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PubMed1997

Does unhappiness make you sick? The role of affect and neuroticism in the experience of common physical symptoms.

The relative strength of both affective state and the personality trait neuroticism in predicting common physical symptoms was tested. The authors used an event-sampling design to overcome methodological limitations of past research in the area. Contrary to much previous research, neuroticism was found to be unrelated to reports of physical symptoms, although it was found to be related to unpleasant affective state. Unpleasant affect bore a strong concurrent relation to the frequency of reported symptoms. Temporal relations between experiences of unpleasant affect and subsequent symptoms were found for some individuals, but wide individual variability was seen in both the strength and direction of this linkage. The findings suggest that when individuals are asked to report their subjective experiences of physical illness without the necessity to retrospect over significant periods of time, unpleasant affective state is more strongly related to experiences of symptoms than is the trait neuroticism.

Adaptation, Psychological↗
PubMed2001

Patient dosimetry after 131I-MIBG therapy for neuroblastoma and carcinoid tumours.

AIM: The aim of the study was to determine the equivalent total body dose (ETBD) using the cytokinesis-blocked micronucleus assay in 22 131 I-meta-iodobenzylguanidine (131 I-MIBG) therapies (18 neuroblastoma, mean 5097 MBq, SD 1591; and four carcinoid tumours, mean 7681 MBq, SD 487). The results are correlated with the total body radiation dose according to the Medical Internal Radiation Dosimetry (MIRD) formalism. METHODS: For each patient, blood samples were taken immediately before and 1 week after 131I-MIBG therapy. The first blood sample was irradiated in vitro with 60Co gamma-rays to determine the dose-response curve. Micronuclei were scored in 1000 binucleated cells. By using the dose-response curve the ETBD was derived from the increase in micronuclei after 131I-MIBG therapy (second blood sample). Based on three consecutive biplanar scans taken at 3, 6 and 9 days post-administration respectively, the total body dose following the MIRD formalism was calculated. RESULTS: The micronucleus assay was evaluable in only 14 out of 22 131I-MIBG therapies due to cell division inhibition caused by previous chemotherapy treatments and lymphocyte dilution due to blood transfusions given shortly after 131I-MIBG therapy. For these 14 therapies, the mean micronucleus yield after 131I-MIBG therapy was significantly increased (P < 0.01) with a mean of 92 (SD 77) for neuroblastoma patients and with a mean of 35 (SD 8) for carcinoid patients. The increase observed in the present study is greater than previously observed after 131I therapy and 89Sr therapy but much lower than after external beam radiotherapy. For all patients treated with multiple therapies, the initial increase in micronucleus yield had at least partially recovered by the time of the next therapy. This might be explained by an increased turnover of lymphocytes. A mean ETBD of 0.95 Gy (SD 0.55) for neuroblastoma patients and a mean of 0.46 Gy (SD 0.09) for carcinoid patients was calculated. A reasonable correlation (R = 0.87) between the ETBD and the MIRD dose was obtained. The slope value of 0.75 can be explained by the low dose rate effect. CONCLUSIONS: The observation in the present study of important inter-individual variability in the total body dose, with the possibility of high dose values, suggests the necessity of individual dosimetry when administering 131I-MIBG therapy, especially considering that generally more than one therapy is given to each patient.

3-Iodobenzylguanidine↗
PubMedDate not supplied

Academic achievement of children with epilepsy.

The academic achievement scores of 122 children with epilepsy were examined in relation to demographic and clinical seizure variables. As a group, these children were making less academic progress than expected for their age and IQ level. Academic deficiencies were greatest in arithmetic, followed by spelling, reading, comprehension, and word recognition. Results of the multiple regression analyses indicated a modest combined predictive significance of the demographic and clinical seizure variables for academic performance. In addition, the magnitude of these relationships varied by academic area. Among the individual variables examined the strongest correlates of academic performance were age of the child, age of seizure onset, lifetime total seizure frequency, and presence of multiple seizures (absence and tonic-clonic). These results are discussed in relation to developing an understanding of the factors which underlie academic vulnerability in children with epilepsy.

Achievement↗
PubMed1988

Discrimination of anterograde from retrograde atrial electrograms for physiologic pacing.

The morphology of bipolar electrograms recorded in the right atrium was examined in nine patients in an attempt to discriminate retrograde from anterograde atrial signals to an extent that would be useful for physiologic pacing. Peak-to-peak amplitude, duration, square root of energy (energy), maximum slew rate, mean slew rate, and polarity were examined in the time domain. Maximum frequency, half-power frequency, Fourier amplitude peak, and frequency of peak were measured in the frequency domain. There was a significant difference between anterograde and retrograde signals for all variables related to amplitude; these variables are peak-to-peak amplitude, energy, Fourier amplitude peak, maximum slew rate and mean slew rate. In seven of nine patients there was at least one variable sufficiently discriminating to insure reliable detection of anterograde signals while systematically rejecting retrograde signals. However, no individual variable was able to effect this discrimination in more than four patients and at least three variables were needed for all seven patients: maximum frequency, one of either energy and Fourier amplitude peak, and one of either frequency of peak or half-power frequency (six possible combinations). Thus, although differences between anterograde and retrograde atrial activity can be demonstrated in most patients, no single parameter displays sufficient discriminating power to facilitate physiologic pacing in patients exhibiting retrograde activity.

Atrial Function↗
PubMed2006

Relevance of assessing drug concentration exposure in pharmacogenetic and imaging studies.

Pharmacodynamic differences are difficult to interpret without drug concentration data. In particular, variability in drug exposure may confound the interpretation of pharmacogenetic, therapeutic outcome, and neuroimaging studies. Inter-individual variability in concentrations can be quite high due to variable adherence and pharmacokinetics. For example, clearance may be influenced by genetics, drug interactions, age and illness. We review findings that acute responses to selective serotonin reuptake inhibitors can have a concentration-response relationship using positron emission tomography and neuroendocrine measures. We also present preliminary evidence that the concentration-response relationship for paroxetine is influenced by genotypic differences at the serotonin transporter promoter. In large clinical studies, the accurate assessment of drug exposure can be challenging, with several techniques used to assess exposure. Population pharmacokinetics (Pop PK) is a method that is ideally suited for analysing concentration data from large trials because both patient-specific and population parameters can be determined with only a small number of plasma samples per patient. As opposed to relying on prescribed doses or a single trough level, the ability to determine more accurately exposure with Pop PK reduces the heterogeneity introduced by exposure variability. Pop PK hierarchic Bayesian approaches have been effective for characterizing anticonvulsants, antibiotics, antineoplastics and antiarrhythmics. We have recently successfully incorporated these pop PK analyses into routine assessments of elderly patients in clinical trials of selective serotonin reuptake inhibitors (SSRIs) and second generation antipsychotics. For the design and interpretation of neuroimaging, pharmacogenetic, and behavioural studies, the assessment of drug concentration exposure is therefore feasible and has potentially important ramifications.

Clinical Trials as Topic↗
PubMed2006

Evidence of the exploitation of marine resource by the terrestrial insect Scapteriscus didactylus through stable isotope analyzes of its cuticle.

BACKGROUND: About 4 x 10(5) eggs in more than 5000 marine turtle nests are deposited every year on a 3.6 km long beach in French Guiana (South America). The dry biomass of eggs is estimated to be 5 x 10(3) kg, yet only 25% of this organic matter will return to the ocean in the form of hatchlings. Such amounts of organic matter are supposed to drive the functioning of the beach ecosystem. Previous studies have shown that egg predators and detritivorous organisms dominate the trophic relationships and the dynamics of the system. The role of a terrestrial insect Scapteriscus didactylus (Latreille), which damages up to 40% of the eggs of the marine turtle (Dermochelys coriacea), was unexpected. However it was impossible from direct observations to prove that the mole cricket consumed a significant amount of these eggs. Therefore, the precise place of the mole cricket in the nitrogen and carbon cycles of the beach ecosystem could not be determined. In order to answer this question, we looked for a marine signature of carbon and nitrogen source metabolized by the mole cricket. RESULTS: This study estimated the individual variability of delta13C and delta15N in the cuticle of Scapteriscus didactylus. The isotopic signature was compared between individuals collected at two sites: a village where mole crickets fed on human food scraps and the nearby Awala-Yalimapo beach, where food availability depends seasonally on the nesting sea turtles. The mole crickets collected near the habitations garbage showed no significant variations in the stable isotopic signature, within-and between age groups. On the contrary, isotopic values shifted from a signature of a terrestrial herbivorous diet in the mole crickets during early developmental stages, to isotopic values in adults in accordance with the exploitation of marine animal resources. CONCLUSION: The heterogeneity of individual signatures during the year is due to a selective exploitation of the food sources, differing in space and time. Some individuals, from the beach sample consumed a sufficient quantity of turtle eggs to induce the increase of isotopic enrichment observed in the cuticle. Scapteriscus didactylus is an opportunist feeder and plays a role in the turn over of the beach organic matter.

Animals↗
PubMed2000

Primary care, income inequality, and self-rated health in the United States: a mixed-level analysis.

Using the 1996 Community Tracking Study household survey, the authors examined whether income inequality and primary care, measured at the state level, predict individual morbidity as measured by self-rated health status, while adjusting for potentially confounding individual variables. Their results indicate that distributions of income and primary care within states are significantly associated with individuals' self-rated health; that there is a gradient effect of income inequality on self-rated health; and that individuals living in states with a higher ratio of primary care physician to population are more likely to report good health than those living in states with a lower such ratio. From a policy perspective, improvement in individuals' health is likely to require a multi-pronged approach that addresses individual socioeconomic determinants of health, social and economic policies that affect income distribution, and a strengthening of the primary care aspects of health services.

Adolescent↗
PubMed1999

Experimental forensic and bioanthropological aspects of soft tissue taphonomy: 1. Factors influencing postmortem tissue desiccation rate.

Euthanized rats' carcasses were exposed in an environmental chamber to multiple variables including: (1) position, (2) enveloping clothing, and (3) soil interment in an effort to determine the individual variables' effect on postmortem rate of body and visceral organ water loss. Results indicated that body water loss was enhanced by a horizontal position versus vertical, probably because of wider spread of bacteria- and enzyme-laden abdominal fluid secondary to diaphragm digestion with consequent greater tissue digestion and liquefaction. Clothing also accelerated the desiccation rate. Desiccation was about equally as effective by soil interment as by air exposure, though simulating windy conditions by tripling the air flow rate resulted in much more rapid desiccation in the air-exposed specimen. These studies suggest that the single most important factor influencing postmortem body water loss rate is the environment at the skin surface that acts to enhance or impair water removal from the skin surface and thus influences the water concentration gradient between the skin and underlying deeper tissues.

Animals↗
PubMed1985

Use of the Bayley Scales to characterize abilities of premature infants.

The Bayley Scales of Infant Development were administered to 92 white, middle-class infants, half of them premature and half full-term, at 1 year of age from term to determine whether this instrument is useful in characterizing the abilities of premature infants. Although both full-term and premature infants achieved mental and motor development scores within the average range, full-term infants attained significantly higher scores on both the Mental and Motor Scales. Both groups scored significantly lower on motor than mental functioning; however, the difference was significantly greater for premature infants. As a group, premature infants also evidenced greater variability in their performance on both the Mental and Motor Scales, and they showed greater intra-individual variability in performance of motor ability. Furthermore, premature infants were less likely to succeed on items testing eye-hand coordination, imitation, and vocalization. Preselected perinatal risk variables accounted for a significant amount of variance in both mental and motor ability of premature infants.

Birth Weight↗
PubMed2000

Development of a disease activity index for the assessment of reactive arthritis (DAREA).

OBJECTIVES: The objectives of this study were to investigate and validate individual variables and to develop a composite score for disease activity measurement in patients with reactive arthritis (REA). METHODS: In the first cross-sectional part, the clinical and laboratory evaluation of 45 patients was used to elaborate the most important individual disease activity measures. In the second prospective part, these variables as well as a composite score for disease activity measurement of REA were prospectively validated in 23 patients at two points in time. RESULTS: The following variables emerged as the most useful for the composite measure: number of swollen and tender joints, patient's pain and global assessment, and C-reactive protein. The score was calculated by simple addition of the individual figures. CONCLUSION: DAREA constitutes a reliable score which can easily be assessed on a day-to-day office work basis.

Adult↗
PubMed1991

Biological exposure and/or effect limits, facts, fallacies and uncertainties: general principles.

When looking for facts, fallacies and uncertainties of the use of biological exposure limits one has at first to discuss the general principles of biological monitoring (BM) and biological effect monitoring (BEM) because they determine the validity of the data that underpin the biological exposure limits. A difference between countries in preferred BM-methods can be observed. The terminology is still confusing: in addition to BM and BEM, biomonitoring and biological markers also are used. There are a number of problems in respect of the inter- and intra-individual variability in internal exposure and effect at similar exposure levels due to differences in for example, physical workload, body composition and genetics. Toxicokinetic models based on data from individual workers should be developed in order to get information on the variability and the cause of this. Both kinetics and dynamics may be sex-dependent. To date, BM methods have been tentatively suggested for only about 10 per cent of the regulated industrial chemicals. BM and BEM programmes yield important extra information on exposure and health risk, not to be gained by environmental monitoring alone.

Environmental Monitoring↗
PubMed1996

Factors related to dissociation among patients with gastrointestinal complaints.

OBJECTIVES: Several recent reports have suggested that the process of dissociation is independently associated with several distressing conditions such as psychiatric diagnoses, somatization, current psychological distress, and past sexual and physical victimization. These studies, however, have not taken into account possible shared variance between these variables. Is dissociation uniquely related to each of these outcomes or do they, as a group, have common underlying factors that account for the relationship with dissociation? METHOD: As part of a larger study of gastroenterology clinic patients with irritable bowel syndrome and patients with inflammatory bowel disease (n = 103), we used stepwise multiple regression to select the factors most associated with dissociation, while controlling for the effects of other variables. Variable domains included demographics, psychiatric diagnoses, personality factors, functional disability, and trauma history. These domains as well as individual variables within these domains were systematically evaluated for their unique contribution to the prediction of dissociation as measured by the Dissociative Experiences Scale (DES). RESULTS: The best multivariable model for estimating dissociation magnitude included severe child sexual abuse, perceived physical disability, and lifetime dysthymia, alcoholism, and generalized anxiety disorder. These factors accounted for 37% of the variance in DES score and increased the correct classification of patients as either low-, middle-, or high-level dissociators. CONCLUSIONS: Dissociation among this convenience sample of IBS and IBD patients is a long-term coping pattern that is associated primarily with past sexual trauma, chronic emotional distress, alcoholism, and physical disability. Prospective studies are needed to test whether these findings also occur in other more generalizable samples.

Adolescent↗
PubMed1992

Reference values for early markers of renal damage.

In addition to the difficulties related to the definition of a reference population and hence of reference limits, special methodological problems have to be dealt with when early markers of renal damage are applied to monitor groups at risk. The urinary excretion of both high and low molecular weight proteins, as measured by sensitive immunoassays, is routinely applied in health surveillance programmes aimed at preventing the occurrence of adverse renal effects resulting from exposure to nephrotoxic chemicals, among which are several metals. Owing to the large intra-individual variability experimentally demonstrated for all indicators of renal impairment, carefully standardized sampling conditions must be adopted. At the individual level, repeated measurements should be performed before a diagnosis of renal disease or dysfunction is established. In fact, several physiological conditions may account for transient changes in renal function, leading to measured levels greatly exceeding reference limits.

Albuminuria↗
PubMedDate not supplied

Parameters to monitor aging with a possible perspective for intervention - an immunological approach.

Reliable aging markers are very rare, which are better than the chronological age or those symptoms which have such great individual variability that their scientific value is questionable. The effect of aging on immunological behavior of human (and animal) individuals is reasonably well established. In this communication an attempt is made to find an immunological marker of aging at the level of cell surface phenomena. It was observed that ion-channel activities, having a complex regulation, loose their flexible responsiveness in lymphocyte membranes during aging. A recently discovered voltage regulation of the calcium-activated potassium channels showed a distinct change with aging of human lymphocytes. A possibility to find a better marker system in complex regulatory processes is also discussed.

Journal Article↗
PubMed2003

A genome-wide search for genes affecting circulating fibrinogen levels in the Framingham Heart Study.

INTRODUCTION: Circulating levels of fibrinogen are associated with atherosclerosis and predict future coronary heart disease and stroke. Levels of fibrinogen are correlated among family members, suggesting a heritable component. Variants of the beta-fibrinogen gene subunit on 4q28 are associated with fibrinogen levels but explain only a small proportion of the total genetic variability. It remains unknown what role, if any, is played by other genetic variants in the inter-individual variability in levels of fibrinogen in the general population. MATERIALS AND METHODS: We conducted a 10-cM spaced genome-wide scan using 402 original cohort subjects and 1193 offspring subjects from 330 extended families of the Framingham Heart Study. Heritability and linkage analyses were carried out using variance component methods. Regression analyses were performed to adjust for traditional risk factors and HindIII beta-148 genotypes. RESULTS AND DISCUSSIONS: The total heritability was estimated as 0.24. The highest and second highest LOD scores of linkage were found on chromosomes 2 (LOD=1.5 at 243 cM) and 10 (LOD=2.4 at 87 cM) using only offspring subjects in the analysis, and on chromosomes 2 (LOD=2.1 at 242 cM) and 10(LOD=1.4 at 86 cM), 17 (LOD=1.4 at 96 cM) and 20 (LOD=1.4 at 80 cM) using both original cohort and offspring. These results suggest that there may be influential genetic regions on these chromosomes. While no linkage with genome-wide significance was detected, further research to confirm our findings is warranted.

Adult↗
PubMed2000

Inter- and intra-individual variation of faecal water - genotoxicity in human colon cells.

Exogenous nutritional factors modulate the faecal contents leading to an enhanced or reduced burden with toxic and cancerogenic factors. These factors are thought to contribute to colon cancer by inducing mutations or enhancing proliferation in colon cells. Faecal water more or less causes these effects in model systems and thus could be the basis for valuable biomarker approaches. Our investigations are aimed at determining geno- and cytotoxicity of faecal water in human colon cell lines in vitro. We are developing techniques for their applicability as biomarker tests during dietary intervention studies. Faecal water is isolated by centrifugation of the faeces at 25000xg and added to cultured human colon cells (HT29). Membrane damage as assessed by trypan blue exclusion is determined as a measure for cytotoxicity. Semiquantitative analysis of inducible DNA damage (breaks and alkali labile sites) are analysed with the single cell microgelelectrophoresis assay (comet-assay) and oxidised DNA bases by the additional use of repair specific enzymes. We have now determined baseline toxic activities and calculated inter- and intra-individual and -experimental coefficients of variation for faecal water from different subjects consuming similar or different diets. Most faecal water induced DNA damage and oxidised DNA bases in HT29 clone 19a cells (0.9-9.14 fold and 1.7-4.9 fold, respectively in comparison to the NaCl controls). Intra- and inter-experimental coefficients (CV) of variation, were in a similar order of magnitude and ranged from 6.9 to 31.4. In contrast both intra- and inter-individual variability were considerably higher (CV-ranges of 29.7-76.6 and 21.3-64.0, respectively). Interestingly, these inter-individual values were not lowered when subjects consumed identical diets (CV-ranges of 28.4-126.0). However, following intervention with certain protective dietary regimens (e.g. lignan containing bread) significant reductions of faecal water-induced genotoxicity can be observed. Therefore, in spite of the expected and observed degrees of variation in this methodology, effective experimental protocols may still lead to detectable modulations of the level of toxic and genotoxic effects.

Adult↗
PubMed1998

Tumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans.

TNF-alpha is involved in infectious and immuno-inflammatory diseases. Different individuals may have different capacities for TNF-alpha production. This might determine a predisposition to develop some complications or phenotypes of these diseases. The aims of our study were to assess the inter-individual variability of TNF-alpha production and to correlate this variability to a single base pair polymorphism located at position -308 in TNF gene. We studied 62 healthy individuals. TNF-alpha production after LPS stimulation was evaluated using a whole blood cell culture model. The TNF gene polymorphism was studied by an allele-specific polymerase chain reaction. Other cytokines produced in the culture, soluble CD14 concentrations and expression of CD14 on blood cells were also measured. Among the 62 individuals, 57 were successfully genotyped. There were 41 TNF1 homozygotes and 16 TNF1/TNF2 heterozygotes. TNF-alpha production after LPS stimulation of whole blood cell culture was higher among TNF2 carriers than among TNFI homozygotes (929pg/ml (480-1473pg/ml) versus 521 pg/ ml (178-1307 pg/ml); P<0.05). This difference was even more significant after correction of TNF-alpha production for CD14 expression on blood cells. In conclusion, the single base pair polymorphism at position -308 in the TNF gene may influence TNF-alpha production in healthy individuals.

Adult↗
PubMed2001

On patient judgement.

Clinical judgement, the keystone of medical expertise, is a hot topic. By contrast, patient judgement, also of central importance in health care, receives little attention. Patients have the last say concerning whether or not they seek medical treatment for symptoms, follow a doctor's advice or accept reassurance. Delay in seeking help for serious symptoms, non-compliance with treatment advice and failure of doctors to reassure many of the 'worried well' have long been recognized as serious problems. We argue that what is common to these important problems is patient judgement. Surveys yielding information about the average influence of a large number of individual variables do not do justice to the complex interaction of influences that can influence the judgements of an individual person under particular social circumstances. This is what explains the wide variety of patient reactions. From the medical standpoint, such unpredictable patient behaviour seems irrational. The patient perspective on the meaning of their actions is a hiatus in our knowledge, which is hampering the planning of effective interventions. Too few studies have sought the perspective of patients by asking them why they acted as they did. Thus, the wide spectrum of patient response in these situations in relation to personality, life experience and social context cannot be studied without interpretive field studies that include interview of patients with qualitative interpretation.

Judgment↗