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PubMed1987

Clonidine and Gilles de la Tourette's syndrome: double-blind study using objective rating methods.

Clonidine has been suggested to be effective in Gilles de la Tourette's syndrome (GTS), but no double-blind study has ever evaluated its effects using objective measures. Thirty patients with GTS completed a 6-month placebo-controlled crossover study of the effectiveness of clonidine. Videotapes were obtained at each 3-week visit and were evaluated randomly at the end of the study for distribution, frequency, and severity of motor and vocal tics. Quantifiable psychometric examinations were performed as well. The use of clonidine did not significantly (p less than 0.05) reduce motor tics, vocalizations, or behavior. The effect of a low dose (0.0075 mg/kg/day) was no different from that of a high dose (0.015 mg/kg/day); children's responses were no different from adults'; and those also receiving neuroleptic agents showed the same lack of efficacy as seen in patients on no other medication. Dosing schedule did not affect the objective ratings; scores from clonidine given twice a day were equivalent to those for three times a day.

Adolescent↗
PubMed1993

Genetic mapping of human heart-skeletal muscle adenine nucleotide translocator and its relationship to the facioscapulohumeral muscular dystrophy locus.

The mitochondrial heart-skeletal muscle adenine nucleotide translocator (ANT1) was regionally mapped to 4q35-qter using somatic cell hybrids containing deleted chromosome 4. The regional location was further refined through family studies using ANT1 intron and promoter nucleotide polymorphisms recognized by the restriction endonucleases MboII, NdeI, and HaeIII. Two alleles were found, each at a frequency of 0.5. The ANT1 locus was found to be closely linked to D4S139, D4S171, and the dominant skeletal muscle disease locus facioscapulohumeral muscular dystrophy (FSHD). A crossover that separated D4S171 and ANT1 from D4S139 was found. Since previous studies have established the chromosome 4 map order as centromere-D4S171-D4S139-FSHD, it was concluded that ANT1 is located on the side of D4S139, that is opposite from FSHD. This conclusion was confirmed by sequencing the exons and analyzing the transcripts of ANT1 from several FSHD patients and finding no evidence of aberration.

Alleles↗
PubMed1989

Food-borne disease in hospitals: prevention in a changing food service environment.

The results of an investigation into an outbreak of food-borne disease at a hospital in Los Angeles County are reported. The outbreak occurred at a luncheon buffet for nonpatient visitors attending an event at the hospital, which was catered by the hospital. The food source and etiologic agent(s) responsible for the outbreak were not identified by our investigation. However, several issues relating to the changing character of hospital food provision and their implications for prevention of food-borne disease in hospitals were conspicuous. Two trends apparent in hospital food service are toward increased use of foodstuffs prepared by wholesale food manufacturers and more frequent invitation to community groups to meet within hospital facilities and use hospital catering services. We found that (1) hospital kitchens in Los Angeles County are undersurveyed with respect to frequency of sanitary inspections; (2) hospitals have no mechanism whereby to assess the sanitary inspection record of wholesale food manufacturers from whom they purchase foodstuffs; and (3) crossover of food items prepared for nonpatient hospital visitors, including catered foods, to the inpatient menu occurs. The potential risks for a food-borne disease outbreak among compromised inpatients resulting from these factors are discussed, and measures to reduce such risk are proposed.

Community-Institutional Relations↗
PubMed2004

Transcranial magnetic stimulation for auditory hallucinations in schizophrenia.

It has been suggested that low frequency transcranial magnetic stimulation (TMS) over left temporo-parietal cortex may reduce the frequency and intensity of auditory hallucinations in schizophrenia. Sixteen patients with hallucinations, treatment-resistant for at least 2 months, were randomised into a placebo-controlled crossover study of TMS at 1 Hz and 80% of motor threshold over left temporo-parietal cortex. Treatment periods lasted for 4 days, with daily duration escalating from 4 to 8, 12 and 16 min on subsequent days. Each minute of stimulation was followed by 15 s of rest to check coil position and allow the patient to move, if necessary. Both patients and symptom raters were unaware of the treatment condition. Patients' hallucination scores improved from baseline with both real and sham TMS, and there was no significant difference between real and sham treatments. There was a trend for second treatments, whether sham or real, to be more effective than first treatments. Other psychopathology scales (apart from positive symptoms) and verbal memory were not affected by real or sham TMS. Previous positive studies could not be replicated with these parameters. TMS is safe if applied within the protocol used.

Adolescent↗
PubMed1987

RNA recombination of coronaviruses: localization of neutralizing epitopes and neuropathogenic determinants on the carboxyl terminus of peplomers.

Murine coronaviruses undergo RNA recombination at a very high frequency. We have obtained a series of recombinant viruses using neutralizing monoclonal antibodies in conjunction with temperature-sensitive markers. All of the recombinants obtained have a crossover within gene C, which encodes the peplomer protein of the virus. The genetic structure of these recombinants suggests that the antigenic regions recognized by these neutralizing monoclonal antibodies are localized on the carboxyl-terminal one-third of the peplomer protein. Since the two monoclonal antibodies used are also associated with the critical determinants of virus neuropathogenicity, we conclude that both the neutralizing antibody binding sites and determinants of pathogenicity are localized at the carboxyl-terminal one-third of the peplomer. The variation of crossover sites in different recombinant viruses also allowed precise mapping of additional antigenic sites. RNA recombination thus presents a powerful genetic tool, and the carboxyl-terminal localization of the biological functions of peplomers suggests a distinct conformation of these viral membrane proteins.

Animals↗
PubMed1982

Dominant X-chromosome nondisjunction mutants of Caenorhabditis elegans.

Eight dominant X-chromosome nondisjunction mutants have been identified and characterized. Hermaphrodites (XX) heterozygous for any one of the mutations produce 20-35% male (XO) self-progeny compared with the wild-type frequency of 0.2%. Seven of the eight mutants carry X-autosome translocations. Three of these, represented by mnT2, involve linkage group (LG) II and show severe crossover suppression for X-linked markers. The two half-translocations comprising mnT2 are separable and of very unequal size. The smaller one includes the left tip of X and the right end of LGII and can exist as a free duplication, being present in addition to the normal chromosome complement, in either hermaphrodites or males; it has no effect on X nondisjunction. The reciprocal half-translocation of mnT2 includes the bulk of both LGII and X chromosomes; it disjoins regularly from a normal LGII and confers the property of X-chromosome nondisjunction. A fourth translocation, mnT10(V;X), is also reciprocal and consists of half-translocations that recombine with V and X, respectively. Either half-translocation of mnT10 can exist in heterozygous form in the absence of the other to give heterozygous duplication-deficiency animals; the property of X-chromosome nondisjunction is conferred, in homozygotes as well as heterozygotes, solely by one of the half-translocations, which is deficient for the left tip of the X. The final three translocations have X breakpoints near the right end of X and autosomal breakpoints near the right end of LGIV, the left end of LGV and the right end of LGI, respectively. All three are homozygous inviable. Males hemizygous for the X portion of any of the seven translocations are viable and fertile. The final mutant, mn164, maps as a point at or near the left tip of the X and causes X-chromosome nondisjunction in both heterozygotes and homozygotes. In heterozygotes, mn164 promotes equational nondisjunction of itself but not its wild-type allele. The mutants are discussed in light of the holocentric nature of the C. elegans chromosomes. It is proposed that the left end of the X chromosome plays a critical structural role in the segregation of X chromosomes during meiosis in XX animals.

Animals↗
PubMed1990

DNA recombination during PCR.

PCR co-amplification of two distinct HIV1 tat gene sequences lead to the formation of recombinant DNA molecules. The frequency of such recombinants, up to 5.4% of all amplified molecules, could be decreased 2.7 fold by a 6 fold increase in Taq DNA polymerase elongation time. Crossover sites mapped essentially to three discrete regions suggesting specific Taq DNA polymerase pause or termination sites. PCR mediated recombination may be a problem when studying heterogeneous genetic material such as RNA viruses, multigene families, or repetitive sequences. This phenomenon can be exploited to create chimeric molecules from related sequences.

Amino Acid Sequence↗
PubMed1979

Chronic recurrent angina.

The natural history of variant angina is described in a patient with multiple exacerbations and remissions over a period of several years. Constant in-hospital electrocardiographic monitoring for 26 days documented 569 episodes of ST elevation, 89% of which were asymptomatic. Episodes ranged in duration from 15 seconds to 11 1/2 minutes, with 4% of episodes associated with premature ventricular contractions. Over the course of hospitalization, the episodes of ST elevation decreased in frequency and length, as did episodes of pain. During this period, a number of therapeutic agents, including propranolol, indomethacin, and chlorpheniramine were evaluated using double-blind crossover trials. No agent had a significant beneficial effect on the course of the disease, and there was an increase in the length of episodes with high doses of propranolol. Because of the great variability in the course of this disease, only double-blind crossover trials should be allowed to dictate the efficacy of therapeutic agents.

Angina Pectoris↗
PubMed2001

Collective pinning of a frozen vortex liquid in ultrathin superconducting YBa2Cu3O7 films.

The linear dynamic response of the two-dimensional (2D) vortex medium in ultrathin YBa2Cu3O7 films was studied by measuring their ac sheet impedance Z over a broad range of frequencies omega. With decreasing temperature the dissipative component of Z exhibits, at a temperature T*(omega) well above the melting temperature of a 2D vortex crystal, a crossover from a thermally activated regime involving single vortices to a regime where the response has features consistent with a description in terms of a collectively pinned vortex manifold. This suggests the idea of a vortex liquid which, below T*(omega), appears to be frozen at the time scales 1/omega of the experiments.

Journal Article↗
PubMed1988

Double-blind study of an alpha 2 agonist in the treatment of irritable bowel syndrome.

A double-blind crossover trial of the alpha 2 agonist lidamidine hydrochloride in 72 patients with irritable bowel syndrome is reported. Lidamidine was found to have no significant effect on frequency and severity of abdominal pain or abdominal bloating. It did cause a statistically significant reduction in frequency of defaecation (P = 0.005), but this was of a degree unlikely to be of clinical importance. Although alpha 2 agonists inhibit gastrointestinal motility in animals this study suggests that lidamidine hydrochloride does not have a useful therapeutic role in irritable bowel syndrome.

Adolescent↗
PubMed1975

Controlled trial of sodium valproate in severe epilepsy.

In a double-blind crossover trial sodium valproate or placebo was added to the existing anticonvulsant treatment of 20 patients with chronic uncontrolled epilepsy. Sodium valproate 1200 mg/day significantly reduced the frequency of both tonic-clonic and minor seizures in these patients. Only mild and transient side effects occurred (drowsiness, ataxia, and nausea), and these may have been due to the effect of adding sodium valproate to existing phenobarbitone or phenytoin treatment. Further controlled trials are needed to assess more fully the efficacy of this drug in various types of epilepsy.

Adult↗
PubMed1996

Double blind placebo controlled trial of short term transdermal scopolamine on heart rate variability in patients with chronic heart failure.

OBJECTIVE: To test the hypothesis that short term application of transdermal scopolamine increases heart rate variability (HRV) and restores sympathovagal balance in patients with stable congestive heart failure (CHF). DESIGN: A double blind placebo controlled crossover study. SETTING: Tertiary referral centre. PATIENTS: Twelve patients (mean age 66 (10)) with New York Heart Association class II-IV CHF. All patients had coronary artery disease (mean left ventricular ejection fraction 26.7 (8.9) %). INTERVENTION: Patients were randomly assigned to receive either a placebo skin patch or a transdermal scopolamine patch (Transderm, 0.05 mg/h). Patches remained in place for 48 hours with a 24 hour washout period before crossover. OUTCOME MEASURES: HRV was derived from (a) 24 hour time domain indices (mean RR interval, standard deviation of interbeat interval, and the baseline width of the frequency distribution of RR intervals) and (b) short data set (2.2 mm) power spectral measurements using autoregressive modelling. Autospectral measures were performed in both resting supine and standing (orthostatic) states. The 24 hour Holter record was obtained during the second day of patch application. RESULTS: There was a small but significant (P < 0.05) increase in all time domain HRV variables with scopolamine. There was a paradoxical fall in low frequency (LF) spectral power induced by orthostasis during baseline (-30%) and placebo (-34%) states. Conversely, scopolamine was associated with a 14% increase in LF power during orthostatic stress. Scopolamine thus significantly reduced the orthostatic fall in LF (P < 0.01) compared with either baseline or placebo values. No difference in circadian rhythm was seen between the scopolamine and placebo treatment periods. However, the abrupt fall in the high frequency (vagal) power during the early morning sleep-wake hours was reduced by scopolamine. Scopolamine was also associated with a significant rightward shift in the resting LF central frequency consistent with a vagomimetic effect. CONCLUSION: Patients with chronic stable CHF showed a paradoxical fall in the low frequency (sympathetic) power during orthostatic stress. Transdermal scopolamine applied over a 48 hour period partially restored the balance between sympathetic tone and vagal activity in CHF patients and maintained this balance during orthostatic stress.

Administration, Cutaneous↗
PubMed2003

Lipid lowering by pravastatin increases parasympathetic modulation of heart rate: Galpha(i2), a possible molecular marker for parasympathetic responsiveness.

BACKGROUND: We have previously demonstrated in an in vitro model for lipid lowering that lipoprotein depletion resulted in a marked increase in the negative chronotropic response to the acetylcholine analogue carbamylcholine. In this study we used heart rate variability analysis to determine the effect of lipid lowering by statins on the response of the heart to parasympathetic stimulation. In parallel, we examined whether changes in parasympathetic responsiveness correlated with changes in the expression of Galpha(i2), a molecular component of the parasympathetic signaling pathway in the heart. METHODS AND RESULTS: Patients were randomized in a crossover study of pravastatin and simvastatin. R-R interval analysis of Holter monitor studies demonstrated that in patients treated initially with pravastatin, the peak high-frequency power fraction during sleep, which reflects parasympathetic modulation of heart rate, increased by 24.0+/-5.02% (SEM, n=13, P<0.001) compared with the untreated control value. Simvastatin had no significant effect. Western blot analysis of lymphocytes from patients treated with pravastatin demonstrated a 90.1+/-27.3% (n=10, P=0.009) increase in Galpha(i2) expression, whereas simvastatin had no effect. Relative changes in Galpha(i2) correlated significantly with the changes in the fraction of high-frequency power (rho=0.574, P=0.016). CONCLUSIONS: Taken together with our in vitro data, these data are the first to suggest that cholesterol lowering by pravastatin might increase the response of the heart to parasympathetic stimulation and that changes in Galpha(i2) expression might serve as a molecular marker for this effect.

Adult↗
PubMed1985

[Objectivation of the effect of antitussive agents using tussometry in patients with chronic cough].

The antitussive effect of several antitussive agents has been objectively evaluated in patients with chronic stable cough due to bronchial carcinoma, pulmonary tuberculosis or chronic obstructive lung disease. The patients received the active antitussive drugs or placebo in a double-blind, randomized crossover design. The preparations were administered at 10 p.m. and 2 a.m. on 7 consecutive nights and no antitussive was given for the following 20 hours. Cough frequency and intensity were recorded from 10 p.m. until 6 a.m. The active medications were noscapine (30 mg), dextromethorphan (20 mg), dihydrocodeine (30 mg) and codeine (20, 30 and 60 mg) at 10 p.m. and 2 a.m. Cough frequency and intensity were objectively assessed with a pressure transducer placed over the trachea and recorded on a chartrecorder. Statistical analysis was performed with analysis of variance and multiple range testing. Noscapine, dextromethorphan, dihydrocodeine and codeine (60 mg) significantly (p less than 0.001) reduced the cough frequency compared to placebo. They also produced a greater reduction of cough intensity than placebo, codeine (20 mg) and codeine (30 mg) (p less than 0.001). The duration of action of low-dose codeine (6 hours) was unsatisfactory. Subjective preference for dextromethorphan indicates a psychotropic central nervous action of this drug not assessed by the measuring device. Noscapine was equally well tolerated but more neutral psychologically.

Adult↗
PubMedDate not supplied

The vestibulo-ocular reflex (VOR) under the influence of cinnarizine.

In a double-blind, placebo controlled, crossover study, we evaluated the effects of cinnarizine on the VOR of 55 healthy young subjects. VOR was evaluated by the Sinusoidal Harmonic Acceleration (SHA) test at frequencies of 0.01, 0.02, 0.04, 0.08 and 0.16 Hz. There was a reduction in VOR gain in 16 of the 20 SHA trials performed under the influence of cinnarizine alone (25 mg and 50 mg) and cinnarizine 25 mg in combination with 10 mg domperidone or 1 transdermal scopolamine patch. This decrease in VOR gain was significant in only a few SHA trials. Phase lead was not consistently affected by cinnarizine. No notable side effects were found for any of the drug groups. Our findings are in accord with the contention that increased resistance to seasickness produced either by drugs, or by the natural process of habituation to sea conditions, may be reflected by a decrease in VOR gain.

Adult↗
PubMed1995

Cin-mediated recombination at secondary crossover sites on the Escherichia coli chromosome.

The Cin recombinase is known to mediate DNA inversion between two wild-type cix sites flanking genetic determinants for the host range of bacteriophage P1. Cin can also act with low frequency at secondary (or quasi) sites (designated cixQ) that have lower homology to either wild-type site. An inversion tester sequence able to reveal novel operon fusions was integrated into the Escherichia coli chromosome, and the Cin recombinase was provided in trans. Among a total of 13 Cin-mediated inversions studied, three different cixQ sites had been used. In two rearranged chromosomes, the breakpoints of the inversions were mapped to cixQ sites in supB and ompA, representing inversions of 109 and 210 kb, respectively. In the third case, a 2.1-kb inversion was identified at a cixQ site within the integrated sequences. This derivative itself was a substrate for a second inversion of 1.5 kb between the remaining wild-type cix and still another cixQ site, thus resembling a reversion. In analogy to that which is known from DNA inversion on plasmids, homology of secondary cix sites to wild-type recombination sites is not a strict requirement for inversion to occur on the chromosome. The chromosomal rearrangements which resulted from these Cin-mediated inversions were quite stable and suffered no growth disadvantage compared with the noninverted parental strain. The mechanistic implications and evolutionary relevance of these findings are discussed.

Bacterial Outer Membrane Proteins↗
PubMed2006

Rescue high frequency jet ventilation versus conventional ventilation for severe pulmonary dysfunction in preterm infants.

BACKGROUND: Chronic pulmonary disease is a major cause of mortality and morbidity in very low birth weight infants despite increased use of antenatal steroids and surfactant therapy. Ventilator injury and oxygen toxicity are thought to be important factors in the pathogenesis of chronic pulmonary disease. There is evidence in animal studies and adult human studies that high frequency jet ventilation may reduce the severity of lung injury associated with mechanical ventilation. OBJECTIVES: In preterm infants with severe pulmonary dysfunction, does the use of high frequency jet ventilation (HFJV) compared to conventional ventilation (CV) reduce mortality and morbidity without an increase in adverse effects? SEARCH STRATEGY: We searched MEDLINE (1966 - August 2005), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2005), and EMBASE (1988 - August 2005). Information was also obtained from experts in the field and cross references were checked. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials of rescue high frequency jet ventilation versus conventional ventilation in preterm infants born at less than 35 weeks of gestation or with a birth weight less than 2000 grams with respiratory distress were included in the systematic review. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Neonatal Review Group were used, including independent trial assessment and data extraction. Data were analysed using relative risk (RR) and risk difference (RD). MAIN RESULTS: Two randomized trials were identified. One trial (Engle 1997) was excluded as the study was restricted to term and near-term infants. The included trial (Keszler 1991) randomized 166 preterm infants and reported data on 144 infants. Cross-over to the alternate treatment was permitted if the initial treatment failed. There was no statistically significant difference in the overall mortality (including survival after cross-over) between the two groups [RR 1.07, (95% CI 0.67, 1.72)]. The survival by original assignment was identical. In a secondary analysis, the study demonstrated rescue treatment with HFJV, up until the time of cross-over, was associated with lower mortality, [RR 0.66 (95% CI 0.45,0.97)]. No significant differences were found in the incidence of CLD in survivors at 28 days of age, IVH, new air leaks, airway obstruction and necrotizing tracheobronchitis. AUTHORS' CONCLUSIONS: There was no significant difference in the overall mortality between rescue high frequency jet ventilation and conventional groups. In a secondary analysis, rescue treatment with HFJV, up until the time of cross-over, was associated with lower mortality. There was no significant increase in adverse effects like intraventricular hemorrhage, new air leaks, airway obstruction and necrotizing tracheobronchitis with rescue high frequency jet ventilation. The included study was done before the introduction of surfactant and widespread use of antenatal steroids. The number of infants included was small and there were high numbers of post randomization exclusions. Due to the crossover design and small numbers of infants in the included study, there is insufficient information to assess the effectiveness of rescue HFJV in preterm infants. Studies that target the most at-risk population and have appropriate power to assess some of the important outcomes are needed. These trials would also need to incorporate long term pulmonary and neurodevelopmental outcomes.

High-Frequency Jet Ventilation↗
PubMed2006

Functional electrical stimulation changes dynamic resources in children with spastic cerebral palsy.

BACKGROUND AND PURPOSE: Children with cerebral palsy (CP) often are faced with difficulty in walking. The purpose of this experiment was to determine the effects of functional electrical stimulation (FES) applied to the gastrocnemius-soleus muscle complex on the ability to produce appropriately timed force and reduce stiffness (elastic property of the body) and on stride length and stride frequency during walking. SUBJECTS AND METHODS: Thirteen children with spastic CP (including 4 children who were dropped from the study due to their inability to cooperate) and 6 children who were developing typically participated in the study. A crossover study design was implemented. The children with spastic CP were randomly assigned to either a group that received FES for 15 trials followed by no FES for 15 trials or a group that received no FES for 15 trials followed by FES for 15 trials. The children who were having typical development walked without FES. Kinematic data were collected for the children with CP in each walking condition and for the children who were developing typically. Impulse (force-producing ability) and stiffness were estimated from an escapement-driven pendulum and spring system model of human walking. Stride length and stride frequency also were measured. To compare between walking conditions and between the children with CP and the children who were developing typically, dimensional analysis and speed normalization procedures were used. RESULTS: Nonparametric statistics showed that there was no significant difference between the children with CP in the no-FES condition and the children who were developing typically on speed-normalized dimensionless impulse. In contrast, the children with CP in the FES condition had a significantly higher median value than the children who were developing typically. The FES significantly increased speed-normalized dimensionless impulse from 10.02 to 16.32 when comparing walking conditions for the children with CP. No significant differences were found between walking conditions for stiffness, stride length, and stride frequency. DISCUSSION AND CONCLUSION: The results suggest that FES is effective in increasing impulse during walking but not in decreasing stiffness. The effect on increasing impulse does not result in more typical spatiotemporal gait parameters.

Cerebral Palsy↗