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PubMed1990

The crossover surface coil: an efficient in vivo NMR detector.

The crossover surface coil is constructed with two turns of copper foil using a unique transposition construction which incorporates an explicit center tap ground of the widened bottom layer. The coil reduces dielectric and inductive losses by effective shielding of electric fields and uniform distribution of magnetic fields for minimum Q losses upon loading of the coil. Flexible, copper foil construction permits easy conformation to tissues of interest, enhancing coil performance. Construction details of the crossover coil and Q data for coils of various sizes operating at a number of frequencies are given.

Equipment Design↗
PubMed1977

Echocardiographic correlate of presystolic pulmonary ejection sound in congenital valvular pulmonic stenosis.

A presystolic ejection click was present in a patient with congenital valvular pulmonic stenosis. The coincidence of this sound with presystolic pulmonary valve opening was demonstrated by simultaneous phonoechocardiography. Hemodynamic confirmation of this observation was made by demonstrating presystolic crossover of RV-PA pressures. This sound was distinguished on phonocardiogram as a high frequency sound separate from a lower frequency presystolic (S4) gallop.

Adolescent↗
PubMed2001

Oxcarbazepine, an antiepileptic agent.

BACKGROUND: Epilepsy is a common neurologic condition. Many of the currently approved pharmacologic agents for its treatment are associated with numerous adverse drug reactions and drug interactions. OBJECTIVE: This review describes the pharmacology and therapeutic use of oxcarbazepine, an analogue of the well-known antiepileptic agent carbamazepine. METHODS: Articles for review were identified through a search of MEDLINE, International Pharmaceutical Abstracts, and EMBASE for the years 1980 through 2000. The terms used individually and in combination were oxcarbazepine, carbamazepine, epilepsy, and seizures. RESULTS: Oxcarbazepine and its primary metabolite have been effective in animal models of epilepsy that generally predict efficacy in generalized tonic-clonic seizures and partial seizures in humans. The exact mechanism of action of oxcarbazepine is unknown, although as with carbamazepine, it is believed to involve blockade of voltage-gated sodium channels. The pharmacokinetic profile of oxcarbazepine is less complicated than that of carbamazepine, with less metabolism by the cytochrome P450 system, no production of an epoxide metabolite, and lower plasma protein binding. The clinical efficacy and tolerability of oxcarbazepine have been demonstrated in trials in adults, children, and the elderly. In a double-blind, randomized, crossover trial in adults, oxcarbazepine 300 mg was associated with a decrease in the mean frequency of tonic seizures (21.4 vs 30.5 seizures during steady-state periods) and tonic-clonic seizures (8.2 vs 10.4) compared with carbamazepine 200 mg (P = 0.05). A multinational, multicenter, double-blind, placebo-controlled, randomized, 28-week trial assessed the efficacy and tolerability of oxcarbazepine at doses of 600, 1200, and 2400 mg as adjunctive therapy in patients with uncontrolled partial seizures. All 3 oxcarbazepine groups demonstrated a reduction in seizure frequency per 28-day period compared with placebo (600 mg, 26% reduction; 1200 mg, 40% reduction; 2400 mg, 50% reduction; placebo, 7.6% reduction; all, P < 0.001). A trial in children assessed the efficacy and toxicity of oxcarbazepine (median dose, 31.4 mg/kg/d) as adjunctive therapy for partial seizures. Patients receiving oxcarbazepine experienced a 35% reduction in seizure frequency, compared with a 9% reduction in the placebo group (P < 0.001). The most common adverse effects associated with oxcarbazepine are related to the central nervous system (eg, dizziness, headache, diplopia, and ataxia) and the gastrointestinal system (eg, nausea and vomiting). Compared with carbamazepine, there is an increased risk of hyponatremia with oxcarbazepine. The frequency and severity of drug interactions are less with oxcarbazepine than with carbamazepine or other antiepileptic agents. CONCLUSIONS: Oxcarbazepine may be considered an appropriate alternative to carbamazepine for the treatment of partial seizures in patients who are unable to tolerate carbamazepine. Its use in nonseizure disorders remains to be examined in large-scale clinical trials, and pharmacoeconomic comparisons of oxcarbazepine with other antiepileptic agents, particularly carbamazepine, are needed.

Adolescent↗
PubMed2004

A pilot safety study of repetitive transcranial magnetic stimulation (rTMS) in Tourette's syndrome.

OBJECTIVE: We designed a randomized, blinded, crossover study to assess safety and test whether transcranial magnetic stimulation at specific regions and frequencies might modify tics. We administered repetitive transcranial magnetic stimulation over prefrontal cortex or motor cortex, with either fast or slow repetitive transcranial magnetic stimulation, to 8 Tourette's syndrome patients. METHODS: Over 5 days, we applied repetitive transcranial magnetic stimulation at 110% of the motor threshold over left motor cortex (twice) or left prefrontal cortex (twice), using either 1 Hz or 15 Hz transcranial magnetic stimulation, or sham transcranial magnetic stimulation (once). RESULTS: All 8 subjects completed the study with minimal side effects and no worsening of tics or other involuntary movements. Ignoring site and frequency, tic symptoms improved significantly over the week of the study. The study design does not allow one to address whether this was due to the presence or frequency of transcranial magnetic stimulation or to nonspecific factors involved in study participation. CONCLUSIONS: Repetitive transcranial magnetic stimulation at these sites, doses, and use parameters appears to be safe in adults with Tourette's syndrome. Further studies using repetitive transcranial magnetic stimulation in Tourette's syndrome are warranted, using balanced parallel designs.

Adult↗
PubMed2001

Identification and mutagenesis by allelic exchange of choE, encoding a cholesterol oxidase from the intracellular pathogen Rhodococcus equi.

The virulence mechanisms of the facultative intracellular parasite Rhodococcus equi remain largely unknown. Among the candidate virulence factors of this pathogenic actinomycete is a secreted cholesterol oxidase, a putative membrane-damaging toxin. We identified and characterized the gene encoding this enzyme, the choE monocistron. Its protein product, ChoE, is homologous to other secreted cholesterol oxidases identified in Brevibacterium sterolicum and Streptomyces spp. ChoE also exhibits significant similarities to putative cholesterol oxidases encoded by Mycobacterium tuberculosis and Mycobacterium leprae. Genetic tools for use with R. equi are poorly developed. Here we describe the first targeted mutagenesis system available for this bacterium. It is based on a suicide plasmid, a selectable marker (the aacC4 apramycin resistance gene from Salmonella), and homologous recombination. The choE allele was disrupted by insertion of the aacC4 gene, cloned in pUC19 and introduced by electroporation in R. equi. choE recombinants were isolated at frequencies between 10(-2) and 10(-3). Twelve percent of the recombinants were double-crossover choE mutants. The choE mutation was associated with loss of cooperative (CAMP-like) hemolysis with sphingomyelinase-producing bacteria (Listeria ivanovii). Functional complementation was achieved by expression of choE from pVK173-T, a pAL5000 derivative conferring hygromycin resistance. Our data demonstrate that ChoE is an important cytolytic factor for R. equi. The highly efficient targeted mutagenesis procedure that we used to generate choE isogenic mutants will be a valuable tool for the molecular analysis of R. equi virulence.

Alleles↗
PubMed2004

Multiple genetic pathways involving the Caenorhabditis elegans Bloom's syndrome genes him-6, rad-51, and top-3 are needed to maintain genome stability in the germ line.

Bloom's syndrome (BS) is an autosomal-recessive human disorder caused by mutations in the BS RecQ helicase and is associated with loss of genomic integrity and an increased incidence of cancer. We analyzed the mitotic and the meiotic roles of Caenorhabditis elegans him-6, which we show to encode the ortholog of the human BS gene. Mutations in him-6 result in an enhanced irradiation sensitivity, a partially defective S-phase checkpoint, and in reduced levels of DNA-damage induced apoptosis. Furthermore, him-6 mutants exhibit a decreased frequency of meiotic recombination that is probably due to a defect in the progression of crossover recombination. In mitotically proliferating germ cells, our genetic interaction studies, as well as the assessment of the number of double-strand breaks via RAD-51 foci, reveal a complex regulatory network that is different from the situation in yeast. Although the number of double-strand breaks in him-6 and top-3 single mutants is elevated, the combined depletion of him-6 and top-3 leads to mitotic catastrophe concomitant with a massive increase in the level of double-strand breaks, a phenotype that is completely suppressed by rad-51. him-6 and top-3 are thus needed to maintain low levels of double-strand breaks in normally proliferating germ cells, and both act in partial redundant pathways downstream of rad-51 to prevent mitotic catastrophy. Finally, we show that topoisomerase IIIalpha acts independently during a late stage of meiotic recombination.

Adenosine Triphosphatases↗
PubMed2004

Characterization, regulation, and phylogenetic analyses of the Penicillium griseoroseum nitrate reductase gene and its use as selection marker for homologous transformation.

Penicillium griseoroseum has been studied because of its efficient pectinases production. In this work, the Penicillium griseoroseum nitrate reductase gene was characterized, transcriptionally analyzed in different nitrogen sources, and used to create a phylogenetic tree and to develop a homologous transformation system. The regulatory region contained consensus signals involved in nitrogen metabolism and the structural region was possibly interrupted by 6 introns coding for a deduced protein with 864 amino acids. RT-PCR analysis revealed high amounts of niaD transcript in the presence of nitrate. Transcription was repressed by ammonium, urea, and glutamine showing an efficient turnover of the niaD mRNA. Phylogenetics analysis showed distinct groups clearly separated in accordance with the classical taxonomy. A mutant with a 122-bp deletion was used in homologous transformation experiments and showed a transformation frequency of 14 transformants/microg DNA. All analyzed transformants showed that both single- and double-crossover recombination occurred at the niaD locus. The establishment of this homologous transformation system is an essential step for the improvement of pectinase production in Penicillium griseoroseum.

Amino Acid Sequence↗
PubMed1995

Triggering of acute myocardial infarction onset by episodes of anger. Determinants of Myocardial Infarction Onset Study Investigators.

BACKGROUND: Many anecdotes and several uncontrolled case series have suggested that emotionally stressful events, and more specifically, anger, immediately precede and appear to trigger the onset of acute myocardial infarction. However, controlled studies to determine the relative risk of myocardial infarction after episodes of anger have not been reported. METHODS AND RESULTS: We interviewed 1623 patients (501 women) an average of 4 days after myocardial infarction. The interview identified the time, place, and quality of myocardial infarction pain and other symptoms, the estimated usual frequency of anger during the previous year, and the intensity and timing of anger and other potentially triggering factors during the 26 hours before the onset of myocardial infarction. Anger was assessed by the onset anger scale, a single-item, seven-level, self-report scale, and the state anger subscale of the State-Trait Personality Inventory. Occurrence of anger in the 2 hours preceding the onset of myocardial infarction was compared with its expected frequency using two types of self-matched control data based on the case-crossover study design. The onset anger scale identified 39 patients with episodes of anger in the 2 hours before the onset of myocardial infarction. The relative risk of myocardial infarction in the 2 hours after an episode of anger was 2.3 (95% confidence interval, 1.7 to 3.2). The state anger subscale corroborated these findings with a relative risk of 1.9 (95% confidence interval, 1.3 to 2.7). Regular users of aspirin had a significantly lower relative risk (1.4; 95% confidence interval, 0.8 to 2.6) than nonusers (2.9; 95% confidence interval, 2.0 to 4.1) (P < .05). CONCLUSIONS: Episodes of anger are capable of triggering the onset of acute myocardial infarction, but aspirin may reduce this risk. A better understanding of the manner in which external events trigger the onset of acute cardiovascular events may lead to innovative preventive strategies aimed at severing the link between these external stressors and their pathological consequences.

Adrenergic beta-Antagonists↗
PubMed1985

The sexual side-effects of antidepressant medication: a double-blind comparison of two antidepressants in a non-psychiatric population.

Clinical reports have suggested that antidepressant medication may contribute to the sexual dysfunction experienced by some depressed patients. A double-blind trial in a non-psychiatric male population compared amitriptyline (tricyclic), mianserin (tetracyclic) and placebo for their effects on nocturnal sexual arousal. In a three-way crossover design active drug or placebo were taken for two weeks preceding measurement of the frequency, amplitude and duration of nocturnal penile tumescence and synchronous sleep indices. Both active compounds significantly decreased the amplitude and the total duration of nocturnal erections. The effects on sleep indices were as previously reported. Few differences were found between the tricyclic and tetracyclic drugs. Some implications of these findings are considered.

Adolescent↗
PubMed1999

Scotopic sensitivity/Irlen syndrome and the use of coloured filters: a long-term placebo-controlled study of reading strategies using analysis of miscue.

This study investigated the long-term effects of using coloured filters on the frequency and type of errors in oral reading. A double-masked, placebo-controlled crossover experimental design was used, with subjects being assessed over a period of 20 months. There were three experimental groups (Placebo tints, Blue tints, and Diagnosed tints) involving 113 subjects with reading difficulties, ranging in age from 9.2 yr. to 13.1 yr. The 35 controls (ranging in age from 9.4 yr. to 12.9 yr.) had reading difficulties but did not require coloured filters. There was a significant improvement for all groups in the accuracy of miscues over the period, although experimental groups over-all did not improve at a significantly different rate than the control group. The failure to find significantly greater improvement for the experimental groups over the control group for the total period, despite subjects' reports of improved print clarity, may be partly related to the lack of effective letter-sound analysis and synthesis skills and to the use of a word-identification strategy of guessing based on partial visual analysis.

Adolescent↗
PubMed1990

The genetic defect in multiple endocrine neoplasia type 2A maps next to the centromere of chromosome 10.

Multiple endocrine neoplasia type 2A (MEN2A) is a rare cancer syndrome that is inherited in an apparently autosomal dominant fashion. Previous linkage studies had assigned the MEN2A locus to chromosome 10 in the pericentromeric region. We recently have described several new easily scorable RFLPs for the chromosome 10-specific alpha satellite DNA (the D10Z1) locus that is known, on the basis of previous in situ hybridization experiments, to lie at the centromere. We report here tight linkage between MEN2A and D10Z1, as demonstrated by a maximum lod score of 12.02 at the recombination frequency of zero (1-lod-unit support interval 0-4 cM), indicating that the genetic defect in MEN2A lies in the immediate vicinity of the centromere. By means of a set of ordered polymorphic DNA markers from the pericentromeric region, multipoint as well as pairwise linkage analyses place the MEN2A locus at the middle of a small region (approximately 11 cM) bracketing the centromere with FNRB (at 10p11.2) and RBP3 (at 10q11.2) on either side, providing further support for the centromeric location of the MEN2A locus. Marked sex difference in recombination frequencies exists in this pericentromeric region: significantly (P less than .01) more female than male crossovers were observed across all of the adjacent intervals D10S24-FNRB, FNRB-D10Z1, and D10Z1-RBP3. However, a sex difference was not seen in the 7-cM interval from RBP3 to D10S5, suggesting that large variation in the sex difference in recombination can occur over small chromosomal regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Centromere↗
PubMed1988

Respiratory response to histamine- and methylcholine-induced bronchospasm in nonsmokers and asymptomatic smokers.

The respiratory response to bronchospasms of the same magnitude induced by inhalation of histamine or methylcholine was measured non-invasively, using bellow pneumographs, in nonsmokers and asymptomatic smokers. In each subject, tidal volume (VT), breathing frequency (f) and inspiratory time (TI) were obtained on two different days, in a randomized crossover fashion, with the following sequence: basal conditions, after inhalation of buffered saline as a control and after histamine or methylcholine inhalation. Basal and control conditions did not differ from each other and were the same for both groups. The respiratory responses to both bronchoconstrictors did not differ from each other and were also the same in both groups: VT increased, f and TI remained unchanged. Thus, VT/TI, an index of respiratory drive, also increased. In nonsmokers the increased VT/TI and the associated increase in minute ventilation were both correlated to the decrease in FEV1. These correlations were not found in smokers. Although they have different effects on airway irritant receptors, inhaled histamine and methylcholine induce the same respiratory response in nonsmokers and smokers. Thus, the presumed smoking-related changes in airway mucosa permeability do not seem to influence the direct stimulating effect of histamine on these endings. The absence of correlation between FEV1 and VT/TI changes in smokers suggest that smoking might affect the respiratory drive in acute drug-induced bronchospasm.

Administration, Inhalation↗
PubMed1996

Clomipramine treatment for self-injurious behavior of individuals with mental retardation: a double-blind comparison with placebo.

The efficacy of the serotonin (5-HT) uptake inhibitor clomipramine in the treatment of self-injurious behavior (SIB) was tested in individuals with severe and profound mental retardation. Six of the 8 subjects who completed a double-blind, placebo-controlled crossover trial exhibited a clinically significant improvement (50% or greater reduction from placebo) in the frequency of SIB. Clomipramine treatment was also associated with improvement in SIB intensity, frequency of stereotypy and compulsions, teacher ratings of stereotypy and social withdrawal, and frequency of staff intervention required for problem behaviors. Adverse effects (seizure and tachycardia/agitation) occurred in 2 of the 8 subjects. These results represent the first controlled trial of a 5-HT uptake inhibitor in the treatment of SIB in mental retardation.

Adult↗
PubMed2002

Transcranial magnetic stimulation of the cerebellum in essential tremor: a controlled study.

BACKGROUND: Growing evidence implicates an overactivity of the cerebellum in the pathophysiology of essential tremor. In a small series of patients, we explored the acute effects and therapeutic possibilities of low-frequency repetitive transcranial magnetic stimulation (rTMS) of the cerebellum in patients with essential tremor in a double-blind, crossover, placebo-controlled design. METHODS: Ten patients with essential tremor underwent an active and a sham rTMS session, at a 1-week interval. The rTMS was performed with a focal double 70-mm butterfly coil (maximum peak field of 2.2 T) applied 2 cm below the inion. Each session consisted of 30 trains of 10-second duration separated by 30-second pauses, at 100% of the maximum output intensity and at 1-Hz frequency. Major evaluation outcomes were the score on the Tremor Clinical Rating Scale and accelerometric recordings obtained before (-5 minutes), immediately after (+5 minutes), and 1 hour after (+60 minutes) each rTMS session. Both clinical and accelerometric measurements were obtained by a blinded neurologist. RESULTS: On the +5-minute assessment, active rTMS produced a notable tremor improvement compared with sham rTMS, as evidenced by a significant reduction in scores on the clinical rating scale and accelerometric values. At +60 minutes, no clinical or accelerometric benefit was evidenced. No adverse effects of rTMS were observed. CONCLUSIONS: This exploratory study of the potential therapeutic properties of rTMS on essential tremor showed an acute antitremor effect. Further investigation in search of a more lasting benefit is warranted.

Aged↗
PubMed1980

Recombination of a eukaryotic DNA in bacteria.

Single, 824 bp repeating units of xenopus laevis oocyte-type 5S DNA were inserted into the recombination vectors, lambda rva and lambda rvb. When the inserts had the same orientation with respect to the lambda chromosomes. Spi- imm434 recombinants were recovered by selection on a P2, lambda double lysogenic host. Because of the structure of the vectors, the crossover point in each recombinant must lie completely within the 5S DNA insert. The physical characteristics of these recombinants were determined by examination of restriction enzyme digests. By use of RecA mutant hosts and the Red- vector, lambda rvc, recombination frequencies were measured separately for the bacterial and phage systems. Some of the recombination events resulted in 5S DNA inserts of altered length due to unequal crossovers within repeated sequences in the 5S DNA spacer. The occurrence of just such events in frog 5S DNA had been predicted, based on the structure of 5S DNA and evolutionary considerations.

Animals↗
PubMed2005

A comparison of the plaque removal efficacy of two power toothbrushes: Oral-b Professional Care Series versus Sonicare Elite.

AIM: To compare the safety and plaque removal efficacy of an oscillating/ pulsating toothbrush (Professional Care Series, Oral-B Laboratories; PCS) and a high frequency toothbrush (Sonicare Elite, Philips Oral Healthcare; SE). METHODS: The study had a randomised, examiner-blind, crossover design. Sixty-one subjects aged 19-64 years were enrolled. After 23-25 hours of no oral hygiene, subjects received an oral tissue examination and those with pre-brushing whole mouth mean plaque scores > or = 0.60 measured by the Rustogi modified Navy Plaque Index were randomly assigned to treatment sequence. Subjects brushed with their assigned toothbrush for 2 minutes using a commercially available dentifrice. Oral tissues were then re-examined and post-brushing plaque scores recorded. After a brief washout period, the above procedures were repeated with the alternate toothbrush. One examiner blinded to the treatment sequence performed all clinical measurements. RESULTS: All 61 subjects completed the study. Both toothbrushes significantly reduced plaque levels after a single brushing (t-test, p < 0.0001). However, the PCS was significantly more effective than the SE in whole mouth plaque removal and in reducing plaque from marginal, buccal, lingual and approximal surfaces (ANOVA, p < 0.0001). Whole mouth plaque was reduced by 88% versus 61% and approximal plaque by 97% versus 73% for the PCS and SE toothbrushes, respectively. There was no evidence of hard or soft tissue trauma after a single-use of either toothbrush. CONCLUSION: Based on the findings of this single-use clinical evaluation, the action of the oscillating/ pulsating power toothbrush is more effective at plaque removal than a high frequency power toothbrush.

Adult↗
PubMed1986

Comparison of alternative outcome measures for antiepileptic drug trials.

Studies to determine the efficacy of antiepileptic drugs often use seizure frequency as an outcome measure. Time to kth seizure (k up to 12) was investigated as an alternative endpoint. Monte Carlo simulations, based on seizure behavior in previous clinical trials, were used to evaluate crossover studies with these endpoints. exhibited the highest power. However, tests on time to the 12th seizure, for a sample size of 50, approached the power of tests on seizure frequency with a sample size of 20. Including patients with less severe epilepsy (two vs four seizures per month) did not change the power of tests on time to the kth seizure and lowered it only moderately for tests on seizure frequency. The simulation methodology presented can be adapted to evaluate other design variations.

Anticonvulsants↗