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PubMed1987

Intracellular calcium recordings from isolated cells of the mammalian central nervous system.

Measurements made with two different techniques of intracellular calcium levels from small isolated cells of the mammalian central nervous system are described and compared. Recordings in cultured mouse embryo spinal cord and dorsal root ganglion neurons, made with double-barrelled borosilicate Ca2+-selective microelectrodes yielded a mean Ca2+ level of 2.3 (SE +/- 0.54) microM for the lowest values recorded in 24 out of 46 cells. Intracellular Ca2+ dependence on membrane potential was apparent with levels of calcium greater than or equal to 4 microM (r = 0.371, n = 29). Both cyclic fluctuations induced by tetraethylammonium and an apparent increase in Ca2+ evoked by the depolarizing excitatory amino acid, L-aspartate, were observed. In contrast, estimates of intracellular Ca2+ obtained by spectrofluorimetry of suspensions of mouse embryo brain cells, loaded with the intracellular Ca-binding fluorescent probe, quin2 provided a approximately equal to 10-fold lower value, 152 (SE +/- 7) nM. This more closely resembles levels reported for large neurons where large-tip microelectrodes with greater sensitivity were used, and in spite of the heterogeneity of the cells this value is presumed to be a more accurate estimate of intraneuronal Ca2+ concentration. In these fluorescence studies KCl readily evoked increases in intracellular Ca2+ which could be blocked by verapamil and Cd2+ and were not induced in the absence of Ca2+. Increases were also produced by N-methyl-D-aspartate, but not by the kainate-like Lathyrus neurotoxin, L-3-oxalylamino-2-aminopropionic acid. These results provide preliminary evidence for both voltage-sensitive and receptor-activated Ca channels in embryonic brain cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Stripe patterns in the magnetic reorientation of a glass-forming nematic liquid crystal.

We study spontaneous pattern formation in a glass-forming nematic liquid crystal during the magnetically induced dynamic Fréedericksz transition. Pattern growth rates and wavelengths as functions of the magnetic field are extracted from optical transmission textures of thin planar cells. The characteristics of the observed stripe pattern can be related to viscoelastic parameters of the nematic by means of a linear stability analysis of director fluctuation modes. The viscous properties of the material allow to vary the time scales of the experiment with temperature by orders of magnitude, leaving the spatial structure of the pattern essentially unchanged. We find that the ratios of shear and rotational viscosity coefficients relevant for the pattern wavelength selection remain constant in the temperature range investigated, whereas their absolute values change by almost two orders.

Journal Article↗
PubMed1975

Population biology of Camallanus oxycephalus Ward and Magath, 1916 (Nematoda: Camallanidae) in white bass in western Lake Erie.

The distribution and abundance of the nematode Camallanus oxycephalus infecting white bass, Morone chrysops, in western Lake Erie was studied for over 2 years. Infection was generally more frequent and of higher intensity in large fish. The frequency distributions of nematode abundance in all segments of the fish population followed the negative binomial distribution. The data show seasonal cycles in population structure, site selection, intensity of infection, maturation, and reproduction. Infection occurs during July and August with a resulting peak in population density; during late summer and autumn, mortality, probably density-dependent, reduces the population by 30 to 60%; surviving worms are eliminated at 1 year of age. Growth and development of female worms is arrested from November to April, then proceeds at a rapid rate until the worms release their larvae and die. This growth pattern is probably related to temperature but may also involve host hormone cycles. The dispersal period of the nematode coincides with the annual maximum density of the intermediate host, a cyclopoid copepod,and is interpreted as an adaptation which increases the probability of successful transmission. Because the number of larvae produced by each female worm is a function of body volume, natural selection has favored rapid spring growth and attainment of large body size relative to the male worm. Both seasonal timing in the life cycle and the number of larvae produced are important factors in determining the abundance of this and perhaps other parasites. Evidence is presented suggesting that fluctuations of environmental parameters may disrupt the timing of transmission and alter the distribution and abundance of the parasite. It is hypothesized that the magnitude of such changes in parasite abundance may be related to the complexity of the host-parasite system.

Animals↗
PubMedDate not supplied

Understanding Parkinson's disease: detection and early disease management.

Parkinson's disease (PD) is a common, debilitating, neurodegenerative disorder characterized by neuronal loss within the basal ganglia and insufficient levels of the neurotransmitter dopamine. Symptoms include resting tremor, rigidity, bradykinesia (slowness of voluntary movement), and postural disturbances. Exact cause is unknown, but theories surrounding environmental or endogenous toxicities have been suggested. Differential diagnoses include genetic and other neurologic disorders that may share symptoms similar to those seen in PD. Clinical progression has been categorized into three phases of the disease: early, nonfluctuating, and fluctuating. Medications generally offer good symptom relief during the early and nonfluctuating phases of the disease. Classifications of anti-PD medications include anticholinergics, dopamine agonists, amantadine, MAO-B inhibitors, levodopa-carbidopa, and Catechol-o-methyl transferase inhibitors. Surgical intervention may be an option for select patients whose conditions are not well controlled though medical management strategies. Primary care providers often can manage patients in the early stage of PD, but later stages require expert neurologic management. Patient/family education and anticipatory guidance is imperative.

Antiparkinson Agents↗
PubMed1986

Erythrocyte rigidity in healthy patients and patients with cardiovascular disease risk factors.

The normal values for erythrocyte rigidity as measured by the "Selective Erythrocyte Rigidometer" were derived from a group of 275 apparently healthy subjects without risk factors. These individuals were randomly selected from an address book. The normal values ranged from 0.83-1.19 (median: 1.01). Quality control was conducted throughout the study and the analytical reliability was verified (day-to-day coefficient of variation VCd was 7.5%; coefficient of variation in series VCs was 3.1%). Inter- and intraindividual fluctuations in erythrocyte rigidity in the 8.3% and 6.1% ranges respectively were found in 20 apparently healthy subjects in the course of a 6-month study. No relationship was found between either age or sex and erythrocyte rigidity. Significantly higher erythrocyte rigidity values were found in patients with risk factors however; this applies to hypertensive patients, patients with diabetes mellitus, but also to apparently healthy subjects who were either overweight or smokers. Patients with disordered lipometabolisms on the other hand did not show any change in erythrocyte deformability when compared with healthy subjects.

Adult↗
PubMed1985

Handedness, language dominance and aphasia: a genetic model.

A simple two-allele Mendelian model of the genetics of handedness is described and fitted to data in the literature. The model proposes that there are two alleles, D (dextral) and C (chance), the homozygous DD genotype producing only right-handers (directional asymmetry), the homozygous CC genotype producing a racemic mixture of 50% right-handers and 50% left-handers (fluctuating asymmetry), and the heterozygote, DC, being intermediate between the homozygotes and producing 25% left-handers, and 75% right-handers. It is also suggested that the true population incidence of left-handedness is 7.75%, deviations from this figure being due to either criterion shifts or selection biases. The same model is then fitted, by means of a number of minor conceptual extensions, to data from the literature on the relationship of handedness to language dominance, acute and permanent aphasia, and visual processing dominance.

Aphasia↗
PubMed1983

[Multiple sclerosis. Current status of research. I].

Multiple sclerosis (MS) affects nearly 40 000 patients in France. Many factors are mixed up in the development of MS. Epidemiologic studies demonstrate the importance of environmental factors and some possible epidemics of MS in Faroe Islands and Iceland. Recent investigations in Orkney Islands present the hypothesis of two periods of peculiar vulnerability. In Caucasians, genetic investigations show the overpresentation of antigens HLA A3, B7, DR2-DW2. It is possible that remittent MS is related to B7, DW2, DR2 and progressive MS to DR3, B8 DR3, A1 B8 DR3. This distinctions could be also applied to response to immunosuppressive treatment. However, studies of familial MS suggest that only one gene is not able to induce susceptibility to MS. Interpretation of virologic studies is difficult; recent advances in virologic research (isolation, hybridization) will perhaps demonstrate the importance of viral components in MS. Interpretation of presence of myelin basic protein, antimyelin antibodies, anti-oligodendrocytes antibodies, antigangliosides antibodies, antibrain antibodies is also difficult because identification methods are in constant progress and it is not possible to know whether these antibodies are cause or only consequence of pathologic process. Lymphocytic populations studies demonstrate that immunoregulation is probably defective in MS and that T lymphocytes subpopulations fluctuate, according to the state of the illness. Variations of NK activity are discussed. MS lymphocyte production of interferon is probably decreased. Recent advances in neuropathologic studies, central nervous system tissue cultures and in experimental demyelination are summarized. Cultures of precursors of oligodendrocytes and their maturation in vitro, selection and culture of mature oligodendrocytes, their applications to MS oligodendrocytes are emphasized. The recent models of chronic experimental allergic encephalomyelitis (EAE), the prevention of EAE by interferon, basic protein, copolymer I have already place and implication in the comprehension and treatment of MS. Virologic models are also in important progress. Interests of evoked potentials, C.T. Scan and of nuclear magnetic resonance are discussed. Main therapeutic trends are emphasized. The underlying ethic problem of the choice of a therapy is discussed.

Antibodies, Viral↗
PubMed1981

The noncycle nose.

Approximately 600 resistance values were obtained for 50 subjects. Of the 50 subjects, 14 did not have evidence of a normal nasal cycle. These 14 subjects were selected for the study of the noncycle nose. The other 36 subjects with normal nasal cycles served as controls. By use of a mask flowmeter technique of rhinomanometry, three separate categories of noncyclicity were determined. Type 1 noncycle nose had no evidence of a nasal cycle and no fluctuation of either the right or the left side. Type 2 noncycle nose had no fluctuation of nasal resistance on one side and moderate fluctuation of nasal resistance on the opposite side. Type 3 noncycle nose had fluctuation of nasal resistance on both sides but the dominance did not reverse or change from one side to the other. This is the first study to characterize the noncycle nose and to subdivide it into three separate types using rhinomanometry.

Adolescent↗
PubMed2000

Fixation probabilities when the population size undergoes cyclic fluctuations.

Let us assume that there is a monoecious random mating population that changes cyclically in size. Then, the probability that a nonrecessive favorable mutant is ultimately fixed, if it is originally present in a single heterozygote, is approximately proportional to the harmonic mean of the effective population sizes in the cycle and inversely proportional to the population size when the mutant appears. This approximation works well if the selective advantage s of the mutant is small and the length k of a cycle is small in comparison with the population sizes in a cycle. If k is large the harmonic mean is, in general, replaced by a weighted harmonic mean that puts the largest weights on reciprocals of effective population sizes in the first few generations after the mutant appears.

Alleles↗
PubMed2006

Centre of mass movement and mechanical energy fluctuation during gallop locomotion in the Thoroughbred racehorse.

During locomotion cyclical interchange between different forms of mechanical energy enhances economy; however, 100% efficiency cannot be achieved and ultimately some mechanical work must be performed de novo. There is a metabolic cost associated with fluctuations in mechanical energy, even in the most efficient animals. In this study we investigate the exchanges between different forms of mechanical energy involved in high-speed gallop locomotion in Thoroughbred race horses during over-ground locomotion using innovative, mobile data collection techniques. We use hoof-mounted accelerometers to capture foot contact times, a GPS data logger to monitor speed and an inertial sensor mounted over the dorsal spinous processes of the fourth to sixth thoracic vertebrae (the withers) of the horse to capture trunk movement with six degrees of freedom. Trunk movement data were used to estimate the movement of the centre of mass (CoM). Linear (craniocaudal, mediolateral and dorsoventral) and rotational (roll, pitch and heading) kinematic parameters (displacement, velocity and acceleration) were calculated for seven horses at gallop speeds ranging from 7 to 17 m s(-1) during their regular training sessions. These were used to estimate external mechanical energy (potential energy and linear kinetic energy of the CoM) as well as selected components of internal energy (angular kinetic energy). Elastic energy storage in the limbs was estimated from duty factor, sine wave assumptions and published leg stiffness values. External mechanical energy changes were dominated by changes in craniocaudal velocity. Potential energy change, which was in phase with craniocaudal energy during the front limb stances, was small. Elastic energy storage in the limbs was small compared to the overall amplitude of fluctuation of external mechanical energy. Galloping at high speeds does not therefore fit classical spring mass mechanics.

Acceleration↗
PubMed2000

Subthalamic stimulation in Parkinson disease: a multidisciplinary approach.

BACKGROUND: High-frequency stimulation of the subthalamic nucleus constitutes a therapeutic advance for severely disabled patients with Parkinson disease. OBJECTIVE: To evaluate the efficacy and safety of continuous bilateral high-frequency stimulation of the subthalamic nucleus in patients with Parkinson disease. DESIGN: A prospective study of patients with Parkinson disease treated at a university hospital. PATIENTS AND METHODS: Electrodes were implanted bilaterally in the subthalamic nucleus of 23 consecutive patients with Parkinson disease who responded well to levodopa but had severe motor complications. There were 16 men and 7 women (mean +/- SEM age, 53 +/- 2 years) who had a mean +/- SEM disease duration of 14.7 +/- 1.0 years. Targets were determined by 3-dimensional magnetic resonance imaging, combined with intraoperative electrophysiologic recordings and stimulation. RESULTS: Six months after surgery, motor disability, levodopa-induced motor fluctuations, dyskinesias, and the daily dose of levodopa equivalent decreased significantly by 67%, 78%, 77%, and 61%, respectively, compared with the preoperative state. No significant morbidity was observed, except transient depression in 4 patients. CONCLUSIONS: The beneficial effects of subthalamic stimulation depend on (1) the criteria used for patient selection, (2) the precision with which the subthalamic nucleus is targeted (dependent on the 3-dimensional magnetic resonance imaging and the intraoperative electrophysiologic and clinical assessments), and (3) the long-term postoperative adjustment of stimulation variables.

Activities of Daily Living↗
PubMed1990

The Zürich amygdalo-hippocampectomy series: a short up-date.

Selective amygdalohippocampectomy was developed as a surgical treatment for temporal lobe epilesy with a well-defined unilateral mesiobasal limbic seizure onset. Since 1975, 236 patients have been operated on in Zürich. We briefly summarize recent studies on the seizure outcome with analysis of the postoperative long-term fluctuations in relation to postoperative anticonvulsant drug treatment, on the underlying neuropathology, and on the relationships between magnetic resonance scanning estimates of total volume of the removed tissue and the resection scores of amygdala, hippocampus and parahippocampus gyrus.

Adult↗
PubMed2003

Heart rate turbulence.

Survivors of acute myocardial infarction are at increased risk of sudden cardiac death. Recent trials have demonstrated that in selected high risk post-myocardial infarction patients mortality can be significantly reduced by implantation of an autonomic cardioverter defibrillator. Therefore, risk stratification strategies have gained increasing importance. Recently, a new method for risk stratification, coined heart rate turbulence, has been published. The method quantifies the physiological short term fluctuation of sinus rhythm cycle lengths following singular ventricular premature complexes. Heart rate turbulence is a consistent phenomenon in low risk patients with ischemic heart disease. The absence of this phenomenon indicates a significantly increased risk of subsequent mortality. The measures for quantifying heart rate turbulence, turbulence onset, and turbulence slope are strong risk predictors, even when adjusted for other established mortality predictors, such as left ventricular ejection fraction, arrhythmia count, heart rate variability, mean heart rate and history of previous myocardial infarction. Heart rate turbulence may be useful not only for risk prediction in post-myocardial infarction patients but also for risk prediction in other patients such as in patients with dilated cardiomyopathy and Chagas disease.

Arrhythmias, Cardiac↗
PubMedDate not supplied

Is there a relationship between clozapine and obsessive-compulsive disorder?: a retrospective chart review.

The emergence of obsessive-compulsive symptoms during clozapine treatment has been reported in recent case studies, yet the incidence and significance of this finding is still unclear pending reliable data from a larger sample of patients. Hospital records of 142 randomly selected inpatients started on clozapine treatment at McLean Hospital before July 1, 1992, were reviewed retrospectively. Based on a limited retrospective chart review, there were no definitive cases of patients who developed obsessive-compulsive disorder (OCD) or whose OCD worsened as a result of clozapine treatment. Although some fluctuation of OCD symptoms may have occurred in two cases, it is unclear whether those symptoms were related to treatment with clozapine (or other psychotropic drugs) or to undulations in the natural history of OCD. No definitive relationship between OCD symptoms and clozapine treatment could be established in this limited study. Further clarification of this matter awaits outcome research using prospective methodologies.

Adult↗
PubMed2002

Aged garlic extract enhances production of nitric oxide.

Nitric oxide (NO) controls several physiological functions of the cardiovascular system. Three kinds of NO synthases (NOSs), neuronal constitutive NOS (ncNOS), inducible NOS (iNOS) and endothelial constitutive NOS (ecNOS), were responsible for NO biosynthesis. This study investigated the effect of aged garlic extract (AGE) on NO production by measuring the NO metabolites nitrite and nitrate in the plasma of mice. AGE (2.86 g/kg, p.o.) temporarily increased NO production by 30-40% from 15 to 60 min after administration. The time course of the fluctuation in NO levels in the AGE-treated group was clearly different to that in a group of mice treated with lipopolysaccharides, a typical iNOS inducer. Arginine (63 mg/kg, p.o.) at the equivalent dose of AGE did not increase NO production. However diphenyleneiodonium chloride (1 mg/kg, i.p.), a selective cNOS inhibitor, administered prior to AGE, overcame the effect of AGE. These results indicate that AGE increased NO production by activating cNOS, but not iNOS. The arginine contained in AGE was not responsible for the effect. AGE may be a useful tool for the prevention of cardiovascular disease.

Animals↗
PubMed2006

Tunable instability mechanisms of polymer thin films by molecular self-assembly.

Incorporation of a block copolymer into a thin polymer film is observed to alter both the rate and mechanism by which the film dewets from an immiscible polymer substrate. Films with little or no copolymer dewet by classical nucleation and growth of circular holes, and the dewetting rate decreases with increasing copolymer concentration. Increasing the copolymer content at constant film thickness generates copolymer micelles that adsorb/aggregate along the polymer/polymer interface and promote nonclassical dewetting fluctuations similar in appearance to spinodal dewetting. At higher copolymer concentrations, dewetting proceeds after a lengthy induction period by the nucleation and growth of flower-shaped holes suggestive of film pinning or viscous fingering. Atomic force microscopy of the polymer/polymer interface after removal of the top film by selective dissolution reveals substantial structural development due to copolymer self-assembly.

Microscopy, Atomic Force↗
PubMedDate not supplied

Comparison of therapeutic gain with therapeutic ratio for the assessment of selective 5HT(1B/1D) agonist efficacy in migraine.

OBJECTIVE: Comparison of use of therapeutic gain (TG) and therapeutic ratio (TR) for relative assessments of selective 5HT(1B/1D) agonist efficacy in the acute treatment of migraine. BACKGROUND: Comparison of selective 5HT(1B/1D) agonist efficacy in the acute treatment of migraine is complicated by the impracticality of conducting high-quality head-to-head active comparator trials for all permutations of drug, dose, and route of administration; the clinical trials that are available are usually noncontemporaneous, and have fluctuating active and placebo response rates (ARR and PRR, respectively) for the necessarily subjective endpoints. The standard primary endpoint is conversion of headache score 2 (moderate pain) or score 3 (severe pain) into score 0 (no pain) or score 1 (mild pain) at a single timepoint (usually 2 or 4 hours postdose). Two principal methods have been used for comparison of ARR between studies: TG = ARR - PRR and TR = ARR/PRR. Secondary endpoints can be treated in the same way, although the 24-hour remedication rate is the only secondary endpoint that is subject to regulatory authority standardization. Does either TG or TR have an advantage over the other? METHODS: Efficacy data were collected from published sources and included pain score conversion at 2- and 4-hour, as well as 24-hour remedication rates. TG and TR were calculated for each endpoint, as shown above. The ranges of these variables were found from all observed measures. Correlations between TG and TR were found using least squares methods. The 95% confidence intervals (CI) for TG and TR were then found for all clinical trials, and for the whole range of observed PRR. RESULTS: Values for TR and TG generally were well correlated for pain score conversion at 2 hours postdose (n = 51 clinical trials). Deviations from this correlation were greatest for drugs that were evidently very efficacious. When standardized for the observed ranges of PRR and ARR, the 95% CI for TR were narrower than for TG. A subset of these studies also reported 4-hour data (n = 23 clinical trials), but the correlation between TR and TG was again good, with narrower 95% CI for TR than TG. For the 24-hour remedication data (n = 18 trials), PRR was less variable; TR and TG again correlated well, but there was little difference in their relative 95% CI. CONCLUSIONS: For comparison of drugs in noncontemporaneous studies, when PRR fluctuates, relative ranges for TR are narrower than for TG. For assessing single clinical trial results (ie, point estimates of efficacy) TR will generally be relatively nearer to its mean than TG. For both these reasons, TR is a more robust statistic than TG.

Acute Disease↗
PubMed2004

Dynamics and the breaking of a driven cage: I2 in solid Ar.

Pump-probe measurements of I2 in solid Ar are reported and analyzed to extract a description of cage response to impulsive excitation, from the gentle kick, up to the breaking point. The most informative data are obtained through wavepacket motion on cage-bound, but otherwise dissociative, potentials where the chromophore acts as a transducer to drive the cage and to report on the local dynamics. This general class of dynamics is identified and analyzed as a function of energy in Ar, Kr, and Xe. The overdriven cage rebounds with a characteristic period of 1.2 ps that shows little dependence on excitation amplitude in all hosts. After rebound, the cage rings as a local resonant mode in Ar, with a period of 1 ps and dephasing time of 3 ps. This mode remains at the Debye edge in Kr and Xe, with periods of 630 and 800 fs, and dephasing times of 8 and 6 ps, respectively. In the bound B-state, the cage fluctuates toward its dilated equilibrium structure on a time scale of 3 ps, which is extracted from the down-chirp in the molecular vibrational frequency. When kicked with excess energy of 4 eV, the Ar cage breaks with 50% probability, and the molecule dissociates. The kinetics of polarization selective, multiphoton dissociation with Gaussian laser intensity profiles is delineated and the ballistics of cage breakout is described: The photodissociation proceeds by destruction of the local lattice, by creating interstitials and vacancies. During large amplitude motion on cage-bound potentials, sudden, nonadiabatic spin-flip transitions can be observed and quantified in space and time. The spin-flip occurs with unit probability in Ar when the I*-I bond is stretched beyond 6 A.

Journal Article↗