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PubMed2005

Prediction of individual response to chemotherapy in patients with acute myeloid leukaemia using the chemosensitivity index Ci.

As the response to chemotherapy in patients with acute myeloid leukaemia (AML) may still not be accurately determined by known prognostic factors, such as karyotype, the ex vivo chemosensitivity profile may help to predict the individual response. The predictive accuracy of an ex vivo assay should be assessed by correlation of assay results with both response rate and survival. We prospectively investigated the prognostic relevance of pre-therapeutic ex vivo chemosensitivity testing in primary cell cultures from adult AML patients by applying a new evaluation methodology, designated the chemosensitivity index, C(i). This C(i) was designed as a prognostic index by taking the area under the curve as an exact measure of the total dose-response relationship. We found an overall predictive accuracy of 98.2% concerning treatment response, which compares favourably with previously published data ranging from 75% to 92%. Moreover, the C(i) proved to be the strongest prognostic factor for overall survival in a multivariate Cox regression analysis including karyotype grouping and age (P < 0.001), and enabled the evaluation of response to combination therapies and selection of possible treatment alternatives. Our data suggest that ex vivo chemosensitivity testing evaluated by the C(i) could serve as a powerful tool for assay-directed therapy strategies in AML.

Acute Disease↗
PubMed2006

Sensitization to caffeine and cross-sensitization to amphetamine: influence of individual response to caffeine.

The present study evaluated the ability of a subchronic intermittent administration of caffeine to induce a sensitized motor response and correlated the individual susceptibility of rats to acute caffeine to the development of sensitization. Moreover, individual susceptibility to caffeine and development of motor behaviour sensitization were correlated to the behavioural response obtained after a challenge with amphetamine. To this end, rats were subdivided in "low" and "high" responders according to their individual susceptibility to acute caffeine established on the basis of the motor activity observed after the first caffeine administration. "Low" and "high" responder rats were then repeatedly and intermittently treated with caffeine (15 mg/kg, i.p.), or vehicle, every other day for fourteen days. Three days after treatment discontinuation, behavioural activation induced by acute amphetamine (0.5 mg/kg, s.c.) was measured in vehicle- and caffeine-pretreated rats. Subchronic caffeine resulted in motor sensitization of a variable degree among rats and no difference were observed between "low" and "high" responders. Moreover, caffeine pretreatment potentiated the behavioural effects of amphetamine according to the degree of caffeine sensitization but not to individual susceptibility to acute caffeine. These results demonstrate that individual susceptibility to acute caffeine does not influence the modifications in caffeine motor effects produced by its subchronic administration and does not affect the enhancement of acute behavioural effects of amphetamine in caffeine-pretreated rats, rather sensitization to subchronic caffeine administration critically influences the behavioural effects of amphetamine.

Amphetamine↗
PubMed2003

Diet, individual responsiveness and cancer prevention.

Dietary recommendations for the prevention of cancer have been based predominantly on large epidemiological studies of diet and lifestyle, conducted 20, and in some cases, almost 30 years ago. Government programs have been successful in educating the public about the benefits of eating fruits and vegetables, yet despite these efforts, Americans have become heavier, diabetes is more prevalent and general health indicators have not greatly improved. Individual response to dietary recommendations may be complicated by a variety of factors. Polymorphisms in genes related to drug activation and detoxification, folate metabolism, DNA repair, vitamin receptors and other cellular receptors could account for a lack of benefit at the level of the individual for consuming cancer preventive foods. Beyond consideration of genetic polymorphisms, the last half century has brought stark changes in lifestyle that depart from normal diurnal cycle and periodic fluctuations in food availability. Thus, modern times may be characterized as being constantly in a "feast" environment. The cellular consequences may be an increase in risk for several diseases including cancer.

Animals↗
PubMedDate not supplied

Defensiveness and individual response stereotypy in asthma.

OBJECTIVE: Previous literature has shown that the psychological trait of defensiveness is related to elevated sympathetic reactivity to stress and to several cardiac risk factors. The aim of this study was to examine whether these previous findings on defensiveness extend to an asthmatic population. METHODS: Defensiveness was measured by the Marlowe-Crowne Social Desirability Scale using a quartile split: high (upper 25%) and low (bottom 75%). Twenty-two defensive and 66 nondefensive participants with asthma were exposed to laboratory tasks (initial baseline rest period, reaction time task, and a shop accident film). RESULTS: During the tasks there was evidence of lower skin conductance levels and greater respiratory sinus arrhythmia amplitudes among defensive patients with asthma. After exposure to the tasks, defensive patients with asthma showed a decline on spirometry test measures compared with nondefensive asthmatic patients, who displayed an increase. CONCLUSIONS: These data confirm individual response stereotypy and suggest that defensiveness may be characterized by sympathetic hypoarousal and parasympathetic hyperarousal among patients with asthma. Future studies are needed to determine whether defensiveness is a risk factor for stress-induced bronchoconstriction.

Adolescent↗
PubMed1990

Hepatitis B immunisation--is there a need to assess individual response to the vaccine?

The response to the new recombinant DNA vaccine has been shown to be variable, with sero-conversion rates ranging from 90-99% being quoted. This study was designed to assess the response to one of the new second generation Hepatitis B vaccines. Of the 955 who had completed the immunisation schedule, of three doses post vaccination testing was carried out in 117. Of these 117, six failed to show any antibodies to the Hepatitis B surface antigen (NBs Ag), and a further seven had a low antibody titre which was considered insufficient to give them adequate protection against the Hepatitis B virus (HBV). So in effect, a total failure rate of 11% was demonstrated. It is concluded that all vaccine recipients should be screened to assess their individual response.

Adult↗
PubMed1993

The etiology of fear of heights and its relationship to severity and individual response patterns.

The acquisition of fear of heights in an undergraduate student sample was investigated. Height-fearful (n = 50) and non-fearful (n = 50) groups were formed on the basis of extreme scores to the heights item on the FSS-III (Wolpe & Lang, Behaviour Research and Therapy, 2, 27-30, 1964). Subjects were then assessed with a battery of measures including the Acrophobia Questionnaire (Cohen, Behaviour Therapy, 18, 17-23, 1977), self-rating of severity (Marks & Mathews, Behaviour Research and Therapy, 17, 263-267, 1979), global rating of severity (Michelson, Behaviour Research and Therapy, 24, 263-275, 1986), and a new comprehensive origins questionnaire constructed by the authors. Results obtained question the significance of simple associative-learning events in the acquisition of fear of heights. Only 18% of fearful Ss were classified as directly conditioned cases. Furthermore, no differences between groups were found in the proportion of Ss who knew other height-fearfuls, had experienced relevant associative-learning events, or the ages at which these events had occurred. Finally, no relationships between mode of acquisition and severity or individual response patterns were obtained. In general, the data were consistent with the non-associative, Darwinian accounts of fear acquisition that continue to attract theorists from a variety of backgrounds (e.g. Bowlby, Attachment and loss. London: Penguin, 1975; Clarke & Jackson, Hypnosis and behaviour therapy: The treatment of anxiety and phobias. New York: Springer, 1983; Marks, Fears, phobias and rituals: Panic anxiety and their disorders. New York, Oxford Univ. Press, 1987). Differences with previous studies in which classical conditioning has accounted for the majority of cases are discussed in terms of the methodological differences across studies.

Adaptation, Psychological↗
PubMed1995

The etiology of acrophobia and its relationship to severity and individual response patterns.

The acquisition of acrophobia in a large clinical sample was investigated. 148 patients from a university-based height phobia clinic and 148 age and sex matched non-phobic controls served as Ss. Subjects were assessed with a battery of measures including the Acrophobia Questionnaire [Cohen, D. C. (1977), Behavior Therapy, 18, 17-23], self-rating of severity [Marks, I.M. & Mathews, A. M. (1979) Behaviour Research and Therapy, 17, 263-267] global rating of severity [Michelson, L. (1986), Behaviour Research and Therapy, 24, 263-275], origins questionnaire [Menzies, R. G. & Clarke, J. C. (1993a) Behaviour Research and Therapy, 31, 355-365], and a height avoidance test. Results obtained question the significance of simple associative-learning events in the acquisition of fear of heights. Only 11.5% of fearful Ss were classified as directly conditioned cases. Furthermore, no differences between groups were found in the proportion of Ss who knew other height-fearfuls, had experienced relevant associative-learning events, or the ages at which these events had occurred. Finally, no relationships between mode of acquisition and severity or individual response patterns were obtained. In general, the data were consistent with the non-associative, Darwinian accounts of fear acquisition that continue to attract theorists from a variety of backgrounds [e.g. Bowlby, J. (1975) Attachment and Loss; Clarke, J.C. & Jackson, J. A. (1983) Hypnosis and behavior therapy: the treatment of anxiety and phobia; Marks, I. M. (1987) Fears, phobias and rituals: panic, anxiety and their disorders; Menzies, R. G. & Clarke, J. C. (1993a), (1993b) Behaviour Research and Therapy, 31, 499-501; Menzies, R. G. & Clarke, J. C. (1995)].

Adult↗
PubMed1996

Individual response patterns and treatment matching in the phobic disorders: a review.

Studies using response profile treatment matching in the phobic disorders are reviewed. It is argued that the research effort to date is plagued by a multitude of methodological problems which bring into question the validity of the major findings. While there have clearly been some encouraging data, too many inconsistent results exist to offer unqualified endorsement of the procedure. At this point, the optimum strategy for clinicians would appear to involve the inclusion of a treatment component consistent with the dominant response system of the individual patient, but not at the expense of well-established procedures (e.g. graduated in vivo exposure).

Follow-Up Studies↗
PubMed2006

Ecophysiological traits associated with drought in Mediterranean tree seedlings: individual responses versus interspecific trends in eleven species.

Species differ regarding their drought tolerance and individuals of a given species can modify their morphology and physiology in response to drought. However, since evolutionary and ecological selective pressures differ, individual and interspecific responses to drought might not match. We determined summer survival and a number of ecophysiological variables in two factorial experiments with seedlings of eleven tree species present in Mediterranean ecosystems, grown under slowly imposed water stress and control conditions. Plants experiencing drought exhibited reduced growth, low specific leaf area, chlorophyll content, and photosynthetic rate when compared to the controls, and species-specific drought tolerance was associated with an analogous set of trait values. However, while species with high leaf area ratio and shoot-root ratio exhibited greater drought tolerance, drought induced the reversed response within species. Contrary to expectations, water use efficiency was lower in drought-tolerant species and decreased in water-stressed individuals compared to the control plants. There was a distinctive phylogenetic signal in the functional grouping of species, with oaks, pines, and other genera being clearly different from each other in their drought tolerance and in their functional responses to drought. However, all relationships between ecophysiological variables and drought tolerance were significant after accounting for phylogenetic effects, with the exception of the relationship between drought tolerance and photochemical efficiency. Our results show that drought tolerance is not achieved by a single combination of trait values, and that even though evolutionary processes and individual responses tend to render similar results in terms of functional traits associated with drought, they do not necessarily match.

Ecosystem↗
PubMed2006

Functional gene analysis of individual response to challenge of SIVmac239 in M. mulatta PBMC culture.

It has previously been shown in macaques that individual animals exhibit varying responses to challenge with the same strain of SIV. We attempted to elucidate these differences using functional genomics and correlate them to biological response. Unfractionated PBMC from three rhesus macaques were isolated, activated, and infected with SIVmac239. Interestingly, one of the three animals used for these experiments exhibited a completely unique response to infection relative to the other two. After repeated attempts to infect the PBMC from this animal, little or no infectivity was seen across the time points considered, and corresponding to this apparent lack of infection, few genes were seen to be differentially expressed when compared to mock-infected cells. For the remaining two animals, gene expression analysis showed that while they exhibited responses for the same groups of pathways, these responses included differences specific to the individual animal at the gene level. In instances where the patterns of differential gene expression differed between these animals, the genes being differentially expressed were associated with the same categories of biological process, mainly immune response and cell signaling. At the pathway level, these animals again exhibited similar responses that could be predicted based on the experimental conditions. Even in these expected results, the degree of response and the specific genes being regulated differed greatly from animal to animal. The differences in gene expression on an individual level have the potential to be used as markers in identification of animals suitable for lentiviral infection experiments. Our results highlight the importance of individual variation in response to viral challenge.

Animals↗
PubMed2000

Monitoring individual response to hormone replacement therapy with bone markers.

Hormone replacement therapy (HRT) induces a rapid decrease in biochemical markers of bone turnover that correlate with a subsequent increase in bone mineral density (BMD). To determine the utility of bone markers in the management of postmenopausal women receiving HRT, we analyzed the relationship between changes in four markers (serum osteocalcin and bone alkaline phosphatase [BAP], serum and urinary C-telopeptide of type I collagen [CTX]) and changes in spine BMD in 569 women treated for 2 years with different doses of a matrix transdermal 17beta-estradiol patch in two placebo-controlled trials. Using a logistic regression model, we found that both the percent change from baseline and the actual value of resorption markers at 3 and 6 months of treatment were predictive of BMD response at 2 years. Comparable results were obtained with formation markers at 6 months only. We determined the sensitivity, probably of positive BMD response, and corresponding cutoff value of markers at 3 and 6 months with a specificity set at a level of 0.90, so that <10% of women classified with markers as responders, i.e., as having a subsequent increase in BMD at 2 years >/=2.26%, would be false positive. All markers provided a high probability of positive BMD response ranging from 0.82 to 0.91, with a sensitivity higher for resorption than for formation markers, and sometimes improved in a model combining the percent change and the actual value of marker under HRT. For example, a decrease in serum CTX >/= 33% at 3 months of HRT provided a 68% sensitivity and 87% probability of positive BMD response at 2 years for a 90% specificity. At 6 months, a decrease in urinary CTX >/= 53% provided a 68% sensitivity and 91% probability of a positive BMD response for a 90% specificity. Half of false-negative cases at 3 months will be correctly identified by a subsequent urinary CTX measurement at 6 months. We conclude that the short-term change in bone markers reflects long-term changes of BMD in postmenopausal women treated with HRT. Our data suggest that bone turnover markers can be used to monitor the BMD response to HRT at the individual level. Whether such monitoring could improve long-term compliance to HRT should be tested prospectively.

Alendronate↗
PubMed1980

Variation in individual responses to the cytotoxicity of cigarette smoke.

There is increasing evidence that elastase may mediate pulmonary damage in emphysema and also that the release of intracellular elastase by cigarette smoke is necessarily associated with cell death. We report consistent and significant variation in response of lymphocytes from different individuals to the cytotoxic effect of cigarette smoke condensate in vitro. This variation which occurred at levels of cigarette smoke likely to be encountered in vivo and which was independent of the age, sex, or smoking habits of the subjects, may be relevant in determining the risk of developing emphysema amongst smokers.

Adolescent↗
PubMed1988

Nifedipine: individual responses and concentration-effect relationships.

Dynamic and kinetic variability account for the large intersubject differences in the antihypertensive response to nifedipine, and a clear concentration-effect relationship has not been established. The effects of placebo, first dose, and chronic (1 and 6 weeks) treatment with nifedipine were studied in 14 subjects with essential hypertension using an integrated kinetic-dynamic model to calculate individual subject responsiveness in terms of fall in blood pressure per unit change in drug concentration. Nifedipine concentrations were well correlated with the fall in systolic blood pressure in individual subjects, and the mean responsiveness was -0.48 mm Hg/ng/ml after the first dose, -0.45 mm Hg/ng/ml after 1 week, and -0.49 mm Hg/ng/ml after 6 weeks. The responsiveness to the first dose of nifedipine was significantly correlated with the responsiveness after 1 (r = 0.83) and 6 weeks (r = 0.78) of therapy and with the height of the pretreatment blood pressure (r = 0.6). This study incorporated kinetic as well as dynamic information to characterize the antihypertensive response to nifedipine and identify nifedipine concentration-effect relationships in individual hypertensive subjects.

Adult↗
PubMed2004

Striatal dopamine D2/D3 receptor availability correlates with individual response characteristics to pain.

We studied in healthy humans the contribution of cerebral dopamine D2/D3 receptors to individual differences in response characteristics to painful stimulation. Positron emission tomography was used to measure the dopamine D2/D3 binding potential (D2/D3 BP) with [(11)C]raclopride in the striatum (n = 8) and with [(11)C]FLB 457 in the extrastriatal regions (n = 11). Sensitivity to cutaneous heat pain was assessed by a traditional threshold method and by an analysis based on the signal detection theory which allows the separation of an individual subject's discriminative capacity from the response criterion, i.e. the area under the receiver operating characteristic curve provides a measure of the sensory discriminability (sensory factor) and the response criterion gives an estimate of the subject's response bias or attitude (nonsensory factor). The pain threshold and response criterion were inversely correlated with the D2/D3 BP in the right putamen, whereas the discriminative capacity was not significantly correlated with the D2/D3 BP in any brain region. The correlation of the D2/D3 BP in the putamen with the pain threshold and the subject's response criterion may rather be explained by a dopaminergic effect on nonsensory factors determining the subject's attitude towards pain than by a dopaminergic effect on the subject's discriminative capacity. Alternatively, striatal dopamine D2/D3 receptors could control a modulatory pathway producing a parallel shift in the stimulus-response function for sensory signals, mimicking a change in the subject's response criterion.

Adult↗
PubMed1984

The extent of individual responsibility for an independent old age.

Encouragement of a degree of personal responsibility for the maintenance of health by individuals and communities is being increasingly advocated by planners of health care. With the increasing numbers of people reaching old age it is particularly desirable that individuals be made aware of potential measures that may ensure a reasonably independent old age. In the course of a study to identify the defining characteristics of referred geriatric patients in a teaching hospital, a number of recurring factors emerged that seemed to favour the retention of independence among the subjects studied as controls. These were adequate retirement planning, the timely development of satisfying interests, the prior adoption of a healthy lifestyle, the sensible use of health services and the presence of adequate family and community support systems. Six cases are described to illustrate the presence or absence of such factors, and these are discussed against the background of the respective degrees of responsibility to be expected of the individual and of society in securing and maintaining independence in old age.

Aged↗
PubMed1989

Concentration-effect relationships and individual responses to doxazosin in essential hypertension.

1. This study investigates aspects of the pharmacokinetics, pharmacodynamics and concentration-effect relationships in 10 patients with essential hypertension during acute and chronic treatment with doxazosin, an alpha 1-adrenoceptor antagonist. 2. Following the first dose of doxazosin (2 mg) there were significant reductions in blood pressure, increases in heart rate and in plasma noradrenaline, and parallel rightward shifts of the phenylephrine pressor response curves, consistent with alpha-adrenoceptor antagonism. There was no significant change in the pressor response to angiotensin II. 3. Using an integrated kinetic-dynamic model, individual blood pressure responsiveness was characterised as the fall in blood pressure (mm Hg) per unit drug concentration. Responsiveness to the first dose of doxazosin was directly correlated with the responsiveness after 1 and 6 weeks treatment although there was a systemic reduction (of approximately 30%) which occurred during the first week of treatment. 4. Neither the acute nor long-term responsiveness to doxazosin was related to age, plasma renin activity, plasma noradrenaline or the pretreatment sensitivity to phenylephrine. There was a significant relationship between responsiveness and the height of the initial (pretreatment) blood pressure. 5. Integration of pharmacokinetic and pharmacodynamic data provides a reproducible index of responsiveness which can be used to investigate the consistency of the long-term anti-hypertensive response, to identify factors which influence the magnitude of the response, and to optimise the choice of dose and dose interval.

Aged↗
PubMed1997

Erythrocyte sodium-lithium countertransport in non-modulating offspring and essential hypertensive individuals: response to enalapril.

Non-modulators are a subset of essential hypertensive individuals in whom renal hemodynamic and adrenal aldosterone responses to angiotensin II fail to modulate appropriately during high dietary salt intake. The main aim of this study was to investigate the familial aggregation of non-modulation and several erythrocyte Na+ transport systems in normotensive and hypertensive individuals as well as offspring of hypertensive parents. An additional aim was to evaluate the effect of treatment with enalapril on erythrocyte Na+ transport. We studied 15 normotensive subjects (6 males, 27+/-6 years), 14 untreated modulating essential hypertensive subjects (7 males, 38+/-7 years), 12 untreated non-modulating essential hypertensive subjects (7 males, 38+/-6 years), 14 modulating offspring of hypertensive parents (8 males, 25+/-6 years), and 14 non-modulating offspring of hypertensive parents (8 males, 26+/-4 years). Blood pressure was recorded with an oscillometric device and renal plasma flow and glomerular filtration rate by clearances of para-aminohippurate and inulin, respectively. Non-modulating subjects were identified as individuals who failed to increase effective renal plasma flow by 30% and decrease filtration fraction by at least 30% 10 days after changing from a low (20 mmol/d) to a high (250 mmol/d) sodium intake. Erythrocyte Na+ transport was characterized by measurements of the Na+-K+ pump, Na+-Li+ countertransport, Na+-K+-Cl- cotransport, passive Na+ permeability, and Na+ content. After the initial studies, hypertensive individuals were treated with enalapril (20 mg/d P.O.) for 6 months, after which erythrocyte Na+ transport measurements were again made. The main findings were that Na+-Li+ countertransport is increased in non-modulating hypertensive subjects and non-modulating offspring of hypertensive parents, that the increase in blood pressure in response to high salt intake is greater in non-modulating than modulating hypertensive subjects, and that enalapril decreases Na+-Li+ countertransport activity to normal in non-modulating hypertensive subjects. These findings provide support for a possible genetic role in the development of salt sensitivity and suggest that Na+-Li+ countertransport and non-modulation are related phenotypes.

Adult↗