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Magnetoencephalographic analysis in children with Panayiotopoulos syndrome.

The aims of this study were to identify the generator of the paroxysmal partial discharges in Panayiotopoulos syndrome by means of magnetoencephalography and to determine the significance of these formations in the epileptogenesis of the developing nervous system. We report magnetoencephalographic data for two cases of Panayiotopoulos syndrome showing the rapid generalization of the source of interictal spikes that explains extraoccipital manifestations such as ictal vomiting and consciousness disturbance.

Cerebral Cortex↗

Raised prorenin and renin concentrations in pre-eclamptic placentae when measured after acid activation.

AIM: The aim of the study was to ascertain if there was any difference in the levels of prorenin and active renin between pre-eclamptic and normotensive feto-placental tissues. METHODS: Supernatants of homogenates from fresh, vaginally delivered placentae from 15 normotensive and 15 pre-eclamptic women were measured for renin concentration (RC), prorenin concentration and renin activity (RA). RA and RC were measured in the absence and presence of nephrectomised sheep plasma, respectively. Prorenin was estimated as the difference between renin concentration in the sample before and after acid activation. All concentrations are expressed as rate of angiotensin generation (ng/ml/h). Angiotensin I was measured by radioimmunoassay. Statistical analysis was performed using Student's 't' test for unpaired samples. All results are presented as mean+/-SEM. RESULTS: The concentrations of renin and prorenin were highest in the chorion laeve when compared to amnion and placenta (p < 0.01) in both the groups. Furthermore, the concentrations of renin and prorenin were significantly higher in all the tissues from women with pre-eclampsia (p < 0.01). CONCLUSION: Renin and prorenin levels are raised in the placental tissues from women with pre-eclampsia. With recent evidence suggesting that both prorenin and renin may have cellular effects independent of angiotensin II generation, there is a need for further study into its role in placentation.

Adult↗

Employing simulated data to illustrate an important cause of the 'steepling' effect in breath alcohol analysis.

The 'steepling' effect (large excursions in analytical data over time) is a debated issue in forensic breath alcohol analysis with various explanations being postulated. Simulated breath alcohol data was generated according to a hypothetical kinetic model where single random samples as well as means of duplicate random samples were plotted with respect to time at 0.2 hour intervals. In addition, the simulated data was compared when both two or more digit treatment was employed. Results showed the occurrence of significant noise or 'steepling' when single, two-digit breath alcohol samples were employed as compared to a four-digit mean computed from three-digit duplicates. The magnitude of variability was quantified by means of nonlinear regression resulting in the residual sum of squares (RSS) = 0.00202 for the single analysis and RSS = 0.00053 for the mean of duplicates. The method of data collection and treatment appears to contribute significantly to the 'steepling' phenomenon. Intuitively, replicate analyses reduce variability and allow for more accurate kinetic modelling employing breath alcohol analysis.

Alcoholic Intoxication↗

Automatic analysis of protein conformational changes by multiple linkage clustering.

An automatic algorithm is presented for analyzing protein conformational changes such as those occurring upon substrate binding or in different crystal forms of the same protein. Using, as sole information, the atomic coordinates of a pair of protein structures, the procedure first generates structure alignments, which optimize the root-mean-square deviation of the backbone atoms. To this end, equivalent secondary structures and/or loops from both proteins are combined by a multiple linkage hierarchic clustering algorithm, which generates several intertwined clustering trees. Automatic analysis of these clustering trees is used to dissect the mechanism of the conformational change. It allows the identification of the static core, representing the collection of secondary structures which undergo no structural changes, as well as other entities which move like rigid bodies. It also permits the description of the movement of secondary structures or loops relative to this core or entities. USing this information, it can be inferred whether a particular conformational change involves shear or hinge motion, or components of both. The algorithm is applied to the analysis of the conformational changes of citrate synthase, lactate dehydrogenase, lactoferrin and beta-glucosyltransferase, representing typical examples of shear- and hinge-type mechanisms, and a varied range in movement size. The results are shown to be in excellent agreement with previous analyses, and to provide additional information which gives a more complete and objective picture of the conformational change. Using our automatic algorithm, we find that any conformational change may be viewed as having components of both shear- and hinge-type motion. Determining which of these is most appropriate requires the combination of the information provided by our procedure with detailed knowledge of the protein tertiary structures.

Algorithms↗

Involvement of fast synaptic inhibition in the generation of high-frequency oscillation in central respiratory system.

During moderate hypercapnia, spectrum analysis of efferent phrenic nerve activity (PNA) of urethane anesthetized rabbits revealed high-frequency oscillations (HFO). The spectral peak (mean frequency 111 Hz) was reversibly eliminated by the glycine receptor antagonist strychnine administered into the 4th cerebral ventricle. In contrast, blockade of brainstem GABAA receptors by bicuculline did not abolish HFO but even reinforced or induced HFO. Thus, there is evidence that fast synaptic inhibition via glycine receptors is involved in the generation of HFO within the medullary respiratory center, whereas GABA may play a modulatory role.

Action Potentials↗

Regional specific mean expiratory gas flow from 81mKr equilibrium inhalation data.

A new method of analysing the data available from routine 81m Kr equilibrium inhalation investigations has been developed. The data for analysis are acquired from a gamma camera in the form of a sequential series of images from which multiple breath activity-time curves are generated for eight regions in the lung. The method is based on a description of the behaviour of the radioactive gas in the lung using a mathematical model. Values of specific mean expiratory gas flow, that is mean expiratory gas flow per unit lung volume, are calculated from the application of the model to the expiratory phase only of a single breath activity-time curve which is generated from the multiple breath activity-time curve using post-acquisition gating. This method overcomes the problem of non-uniform inspiratory concentration of tracer gas experienced in previously reported techniques of analysing inhalation data obtained using poorly soluble radioactive gases. The model is shown, in simulation studies, to be an adequate description of the behaviour of radioactive gas in the lung and the analysis technique is shown, in clinical studies, to be both reproducible and sensitive to disease state.

Humans↗

Verb generation in children and adolescents with acute cerebellar lesions.

The aim of the present study was to examine verb generation in a larger group of children and adolescents with acute focal lesions of the cerebellum. Nine children and adolescents with cerebellar tumours participated. Subjects were tested a few days after tumour surgery. For comparison, a subgroup was tested also 1 or 2 days before surgery. None of the children had received radiation or chemotherapy at or before the time of testing. Eleven age- and education-matched control subjects participated. Subjects had to generate verbs to blocked presentations of photographs of objects. As control condition, the objects had to be named. Furthermore, dysarthria was quantified by means of a sentence production and syllable repetition task. Detailed analysis of individual 3D-MR images revealed that lesions affected cerebellar hemispheres in all children and adolescents. The right cerebellar hemisphere was affected in four and the left hemisphere in five subjects. In the present study, naming and verb generation accuracy were preserved in the majority of subjects with cerebellar lesions. No significant signs of learning deficits were observed, as reduction of reaction times over blocks was not different compared to controls. There was a trend of children and adolescents with right-hemispheric lesions to perform worse compared to controls. In this group, however, significant signs of dysarthria were present. In sum, no significant signs of disordered verb generation were observed in children and adolescents with acute cerebellar lesions. Findings suggest that the role of the cerebellum in verb generation may be less pronounced than previously suggested. Findings need to be confirmed in a larger group of subjects with acute focal lesions.

Acute Disease↗

Heritability of age at natural menopause in the Framingham Heart Study.

BACKGROUND: Twin registries and family history studies provide evidence that genetic factors contribute to the onset of menopause, but heritability estimates in population-based samples are limited. We sought to estimate heritability of age at natural menopause in women participating in the multigenerational Framingham Heart Study, a community-based epidemiological study. METHODS: A total of 1500 original cohort and 932 offspring cohort women from 1296 extended families reported a natural menopause defined as the natural cessation of menses for 1 yr or more. Correlation coefficients were calculated using family correlations in Statistical Applications for Genetic Epidemiology for mother-daughter, sister-sister, and aunt-niece pairs. Heritability was estimated using variance-components methods in the Sequential Oligogenic Linkage Analysis Routines (SOLAR) computer package. Covariates in the multivariable models included generation, number of cigarettes smoked, body mass index, and parity. RESULTS: The mean age at natural menopause was 49.1 and 49.4 yr in original cohort and offspring women, respectively. The multivariable-adjusted correlation coefficients for mother-daughter, sister-sister, and aunt-niece pairs were 0.21, 0.22, and 0.12, respectively. The crude and multivariable-adjusted heritability estimates for age at natural menopause were 0.49 (0.37, 0.61) and 0.52 (0.35, 0.69). CONCLUSIONS: Our data suggest that at least 50% of the interindividual variability in menopausal age appears to be attributable to genetic effects.

Adult↗

Fabrication of submicron titanium-alloy particles for biological response studies.

Biologic response to generated wear particles and subsequent aseptic loosening is a critical factor limiting the long-term survival of total hip replacements. To better understand the sequence of events leading to aseptic loosening and the role of the individual material components, fabricating metal particles similar to those present clinically is very important. We describe a simple milling technique to generate significant amounts of fine titanium-alloy (TiAlV) debris. A TiAlV rod was milled against a TiAlV plate in distilled water supplemented with antibiotics. The resulting debris were sedimented in alcohol and the fine debris were separated. Scanning electron microscopy analysis and particle size analysis demonstrated that the mean size of particles was 1.1 +/- 0.9 microm (range 0.2-4.2 microm). Sixty-two percent were smaller than 1.0 microm, and 85% were smaller than 2.0 microm. The particles generated had varying shapes, including angular or shard-like shapes with jagged and irregular outlines.

Alloys↗

The Rancho EMG analyzer: a computerized system for gait analysis.

This paper describes a computer system which accurately defines the EMG patterns of the lower extremities during gait. Footswitches are used to identify the temporal relationships and determine the phases of the gait cycle. Fine wire electrodes, inserted in the desired muscles of the patient being tested, provide EMG signals for comparison with a normal database. The system is also usable with surface electrodes when an appropriate normal database for surface electrodes is incorporated. Descriptive qualifiers (such as 'premature onset', 'delayed cessation', 'no clinically significant EMG', 'continuous activity' etc.) are used to produce a clinically relevant printed (textual) report. The intensity filtered average (IFA) of the EMG is shown graphically with the representative profile of each stride. The IFAs for all muscles tested can be plotted together (up to six on a page) and the graphic representation of the 'raw' EMG can be produced. The methods of generating the normal database by creating time-adjusted mean profiles (TAMP) are enumerated. The clinical use of the system is discussed. A detailed analysis of 31 of the most recent patient tests for which the system was used provides an indication of its accuracy. For 86% of the 428 muscle tests examined, the EMG analyser was considered to have given the correct result as compared with a visual analysis of the raw EMG record by a trained expert. Recommendations for the use and future improvements of the EMG analyser are made.

Adolescent↗

Schizophrenia and migration: a meta-analysis and review.

OBJECTIVE: The authors synthesize findings of previous studies implicating migration as a risk factor for the development of schizophrenia and provide a quantitative index of the associated effect size. METHOD: MEDLINE was searched for population-based incidence studies concerning migrants in English-language publications appearing between the years 1977 and 2003. Article bibliographies and an Australian database were cross-referenced. Studies were included if incidence reports provided numerators and denominators and if age correction was performed or could be performed by the authors. Relative risks for migrant groups were extracted or calculated for each study. Significant heterogeneity across studies indicated the need for a mixed-effects meta-analytic model. RESULTS: The mean weighted relative risk for developing schizophrenia among first-generation migrants (40 effect sizes) was 2.7 (95% confidence interval [CI]=2.3-3.2). A separate analysis performed for second-generation migrants (seven effect sizes) yielded a relative risk of 4.5 (95% CI=1.5-13.1). An analysis performed for studies concerning both first- and second-generation migrants and studies that did not distinguish between generations (50 effect sizes) yielded a relative risk of 2.9 (95% CI=2.5-3.4). Subgroup comparisons yielded significantly greater effect sizes for migrants from developing versus developed countries (relative risk=3.3, 95% CI=2.8-3.9) and for migrants from areas where the majority of the population is black (relative risk=4.8, 95% CI=3.7-6.2) versus white and neither black nor white. CONCLUSIONS: A personal or family history of migration is an important risk factor for schizophrenia. The differential risk pattern across subgroups suggests a role for psychosocial adversity in the etiology of schizophrenia.

Anthropology, Cultural↗

Cigarette smoking, blood pressure and pulse rate in the Jerusalem Lipid Research Clinic Prevalence Study.

The relationship between cigarette smoking and blood pressure (BP) and pulse rate (PR) was studied in a sample of 1,242 Jerusalem youngsters and 1,703 adults. Confounding effects of age, body mass, ethnic origin and season were controlled in the analysis. Both mean systolic (SBP) and diastolic blood pressure (DBP) were lower in smokers than in nonsmokers, with greater differences in both generations in females (women 4.5 mm Hg, P = 0.004 and girls 3.9 mm Hg, P less than 0.001 for SBP; women 2.3 mm Hg, P = 0.024 and girls 2.6 mm Hg, P = 0.002 for DBP) than among the males (men 1.5 mm Hg, P = 0.15 and boys 2.0 mm Hg, P = 0.022 for SBP; men 1.3 mm Hg, P = 0.05 and boys 1.8 mm Hg, P = 0.01 for DBP). The relative odds of being in the upper age, ethnic and body mass index-adjusted quintiles of SBP for nonsmokers were 1.3, 1.9, 2.1, and 3.5 for men, boys, women, and girls, respectively. For DBP they were 1.3, 1.7, 1.1, and 2.1, respectively. No significant trends for BP varying with number of cigarettes smoked were noted in either adults or youngsters. Only adult male smokers had slightly higher PRs. The relatively small differences in BP may be of pharmacologic or psychobehavioral interest, but do not counter the well-described deleterious effects of cigarette smoking.

Adolescent↗

[Longitudinal study of hospital readmission for congestive heart failure in Cataluña. 1996-1999].

BACKGROUND: This study is aimed at describing the readmission phenomenon for heart failure patients and identifying some of their related clinical factors by means of a follow-up study with administrative data. METHODS: Longitudinal study of readmissions due to heart failure (HF) among a population > or = age 65 in Catalonia throughout the 1996-1999 period. Information source: Minimum Basic Set of Data of Hospital Discharges from the Catalan Health Service. Definition of HF, etiological or precipitating cause, and comorbility by means of a ICD-9 discharge release codes combination. Analysis units "patient with HF" and an index population or cohort". STATISTICS: Survival analysis (Kaplan-Meier and Log-rank test) and regression models (Cox). RESULTS: The follow-up populations, comprised of 16,919 patients, generated 44,283 admissions (61.8%). The length of time free of readmissions (Mean "ME" in months) and the comparison of the survival curves is statistically significant with lower values in the following categories: 'age 65-74' (ME = 21.6 months); 'male' (23.3); 'healthcare region 6' (16.3); 'reference hospital' (22.9) and 'pure COPD related to the HF (17.7),. The highest risk of readmission, adjusted by the other variables under study, has been found for 'pure COPD' [RR = 1.03, (95% CI: 1.02-1.04), p < 0.001], and ischaemic heart disease [RR = 1.03, (95% CI: 1.01-1.05), p = 0.003]. CONCLUSIONS: This study reveals the clinical complexity and patterns of utilization of hospitals on the part of patients with heart failure, identifying that those having COPD or ischaemic heart disease being top-priority groups for care intervention and thus revealing the potential which administrative data has for clinical planning and management.

Aged↗

A general method of in vitro preparation and specific mutagenesis of DNA fragments: study of protein and DNA interactions.

Specific, end-labeled DNA fragments can be simply and rapidly prepared using the polymerase chain reaction (PCR). Such fragments are suitable for use in DNase I protection footprint assays, chemical sequencing reactions, and for the production and analysis of paused RNA polymerase transcription complexes. Moreover, a general means of introducing a specific mutation at any position along the length of such PCR-generated fragments is described. These procedures, which can circumvent the need for large-scale phage or plasmid growths, preparative gel-electrophoresis and the screening of molecular clones, can facilitate the rapid study of sequence-specific interactions of proteins and DNA. A rapid means of removing excess oligonucleotide primers from completed PCRs is also described.

Base Sequence↗

Analysis of the signals generated by networks of neurons coupled to planar arrays of microtransducers in simulated experiments.

Planar microelectrode arrays can be used to characterize the dynamics of networks of neurons reconstituted in vitro. In this paper simulations related to experiments of the electrical activity recording by means of planar arrays of microtransducers coupled to networks of neurons are described. First a detailed model of single and synaptically connected neurons is given, appropriate to computer simulate the action potentials of neuronal populations. Then 'realistic' signals are generated. These signals are intended to reproduce, both in shape and intensity, those recorded by a microelectrode array. Typical experimental conditions are considered, and a detailed analysis given, of the bioelectronic coupling and of its influence on the shape of the recorded signals. Finally, simulated experiments dealing with dorsal root ganglia neurons are described and analysed in comparison with experimental results reported in the literature and obtained in our own laboratory. The effectiveness of the planar microelectrode technique is briefly discussed.

Animals↗

Fluctuations in rotation rate of the flagellar motor of Escherichia coli.

The purpose of this work was to study the changes in rotation rate of the bacterial motor and to try to discriminate between various sources of these changes with the aim of understanding the mechanism of force generation better. To this end Escherichia coli cells were tethered and videotaped with brief stroboscopic light flashes. The records were scanned by means of a computerized motion analysis system, yielding cell size, radius of rotation, and accumulated angle of rotation as functions of time for each cell selected. In conformity with previous studies, fluctuations in the rotation rate of the flagellar motor were invariably found. Employing an exclusively counterclockwise rotating mutant ("gutted" RP1091 strain) and using power spectral density, autocorrelation and residual mean square angle analysis, we found that a simple superposition of rotational diffusion on a steady rotary motion is insufficient to describe the observed rotation. We observed two additional rotational components, one fluctuating (0.04-0.6 s) and one oscillating (0.8-7 s). However, the effective rotational diffusion coefficient obtained after taking these two components into account generally exceeded that calculated from external friction by two orders of magnitude. This is consistent with a model incorporating association and dissociation of force-generating units.

Antibodies↗

The information content of Doppler ultrasound signals from the fetal heart.

Knowledge of the content of Doppler ultrasound signals from the fetal heart is essential if the performance of fetal heart rate (FHR) monitors based upon this technology is to be improved. For this reason instrumentation was constructed to enable the simultaneous collection of Doppler audio signals and the transabdominal fetal ECG (for signal registration), with a total of 22 recordings being made with an average length of around 20 minutes. These data demonstrate the transient nature of the Doppler audio data with wide variations in the signal content observable on a beat-to-beat basis. Short-time Fourier analysis enabled the content of the Doppler signals to be linked to six cardiac events, four valve and two wall motions, with higher frequency components being associated with the latter. This differing frequency content together with information regarding the direction of movement that can be discerned from Doppler signals provided a potential means of discriminating between these six events (which are unlikely to all contribute to the Doppler signal within the same cardiac cycle). Analysis of 100 records showed that wall contractions generate the most prominent signals, with atrial contraction recognisable in all records and ventricular wall contraction in 95% (although its amplitude is only around 30% of that of the atrial signal). Valve motion, with amplitudes between 15 and 25% that of the atrial wall signal, were visible in 75% of records. These results suggest means by which the six events that contribute to the Doppler signal may be distinguished, providing information that should enable an improvement in the current performance of Doppler ultrasound-based FHR monitors.

Electrocardiography↗

Conversion of 5-hydroperoxyeicosatetraenoic acid into leukotriene B4 by rat hepatocytes: a novel cellular source for leukotriene B4.

Rat hepatocyte homogenates converted 5-hydroperoxyeicosatetraenoic acid into leukotriene B4 (LTB4). The reaction was dependent on time and protein and substrate concentration, did not require NADPH or oxygen, and was not supported by heat-inactivated hepatocyte homogenates. The authenticity of the biologically generated LTB4 that eluted at the position of synthetic LTB4 during high performance liquid chromatography was established by UV spectrophotometry, mass spectral analysis, radioimmunoassay, and a LTB4 receptor displacement assay. In addition, a leukotriene bioassay is described in which transient increases in cytosolic Ca2+ within human neutrophils are measured by means of fura-2 fluorescence. Biologically generated LTB4 was 40, 40, and 33% as active as synthetic LTB4 in the radioimmunoassay, receptor displacement assay, and cytosolic calcium bioassay, respectively. This activity is consistent with the biologically derived LTB4 being an epimeric mixture of (5S),(12R)-LTB4 and the much less active (5S),(12S)-LTB4. The formation of LTB4 was inhibited by 5,8,11,14-eicosatetraynoic acid (1 mM), 5,6-dehydro-arachidonic acid (50 microM), propanethiol (1 mM), and O2 (100%) to the extent of 53, 42, 48, and 66%, respectively. No inhibition was observed in the presence of diethylcarbamazine (1 mM) and desferal (1 mM). A possible contribution towards LTB4 formation by contaminating Kupffer cells was excluded (less than 0.2%). These results suggest that hepatocytes can convert lipid peroxides into potent chemoattractants that may alter the homeostasis of immunomediators within the liver.

Animals↗