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PubMed1982

Forms of binaural summation and the implications of individual variability for binaural hearing aids.

The advantages which a two-ear system has over a one-ear system appear to be manifold, but not all understood in detail. All probably play some role in the generally recognised advantage of binaural aids in offsetting auditory disabilities. Several possible forms of binaural summation are distinguished here and their possible role discussed. Experimental results with normally-hearing listeners and with aid users show that binaural summation is likely to lead to gain settings of about 6 dB lower than with otherwise equivalent monaural amplification. In some cases this may be a direct cause of benefit. However individuals differ systematically in the extent to which they show this effect, which may be relevant to prognosis for binaural aiding. Evidence is reported of an association between binaural summation and binaural advantage. Individuals also differ systematically in binaural summation for uncomfortable loudness level.

Auditory Perception↗
PubMed2005

Individual variability in esterase activity and CYP1A levels in Chinook salmon (Oncorhynchus tshawytscha) exposed to esfenvalerate and chlorpyrifos.

Acetylcholinesterase (AChE) activity has traditionally been monitored as a biomarker of organophosphate (OP) and/or carbamate exposure. However, AChE activity may not be the most sensitive endpoint for these agrochemicals, because OPs can cause adverse physiological effects at concentrations that do not affect AChE activity. Carboxylesterases are a related family of enzymes that have higher affinity than AChE for some OPs and carbamates and may be more sensitive indicators of environmental exposure to these pesticides. In this study, carboxylesterase and AChE activity, cytochrome P4501A (CYP1A) protein levels, and mortality were measured in individual juvenile Chinook salmon (Oncorhynchus tshawytscha) following exposure to an OP (chlorpyrifos) and a pyrethroid (esfenvalerate). As expected, high doses of chlorpyrifos and esfenvalerate were acutely toxic, with nominal concentrations (100 and 1 microg/l, respectively) causing 100% mortality within 96 h. Exposure to chlorpyrifos at a high dose (7.3 microg/l), but not a low dose (1.2 microg/l), significantly inhibited AChE activity in both brain and muscle tissue (85% and 92% inhibition, respectively), while esfenvalerate exposure had no effect. In contrast, liver carboxylesterase activity was significantly inhibited at both the low and high chlorpyrifos dose exposure (56% and 79% inhibition, respectively), while esfenvalerate exposure still had little effect. The inhibition of carboxylesterase activity at levels of chlorpyrifos that did not affect AChE activity suggests that some salmon carboxylesterase isozymes may be more sensitive than AChE to inhibition by OPs. CYP1A protein levels were approximately 30% suppressed by chlorpyrifos exposure at the high dose, but esfenvalerate had no effect. Three teleost species, Chinook salmon, medaka (Oryzias latipes) and Sacramento splittail (Pogonichthys macrolepidotus), were examined for their ability to hydrolyze a series of pyrethroid surrogate substrates and in all cases hydrolysis activity was undetectable. Together these data suggest that (1) carboxylesterase activity inhibition may be a more sensitive biomarker for OP exposure than AChE activity, (2) neither AChE nor carboxylesterase activity are biomarkers for pyrethroid exposure, (3) CYP1A protein is not a sensitive marker for these agrochemicals and (4) slow hydrolysis rates may be partly responsible for acute pyrethroid toxicity in fish.

Acetylcholinesterase↗
PubMed2005

Resistance and susceptibility to weight gain: individual variability in response to a high-fat diet.

An obesigenic environment is a potent force for promoting weight gain. However, not all people exposed to such an environment become obese; some remain lean. This means that some people are susceptible to weight gain (in a weight-promoting environment) and others are resistant. Identifying the characteristics of appetite control and food motivation in these two groups could throw light on the causes of weight gain and how this can be either treated or prevented. We have investigated the issue experimentally by identifying people who habitually consume a high-fat diet (greater than 43% fat energy). These individuals have been termed high-fat phenotypes. We have compared individuals, of the same age (mean=37 years old) and gender (male), who have gained weight (BMI=34) or who have remained lean (BMI=22). The susceptible individuals are characterised by a cluster of characteristics including a weak satiety response to fatty meals, a maintained preference for high-fat over low-energy foods in the post-ingestive satiety period, a strong hedonic attraction to palatable foods and to eating, and high scores on the TFEQ factors of Disinhibition and Hunger. The analysis of large databases suggests that this profile of factors contributes to an average daily positive energy balance from food of approximately 0.5 MJ. This profile of characteristics helps to define the symptomatology of a thrifty phenotype.

Appetite↗
PubMed2006

Individual variability and photic entrainment of circadian rhythms in golden spiny mice.

Golden spiny mice are diurnally active in most of their natural habitat. Their diurnal activity is ascribed to non-photic cues: competitive exclusion from the nocturnal niche, or thermoregulatory considerations. Here we studied the entrainment of golden spiny mice to light. In the laboratory, golden spiny mice were primarily nocturnal and displayed an unusual variety of rhythm patterns, with activity bursts occurring during both activity and rest periods. Spontaneous shifts of activity rhythms between light phases were sometimes recorded. In all cases but one, body temperature shifted in parallel with activity. Under DD conditions, the free running period (tau) of all individuals but one was shorter than 24 h, and in all individuals but the same one it was shorter than tau under LL conditions. In response to a 6 h phase delay, all individuals entrained to the new LD cycle in a relatively uniform way. During phase advance four out of the twelve individuals further delayed their activity and body temperature rhythms, and eight individuals advanced their activity rhythm, but the re-entrainment took them over twice as long as to re-entrain to the phase delay. We suggest that the golden spiny mouse is a nocturnal rodent whose circadian system developed the flexibility to be nocturnal or diurnal according to environmental conditions, or a nocturnal rodent in the process of turning diurnal, and that it has low sensitivity to the immediate masking effect of light on activity.

Animals↗
PubMed1990

Diurnal and monthly intra-individual variability of the concentration of lipids, lipoproteins and apoproteins.

Diurnal and monthly variability of the serum concentration of lipids, lipoproteins and apoproteins were examined in 11 healthy subjects aged 32-63 (mean 46) years. For diurnal measurements, blood samples were drawn at 0800, 1200, 1500, 1800, and 2100 hours. The variability over 1 month was assessed from four analyses taken weekly at 0800 hours after at least 8 h fast. The analytical variability expressed as mean coefficient of variation (CV) ranged from 0.95% for cholesterol to 7.6% for apoprotein B. The mean CVs for diurnal biological variability were 2.4% for cholesterol, 3.5% for HDL-cholesterol, 5.1% for LDL-cholesterol, 29.5% for triglycerides, 6.5% for apoprotein A and 6.5% for apoprotein B. The respective biological CVs for monthly variability were 4.2%, 4.1%, 5.2%, 20.7%, 9.4% and 9.7%. A repeated-measures ANOVA revealed a significant increase of triglycerides (p less than 0.01) and decrease of LDL-cholesterol (p less than 0.01) during the day. Within 1 month, apoprotein A tended to rise (0.05 less than p less than 0.10). Although the best reproducibility was found for cholesterol, the results obtained indicate that six tests have to be taken before and after intervention by drug or diet to detect a reduction of 10% in an individual with a probability of 0.95.

Adult↗
PubMed1986

Cerebrospinal fluid monoamine precursor and metabolite levels in children treated for leukemia: age and sex effects and individual variability.

Lumbar cerebrospinal fluid (CSF) was obtained from children during and following treatment for acute lymphoblastic leukemia (ALL). One hundred ninety-two CSF samples from 50 subjects, which were selected to minimize the effects of the disease and its treatment (i.e., to approach "normality" as closely as possible), were analyzed for the monoamine precursors tyrosine (Tyr) and tryptophan (Trp) and the metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA). Levels of HVA (p less than 0.0001), 5-HIAA (p less than 0.002), and Tyr (p less than 0.05) decreased with age from 3 to 17 years. Significant correlations were observed between the acid metabolites HVA and 5-HIAA (r = 0.79) and between the amino acid precursors Tyr and Trp (r = 0.71). Within individuals, levels of all four compounds were relatively stable over time, with total mean coefficient of variation ranging from 20% to 25%. No significant sex differences for CSF levels of HVA, 5-HIAA, Tyr, or Trp were found. Assessment of CSF monoamine precursors and metabolites in children treated for ALL may provide a method for understanding the chronic effect of CNS trauma on the ontogeny of monoamine systems.

Adolescent↗
PubMed2005

Psychophysiological correlates of the inter-individual variability of head movement control in seated humans.

We recently conducted experiments where 24 seated participants were subjected (with eyes closed) to small amplitude, high-jerk impulses of linear acceleration. Responses were distributed as a continuum between two extremes. The "stiff" participants showed little movement of the head relative to the trunk, whereas the "floppy" participants showed a large head rotation in the direction opposite the sled movement. We hypothesized that the stiff behavior resulted from the spontaneous use of an imagined visual frame of reference and undertook this larger-scale study to test that idea. The distribution along the "stiff-floppy" continuum was compared with the scores on psychophysiological tests measuring vividness of imagery, visual field-dependence and motion sickness susceptibility. Multivariate regression analysis revealed that the "stiffness" of individuals was loosely, but significantly related to the vividness of their imagery. However, "stiffness" was not linked to visual field-dependence or motion sickness susceptibility. Even if it explains only 20% of the variance of the data, the increase of "stiffness" with vividness of imagery fits our hypothesis. With eyes closed, stiff people may use imagined external visual cues to stabilize their head and trunk. Floppy people, who are poorer imagers, may rely more on "egocentric", proprioceptive and vestibular inputs.

Acceleration↗
PubMed2000

Individual variability of dopamine release from nucleus accumbens induced by nicotine.

Effects of subcutaneous administration of vehicle, amphetamine (1 mg/kg) or nicotine (0.4 mg/kg, injected twice, 90 min apart) on extracellular dopamine (DA) concentration in the nucleus accumbens (ACC) and ventral tegmental area (VTA) of the Sprague-Dawley rat were studied using microdialysis. Experiments were conducted at least 10 days following implantation of guide cannulae, and at least 2 h following insertion of microdialysis probes into the guides on the morning of each experiment. Probes were perfused at 2.5 microl/min and several fractions were collected every 10 min before and after the two test injections. Samples were analyzed by high-performance liquid chromatography with electrochemical detection for the major neurotransmitters and their metabolites. Significant DA release following nicotine administration was observed in ACC but not in VTA. By classifying ACC DA responses of individual rats, three major subgroups were identified which exhibited more robust responses. Nicotine appeared to be acting as a modulator of ACC DA, increasing DA output if baseline was <5 nM, but slowing release when the baseline exceeded 5 nM. These data are consistent with previous reports of modulation of arousal level by nicotine via DA.

Animals↗
PubMed1999

Adrenocorticotropin-related modulation of the human EEG and individual variability.

During a 6-h period in resting conditions, the blood concentrations at rest of cortisol, glucose and the adrenocorticotropic hormone (ACTH) varied spontaneously within physiological ranges in eight healthy male volunteers (24.5+/-1.7 years), without pulsatile changes, correlation among variables, or indications of stress response. The power of the 6.5-14.0 Hz physiological 'alpha' rhythm of the electroencephalogram (EEG) proved inverted-U correlated with the ACTH concentration (with maximum power at 12-14 pmol/l ACTH) but was independent from the extent of ACTH change or from cortisol/glucose concentrations. Two subgroups of subjects with low/high EEG power values could be separated depending on ACTH concentration, with estimated cut-off at 7-8 pmol/l. A direct ACTH modulation of brain electrophysiology or common factors (e.g. the corticotropin-releasing hormone) pacing both ACTH and EEG are suggested and may account for individual EEG differences.

Adrenocorticotropic Hormone↗
PubMed1992

Individual variability of pathological parameters in chemically induced rat colon tumors.

The development of tumorigenic conditions in the carcinogen-exposed rat colon was studied using selected morphological, histochemical, immunohistochemical and biochemical methods of analysis. Rats were treated with two carcinogens: 1,2-dimethylhydrazine and N-methyl-N'-nitro-N-nitrosoguanidine alone or with deoxycholic acid as a tumor promoter. It was found that 3 months after treatment of animals with the carcinogens the following changes were developed in colonic tissue: infiltration of lymphocytes in the mucous membrane, high increase in mitotic index among epithelial cells, negative reactions of colonic cells for neutral mucopolysaccharides and sulfomucins and positive reactions to carboxyl groups, nonsulfated acid mucosubstances and tissue polypeptide antigens. An increase in the activity of ornithine decarboxylase in colonic tissue was developed within the same time period and has been seen only in those tissues which were characterized by the development of precancerous conditions. Individual variations were observed in the manifestation of the studied parameters in rat neoplastic colonic tissues. It is suggested that these differences reflect an individual sensitivity of animals to carcinogens and the magnitude of the dysplastic processes induced in the colon.

1,2-Dimethylhydrazine↗
PubMedDate not supplied

[The cytoarchitectonic characteristics of the speech center of the brain in gifted people in the plan to study individual variability of human brain structure].

Cytoarchitectonics of cerebral cortical fields 44 and 45 was studied in gifted people in comparison with the group of people without creative professional talents. Frontal paraffin sections 20 mkm thick were examined. Both histological and modern quantitative methods were used with the aid of "Videoplan" computer. Peculiarities in the cytoarchitectonics of cortical fields 44 and 45 and, in particular, in expression of the nerve cell horizontal and vertical orientation and in the characteristics of the certain cortical fields delimination were demonstrated. Increase of pyramidal neuron glial index and of peculiarities of neurons regrouping in cytoarchitectonic layers III and IV was noted.

Adult↗
PubMed2005

Osteosarcoma cell lines display variable individual reactions on wildtype p53 and Rb tumour-suppressor transgenes.

BACKGROUND: One of the most widely studied gene therapeutic strategies for cancer is the introduction of tumour-suppressor genes-generally p53-into the target cells. As the genes of p53 and/or retinoblastoma (Rb) are mutated in the major part of osteosarcomas (OS), we aimed to study the effect of p53 and Rb transgenes on a panel of five different osteosarcoma cell lines. METHODS: OS cell lines were transduced by adenoviral vectors delivering the transcription units of the wildtype p53 and the Rb gene. Effects of the transgenes alone and at additional cytostatic stress were studied by proliferation, alive/dead and cell cycle assays. RESULTS: The individual cells lines displayed divergent reactions to p53- or Rb-transgene delivery reaching from cell death (SaOs-2, U2OS at p53 transduction) over stopped or lowered cell division (MG-63, K-HOS, SJSA-1 at p53 and Rb transduction) to nearly unhindered cell growth (U2OS at Rb transduction). In those OS cell lines reacting with lowered cell division to p53 or Rb delivery, cytostatics only moderately intensified the transgene effects. Surprisingly, these reactions were apparently not dependent on the functional status of the cellular p53 and/or Rb genes or on differences in the infectability of the cell lines by the adenoviral vectors. Most interestingly, the respective effects of the p53 or Rb transgenes were not multiplied by simultaneous transduction of both tumour-suppressor genes. CONCLUSIONS: The application of wildtype tumour-suppressor gene therapy on genetically variable osteosarcomas may be efficient only in yet not identified genetic subgroups of this tumour entity. Hyperactive tumour-suppressor transgenes could be an alternative.

Adenoviridae↗
PubMed2005

Intra-individual variability of cardiac uptake on serial whole-body 18F-FDG PET.

OBJECTIVE: To measure the variability of cardiac uptake on serial whole-body F-FDG PET scans. METHODS: Two hundred and eighteen whole-body PET scans were performed in 47 patients with different primary malignancies between October 1996 and April 2003 on a dedicated PET system. The number of scans per patient ranged between four and nine. Two experienced nuclear medicine physicians reviewed the scans retrospectively using the non-attenuation corrected images to assess the cardiac FDG uptake. Patients with cardiac uptake less or equal to lung uptake were assigned in the "low" uptake group, and those with cardiac uptake more than the lung uptake were assigned to the "high" uptake group. The reproducibility of cardiac uptake on serial whole-body PET scans and the effect of age, sex, weight, diabetes and primary diagnosis on cardiac uptake was evaluated. RESULTS: There was very good reproducibility (intra-class correlation coefficient=0.77) of individual cardiac FDG uptake on serial whole-body PET scans. Diabetics (n=6) in comparison to non-diabetics were less likely to have high cardiac uptake (odds ratio (OR)=0.24, P<0.05). Patients with lymphoma (n=12) in comparison to patients with other primary diagnoses were more likely to have high cardiac uptake (OR=8.6, P<0.05). There was no association between cardiac uptake and age, sex or weight. CONCLUSION: Cardiac FDG uptake on whole-body PET does not appear to change significantly over time. It is likely that uptake is determined by individual characteristics; these likely include diabetes and primary diagnosis of lymphoma.

Adult↗
PubMed1996

Lung function testing: the dilemma of predicted values in relation to the individual variability.

Quantitated lung function parameters are usually interpreted in relation to so-called "normal ranges' obtained from healthy study groups. The aim of this paper is the critical review of formulas and the evaluation of intraindividual variation in modern lung function testing. To which extent is the total variation of lung function parameters in cross-sectional studies (usually serving as basis for the normal range) attributed to the intraindividual variation between repeated measurements? This question raises a further question: are lung function values in the normal range really normal? To assess spirometric and body plethysmographic parameters 26 healthy subjects from three medical centers underwent 30-72 measurements over a period of 2 months for the determination of variations due to (1) intraindividual variation over time and (2) interindividual variation. For each subject, predicted values of different lung function parameters published by Quanjer et al. [Eur Respir J 1993; 6:5-40.1], of intrathoracic gas volume by Ulmer et al. [Die Lungenfunktion; Stuttgart, Thieme, 1991] and of total airway resistance by Ruehle and Matthys [Pneumologie 1976;153:223] were applied. When converted into percent predicted and adjusted for differences in medical centers, the intraindividual standard deviation was estimated to be about half of the interindividual standard deviation. We conclude that the normal range of lung function parameters derived from the standard deviation within populations is too wide for the assessment of individual values. Interpretation of individual lung function measurements should primarily be based on the "individual normal range' derived from former lung function measurements of the individual and only secondly on the "predicted value'.

Adult↗
PubMed1996

Excretion of urinary N-telopeptides reflects changes in bone turnover during ovarian suppression and indicates individually variable estradiol threshold for bone loss.

OBJECTIVE: To evaluate the effectiveness of N-telopeptides and E2 in monitoring bone turnover during GnRH agonist- (GnRH-a) or danazol-induced hypoestrogenism. DESIGN: Comparative, nonrandomized prospective study. SETTING: Institute for the Study and Treatment of Endometriosis. PATIENT(S): Premenopausal women undergoing ovarian suppression with GnRH-a (n = 16) or danazol (n = 9). INTERVENTION(S): Serum and urine samples were collected and bone mineral density was measured before, during, and after treatment. MAIN OUTCOME MEASURE(S): N-telopeptide excretion, serum E2, and bone mineral density at L1 to L4 and femoral neck. RESULT(S): During treatment in the GnRH-a group, mean E2 levels were 53% below and N-telopeptides were 38% above the mean baseline. At 1 month post-treatment, L1 to L4 bone mineral density decreased by 3.85%. In the danazol group, E2, N-telopeptides and L1 to L4 bone mineral density changed nonsignificantly in the opposite direction with the mean 1.25% increase in L1 to L4 at 1 month post-treatment. In combined groups, L1 to L4 bone mineral density better correlated with other measures than femoral neck bone mineral density. N-telopeptide excretion was more predictive of L1 to L4 change, with correlation the highest between N-telopeptides at month 4 and bone mineral density at month 1 afterward, while E2 appeared more predictive of the less reliable femoral neck bone mineral density. Individual exceptions to the model of an E2 threshold for bone loss were observed. Also noted were high correlation between on-therapy levels of E2 and N-telopeptides, as well as the presence of a 1-month time lag between E2 and N-telopeptide changes. CONCLUSION(S): Bone density decreases during GnRH-a and may slightly increase during danazol treatment. However, E2 threshold for bone loss varies individually. N-telopeptides predict changes in bone mineral density at L1 to L4 better than E2.

Adult↗
PubMed2002

Cerebral blood flow changes in depressed patients after treatment with repetitive transcranial magnetic stimulation: evidence of individual variability.

OBJECTIVE: To elucidate the neural mechanisms of depression. BACKGROUND: Despite extensive study, the neurophysiology of the brain's state(s) corresponding to depression remains uncertain. METHODS: HMPAO single photon emission computed tomographic (SPECT) scans were obtained from eight adults diagnosed with major depression resistant to medication (average age 51 years; 4 men) before and immediately after 10 days of 20 Hz repetitive transcranial magnetic stimulation (rTMS) (2000 stimuli/daily 30' treatment). To maximize the likelihood that SPECT scans reflected the state of depression, rather than uncontrolled responses of patients to poorly constrained environments, HMPAO was administered while subjects performed a simple task involving continuous monitoring of the direction of a large arrow on a computer screen and continuously tapping with the left or right index finger according to the direction of the arrow. Mean baseline Beck Depression Inventory (BDI) score was 27.4 (SD = 8.3) and mean posttreatment BDI score was 17.5 (SD = 8.5). RESULTS: Treatment responders (defined by reduction in BDI score of > or = 30%) had significantly less pretreatment blood flow in the left amygdala compared with nonresponders. Responders demonstrated two patterns of change in regional blood flow with treatment: a reduction in orbitofrontal blood flow and/or a reduction in anterior cingulate blood flow. Nonresponders did not demonstrate any regional changes in blood flow with treatment. CONCLUSIONS: These results suggest that there may be either more than one state of depression, or that depression may be associated with more than one pattern of psychologic activity, which in turn defines the depressive experience for individual patients.

Adult↗
PubMed2000

[The p300 cognitive event-related potential. II. Individual variability and clinical application in psychopathology].

The P300 wave is one of the cognitive components of the event-related potential (ERP) that is used to investigate the cognitive processes, and which can be used to study patient populations with a variety of psychiatric disorders. Its clinical utility has been increased by the identification of factors that contribute to the variability in its amplitude and latency. However, its value as a diagnostic index has not been entirely established. It can provide a useful recording of patients' information processing, and indicate the severity of the clinical state and its possible evolution. It can also assist in determining what therapeutic approach to adopt. In the present review, the findings in the literature concerning interindividual variation in the P300 wave are first described; several variables significantly influence the amplitude and latency of this wave, such as age, gender, intelligence and personality. Following this, the relevance of the data in the literature on the clinical applications of P300 in psychopathology is examined, including the studies undertaken to obtain an objective diagnostic index for mental disorders and also those carried out to assess the problems concerning the interpretation of information connected with the mental pathologies examined. P300-associated findings on dementia, schizophrenia, depression, alcoholism, drug addiction, anxiety disorders (panic disorder, obsessive-compulsive disorder, and post-traumatic stress syndrome) and on personality disorders (schizoid, antisocial or borderline personality disorder) have been examined in detail.

Aging↗
PubMed2000

Individual variability in the zinc inducibility of metallothionein-IIA mRNA in human lymphocytes.

The metallothionein-III gene (MT-IIA) is a major member of the human MT gene family. Metallothioneins (MTs) are low-molecular-weight, cysteine-rich proteins that bind and detoxify heavy metals. At least two different MT-IIA polymorphisms have been identified in humans, one or both of which may affect susceptibility to metal toxicity. The purpose of this study was to investigate whether these different genotypes affect the inducibility of MT-IIA mRNA in human lymphocytes treated with zinc (Zn), the major known inducer of MT-IIA in vitro. Fresh lymphocytes obtained from 16 healthy volunteers, aged 23-38 yr, were genotyped for the MT-IIA gene and tested for expression. A 43.5-bp HindIII-Taql fragment of the MT-IIA promoter was used to probe for the two known polymorphisms (a 7.8-kb vs. a 5.3-kb fragmnent, and a 1.7-kb vs. a 1.6-kb fragment). The allele frequencies of the 16 subjects were 14%, for 5.3-kb allele and 19% for 1.6-kb allele. In Northern blotting experiments, MT-II mRNA levels were induced over a wide range of Zn concentrations during 2-h exposures; specifcally, levels increased by 9- to 115-fold with exposure to 100 microM ZnCl, and by 16- to 311-fold with exposure to 200 microM ZnCl2. However, no significant differences in MT-IIA inducibility were found between the 7.8/5.3-kb allele pair (n = 4) and the 7.8/7.8-kb allele pair (n = 12) or between the 1.7/1.6-kb allele pair (n = 5) and the 1.7/1.7-kb allele pair (n = 11). Thus. MT-IIA is strongly inducible by Zn in human lymphocytes, but individual variations exceed those that can be attributed to the known promoter-region polymorphisms.

Adult↗