↗
PubMed2003

Effect of salmeterol xinafoate on lung mucociliary clearance in patients with asthma.

Lung mucociliary clearance is impaired in stable asthma. The long-acting beta2-agonist salmeterol has been shown in vitro to cause a significant increase in ciliary beat frequency. It seemed possible therefore that salmeterol may also have a favourable effect on lung mucociliary transport in asthmatic patients. Fourteen patients with asthma participated in a double-blind, placebo-controlled, crossover study to assess the effect of 2 weeks of treatment with salmeterol MDI (50 microg b.d.) on lung mucociliary clearance. The 11 patients who completed the study (seven males, four females) had a mean +/- SE age of 50 +/- 4 years, % predicted FEV1 of 74 +/- 8% and a tobacco consumption history of 13 +/- 7 pack-years (seven non-smokers, four exsmokers). Lung mucociliary transport was measured by a radioaerosol technique. Pulmonary function indices (FEV1, FVC, and PEF) were significantly improved on salmeterol relative to placebo. The main radioaerosol finding was a significant increase in the penetration of radioaerosol into the lung with 24-h radioaerosol rising from 40 +/- 5% on placebo to 49 +/- 4% (P < 0.01) on salmeterol. Despite this increased penetration, a slight favourable change occurred in tracheobronchial aerosol clearance. This study demonstrates that 2 weeks salmeterol treatment influences deposition of particles within the lung by increasing airway patency and indicates a beneficial effect of MDI salmeterol on lung mucociliary clearance.

Adrenergic beta-Agonists↗
PubMed2000

Multicenter, double-blind, placebo-controlled, multiple-challenge evaluation of reported reactions to monosodium glutamate.

BACKGROUND: The frequency of reactions reported to occur after the consumption of monosodium glutamate (MSG) is the subject of controversy. OBJECTIVE: We conducted a multicenter, multiphase, double-blind, placebo-controlled study with a crossover design to evaluate reactions reportedly caused by MSG. METHODS: In 3 of 4 protocols (A, B, and C), MSG was administered without food. A positive response was scored if the subject reported 2 or more symptoms from a list of 10 symptoms reported to occur after ingestion of MSG-containing foods within 2 hours. In protocol A 130 self-selected reportedly MSG-reactive volunteers were challenged with 5 g of MSG and with placebo on separate days (days 1 and 2). Of the 86 subjects who reacted to MSG, placebo, or both in protocol A, 69 completed protocol B to determine whether the response was consistent and dose dependent. To further examine the consistency and reproducibility of reactions to MSG, 12 of the 19 subjects who responded to 5 g of MSG but not to placebo in both protocols A and B were given, in protocol C, 2 challenges, each consisting of 5 g of MSG versus placebo. RESULTS: Of 130 subjects in protocol A, 50 (38. 5%) responded to MSG only, 17 (13.1%) responded to placebo only (P <. 05), and 19 (14.6%) responded to both. Challenge with increasing doses of MSG in protocol B was associated with increased response rates. Only half (n = 19) of 37 subjects who reacted to 5 g of MSG but not placebo in protocol A reacted similarly in protocol B, suggesting inconsistency in the response. Two of the 19 subjects responded in both challenges to MSG but not placebo in protocol C; however, their symptoms were not reproducible in protocols A through C. These 2 subjects were challenged in protocol D 3 times with placebo and 3 times with 5 g of MSG in the presence of food. Both responded to only one of the MSG challenges in protocol D. CONCLUSION: The results suggest that large doses of MSG given without food may elicit more symptoms than a placebo in individuals who believe that they react adversely to MSG. However, neither persistent nor serious effects from MSG ingestion are observed, and the responses were not consistent on retesting.

Adult↗
PubMed2003

Effectiveness of transcutaneous electrical nerve stimulation on postoperative pain with movement.

This study tested the effectiveness of episodic transcutaneous electrical nerve stimulation (TENS) as a supplement to pharmacologic analgesia on pain with movement and at rest after abdominal surgery and evaluated whether its use during walking and vital capacity maneuvers enhances performance of these activities. TENS, with a modulated frequency, intensity as high as the subject could tolerate, and electrodes placed on either side and parallel to the incision, was compared to placebo TENS and pharmacologic analgesia alone (control) by using a crossover design. Self-report of pain intensity, walking function, and vital capacity were assessed on 33 subjects. TENS resulted in significantly less pain than the control during both walking (P <.5) and vital capacity activities (P <.1) and significantly less pain than placebo TENS during vital capacity (P <.01). TENS also produced significantly better gait speeds than the control (P <.05) and greater gait distances (P <.01) than the control and placebo TENS. Vital capacity and pain intensity at rest were not significantly different among the 3 treatments. These results suggest TENS reduces pain intensity during walking and deep breathing and increases walking function postoperatively when used as a supplement to pharmacologic analgesia. The lack of effect on pain at rest supports the hypothesis that TENS works through reducing hyperalgesia.

Abdomen↗
PubMed1986

Recombination between IS5 elements: requirement for homology and recombination functions.

Intermolecular recombination between two IS5 elements was measured, using bacteriophage lambda recombination vectors, and was compared to recombination between two copies of an SV40 segment cloned into the same vectors. Experiments were conducted in the presence and in the absence of RecA and Red functions, and with the recombining inserts in the same or in reversed orientation. Under all conditions, IS5 elements recombined in a manner similar to the SV40 inserts, indicating that IS-encoded functions did not confer measurable additional intermolecular recombination ability to IS5 in E. coli K-12. Bacteriophages containing reversed IS5 inserts, for which the 16 base pair (bp) termini are identical in 15 positions and which display 12 bp of uninterrupted homology, recombined at approximately the same low frequency under Rec+ and Rec- conditions, indicating that these short homologies were not good substrates for the Rec system. Bacteriophages having reversed inserts recombined better under Red+ than under Red- conditions, but the crossovers were located in nonhomologous regions flanking the element termini. This suggests that 12-bp homologies are not good substrates for the Red system.

Bacteriophage lambda↗
PubMed2004

Etomidate versus propofol for electroconvulsive therapy in patients with schizophrenia.

Among drugs used for the anesthesia of electroconvulsive therapy (ECT), propofol reduces seizure duration to a greater degree than etomidate. The perceived difference between the 2 anesthetics is smaller in patients with schizophrenia than in patients who suffer depression. In this study, propofol and etomidate were compared during the ECT of patients with schizophrenia, on the basis of their impact on seizure activity and on seizure-induced hemodynamic reactions. Schizophrenics (n = 34) who were treated with ECT participated in this randomized crossover study. Propofol (1 mg/kg) and etomidate (0.2 mg/kg) were used alternately. The 2 drugs were compared on the basis of EEG- and EMG-registered seizure duration, mean arterial pressure (MAP), pulse frequency, energy index, and postictal suppression. We also analyzed the number of necessary restimulations. In case of anesthesia with etomidate, both EEG- (61.29 +/- 22.4 s, 47.9 +/- 21.3 s P = 0.014) and EMG- (46.3 +/- 23.8 s, 33.6 +/- 15.9 s P = 0.006) registered seizure durations were significantly longer than in case of propofol. When using propofol, the increase in MAP was significantly lower than when etomidate was used (8.1 +/- 10.2 mm Hg, 18.3 +/- 11.2 mm Hg, P = 0.001). There were no significant differences found in the postseizure increase in pulse frequency, in postictal suppression, or in the energy index, nor did the numbers of necessary restimulations differ significantly. Propofol was found to reduce seizure duration to a significantly greater extent than etomidate. At the same time, in electrophysiological parameters that show a correlation with clinical efficacy, there was no significant difference found between the 2 anesthetics. However, the seizure-induced increase in MAP was reduced by propofol to a significantly greater degree than by etomidate.

Adult↗
PubMed1990

Oxybutynin hydrochloride (3 mg) in the treatment of women with idiopathic detrusor instability.

Oxybutynin hydrochloride (3 mg) was compared with placebo by randomised, double-blind crossover trial in 53 females with idiopathic detrusor instability. Symptoms were cured or markedly improved in 60% of patients on oxybutynin and 2.3% on placebo. During the first treatment period, oxybutynin reduced the frequency of voiding by 35%, compared with 9% for placebo. Oxybutynin gave a significantly greater improvement than placebo in volume at the first desire to void (70 ml increase versus 7.7 ml), maximum filling-phase detrusor pressure (17 cm H2O reduction versus no benefit) and cystometric capacity (104 ml increase versus 7.0 ml). A marked oxybutynin carry-over effect was seen during the second treatment period. Side effects from the 3 mg dose of oxybutynin caused 7.5% of subjects to discontinue therapy.

Double-Blind Method↗
PubMed1983

Two new X-autosome translocations in the mouse.

The reciprocal translocations T(X;4)37H and T(X;11)38H were induced by acute X-irradiation of spermatozoa. Male heterozygotes are completely aspermic with a spermatogenic block at pachytene and testis masses about one third of normal, though metaphase I is very occasionally reached in T37H. For both translocations the X chromosome breakpoints are in band XA2, and the autosomal breakpoints are in 4D3 for T37H and 11E1 for T38H, leading to long and short marker chromosomes. Chain quadrivalents predominated in oocytes at MI, with no rings; there were 32% trivalent + univalent configurations in T37H and 40% in T38H. These generated (1) XO mice, (2) tertiary trisomics carrying 20 bivalents and the small X4 (T37H) or X11 (T38H) markers. These trisomics were apparently lethal in T37H but sub-viable in T38H and sometimes fertile as XX11 and trisomic XXX11 females, though sterile as XX11Y males. However, many developed exencephaly in utero, probably because of the distal duplication on chromosome 11. No tertiary monosomics were found in 12 to 14 day embryos. Seven percent of all female progeny were XO, with a higher than expected frequency in T37H and a lower than expected one in T38H. T37H is about two units and T38H about five units from the spf locus on the X chromosome with evidence for some crossover suppression between the T38H breakpoint and Ta. Autosomal linkages found were T37H-m-b (R.F. of 16 +/- 4% between T37H and m) and T38H-Rewc (R.F. of 5 +/- 3%). T37H/+ females weighed about 10% less than normal females at birth and about 30% less at weaning; there was little if any effect in T38H/+ females or in males carrying either translocation. Neither translocation had any marked effect on viability. T37H/+ females showed variegation when heterozygous for b with the wild type allele in the long 4X marker. On average, about 20% of the coat was brown rather than black. However, no clear evidence for m variegation was found.

Animals↗
PubMed1998

Three candidate genes and angiotensin-converting enzyme inhibitor-related cough: a pharmacogenetic analysis.

Unexplained, persistent cough limits the use of angiotensin-converting enzyme (ACE) inhibitors in a significant number of patients. It has been speculated that occurrence of this adverse effect is genetically predetermined; in particular, variants of the genes encoding ACE, chymase, and B2-bradykinin receptor have been implicated. To investigate this question, we determined genotypes for common polymorphisms for these three genes in subjects with a history of ACE inhibitor-related cough. Specificity of the adverse effect was confirmed by a blinded, double-crossover design protocol in which subjects were rechallenged with either lisinopril or placebo. In 99 case subjects and 70 control subjects (who failed to develop cough on rechallenge with ACE inhibitor) thus selected, frequencies for the ACE D and I alleles were 0.56 and 0.44 (cases) and 0.56 and 0.44 (controls), respectively; frequencies for chymase A and B alleles (absence/presence of BstXI site) were 0.56 and 0.44 (cases) and 0.46 and 0.54 (controls), respectively; frequencies for B2-bradykinin receptor + and - alleles (presence/absence of a 21 to 29 nonanucleotide sequence) were 0.52 and 0.48 (cases) and 0.53 and 0.47 (controls), respectively. All observed genotype frequencies were in Hardy-Weinberg equilibrium. There was no evidence for association between genotype at either gene examined and cough (adjusted for gender and age). Our data indicate that common genetic variants of ACE, chymase, and B2-bradykinin receptor do not explain the occurrence of ACE inhibitor-related cough.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

New polyethylene glycol laxative for treatment of constipation in adults: a randomized, double-blind, placebo-controlled study.

BACKGROUND: This study evaluated the safety and effectiveness of a new polyethylene glycol (PEG) laxative (MiraLax, Braintree Laboratories Inc, Braintree, Mass) in 23 patients reporting a history of constipation. METHODS: After a 7-day placebo control period, patients were randomized into a double crossover trial of placebo versus 17 g of PEG daily for 4 days. Patient maintained a stool diary. RESULTS: Daily ingestion of a 17 g dose of PEG increased mean daily bowel movement frequency to once per day by the last 7 days of the 14-day treatment period. This was a statistically significant improvement over placebo, which provided about 1 bowel movement every 2 days during the last week of therapy. Patient diary ratings of related subjective symptoms were improved with PEG treatment over placebo. Both investigator and patients rated PEG therapy superior to placebo. No clinically significant changes in blood chemistry, complete blood count (CBC), or urinalysis were observed. CONCLUSIONS: Daily therapy with 17 g of PEG laxative for 14 days resulted in a significant improvement in bowel movement frequency in constipated patients relative to placebo by the second week of treatment.

Adult↗
PubMedDate not supplied

Subcutaneous use of regular human insulin (Novo): pharmacokinetics and continuous insulin infusion therapy.

The absorption kinetics of human insulin (Novo) were studied and compared with those of purified porcine insulin preparations in seven healthy men. The absorption of insulin after subcutaneous injection of human insulin (Actrapid, Novo) was significantly accelerated and its hypoglycemic effect significantly stronger when compared with porcine insulin (Actrapid). No differences in the absorption kinetics were observed using human insulin (Monotard, Novo) and porcine insulin (Monotard) preparations, respectively. A clinical trial was designed to determine whether the pharmacokinetic differences were relevant for the clinical use of regular human insulin. The efficacy of human and porcine insulin (Actrapid) was tested in a double-blind crossover protocol in 12 type I diabetic patients treated with continuous subcutaneous insulin infusion. Near-normoglycemia was achieved with both types of insulin. Diurnal blood glucose values and excursions, insulin requirements, the frequency of mild hypoglycemic episodes, and the carbohydrate content of the diet were essentially identical. Thus, the differences between the absorption of human insulin and porcine regular insulin from a subcutaneous depot as observed in the pharmacokinetic studies in normal man do not appear to be relevant in the clinical practice of the subcutaneous insulin replacement therapy in type I diabetes mellitus at near-normoglycemia.

Absorption↗
PubMed1998

[Validity of alcohol consumption records: comparison of clinical history and telephone survey].

OBJECTIVES: To compare primary care clinical records (PCCRs) and a telephone survey of the population group seeking health care, for the prevalence of alcohol consumption. To determine factors linked to screening and observation of alcohol consumption, and to analyse the perception and recording of medical counselling on alcohol and tobacco consumption. DESIGN: Descriptive, crossover study. SETTING: Urban Health Centre. PARTICIPANTS: Random sample of 320 patients with PCCRs, aged between 15 and 75. MEASUREMENTS AND MAIN RESULTS: The PCCR was reviewed for age, sex, educational level, profession, frequency of attendance, chronic illnesses, alcohol and tobacco consumption, pathologies linked to alcohol consumption, screening and observance of this consumption as recommended by the preventive activities and health promotion programme (PAHPP), and the recording of counselling to smokers and at-risk drinkers. Later a standard questionnaire on the patients' alcohol and tobacco consumption and their perception of medical counselling was filled in by phone, 36.1% of patients consumed alcohol, according to the PCCR, which rose to 51.1% in the questionnaire (95% CI variation, 6.2-23.8). Initial screening of alcohol consumption was recorded in 67.4% of the PCCRs, with a significant association to age of 20 or over (OR = 20.5; CI, 2.9-142.6), and to education beyond primary level (OR = 8; CI, 1.7-38.5). The observation recommended by the PAHPP was correctly followed for 24.8% of patients, and was associated with being a smoker (OR = 2; CI, 1.2-3.4) and male (OR = 1.9; CI, 1.1-3.3). No significant differences were found when the under-recording in the PCCRs of alcohol counselling to at-risk drinkers (27.8% PCCRs and 35.7% questionnaire) was studied: but there were significant differences for tobacco dependency (20.7% PCCRs and 55.7% questionnaire; CI of variance: 23.6-46.4). CONCLUSIONS: We found considerable under-recording of alcohol consumption in the clinical records, along with little medical counselling. Preventive activities should be given priority, especially among young people, since consumption starts in adolescence, and young people, along with women and patients of low educational level, are more susceptible to medical counselling.

Adolescent↗
PubMed1983

Gene order and gene distances in the HLA region studied by the haplotype method.

The present report describes a method to establish gene order and gene distances in chromosomal regions where several genes are located closely together. The method is applied to the study of the complement loci in the HLA complex on chromosome 6 in man. The method is based on allelic association, i.e. alleles of closely linked loci are nonrandomly associated on haplotypes. A haplotype which yields information has a frequency higher than would be expected from the frequencies of each of its alleles. They occur, moreover, with a frequency which makes them the main source of the least frequent of the alleles in the combinations. Other haplotype combinations involving this allele (these alleles) are most likely the results of recombinational events involving a main haplotype. Such crossovers may therefore, on certain conditions, be used for gene mapping purposes. Some basic rules for the use of the method are given. A total of 701 haplotypes involving the short arm of chromosome 6 have been studied. Typings have been performed with regard to HLA-A, -B, -C, -D/-DR, C4, C2 and Bf. The study confirms previous localization of the complement loci between HLA-D and -B. The investigation suggests the order HLA-D-Bf-C4-C2-HLA-B. There is, moreover, slight evidence in favour of a localization of the C4A gene on the HLA-B side of C4B. Given an HLA-A-HLA-B distance of 0.8 cM, suggested relative distances are: HLA-D-Bf:0.44 cM, Bf-C4:0.04 cM, C4-C2:0.11 cM, and C2-HLA-B:0.12 cM.

Alleles↗
PubMed1978

Baclofen for spasticity in multiple sclerosis. Double-blind crossover and three-year study.

Baclofen is a safe and effective means for treating spasticity associated with multiple sclerosis. We found no toxic effects on hepatologic, hematopoietic, or renal function, acutely or for over 3 years of follow-up. A statistically significant reduction was noted in frequency of spasms, and clonus, and there was improved range of joint movement, which enabled patients to maintain functional status for prolonged periods. For the more disabled patients, treatment with baclofen gave symptomatic relief of painful spasms and made immobility more tolerable. Optimum effect was achieved when baclofen was administered in the early stages of disease, before major disabilities became permanent.

Activities of Daily Living↗
PubMed2005

Relation between solvent and protein dynamics as studied by dielectric spectroscopy.

We present results obtained by dielectric spectroscopy in wide frequency (10(-2)-10(9) Hz) and temperature ranges on human hemoglobin in the three different solvents water, glycerol, and methanol, at a solvent level of 0.8 g of solvent/g of protein. In this broad frequency region, there are motions on several time-scales in the measured temperature range (110-370 K for water, 170-410 K for glycerol, and 110-310 K for methanol). For all samples, the dielectric data shows at least four relaxation processes, with frequency dependences that are well described by the Havriliak-Negami or Cole-Cole functions. The fastest and most pronounced process in the dielectric spectra of hemoglobin in glycerol and methanol solutions is similar to the alpha-relaxation of the corresponding bulk solvent (but shifted to slower dynamics due to surface interactions). For water solutions, however, this process corresponds to earlier results obtained for water confined in various systems and it is most likely due to a local beta-relaxation. The slowing down of the glycerol and methanol relaxations and the good agreement with earlier results on confined water show that this process is affected by the interaction with the protein surface. The second fastest process is attributed to motions of polar side groups on the protein, with a possible contribution from tightly bound solvent molecules. This process is shifted to slower dynamics with increasing solvent viscosity, and it shows a crossover in its temperature dependence from Arrhenius behavior at low temperatures to non-Arrhenius behavior at higher temperatures where there seems to be an onset of cooperativity effects. The origins of the two slowest relaxation processes (visible at high temperatures and low frequencies), which show saddlelike temperature dependences for the solvents water and methanol, are most likely due to motions of the polypeptide backbone and an even more global motion in the protein molecule.

Glycerol↗