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At least 379 records · Page 21Linked to original sources
PubMed1993

Population pharmacokinetics of theophylline. I: Intravenous infusion to children in the acute episode of asthma.

The population pharmacokinetics of theophylline during constant-rate intravenous infusion has been studied in 66 children (8.7 +/- 4.7 year of age; 26.0 +/- 12.8 kg, mean +/- S.D.) with an episode of acute asthma. One hundred and twelve theophylline serum concentrations (13.9 +/- 4.8 micrograms/ml) collected retrospectively were analyzed using a nonlinear mixed-effect model. The influence of hepatic dysfunction, age, gender, days after admission, blood gas measurements (PaO2, PaCO2, blood pH) and clinical analyses data (total serum protein, albumin concentration, haemoglobin concentration, haematocrit) on theophylline clearance was examined by the likelihood ratio test. A final estimate of population mean clearance was 58.6 ml/kg/h, which was decreased by 36% in patients with hepatic dysfunction. Other factors tested displayed no statistically significant effect on theophylline clearance. The inter-individual variability in clearance was 26% while the intra-individual variability in theophylline concentrations was 2.6 micrograms/ml as a standard deviation, which was almost double that observed for stable patients. Taking into account that the therapeutic window of this drug is 10-20 micrograms/ml, this value indicates a relatively large intra-individual variability and suggests that frequent (daily) monitoring of serum concentrations is necessary for patients with an episode of acute asthma.

Acute Disease↗
PubMed1999

Target-controlled infusion of alfentanil for postoperative analgesia: contribution of plasma protein binding to intra-patient and inter-patient variability.

We have examined the influence of plasma protein binding on inter-individual and intra-individual variability in the effective postoperative analgesic concentration (EAC) of alfentanil and on the performance of the target-controlled infusion system used. Ten patients received standardized anaesthesia and target-controlled alfentanil for postoperative analgesia. Analgesia was assessed using a visual analogue scale (VAS). Plasma protein binding of alfentanil was assessed at four different times (on arrival in the recovery room, at 21:00 on the day of surgery and at 09:00 and 21:00 on the first postoperative day). Bias and inaccuracy were examined on the day of surgery and on the first postoperative day. Unbound fractions of alfentanil varied from 5 to 15% and varied in time. In general, the unbound fractions on the day of surgery were higher than those on the first postoperative day. Thirty-nine percent of inter-individual variability in the EAC of alfentanil (range 33-140 ng ml-1) at the onset of therapy could be explained by protein binding. At the other observation times, correlations between unbound fraction and EAC were only moderate. Bias on the day of surgery was -19% and 12% on the first postoperative day (ns). Inaccuracy was 23% and 18%, respectively (ns). We conclude that inter-individual variations in plasma protein binding can explain a significant portion of inter-individual variability in the EAC of alfentanil in the early postoperative phase.

Adolescent↗
PubMed2006

Individual variation in the location of the parietal eye fields: a TMS study.

Transcranial magnetic stimulation (TMS) is a popular technique that can be used to investigate the functional role of specific cortical areas with reference to a particular behavioural task. Single-cell recording studies performed in non-human primates have demonstrated that a region of the parietal lobe known as the lateral intraparietal area is specialized in the planning and control of saccadic eye movements. The homologue of this area in humans is termed the parietal eye fields (PEF) and its role in relation to saccades has previously been examined using TMS. In this paper individual variability in the functional effect of parietal TMS on the latency, amplitude and angular direction of visually-guided saccades has been assessed. By examining individual variability in the spatial distribution of scalp-based localization and brain surface anatomy and stereotaxic localizations of the PEF it was shown that the distances between the sites determined by these three methods were not negligible, which raises problems regarding the most reliable anatomical localization technique to use. An assessment of the effect of TMS on saccade metrics (latency, amplitude error and angular error) at a grid of locations over parietal cortex demonstrated a large amount of intra-individual variability in the site where TMS had most affected saccades, leading to the conclusion that there is individual variability in the functional effects of parietal TMS on saccade planning and execution. This study confirms the idea that it may be problematic to use a fixed scalp location for every participant in a study. It may in fact be more appropriate to determine TMS sites functionally on an individual basis if possible. This finding may guide further studies using TMS and saccade planning in order to optimize their capability to investigate this area and to draw meaningful biological conclusions.

Adult↗
PubMed1977

Reaction time variability in epileptic and brain-damaged patients.

Median reaction times and intra-individual variability were studied in epileptic (N = 63), brain-damaged (non-epileptic) (N = 25) and control patients (N = 25) using a six and one half minute visual, continuous reaction time task. Epileptic and brain-damaged groups were significantly slower than control patients on median reaction times at the 10th, 50th, and 90th percentiles and on the differences between the 10th and 90th percentiles. Thus both general slowing and greater intra-individual variability were found in the epileptic and brain-damaged patients. Reaction times were not related to presence, type and severity of EEG abnormality or to age of onset of epilepsy. Grand mal patients did have significantly greater variability than other types of seizure patients. Epileptic and brain-damaged patients did not differ significantly on any reaction time variables. Both groups were discriminated significantly from the controls on all reaction time measures, especially on the intra-individual variability measure.

Adolescent↗
PubMed1980

[Individual anatomical variability of the intestines in newborn infants and its surgical significance].

The investigation of the individual anatomical variability of organs of the abdominal cavity in newborns has shown that the variant of fixation of the duodenum, structure of the small intestine mesenterium, pattern of the organization of the peritoneal lining as well as the disposition and fixation of the large intestine are of major practical importance in urgent operations for congenital ileus. Variants of the shape and disposition of the large intestine in neonatals should be taken into consideration in roentgenological examinations and in mobilization of the large intestine.

Humans↗
PubMedDate not supplied

Lymphocyte P-glycoprotein expression and activity before and after rifampicin in man.

It has recently been shown that P-glycoprotein (P-gp) is inducible by rifampicin in the human gut as shown in intestinal biopsies. The present study was performed in order to test the hypothesis that human peripheral lymphocytes can be used to assess such an inducibility. We also assessed inter- and intra-individual variability of P-gp expression and activity in peripheral lymphocytes. Blood samples from 13 healthy volunteers were collected 1.7, 14 and 19 days after inclusion. Rifampicin treatment (600 mg/day) was administered from day 15 to day 18. Lymphocyte P-gp expression was measured at the messenger RNA level by semi-quantitative RT-PCR and at the protein level by immunostaining flow cytometry. P-gp activity was determined by flow cytometry with rhodamine 123 efflux. Cytochrome P4503A4 (CYP3A4) inducibility was measured by comparing the urinary metabolic ratio of 6beta-hydroxycortisol/cortisol on day 14 and 19, Lymphocyte P-gp expression and activity was not induced by rifampicin, while it increased CYP3A4 activity from 5.0 +/- 4.0 to 22.9 +/- 16.6 (P < 0.001). There was a 3 - 4-fold inter-individual variability and a 3 - 44 % intra-individual variability of lymphocyte P-gp expression and activity. Peripheral lymphocytes are not an appropriate material to assess P-gp inducibility in humans. P-gp shows significant inter- and intra-individual variability in human lymphocytes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

The evoked cardiac response as a function of cognitive load in subjects differing on the individual difference variable of reaction time.

We report research on different phasic evoked cardiac responses associated with differences in cognitive activity. These were examined in relation to a stable individual difference variable, mean simple reaction time (RT). Individual means on RT were found to be sufficiently stable over a 10 month period to consider them as individual functional characteristics. Subjects were divided into two subgroups on the basis of the first measure of their individual mean RT (above and below the group median). Each subject received 10 innocuous auditory stimuli with randomly varying interstimulus intervals. Stimuli were presented in one of two conditions defined by instructions allowing them to ignore (irrelevant condition), or requiring them to count the stimuli (relevant condition). A main effect of instruction was obtained in the evoked cardiac response. The initial heart rate deceleration was significantly larger in the irrelevant condition and a later acceleration was significantly larger in the relevant condition. Short-RT subjects had smaller heart rate changes to the irrelevant stimuli. The data are discussed in terms of the intensity of stimulus processing (both physical and cognitive) as a factor which may be related fundamentally to stable individual differences in RT.

Adult↗
PubMed2004

Effects of methylphenidate on attention deficits after traumatic brain injury: a multidimensional, randomized, controlled trial.

OBJECTIVE: To evaluate the effects of methylphenidate on a variety of aspects of attention, ranging from laboratory-based impairment measures to caregiver ratings and work productivity, in individuals after traumatic brain injury. DESIGN: A total of 34 adults with moderate to severe traumatic brain injury and attention complaints in the postacute phase of recovery were enrolled in a 6-wk, double-blind, placebo-controlled, repeated crossover study of methylphenidate, administered in a dose of 0.3 mg/kg/dose, twice a day. A wide range of attentional measures was gathered weekly, including computerized and paper-and-pencil tests of attention, videotaped records of individual work in a distracting environment, real-time observational scoring of attentiveness in a classroom environment, and caregiver and clinician rating scales of attentiveness. Participants also attempted to guess their drug condition each week. Data from the first ten participants were used for pilot purposes, to develop attentional factors for composite scoring, and to identify attentional dimensions suggestive of a treatment effect for independent replication. The remaining 24 participants' results were used to confirm potential treatment effects seen in the pilot sample, using Wilcoxon's signed-ranks test on composite factor scores and individual variables. RESULTS: A total of 54 dependent variables were reduced to 13 composite factors and 13 remaining individual variables. Of the 13 attentional factors, five showed suggestive treatment effects in the pilot sample. Of these, three showed statistically significant treatment effects in the replication sample: speed of information processing (effect sizes, -0.06 to 0.48; P < 0.001), attentiveness during individual work tasks (effect sizes, 0.15-0.62; P = 0.01), and caregiver ratings of attention (effect sizes, 0.44-0.50; P = 0.01). Of the individual variables, four showed suggestive treatment effects in the pilot sample, but only one showed significant treatment effects in the replication sample: reaction time before errors in the Sustained Attention to Response Task (effect size, 0.20; P = 0.03). No treatment-related improvement was seen in divided attention, sustained attention, or susceptibility to distraction. None of the variables showed suggestive or definite negative treatment effects. Effect sizes for those performance measures positively affected by methylphenidate were in the small to medium range and included both impairment and activity level measures. Improvements in processing speed did not seem to come at the expense of accuracy. CONCLUSIONS: Methylphenidate, at 0.3 mg/kg/dose, given twice a day to individuals with attentional complaints after traumatic brain injury, seems to have clinically significant positive effects on speed of processing, caregiver ratings of attention, and some aspects of on-task behavior in naturalistic tasks. Further research is needed to identify the optimal dose and to extend these findings to less carefully selected individuals.

Adult↗
PubMed2006

Agreement of medical decisions in occupational health as a quality requirement.

OBJECTIVE: Workers' medical examination by the occupational physician (OPs) is a decision-making process whose output consists of a variety of evaluations, including assessment of fitness for work. The medical literature reports that there is no complete agreement among OPs assessing the same workers, evidencing a critical aspect of professional performance. This study aims at evaluating the inter-individual variability of medical decisions by different occupational physicians. METHODS: Four specialists in occupational medicine participated in the study. Each specialist examined 100 records of subjects with different medical conditions selected from about 2,500 health care workers. Each physician completed a form including the following items: assessment of fitness for work, advice to workers, need of further investigations, report of occupational disease, recommendation for the general practitioner. To assess the inter-individual variability the percent agreement and the agreement strength or Cohen's kappa were measured. RESULTS: The study shows a variable agreement in the assessment of fitness for work among different professionals, with percent agreement ranging from 58% for the whole group to an average of 77% for physicians' pairs. By taking into account the variability expected by chance, the agreement ranged from fair to substantial. The agreement of other decisions (workers' advice, referral to other specialists, request of further investigation, report of occupational disease, recommendation for the general practitioner) was more variable. CONCLUSION: The study shows that an inter-individual variability exists for some decisions taken by OPs. According to the need to continuously improve professional practice, in the absence of qualitative standards based on the outcome, reduction of inter-individual variability that should be considered as a quality requirement of the performance of the occupational physician.

Clinical Competence↗
PubMed2002

Variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects.

The aim of this study was to assess regional and global variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects and to evaluate potentially responsible factors. Twenty men with a mean age of 64 years, no history of cardiovascular disease, and normal blood pressure, bicycle exercise test, electrocardiogram and echocardiography were studied [ P(coronary artery disease) <5%]. Whole-body insulin sensitivity and insulin-stimulated myocardial glucose uptake were measured during hyperinsulinaemic euglycaemic glucose clamp with fluorine-18 fluorodeoxyglucose, and myocardial rest and hyperaemic blood flow during dipyridamole infusion were measured with nitrogen-13 ammonia and positron emission tomography in 16 left ventricular myocardial segments. Intra-individual and inter-individual variability of insulin-stimulated myocardial glucose uptake [relative dispersion = (standard deviation/mean)] was 13% and 29% respectively. Although inter-individual variability of glucose uptake and blood flow at rest was of the same magnitude, no correlation was found between these measures. Regional and global insulin-stimulated myocardial glucose uptake correlated linearly with whole-body insulin sensitivity ( r=0.51, P<0.05 and r=0.56, P<0.01). The strongest independent association by multivariate linear regression analysis was found between myocardial glucose uptake and hyperaemic blood flow ( r=0.63, P<0.005). We conclude that in healthy elderly subjects, insulin-stimulated myocardial glucose uptake is homogeneous throughout the left ventricle, but has moderate inter-individual variability. Inter-individual variability of insulin-stimulated myocardial glucose uptake is primarily explained by variability in coronary vascular reactivity and tissue insulin sensitivity.

Ammonia↗
PubMed2005

Concentration of polychlorinated biphenyls (PCBs) in beached resin pellets: variability among individual particles and regional differences.

Concentrations of polychlorinated biphenyls (PCBs) in beached resin pellets were examined to reveal variability between individual particles and differences among beaches. Fifty-five resin pellets from a beach in Tokyo were individually analyzed for PCBs, and showed concentrations ranging from <28 to 2,300 ng/g. This indicates that concentrations are highly variable between particles. Among several characters, discoloration (e.g., yellowing) had a positive relationship with PCB concentration: discolored pellets contained more PCBs than others on most of the beaches sampled. Given the color-selective ingestion of food by some organisms, this may be ecotoxicologically important. Measurements of samples from 47 beaches in Japan showed regional differences in PCB concentrations in resin pellets consistent with those in mussels. Sporadic high concentrations of PCBs were also found in pellets from remote islands, suggesting that resin pellets could be the dominant route of exposure to the contaminants at remote sites. The similarity of PCB concentrations between resin pellets and mussels suggests a potential use of resin pellets to monitor pollution in seawater.

Bathing Beaches↗
PubMedDate not supplied

Usefulness of measures of Svo2, Spo2, vital signs, and derived dual oximetry parameters as indicators of arterial blood gas variables during weaning of cardiac surgery patients from mechanical ventilation.

OBJECTIVES: To determine whether combined use of the parameters of mixed venous oxygen saturation, arterial oxygen saturation obtained by pulse oximetry (Spo2), and vital signs correlated with arterial blood gas variables (ABGs) better than each individual variable during weaning of postoperative cardiac surgery patients from mechanical ventilation; and to evaluate the relationship of derived parameters: oxygen extraction index and ventilation/perfusion index (VQI), and ABGs. DESIGN: Secondary analysis of previous correlational study. SETTING: The cardiac care unit in a large medical center in central Florida. PATIENTS: Thirty postoperative coronary artery bypass graft patients being weaned from mechanical ventilation. METHODS: After a change in ventilator settings during systematic weaning towards extubation, measurements of variables were taken during a 30-minute period. At 30 minutes, an ABG was drawn for comparison. Data were collected after two ventilator changes. A total of 57 data sets were used for analysis. RESULTS: By use of multiple regression analyses, statistically significant (p < 0.01) independent variables predicting pH and partial pressure of carbon dioxide were Spo2 and respiratory rate. The independent variable contributing to the model versus partial pressure of oxygen was Spo2. The oxygen extraction index did not correlate with ABGs; however, the VQI correlated significantly with all ABG variables except bicarbonate. CONCLUSIONS: The use of multiple parameters was no more useful in predicting ABGs than individual variables of Spo2 and respiratory rate. The derived VQI parameter correlated with ABGs. The use of VQI in conjunction with Spo2 and respiratory rate may assist in patient monitoring during weaning and reduce the number of ABGs needed.

Adult↗
PubMed1993

Variability in individual responses of 532 patients with rheumatoid arthritis to first-line and second-line drugs.

Variability in individual responses to drugs used to treat rheumatoid arthritis was studied in 532 patients under care in seven U.S. rheumatology private practices. Among 15 nonsteroidal anti-inflammatory drugs (NSAIDs), estimated continuation of 1,775 courses was 48% at 12 months and 20% at 60 months. Acetylated salicylates, other than plain aspirin, were continued significantly longer than other NSAIDs. Among second-line drugs, estimated continuation of 50% of courses was 10 months for oral gold, 20 months for hydroxychloroquine, 21 months for penicillamine, 25 months for parenteral gold, 27 months for azathioprine, and more than 60 months for methotrexate and prednisone, the only drugs continued by more than 50% of patients 60 months after initiation.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

Within-person variability as a dynamic measure of late-life development: new methodologies and future directions.

BACKGROUND: Intra-individual variability is becoming a focus of research in behavioural gerontology due to theoretical and methodological advances. OBJECTIVE: New directions in the study of intra-individual variability are described and unanswered questions are proposed. METHODS: Papers from the special issue of Gerontology on Intra-individual Change are reviewed. RESULTS: Key findings and approaches from this set of papers are identified, including types of latent growth curve models that incorporate dynamic elements and applications to the study of late-life cognition and affect. Theoretical issues that remain unresolved are outlined. CONCLUSION: Dynamic approaches to the measurement of change provide novel methods to answer new questions and evaluate existing theories. The focus on intra-individual variability adds a valuable dimension to gerontological research that may refine the way we describe behaviour and measure change.

Age Factors↗
PubMed1994

Variability in individual response to various doses of omeprazole. Implications for antiulcer therapy.

This study was carried out in order to perform a combined prospective assessment of the individual pharmacodynamic response and of duodenal ulcer healing in patients treated with three different doses of omeprazole. Ninety-nine patients with endoscopically proven duodenal ulcers were subdivided into three parallel groups of 33 cases, who were randomly assigned to receive orally at 0800 hr, in single blind fashion, either 10 mg, 20 mg, or 40 mg of omeprazole. All of them underwent continuous intragastric pH monitoring both in basal conditions and on the fifth day of each dose regimen; ulcer healing was then assessed endoscopically after four weeks of treatment. All three doses of omeprazole caused pH values to increase significantly (P < 0.001) over the whole 24-hr period. In patients treated with omeprazole 10 mg, the individual responses showed the highest variability: the acid inhibition, expressed in terms of time spent above pH 3.0, lasted for more than 16 hr in 42% of cases, for more than 8 hr in 28%, and for less than 6 hr in 30%. In patients treated with omeprazole 20 mg, the pharmacological response was more marked and uniform and lasted for more than 16 hr in 79% of cases; however, it is worth noting it lasted for less than 6 hr in three patients (10%). In patients treated with omeprazole 40 mg, the individual response was excellent (more than 16 hr) in 94% of cases, and it lasted for less than 6 hr in only one patient (3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-Response Relationship, Drug↗
PubMed1989

Biological basis of follicle growth.

Ovarian stimulation therapy is notoriously difficult to manage, partly because of the individual variability in response to exogenous hormones and hormone antagonists. The varied underlying pathophysiological conditions necessitating ovulation induction therapy were in great part causative of the different responses between patients. However, in-vitro fertilization therapy has provided a wider experience, particularly with ovarian stimulation in endocrinologically normal women. From these data, there is much inherent variability of response to exogenous gonadotrophins evident, even in these 'normal patients'. Furthermore, individual response types tend toward a consistent pattern from cycle to cycle, suggesting a constancy of physiological status, as opposed to a stoichastic response. In this study, we are seeking ways of reducing individual variability of responses to gonadotrophin therapy based on understanding the physiological origin. Our first objective is to identify the source of individual variability in the hypothalamic--pituitary ovarian axis. We developed a new experimental primate model, the reversible 'medical hypophysectomy', achieved by administration of a gonadotrophin-releasing hormone (GnRH) antagonist to negate endogenous gonadotrophin secretion. The second objective is to assess the validity of our model for medical hypophysectomy. Effective doses and regimens of the GnRH antagonist applications are determined. The third objective is to study the differential actions of follicle-stimulating hormone (FSH) treatment alone versus combined FSH/luteinizing hormone (LH) therapy on the ovary. In summary, it is concluded: (i) individual variation in ovarian response to gonadotrophin therapy in monkeys is, in large part, supra-ovarian in origin, although failure to respond to gonadotrophins was not negated by GnRH antagonist treatment. Furthermore, a milieu approaching 'medical hypophysectomy' using a potent GnRH antagonist deserves consideration as a clinically applicable strategy to reduce variability among responders, thereby improving patient management. (ii) In our monkey model, the GnRH antagonist promptly produced a relatively hypogonadotrophic state that was reversible. These findings have implications for both fertility and anti-fertility research. (iii) The two-cell theory requiring co-ordinate action of both FSH and LH to achieve ovarian steroidogenesis culminating in a dynamic oestrogen production, may be re-examined. Indeed, the importance credited to the ratios of these gonadotrophins is surely open to question.

Animals↗
PubMed2000

Variability of relative blood volume during haemodialysis.

BACKGROUND: A decrease in blood volume is thought to play a role in dialysis-related hypotension. Changes in relative blood volume (RBV) can be assessed by means of continuous haematocrit measurement. We studied the variability of RBV changes, and the relation between RBV and ultrafiltration volume (UV), blood pressure, heart rate, and inferior caval vein (ICV) diameter. METHODS: In 10 patients on chronic haemodialysis, RBV measurement was performed during a total of one hundred 4-h haemodialysis sessions. Blood pressure and heart rate were measured at 5-min intervals. ICV diameter was assessed at the start and at the end of dialysis using ultrasonography. RESULTS: The changes in RBV showed considerable inter-individual variability. The average change in RBV ranged from -0.5 to -8.2% at 60 min and from -3.7 to -14.5% at 240 min (coefficient of variation (CV) 0.66 and 0.35 respectively). Intra-individual variability was also high (CV at 60 min 0.93; CV at 240 min 0.33). Inter-individual as well as intra-individual variability showed only minor improvement when RBV was corrected for UV. We found a significant correlation between RBV and UV at 60 (r= -0.69; P<0.001) and at 240 min (r= -0.63; P<0.001). There was a significant correlation between RBV and heart rate (r= -0.39; P<0.001), but not between RBV or UV and blood pressure. The level of RBV reduction at which hypotension occurred was also highly variable. ICV diameter decreased from 10.3+/-1.7 mm/m(2) to 7.3+/-1. 5 mm/m(2). There was only a slight, although significant, correlation between ICV diameter and RBV (r= -0.23; P<0.05). The change in ICV-diameter showed a wide variation. CONCLUSIONS: RBV changes during haemodialysis showed a considerable intra- and inter-individual variability that could not be explained by differences in UV. No correlation was observed between UV or changes in RBV and either blood pressure or the incidence of hypotension. Heart rate, however, was significantly correlated with RBV. Moreover, IVC diameter was only poorly correlated with RBV, suggesting a redistribution of blood towards the central venous compartment. These data indicate that RBV monitoring is of limited use in the prevention of dialysis-related hypotension, and that the critical level of reduction in RBV at which hypotension occurs depends on cardiovascular defence mechanisms such as sympathetic drive.

Aged↗
PubMed1985

Factors in family decision-making about placement for developmentally disabled individuals.

Variables that affect placement requests by families for their developmentally disabled members were examined. Results reaffirmed the importance of degree of disability, behavior problems, and external stressors for the decision-making process but also demonstrated that previous assumptions concerning their relative importance should be reexamined. Among younger disabled individuals (under 21), behavior problems were most important; for older individuals (over 21), disruption of family relations and perceived burden of care were more important. Different decision-making processes appeared to operate for younger and older disabled individuals. These results highlight the need for better specified theories that can explain placement requests among different types of individuals and families.

Adolescent↗