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PubMed1995

[Treatment of severe asymptomatic carotid stenosis].

Severe (reduction of vessel diameter by more than 70%) asymptomatic carotid artery stenosis is associated with a risk of cerebrovascular accident of 2-5% in the year following diagnosis. Results of large, prospective, randomized studies suggest that prophylactic carotid endarterectomy may be beneficial in this situation. However, the elements that must be taken into consideration before deciding to operate on an individual patient are extremely complex. Age and comorbidity (especially cardiovascular conditions) must be considered, as well as perioperative risk and expected medium- and long-term benefits, as compared with optimal conservative treatment. Decision analysis may be of considerable help in such a complex situation by considering objectively and explicitly all these epidemiologic and individual variables. Specifically, the technique makes it possible to simulate threshold probabilities of perioperative complications above which the risks of prophylactic endarterectomy outweigh its benefit, expressed as 5-year survival free of cerebrovascular event. These thresholds are 4%, 3% and 2% for a patient aged 65, 75 and 85 respectively. If 2-year event-free survival is considered, the surgical risk should not exceed 1.5% for a patient aged 65 years or 1% above that age. This type of analysis makes it possible to individualize the guidelines of international panels of experts, but ultimately the decision to operate or not must also consider the psychological profile of the patient and his attitude towards risk ("risk-seeking or risk-averse").

Age Factors↗
PubMed1995

[Heart rate fluctuations in the horse at rest: (2) Biological variation factors related to behavioural profile].

Variability of heart rate was analysed within a sample of 30 horses in order to determine the influence of factors (animal, age, sex and breed) associated with different behavioural patterns. The heart rate fluctuations were analysed by computing the power spectral density of a series of heartbeat intervals. A generalized linear model was used to compare the spectra and to reveal the effect of each factor: animal age, sex and breed. The scale and shape of spectral densities were significantly different between animals. This individual variability was partly explained by the sex and age effects while the breed effect had only a weak influence. Young horses and mares exhibited a greater heart rate fluctuation which may be related to their higher emotionality.

Age Factors↗
PubMed1994

Audiometry in industry.

Pure tone audiometry is the most common method of screening for hearing loss. The test itself is straightforward and the equipment readily available, so it forms part of the hearing conservation programmes of many industries. Whilst the test itself is straightforward, because of individual variability in response, interpretation of the results may be difficult. There has therefore been considerable debate on the role of audiometry in hearing conservation. The last official publication dealing with audiometry was a Health and Safety Executive discussion document 'Audiometry in Industry' published in 1978: no current recommendations are available. This article is a critical review of the advice given in that document, which aims to clarify the role that audiometry may play in the conservation of hearing. It was concluded that audiometry in the individual may perform poorly in strict cost benefit terms when used serially to detect a deterioration in hearing of an individual, but as the only form of biological monitoring it should be available to all employees who are advised to wear hearing protection at work. A distinction between audiometry in the individual and group audiometry is then made: the analysis of the hearing of a group may be useful in assessing risk to hearing. Graphical methods of analysis are shown, and more formal methods of statistical analysis discussed.

Audiometry, Pure-Tone↗
PubMed2002

Variability in aflatoxin B(1)-macromolecular binding and relationship to biotransformation enzyme expression in human prenatal and adult liver.

Studies of transplacental transfer of aflatoxin B(1) (AFB(1)) suggest that the developing human fetus may be a sensitive target for AFB(1) injury. Because AFB(1) requires metabolic activation to the reactive AFB(1)-8,9-exo-epoxide (AFBO) to exert its carcinogenic effects, ontogenic and interindividual differences in AFB(1) biotransformation enzymes may underlie susceptibility to AFB(1)-induced cell injury. The present study was initiated to compare the rates of in vitro AFB(1)-DNA and AFB(1)-protein adduct formation among a panel of 10 adult and 10 second-trimester prenatal livers and to examine the relationship among AFB(1) metabolizing enzyme expression and AFB(1) binding. Mixtures of cytosolic and microsomal proteins from prenatal and adult livers catalyzed the formation of AFB(1)-DNA and AFB(1)-protein adducts at relatively similar rates, although greater individual variability in AFB(1) adduct formation was observed in adult tissues. Extensive interindividual variation among adult tissues was observed in the expression of the AFB(1) activation enzymes cytochrome P4501A2 (CYP1A2), CYP3A4/5, and lipoxygenase (LO). Prenatal CYP3A7 expression was also highly variable. LO expression was eightfold higher in prenatal liver tissues than adults, whereas the expression of the AFBO detoxification enzyme microsomal epoxide hydrolase was twofold higher in adult liver. The levels of the polymorphic glutathione S-transferase M1 (hGSTM1-1), which may potentially protect against AFBO injury, were higher in the hGSTM1-1-expressing tissues of adults in relation to prenatal livers. In general, there was not a strong relationship among AFB(1)-DNA or AFB(1)-protein adduct formation and expression levels of individual AFB(1) metabolizing enzymes. In summary, despite the presence of marked individual and ontogenic differences in the expression of AFB(1) metabolizing enzymes, human second trimester prenatal liver tissues compared to adults do not exhibit a marked sensitivity to the in vitro formation of macromolecular AFB(1) adducts.

Aflatoxin B1↗
PubMed2003

[Rett syndrome: individual differences in developmental and behavioral markers and psychosocial stress].

OBJECTIVES: Rett Syndrome is a severe neurological developmental disorder caused by a genetic mutation on the long arm of the X chromosome (Xq28). This disorder is characterized by a loss of purposeful hand use, verbal language, and specific behaviors. METHODS: Data were obtained from a survey of the parents of 83 girls on pre-verbal skills (Pre-verbal Communication Schedule), behavioral characteristics and emotional expression (Rett Syndrome Behaviour Questionnaire) and on maternal psychosocial stress (Handicap-related Problems for Parents Inventory). RESULTS: There is considerable individual variability in the developmental and behavioral characteristics which is not explained as a function of age. Maternal stress correlates with the daughters' mood, anxious reactions and night-time behaviors. CONCLUSIONS: Some implications for diagnosis and family counseling are discussed.

Activities of Daily Living↗
PubMed2006

Combining short interval MRI in Alzheimer's disease: Implications for therapeutic trials.

Cerebral atrophy calculated from serial MRI is a marker of Alzheimer's disease (AD) progression, and a potential outcome measure for therapeutic trials. Reducing within-subject variability in cerebral atrophy rates by acquiring more than two serial scans could allow for shorter clinical trials requiring smaller patient numbers. Forty-six patients with AD and 23 controls each had up to 10 serial MR brain scans over two years. Whole brain atrophy was calculated for each subject from every scan-pair. 708 volumetric MRI scans were acquired: 2199 measures of atrophy were made for patients, and 1182 for controls. A linear mixed model was used to characterise between and within-individual variability. These results were used to investigate the power of combining multiple serial scans in treatment trials of varying lengths. In AD, the mean whole brain atrophy rate was 2.23%/year (95% CI: 1.90-2.56%/year). The linear mixed model was shown to fit the data well and led to a formula (0.99(2) + (0.82/t)2) for the variance of atrophy rates calculated from two scans "t" years apart. Utilising five optimally timed scans with repeat scans at each visit reduced the component of atrophy rate variance attributable to within-subject variability by approximately 56%, equating to a approximately 40% sample size reduction (228 vs 387 patients per arm to detect 20% reduction in atrophy rate) in a six-month placebo-controlled trial. This benefit in terms of sample size is relatively reduced in longer trials, although adding extra scanning visits may have benefits when patient drop-outs are accounted for. We conclude that sample sizes required in short interval therapeutic trials using cerebral atrophy as an outcome measure may be reduced if multiple serial MRI is performed.

Aged↗
PubMed1990

Analyzing chronic low back pain: the relative contribution of pain coping strategies.

Sixty-two chronic low back pain patients were administered the Coping Strategies Questionnaire (CSQ) to assess the frequency of use and perceived effectiveness of a variety of cognitive and behavioral pain coping strategies. Analysis of individual variables revealed that CSQ factors, gender, physical examination findings, and chronicity of pain had significant effects on one or more of a series of pain, psychological distress or behavioral measures. To assess the relative contribution of each of these variables hierarchical stepwise regression analyses were carried out. These analyses revealed that the Helplessness factor of the CSQ explained 50% of the variance in psychological distress (Global Severity Index of the SCL-90R), and 46% of the variance in depression (Beck Depression Inventory). Patients scoring high on this CSQ factor had significantly higher levels of psychological distress. None of the demographic or medical status variables explained a significant proportion of variance in the psychological distress measures. The Diverting Attention and Praying factor of the CSQ explained a moderate (9%), but significant amount of variance in pain report. Patients scoring high on this factor had higher scores on the McGill Pain Questionnaire. Coping strategies were not strongly related to pain behavior measures such as guarding or uptime. A consideration of pain coping strategies may allow one to design pain coping skills training interventions so as to fit the needs of the individual low back pain patient.

Adaptation, Psychological↗
PubMed2005

Can patients use all dry powder inhalers equally well?

If patients are unable to use their inhaler, drug delivery may be unsatisfactory and the patients may fail to benefit from the prescribed medication. It is important to consider whether patients can use all dry powder inhalers equally well. Changing a patient from a dry powder inhaler used well to one that the patient is unable to operate effectively could compromise asthma control. The many marketed dry powder inhalers reflect differences in design decisions that could affect lung deposition. Studies using different dry powder inhalers have confirmed that different lung deposition patterns are observed. Furthermore, there may be considerable individual variability in lung deposition. Differences in lung deposition patterns could have clinical effects. Studies may show similar clinical effectiveness with two inhalers, because most products are used at the plateau phase of the dose-response curve, although there may be differences in the adverse event profile. The ideal inhaler does not yet exist. Different dry powder inhalers show some but not all features of the ideal inhaler; hence, patients may prefer some aspects of one inhaler while favouring a different inhaler for other features. The individual balance of features will govern the overall preference for one inhaler over others. The method for operation of dry powder inhalers varies. Ease of use is seen as an important consideration when selecting an inhaler device, which should be evaluated in real-life studies using unselected patient populations. In conclusion, the evidence suggests that patients cannot use all dry powder inhalers equally well.

Administration, Inhalation↗
PubMed1989

Posture and spontaneous motility in fullterm infants.

Posture and spontaneous motor patterns during the first days of life were studied in ten healthy fullterm infants by direct observation and videorecording. The aim of the study was to provide a description of motor and postural characteristics of normal newborns. The infants were recorded for 1 h on their first and fourth day of life, when unstimulated in an incubator. Incidence and duration of the different body postures and motor patterns were scored during the replay of the videorecordings. The preference for the fully flexed posture of arms and legs described in the literature could not be confirmed. There was a large intra- and inter-individual variability in the postural repertoire. No particular posture, characteristic for each behavioural state, existed. Similar postures rarely occurred in the same infant on the first and fourth day. Extended postures more often occurred on the fourth day. Spontaneous motility consisted of several distinct movement patterns, the occurrence of which in states 1 and 2 was computed for day 1 and day 4. Motor patterns were differently related to the states. No differences were noted in the motor activity between the first and fourth days. Large inter-individual differences, but an intra-individual consistency, were found in the rates of specific motor patterns: infants who showed a low or high rate of particular movements on day 1 maintained the same characteristic on day 4. There was no overall low or high motor activity.

Female↗
PubMed2001

Inhaled endotoxin, a risk for airway disease in some people.

Despite the tremendous inter-individual variability in the response to inhaled toxins, we simply do not understand why certain people develop disease when challenged with environmental agents and others remain healthy. To address this concern, we investigated whether the toll-4 (TLR4) gene, that has been shown to affect lipopolysaccharide (LPS) responsiveness in mice, underlies the variability in airway responsiveness to inhaled LPS in humans. Here we show that common, co-segregating missense mutations (Asp299Gly and Thr399Ile) in the extracellular domain of the TLR4 receptor are associated with a significantly blunted response to inhaled LPS in 83 humans. Transfection of THP-1 cells demonstrates that the Asp299Gly mutation (but not the Thr399Ile mutation) interrupts TLR4-mediated LPS signaling. Moreover, the wild type allele of TLR4 rescues the LPS hyporesponsive phenotype in either primary airway epithelial cells or alveolar macrophages obtained from individuals with the TLR4 mutations. Our findings provide the first genetic evidence that common mutations in TLR4 are associated with differences in LPS responsiveness in humans, and demonstrate that gene sequence changes can alter the ability of the host to respond to environmental stress.

Administration, Inhalation↗
PubMedDate not supplied

Description of anxiety levels by individual differences and clinical factors in patients receiving mechanical ventilatory support.

BACKGROUND: Though anxiety is a common experience for patients receiving mechanical ventilatory support, little is known about how it may vary among patients on the basis of individual or clinical factors. There is an absence of data objectively describing anxiety levels in ventilated patients on the basis of salient factors that could be useful in designing and tailoring interventions. PURPOSE: The purpose of this study was to describe anxiety levels in a sample of mechanically ventilated patients by individual differences (eg, gender or ethnicity) and clinical factors (eg, medical indication for and length of mechanical ventilation). SAMPLE: Two hundred alert, mechanically ventilated adult patients were recruited from 9 intensive care units in the urban Midwest. METHODS: This study was a secondary analysis of existing data that used a descriptive design. Anxiety was assessed via the 20-item Spielberger State Anxiety Inventory. RESULTS: Whereas state anxiety varied widely, participants receiving mechanical ventilatory support reported moderate anxiety (mean = 49.2) with comparable levels by gender and ethnicity. Patients receiving ventilatory support for greater than 22 days tended to report slightly higher state anxiety (mean = 54.2) compared with those chronically ventilator dependent (mean = 45.8). Those participants with primarily respiratory diagnoses reported the highest levels (50.5) among the diagnostic groups. Findings from this study document the individual, variable nature of state anxiety. Additional research is needed to further elucidate whether these and other important clinical factors, such as illness severity or dyspnea, affect state anxiety ratings in ventilated patients to guide the researcher and clinician in appropriately testing and tailoring interventions.

Adaptation, Psychological↗
PubMed2001

The Behavior Problems Inventory: an instrument for the assessment of self-injury, stereotyped behavior, and aggression/destruction in individuals with developmental disabilities.

The Behavior Problems Inventory (BPI-01) is a 52-item respondent-based behavior rating instrument for self-injurious, stereotypic, and aggressive/destructive behavior in mental retardation and other developmental disabilities. Items are rated on a frequency scale and a severity scale. The BPI-01 was administered by interviewing direct care staff of 432 randomly selected residents from a developmental center between the ages of 14 to 91 years. For 73% of those selected, at least one problem was endorsed on the BPI-01. A total of 43% showed self-injury, 54% stereotyped behavior, and 38% aggressive/destructive behavior. Confirmatory factor analysis and item-total correlations supported the three a priori factors. Analyses of variance (ANOVA) showed that of the variables age, sex, and level of mental retardation, only the latter had a significant effect on the BPI-01 total score, the SIB subscale score, and the Stereotyped Behavior subscale score. Aggression/destruction was not significantly related to any of the three variables. Individuals with a diagnosis of pervasive developmental disorder had higher scores on all three subscales than those without, whereas residents with a diagnosis of stereotyped movement disorder had higher Stereotyped Behavior scale scores than those without. The BPI-01 was found to be a reliable (retest reliability, internal consistency, and between-interviewer-agreement) and valid (factor and criterion validity) behavior rating instrument for problem behaviors in mental retardation and developmental disabilities with a variety of potentially useful applications. Strengths and limitations of the instrument are discussed.

Adolescent↗
PubMed2003

Is the effect of fine-needle aspiration biopsy on the thyroid nodule volume important to evaluate the effectiveness of suppression therapy?

Fine-needle aspiration biopsy (FNAB) is recommended for the initial evaluation of thyroid nodule. If a benign cytology is obtained, suppression therapy with levothyroxine is the first choice in the management of nodular goiter with a follow-up of nodule size with ultrasonography, but the effects of FNAB have not been taken into consideration in this approach. We aimed at evaluating the effect of FNAB on thyroid volume and other ultrasonographic dimensions by measurement of these parameters before and immediately after the procedure, and in later periods, and to clarify the necessity of regarding the effects of FNAB on thyroid. Forty-six patients (34 females, 12 males; mean age: 36.3+/-10.7 yr) with solitary thyroid nodules were included in the study. The nodules were solid in ultrasonography, thyroid function tests were normal and results of FNAB were found as benign cytology. Thyroid hormone suppression therapy was not initiated. Ultrasonographic measurements were made before FNAB, repeated immediately after FNAB, and 1 month and 6 months later. There were no statistically significant changes in the mean thyroid nodule volume, nodule area and circumference of patients before, immediately after FNAB, 1 month and 6 months later. Size differences and individual variability at each time period were analyzed. These parameters changed by more than 10% in a great majority (69.5-78.2%) of patients, and more than 50% change was observed in 17.3-26.0% of patients. Changes in thyroid dimensions were bi-directional, both increment and decrement being noticed. It was thought that this is the reason why there was no significant change in mean nodule volume, area and circumference. Evaluating the difference in nodule volume according to ultrasonographic parameters obtained before FNAB may be misleading because of the individual change in these parameters with FNAB. It may be useful to evaluate the nodule size and volume closely after FNAB to make a true correspondence of these parameters in the long term.

Adult↗
PubMed1982

Ovarian follicular populations in pony and saddle-type mares.

Five pony and 5 saddle-type mares were used to compare total ovarian follicular populations between breeds. The animals were hemi-ovariectomized at the preovulatory stage during the breeding season and the ovary bearing the large preovulatory follicle was studied using histological techniques. Pony and saddle-type mares did not differ as to mean number of primordial follicles, mean number of growing follicles, the variability of these numbers and follicular distribution into various size classes. No difference was detected either in the initiation processes of follicular growth, oocyte growth, granulosa cell multiplication and follicular atresia. However, significant differences were found in the pattern of antral formation (P less than 0.01). The present data suggest that pony mares are a valuable tool for the study of follicular populations in equines. The main features of the equine ovary are the small number of follicles (35 950 primordial and 100 growing follicles) and the high individual variability of this number (5 600 to 75 000 primordial and 20 to 300 growing follicles).

Animals↗
PubMed1999

Clocks, engines, and quarks--love, dreams, and genes. What makes development happen?

That psychological growth and maturation throughout the lifespan involve progressive linear processes is an implicit assumption of all models of development. Within psychoanalysis, a particular focus has been those processes that hinder forward development and manifest themselves as regressions or fixations or in character structure. However, the implicit assumption of progressive, linear development leaves unexplored the central question of what are the processes that govern developmental progressions. What makes psychological development happen in more or less predictable ways and yet allows for considerable individual variability? And are those developmental progressions inevitably forwardly progressive? Questions regarding what regulates and integrates development are relevant not only for understanding the normal building up of the internal world and of childhood psychopathology but also for those times of dramatic mental reorganization in adulthood surrounding events such as pregnancy and aging and for issues of psychological change during and after an analysis. Clinical material from analyses with a child and an adult and from interviews with four- to five-year-old children is used to explore individual fantasies of how development and change happens. The central role of internalization and object relations in regulating psychological development is emphasized.

Adult↗
PubMed2001

The role of TLR4 in endotoxin responsiveness in humans.

Despite the tremendous inter-individual variability in the response to inhaled toxins, we simply do not understand why certain people develop disease when challenged with environmental agents and others remain healthy. To address this concern, we investigated whether the Toll-4 (TLR4) gene, that has been shown to affect lipopolysaccharide (LPS) responsiveness in mice, underlies the variability in airway responsiveness to inhaled LPS in humans. Here we show that common, co-segregating missense mutations (Asp299Gly and Thr399Ile) in the extracellular domain of the TLR4 receptor are associated with a significantly blunted response to inhaled LPS in 83 humans. Transfection of THP-1 cells demonstrates that the Asp299Gly mutation (but not the Thr399Ile mutation) interrupts TLR4-mediated LPS signaling. Moreover, the wild-type allele of TLR4 rescues the LPS hyporesponsive phenotype in either primary airway epithelial cells or alveolar macrophages obtained from individuals with the TLR4 mutations. Our findings provide the first genetic evidence that common mutations in TLR4 are associated with differences in LPS responsiveness in humans, and demonstrate that gene sequence changes can alter the ability of the host to respond to environmental stress.

Administration, Inhalation↗
PubMed1996

[Sympathetic skin responses and variability of the R-R interval: correlation with the severity stages of diabetic polyneuropathy].

The sympathetic skin responses (SSR) and the variations of the R-R interval of the electrocardiogram (the difference between the maximum and minimum heart rates at rest, the ratio between the maximum and minimum heart rates during the Valsalva manoeuvre or Valsalva ratio, and during an active orthostatic test or orthostatic ratio) have been measured in 32 control subjects and 53 diabetic patients. These latter ones were classified according to the existence and the increasing severity of a polyneuropathy (PNP) into 4 grades (0 to III) based on Dyck's classification modified depending on the presence or the absence of cutaneous impairments in grade II. There was an important inter-individual variability for SSR as well as R-R interval results, in the control group. In the absence of PNP, the vegetative tests showed normal values. These tests were severely degraded in the diabetic patients with a PNP grade III, ov even could not be performed. The SSR amplitude was decreased in all diabetic patients. In the presence of clinical signs of dysautonomia, the SSR amplitude, the heart rate variability at rest and the orthostatic ratio were significantly different from those of the control subjects. The presence of trophic disorders appearing at PNP grade II did not significantly modify the results of the tests. Although they did not allow any differentiation of the PNP intermediary grades. SSR and R-R intervals are of interest in appreciating the infra-clinical existence and the importance of the neurovegetative disorders occurring during diabetic polyneuropathies.

Adrenergic Fibers↗
PubMed2004

Discrimination ratio analysis of inflammatory markers: implications for the study of inflammation in chronic disease.

To understand the role of inflammation in chronic disease it is important to have a reliable measure of habitual inflammatory status. A number of acute-phase response markers have been used as measures of inflammatory status, but the ability of a single measure to appropriately reflect habitual inflammatory status has not been assessed. This study compares the ability of different inflammatory markers to characterize habitual inflammatory status in overweight women. A single fasting blood sample was taken from 86 overweight women (mean body mass index [BMI], 35.2 kg/m2; range, 26.2 to 47.6 kg/m2) and a number of inflammatory markers (both acute-phase response markers and cytokines) were measured. A randomly selected subpopulation of 15 women attended on 2 further occasions for further blood samples. Using the subpopulation, discrimination ratios (DRs) were calculated for each inflammatory marker to assess the within-subject variability. The DRs were then used to determine the relationship between these markers, adjusted for within-subject variability, in the whole population. In this highly controlled experimental environment, interleukin-6 (IL-6), with a DR of 3.71, was the cytokine with the greatest ability to discriminate between subjects, suggesting that it is best able to characterize habitual inflammatory status. Sialic acid was the acute-phase response marker with the highest DR (3.16), and showed stronger correlations with other inflammatory markers, including C-reactive protein (CRP), than IL-6. This study suggests that use of some inflammatory markers, such as CRP, with large within-individual variability, will underestimate the relationship between inflammation and disease, and thus relationships between inflammation and chronic disease may be stronger than previously appreciated. Future studies should consider IL-6 or sialic acid to provide a more robust measure of inflammatory status.

Acute-Phase Proteins↗