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Ambulatory ECG and analysis of heart rate variability in Parkinson's disease.

OBJECTIVES: Cardiovascular reflex tests have shown both sympathetic and parasympathetic failure in Parkinson's disease. These tests, however, describe the autonomic responses during a restricted time period and have great individual variability, providing a limited view of the autonomic cardiac control mechanisms. Thus, they do not reflect tonic autonomic regulation. The aim was to examine tonic autonomic cardiovascular regulation in untreated patients with Parkinson's disease. METHODS: 24 Hour ambulatory ECG was recorded in 54 untreated patients with Parkinson's disease and 47 age matched healthy subjects. In addition to the traditional spectral (very low frequency, VLF; low frequency, LF; high frequency, HF) and non-spectral components of heart rate variability, instantaneous beat to beat variability (SD1) and long term continuous variability (SD2) derived from Poincaré plots, and the slope of the power law relation were analysed. RESULTS: All spectral components (p<0.01) and the slope of the power-law relation (p<0.01) were lower in the patients with Parkinson's disease than in the control subjects. The Unified Parkinson's disease rating scale total and motor scores had a negative correlation with VLF and LF power spectrum values and the power law relation slopes. Patients with mild hypokinesia had higher HF values than patients with more severe hypokinesia. Tremor and rigidity were not associated with the HR variability parameters. CONCLUSIONS: Parkinson's disease causes dysfunction of the diurnal autonomic cardiovascular regulation as demonstrated by the spectral measures of heart rate variability and the slope of the power law relation. This dysfunction seems to be more profound in patients with more severe Parkinson's disease.

Aged↗

Multilocus approach to cardiovascular risk.

Until now, our familial studies have showed that shared genetic and environmental factors are involved on lipid parameters variability. More precisely, being working on 119 families we have showed that: a) The apolipoprotein E (apo E) common polymorphism is involved in the total cholesterol, low density lipoprotein cholesterol (LDL-Chol), apo E, apo B levels variability, b) the apolipoprotein A-IV gene had no effect on lipid metabolism parameters variability, apo A-IV levels included, c) the apolipoprotein B gene was associated with total cholesterol, high density lipoprotein cholesterol, LDL-Chol, triglycerides and apo B levels genetic variability, d) the lipoproteine lipase (LPL) gene was responsible for 6.5% of the triglycerides variability, e) the apo E and LPL 447 polymorphisms influence in conjunction lipid parameters. These preliminary results on effects and combination effects of polymorphic genes show the interest of a multilocus approach. We have used in a subgroup of 416 individuals of a familial cohort (Stanislas Cohort) a prototype assay that genotypes a panel of 35 polymorphic sites on 15 candidate genes of Cardiovascular diseases. Each sample is amplified by two multiplex polymerase chain reactions, then hybridized to an array of immobilized, oligonucleotide probes. The frequencies of the rare alleles were in agreement with those reported by others in caucasian populations. The realisation of this multiplex assay in the 1,006 families of the Stanislas Cohort, which is underway, will allow us a better understanding of the inter-individual variability of lipids and will contribute to the determination of the genetic susceptibility of one's individual to cardiovascular risk.

Adult↗

Diurnal patterns of urinary steroid excretion in wild chimpanzees.

Urinary testosterone and cortisol concentrations were quantified in a large number of samples (>500) collected from wild male chimpanzees (n=11) over the course of 1 year. For both steroids, urinary concentrations were higher and more variable in the morning than in the afternoon. Urinary creatinine levels showed no such diurnal pattern. These patterns are consistent with studies of steroid excretion in humans and gorillas. This study emphasizes the importance of considering time of day as a confounding variable in field studies of primate endocrine function. It also suggests that if a small number of samples are to be used to characterize an individual's basal steroid levels, afternoon samples may be preferable because they show less intra-individual variability.

Animals↗

Apomorphine-susceptible rats and apomorphine-unsusceptible rats differ in the tyrosine hydroxylase-immunoreactive network in the nucleus accumbens core and shell.

Individual variability in behavioural responses to stressors such as novelty and drugs of abuse is a well-known phenomenon in both animals and man. These individual differences are largely associated with differences in dopamine transmission in mesolimbic areas such as the nucleus accumbens. Apomorphine-susceptible (APO-SUS) rats and apomorphine-unsusceptible (APO-UNSUS) rats serve as a valid animal model for individual differences and these two types of rat differ in a number of behavioural, physiological, endocrinological and pharmacological parameters. In order to study the differences in the catecholaminergic network in the nucleus accumbens, possibly underlying at least some of the differences between the two types of rat, we quantified the extent of the tyrosine-hydroxylase immunoreactive (TH-IR) network and the number of TH-IR varicosities in subareas of the nucleus accumbens core and shell in naive rats. This study shows that the nucleus accumbens of APO-SUS rats has a more extensive fibre network and more varicosities than the nucleus accumbens of APO-UNSUS rats, and that the subarea of the shell contains more varicosities than the subarea of the core. These data provide a basis for further studying the structural and neurochemical properties of the nucleus accumbens contributing to individual differences in response to stressors such as novelty and drugs of abuse.

Animals↗

Behavioral plasticity and virus propagation: the FIV-cat population example.

A new theoretical approach is proposed to investigate the effect of intra-individual variability in behavior on the spread of directly transmitted diseases within host populations. The classical hawk-dove game is used to describe interactions between individuals on a fast time scale (the day). Individuals may exhibit both tactics according to their own experience, to environment conditions, and to the opponent. They are not able to recognize the epidemiological state of their opponents. This fast-time part of the model is coupled to a classical compartmental epidemic model describing the demography of the population and the transmission of the disease from an infected individual to a healthy one on a slow time scale (the year). The model is applied to the case of feline immunodeficiency virus (FIV)-domestic cat population system. Our model gives rise to different predictions according to values of cost and gain due to fights: extinction of the epidemic, FIV endemicity at low, intermediate and high prevalence. These predictions are in good agreement with results from domestic cat populations living in different environmental conditions.

Animals↗

Use of a non-linear spline regression to model time-varying fluctuations in mammary-secretion element concentrations of periparturient mares in Michigan, USA.

A study was designed to model the fluctuations of nine specific element concentrations in mammary secretions from periparturient mares over time. During the 1992 foaling season, serial samples of mammary secretions were collected from all 18 pregnant Arabian mares at the Michigan State University equine teaching and research center. Non-linear regression techniques were used to model the relationship between element concentration in mammary secretions and days from foaling (which connected two separate sigmoid curves with a spline function); indicator variables were included for mare and mare parity. Element concentrations in mammary secretions varied significantly during the periparturient period in mares. Both time trends and individual variability explained a significant portion of the variation in these element concentrations. Multiparous mares had lower concentrations of K and Zn, but higher concentrations of Na. Substantial serial and spatial correlation were detected in spite of modeling efforts to avoid the problem. As a result, p-values obtained for parameter estimates were likely biased toward zero. Nonetheless, results of this analysis indicate that monitoring changes in mammary-secretion element concentrations might reasonably be used as a predictor of impending parturition in the mare. In addition, these results suggest that element concentrations warrant attention in the development of neonatal milk-replacement therapies. This study demonstrates that non-linear regression can be used successfully to model time-series data in animal-health management. This approach should be considered by investigators facing similar analytical challenges.

Animal Husbandry↗

Protein metabolism, the costs of growth, and genomic heterozygosity: experiments with the mussel Mytilus galloprovincialis Lmk.

A single cohort of small individuals (31 mm mean shell length, 112 mg mean dry flesh weight) of the marine bivalve mollusc Mytilus galloprovincialis Lmk. was held sequentially for 2 wk at each of four food levels equivalent to ingested rations of less than 0.1%, 2.6%, 3.1%, and 7.4% of dry body weight per day. Growth rate reached a maximum at the highest ration level and was strongly correlated, amongst individuals, with mean heterozygosity measured across nine enzyme loci. Rates of energy expenditure were analysed separately as maintenance metabolic rate and the energy costs of growth (J mg-1 dry tissue). The maintenance metabolic rate correlated with traits of protein metabolism (protein synthesis, deposition, and breakdown), and the separate energy costs of both maintenance and growth correlated with the efficiency of protein deposition (protein growth as a proportion of synthesis). The energy costs of growth also varied in negative relation to mean individual heterozygosity. In a multiple regression analysis, the energy allocation to the costs of growth, body size, mean heterozygosity, and the efficiency of protein deposition together explained 90% of the variance amongst individuals in observed rates of growth. The results support the hypothesis that individual variability in the energy costs of protein turnover and in the efficiency of protein deposition during rapid growth are significant factors providing a link between individual genotype and its phenotypic expression as growth.

Animal Nutritional Physiological Phenomena↗

Corneal desiccation in rigid contact lens wear: 3- and 9-o'clock staining.

The current knowledge of treatment options together with signs and symptoms, classification, prevalence, and etiology of 3- and 9-o'clock staining in rigid contact lens wear are described in this review article. In total, 11 treatment options for the management of 3- and 9-o'clock staining were found in the literature. Five of these treatment options are related to lens parameters, namely edge lift, edge thickness and shape, back surface geometry, total diameter, and back optic zone radius. Three other options are related to lens performance: movement, centration, and surface wettability. Three more variables can be identified: blinking habits, tear supplements, and, finally, switching to a hydrogel material. There is controversy on how to adjust the most important individual variables for management of 3- and 9-o'clock staining. The advocated treatment options are often related to the fitting techniques used: lid attachment or interpalpebral fit. Implications for practice and for further research are discussed.

Contact Lenses↗

Modulation of clinical expression of plaque-induced gingivitis. I. Background review and rationale.

OBJECTIVES: The purpose of this article is to provide the necessary background and rationale for the accompanying studies, which are ultimately aimed at identifying genetic and environmental factors determining gingivitis susceptibility. MATERIALS AND METHODS: The literature on factors reported to modify the clinical expression of gingivitis, i.e., factors that determine individual variability in gingival inflammatory response to plaque, is presented. RESULTS: Clinical evidence suggests that the gingival inflammatory response to plaque accumulation may differ substantially among individuals. However, most of the available studies are of small scale and not purposely designed to address the issue. Systemic factors implicated in modulation of the clinical expression of gingivitis include metabolic, genetic, environmental and other factors. The significance of such factors in designing and conducting a large-scale experimental gingivitis trial and means to account for them are discussed. CONCLUSION: Although several factors have been implicated, genetic or environmental factors underlying differences in gingivitis expression are not fully elucidated. The accompanying studies aim to identify and characterize, among participants in a specifically designed large-scale experimental gingivitis trial, subjects that differ significantly in their gingival inflammatory response to plaque. This is the first step in an effort to determine genetic or environmental factors underlying such differences.

Dental Plaque↗

Overdoses of pethidine given to two preterm neonates.

This paper reports two mechanically ventilated preterm babies who received overdoses of pethidine in the neonatal period. One of the neonates (gestational age 26 weeks, birthweight 1040 g) received repeated appropriate doses, which resulted in central nervous system irritability and convulsion due to accumulation of the drug and its metabolite, norpethidine. The other neonate (gestational age 27 weeks, birthweight 980 g) received a major (10-fold) overdose with little clinical effect. These two cases indicate notable individual variability in the responses of babies to pethidine. This is typical of other opioids, too. Therefore, the dosing of opioids to neonates should be titrated individually, and the patients should be observed carefully.

Analgesics, Opioid↗

Evaluation of an enzyme-immunometric assay for serum alpha-glutathione S-transferase.

A commercially available enzyme-immunometric assay for serum alpha-glutathione S-transferase (GST) was evaluated. Endogenous serum alpha-GST diluted linearly within the calibration range. However, we recommend that the sample and second antibody reagent are always added sequentially in the assay to avoid hook effect. Between-assay variability was below 7% across the calibration range and the upper limit of the reference range in adults (n = 219) was 11.4 micrograms/L. Within-individual variability in serum alpha-GST concentrations measured over a 4-6 week period in 4 healthy adults was small. Serum alpha-GST concentrations did not change significantly 6 h after a therapeutic dose of paracetamol. Studies in two patients after liver transplantation showed that serum alpha-GST is a better discriminant of acute changes in liver function than conventional tests. Serum alpha-GST concentrations were unaffected by gross muscle damage, extrahepatic inflammation, or haemolysis and thus appear to be more liver specific than transaminase activities. The effect of renal impairment on serum alpha-GST concentrations requires further investigation.

Acetaminophen↗

Time-series analysis--spectral analysis and the search for cycles.

In summary, spectral analysis is one analytic strategy for analyzing time-series data. Specifically, spectral analysis enables researchers to detect cyclicity and determines the variance in the data accounted for by cyclic activity. Results describe cycle frequency, period, and amplitude. Unlike cosinor analysis (Lentz, 1990b), spectral analysis does not directly determine peak time nor directly indicate time-ordered relationships, as does autocorrelation (Taylor, 1990). Cyclic relationships between time-series data can be detected using coherency (Gottman & Ringland, 1981), an extension of spectral analysis which is beyond the scope of this article. A word of caution is in order for the uninitiated researcher. Spectral analysis, as well as autocorrelation and cosinor analysis, entails within-subject analysis of single variables. Currently, means of determining relationships between time series, such as cross-correlation and coherency, are bivariate. The need to analyze the pattern of individual variables within-subject, followed by examination of bivariate relationships between pairs of variables, is wisely balanced by limited numbers of variables and small sample size.

Nursing Research↗

Factors associated with pilot error in aviation crashes.

BACKGROUND: The importance of pilot error in aviation crashes has long been recognized. However, understanding and preventing pilot error remains the foremost challenge in aviation safety. OBJECTIVE: This study aims to identify pilot characteristics and crash circumstances that are associated with the presence of pilot error in a large sample of aviation crashes. METHODS: Different data files compiled by the National Transportation Safety Board for 329 major airline crashes, 1,627 commuter/air taxi crashes, and 27,935 general aviation crashes for the years 1983-96 were merged; and the presence of pilot error was analyzed in relation to variables indicating the characteristics of the pilot-in-command, crash circumstance, and aircraft. Multivariate logistic regression modeling was performed to assess the associations of individual variables with the likelihood of pilot error given a crash. RESULTS: Pilot error was a probable cause in 38% of the major airline crashes, 74% of the commuter/air taxi crashes, and 85% of the general aviation crashes. Among the factors examined, instrument meteorological condition and on-airport location were each associated with a significantly increased odds of pilot error. The likelihood of pilot error decreased as pilot certificate rating increased in commuter/air taxi and general aviation crashes. Neither pilot age nor gender was independently associated with the odds of pilot error. With adjustment for pilot characteristics and crash circumstances, flight experience as measured in total flight time showed a significant protective effect on pilot error in general aviation crashes. CONCLUSIONS: The prevalence and correlates of pilot error in aviation crashes vary with the type of flight operations. Adverse weather is consistently associated with a significantly elevated likelihood of pilot error, possibly due to increased performance demand.

Accidents, Aviation↗

[Spatial variability and quantitative analysis of field factors based on GIS].

The objective of this research was to investigate the variability and the quantitative relationships among soil nutrients and crop growth status and yield. All data were analyzed by both classical statistics and geostatistics based on GIS. Soil properties included soil pH, total N, organic matter, available P and available K, while crop growth status was indicated by SPAD, LAI and SPAD x LAI. All parameters except soil pH exhibited spatial correlation. Soil total N and organic matter, SPAD, LAI and SPAD x LAI were all correlated to rice yield. Kriged interpolation maps provided good indication of the spatial variability in crop yield and growth status. Spatial interpolation and correlation analysis proved that SPAD x LAI was more indicative of crop growth status than individual variables, and useful for implementing growth season and topdressing as needed.

Biomass↗

Quantitative analysis of ultradian luteinizing hormone secretion in normal men.

Basal pulsatile secretion of luteinizing hormone (LH) was studied in 8 healthy adult men and analyzed by mathematical and statistical techniques. LH pulses previously defined by semiquantitative criteria resisted the data-smoothing techniques employed. LH values were shown to have normal distribution in normal men. No correlation was found between mean LH and testosterone levels for the same individual. On the basis of analysis of variance it was shown that the individual variability and not the collection time is important in determining each isolated LH value. The LH levels were located within a particular channel for each individual for each collection time.

Activity Cycles↗

Dietary fat clearance is modulated by genetic variation in apolipoprotein A-IV gene locus.

Previous studies have shown that the A-IV-347Ser polymorphism is associated with the variability in low density lipoprotein (LDL)-cholesterol response to dietary therapy. The present study was designed to evaluate the association of this polymorphism with the individual variability observed in postprandial lipemic response. This polymorphism was characterized in 50 healthy male subjects homozygous for the apolipoprotein (apo)E3 allele. All subjects were subjected to a vitamin A-fat load test. Blood was drawn at time 0 and every hour over a period of 11 hours. Cholesterol and triglycerides (TG) in plasma and lipoprotein fractions of CH, TG, and retinyl palmitate (RP) were determined. Data from the postprandial lipemia revealed that subjects with the A-IV-347Ser allele (n = 14) have a lower postprandial response in total TG (P < 0.025), large triglyceride rich lipoproteins (TRL) TG (P < 0.02), and small-TRL TG levels (P < 0.007), and a higher postprandial response in large-TRL apoA-IV (P < 0.006) and apoB-100 (P < 0.041) levels than subjects homozygous for the A-IV-347Thr subjects (n = 36). In conclusion, the modifications observed in postprandial lipoprotein metabolism associated with this polymorphism within the apoA-IV gene locus may be involved in the variability in LDL-CH response observed in subjects consuming high saturated fat diets.

Adolescent↗

Cardiologists' use of clinical information for management decisions for patients with unstable angina: a policy analysis.

Previous studies of management of unstable angina have revealed substantial differences in management between different hospitals, especially with respect to the use of coronary angiography. Physicians in a hospital with angiography facilities were more inclined to perform angiography than were physicians in hospitals without these facilities, even when differences in patient populations were taken into account. The authors compared the management strategies of 18 cardiologists, working in hospitals with and without angiography facilities, using a series of paper-case summaries, in order to assess the contribution of individual variability between physicians to practice differences. Physicians who worked in a hospital with in-house angiography facilities were more inclined to request angiography in similar case summaries, but the inter-individual variation exceeded the between-hospital variation. The variation in individual policies with respect to the decision to initiate coronary angiography could be associated with differences in weighting clinical information. These results confirm that practice variations may have many causes: variability in patients' characteristics, variations in how physicians react to these, differences in the availability of services, and variability in thresholds for action.

Angina Pectoris↗

Variability of near-fainting responses in healthy 6-16-year-old subjects.

1. Fainting is a common phenomenon in young subjects, but the final events before the actual faint are not well known. The aim of the present study was to study the inter-individual variability of haemodynamic events associated with near-fainting in children and teenagers. 2. Sixty-eight healthy subjects (aged 6-16 years) performed a 70 degrees tilt-up test with intravascular instrumentation for 5 min. Responses in 29 near-fainting subjects were analysed and compared with 39 non-fainting subjects. Arterial pressure was measured by Finapres. Left ventricular stroke volume was computed from the pressure pulsation waveform. 3. Inability to maintain vasomotor tone was the mechanism underlying near-fainting in the vast majority of near-fainting subjects. The three classical haemodynamic responses (vasovagal, vasodepressor and vagal) could be recognized, but large individual differences were found. After tilt back, blood pressure in near-fainters showed a mirror response to the stage before tilt-back; blood pressure gradually increased and was normal at 1 min after tilt-back. 4. The variability in haemodynamic responses on approach of an orthostatic faint is wide in the young.

Adolescent↗