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PubMed2005

Inter-device reproducibility of the scanning laser polarimeter with variable cornea compensation.

OBJECTIVE: To evaluate the interdevice reproducibility of retinal nerve fibre layer (RNFL) thickness measurements obtained with the commercially available GDx-VCC, a scanning laser polarimeter with variable (individualized) corneal compensation. METHODS: A prospective instrument validation study in which 13 GDx-VCC devices were tested. One eye each, from three normal subjects were used to test each of the devices, on the same day, by an experienced operator. Variability and reproducibility for each of five GDx parameters were calculated. RESULTS: For each of five tested GDx parameters, the coefficient of variation and 95% confidence interval range (microm), for the 13 devices, respectively, were: TSNIT avg: 5.1%, 3.84 microm; Superior avg: 5.3%, 4.82 microm; Inferior avg: 6.1%, 5.50 microm; TSNIT standard deviation: 8.6%, 2.92 microm; and nerve fibre indicator (NFI): N/A, 5.69. Item reliability (Cronbach's alpha) for the five GDx parameters are: TSNIT-Avg: 0.97, Sup-Avg: 1.00, Inf-Avg: 0.84, TSNIT-SD: 0.99, NFI: 0.99. CONCLUSIONS: With the commercially available GDx-VCC, our results indicate that RNFL measurements appear reproducible across devices.

Adult↗
PubMed2005

Conversational versus expository discourse: a study of syntactic development in children, adolescents, and adults.

In this cross-sectional investigation, syntactic development was compared in conversational versus expository discourse in 120 typically developing children, adolescents, and adults, age 7 to 49 years. Each participant was asked to discuss common topics such as school, family, and friends to elicit conversational discourse and to explain the rules and strategies of a favorite game or sport to elicit expository discourse. The results showed greater syntactic complexity in expository discourse than in conversational for all age groups, supporting the view that complex thought is driving the development of complex language. For both genres, growth in syntax continued throughout childhood and adolescence and into early adulthood (age 20-29 years) and remained stable into middle age (age 40-49 years). The 2 best indicators of growth were mean length of T-unit and relative clause production, both of which showed age-related increases into early adulthood. Another variable that was sensitive to growth was the total number of T-units produced, a measure of language output. In general, older speakers talked more than younger ones regardless of genre. Despite the statistically significant group effects, there were wide individual differences. For example, in the expository genre, some of the younger children used rather elaborate syntax whereas some of the older adults spoke quite simply. Thus, it appears that individual variability can exist at all points along the age continuum, despite the trend toward greater syntactic complexity as a function of increasing chronological age.

Adolescent↗
PubMed2005

Extended-release divalproex in child and adolescent outpatients with epilepsy.

PURPOSE: To determine whether valproic acid [divalproex (DVP)] extended-release, administered at a higher proportionate once-daily dosage, can be safely substituted for delayed-release or sprinkle in pediatric patients with epilepsy. METHODS: Patients between ages 6 and 17 years with stable epilepsy taking DVP were randomized to 7 days of either DVP delayed-release/sprinkle (at the usual daily dose taken before study entry) or extended-release DVP (daily dose, 8% to 25% higher than their usual dose), and then (crossed over to) 7 days of the comparator formulation. Patient's clinical status was evaluated at a screening visit and on days 8 and 15, and with telephone follow-up 1 month after study completion. RESULTS: No statistically significant difference in mean plasma VPA levels measured at the end of treatment was observed: 99, 92, and 103 mug/ml with the delayed-release tablets (n = 4), the sprinkle formulation (n = 11), and the extended-release tablets (n = 16), respectively. Seizure-control rates were stable during patients' use of the extended-release formulation. None of the study patients experienced a treatment-related adverse event. CONCLUSIONS: The total daily dose for patients taking the delayed-formulation may need to be increased by < or = 20% when they are switched to the extended-release formulation. When switching from sprinkles to the extended-release formulation, individual variability must be considered. In patients who have VPA levels near the very high end of the therapeutic range (>100 microg/ml), it may be more prudent to make only minor modifications to the total daily dose during conversion and then to individualize the DVP extended-release dose based on plasma levels.

Adolescent↗
PubMed2004

Pharmacogenetics and pharmacogenomics as new tools to optimise cancer chemotherapy.

Pharmacogenetics takes into account the individual variability of the genome and its relationships with drug activity. Numerous gene polymorphisms occurring at the level of drug metabolising enzymes, drug transporters or drug targets have been identified; they may be responsible for an alteration of the phenotype, and of individual changes in drug efficacy and/or toxicity. Pharmacogenomics takes into account the genetic alterations present in tumours and their role in drug activity. It may be possible to establish correlations between the activity of a drug and the level of expression of tumour genes, and thus select the most appropriate drugs to prescribe for the treatment of individual tumours. Pharmacogenetics and pharmacogenomics are acting synergistically for the personalisation of treatments, on the basis of the constitutive singularity of patients and of the molecular characteristics of tumours.

Antineoplastic Agents↗
PubMed1995

Comparison of body size measurements as predictors of NIDDM in Pima Indians.

OBJECTIVE--To determine and compare the abilities of various anthropometric measurements to predict the development of non-insulin-dependent diabetes mellitus (NIDDM) in Pima Indian men and women. RESEARCH DESIGN AND METHODS--A total of 290 male and 443 female Pima Indians were followed for up to 6 years for the development of NIDDM. A proportional hazards analysis was used to assess the ability of anthropometric measurements evaluated at baseline to predict NIDDM. Receiver operating characteristic (ROC) curves were used to compare individual variables in predicting NIDDM. RESULTS--In separate models controlled for age and sex, body mass index (BMI), waist circumference, thigh circumference, waist-to-thigh ratio (WTR), weight, and percentage body fat (PBF) estimated by bioelectric resistance each predicted NIDDM, which developed in 30 men and 52 women. The highest incidence rate ratios (IRRs; for 1 SD of a variable) were for WTR in men and for PBF in women, although the confidence interval (CI) for PBF was wide. In stepwise analyses, WTR was the most significant predictor in men (IRR for 1 SD = 1.58, 95% CI = 1.20-2.07), and BMI was the most significant predictor in women (IRR for 1 SD = 1.65, 95% CI = 1.29-2.11). However, by ROC analyses, thigh circumference was the only variable significantly worse than WTR in men or BMI in women at predicting NIDDM. CONCLUSIONS-- Measurements such as waist circumference, WTR, weight, and BMI may be useful as more complicated measurements, such as PBF by bioelectrical resistance, for identifying groups of individuals whose body habitus places them at high risk of developing NIDDM.

Adolescent↗
PubMed1989

Vinblastine, cisplatin and bleomycin (VPB) adjuvant therapy does not induce dose-dependent damage in human chromosomes.

Chromosome aberrations and sister chromatid exchanges were examined in testicular tumor patients treated by 4 cycles of vinblastine, cisplatin and bleomycin adjuvant therapy. The predominant aberrations in cells varied among the patients, and due to interindividual variability no time- or dose-dependent changes were observed in cytogenetic data. There was found an overdispersion of aberrations which might be explained by the effect of bleomycin. Sister chromatid exchange (SCE) frequency was slightly increased and showed also an individual variability in the response to vinblastine, cisplatin and bleomycin (VPB) therapy. No correlation with chromosome aberration rate was found. Further data are required for the real estimation of long-term effects of VPB therapy.

Adolescent↗
PubMed2003

Long-term cognitive and functional decline in late onset Alzheimer's disease: therapeutic implications.

BACKGROUND: National Institute of Clinical Excellence guidelines advocate the use of the Mini-Mental Test Examination and a functional assessment as a means of measuring treatment response. However, there is little knowledge of the change expected in those with Alzheimer's disease in clinical practice. OBJECTIVE: to describe the long-term variability of the Mini-Mental Test Examination and Blessed Dementia Rating Scale. METHOD: 374 Alzheimer's disease patients referred to psychiatric services in southeast London were followed annually over a 3-year period. RESULTS: the mean Mini-Mental Test Examination score for the total group at baseline was 9.9 points. Individual variability in the rate of cognitive and functional decline is large and around 40% of patients after 1 year, and up to one-quarter of patients after 3 years who survived, show no change or an improvement in scores compared with baseline measures. CONCLUSIONS: in the evaluation of individual treatment response the rate of change, as measured by the Mini-Mental Test Examination and Blessed Dementia Rating Scale, is of limited value.

Aged↗
PubMed1986

Blood platelet activation and increase in thrombin activity following a marathon race.

To see whether strenuous prolonged exertion increases blood platelet activation and thrombin activity in healthy well-trained men, 16 male amateur runners (mean age 31,8) were studied. A marathon race (mean time 2 h 44 min 30 s) caused a significant increase in plasma beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), fibrinopetide A (FPA) and factor VIII (F VIII) activity. Sixty min after exertion beta-TG and F VIII activity were still significantly elevated. FPA continued to rise, reaching peak values 60 min after the run. 22 h after finishing the race F VIII activity was still significantly elevated. The study has demonstrated the great inter-individual variability of marathon race-induced haemostatic changes. The elevation of beta-TG varied from 42% to 156%, F VIII from 112% to 625%, and in three runners FPA reached more than 900% of its pre-exercise value. In some individuals the haemostatic changes observed could be potentially unfavourable for coronary heart disease prevention.

Adolescent↗
PubMed2006

Tumor necrosis factor-alpha genetic polymorphism may contribute to progression of bovine leukemia virus-infection.

In a previous report, we had indicated that in a sheep model, the expression of tumor necrosis factor (TNF)-alpha was closely associated with disease progression in sheep experimentally infected with bovine leukemia virus (BLV). However, individual variabilities are observed in these responses in BLV-infected animals. To attempt to identify genetic factors promoting the progression to BLV-induced lymphoma, we endeavored to determine whether there are any polymorphisms in the TNF-alpha gene among 291 individuals and whether this would affect the level of TNF-alpha expression and concomitant progression of BLV-induced disease or increase in the provirus load in the carriers. We found that the frequency of the TNF-alpha -824G allele, which has been associated with low transcription activity of the promoter/predicted enhancer region of the bovine TNF-alpha gene, was higher in individuals with BLV-induced lymphoma than in asymptomatic carrier individuals. In addition, we observed a tendency for increased BLV-provirus load in cattle with TNF-alpha -824G/G homozygote compared to TNF-alpha -824A/A homozygote or TNF-alpha -824A/G. These data suggest that the observed polymorphism in the promoter region of TNF-alpha gene could at least in part contribute to the progression of lymphoma in BLV-infection.

Animals↗
PubMed2002

Site-specific variability in trabecular bone dosimetry: considerations of energy loss to cortical bone.

With continual advances in radionuclide therapies, increasing emphasis is being placed on improving the patient specificity of dose estimates to marrow tissues. While much work has been focused on determining patient-specific assessments of radionuclide uptake in the skeleton, few studies have been initiated to explore the individual variability of absorbed fraction data for electron and beta-particle sources in various skeletal sites. The most recent values of radionuclide S values used in clinical medicine continue to utilize a formalism in which electrons are transported under a trabecular bone geometry of infinite extent. No provisions are thus made for the fraction of energy lost to the cortical bone cortex of the skeletal site and its surrounding tissues. In the present study, NMR microscopy was performed on trabecular bone samples taken from the femoral head and humeral proximal epiphysis of three subjects: a 51-year male, an 82-year female, and an 86-year female. Following image segmentation and coupling to EGS4, electrons were transported within macrostructural models of the various skeletal sites that explicitly include the spatial extent of the spongiosa, as well as the thickness of the surrounding cortical bone. These energy-dependent profiles of absorbed fractions to marrow tissues were then compared to transport simulations made within an infinite region of spongiosa. Ratios of mean absorbed fraction, as weighted by the beta energy spectra, under both transport methodologies were then assembled for the radionuclides 32P and 90Y. These ratios indicate that corrections to existing radionuclide S values for 32P can vary by as much as 5% for the male, 6% for the 82-year female, and 8% for the 86-year female. For the higher-energy beta spectrum of 90Y, these same corrections can reach 8%, 10%, and 11%, respectively.

Aged↗
PubMed2005

Effect of catechol-O-methyltransferase val158met genotype on attentional control.

The cingulate cortex is richly innervated by dopaminergic projections and plays a critical role in attentional control (AC). Evidence indicates that dopamine enhances the neurophysiological signal-to-noise ratio and that dopaminergic tone in the frontal cortex is critically dependent on catechol-O-methyltransferase (COMT). A functional polymorphism (val158met) in the COMT gene accounts for some of the individual variability in executive function mediated by the dorsolateral prefrontal cortex. We explored the effect of this genetic polymorphism on cingulate engagement during a novel AC task. We found that the COMT val158met polymorphism also affects the function of the cingulate during AC. Individuals homozygous for the high-activity valine ("val") allele show greater activity and poorer performance than val/methionine ("met") heterozygotes, who in turn show greater activity and poorer performance than individuals homozygous for the low-activity met allele, and these effects are most evident at the highest demand for AC. These results indicate that met allele load and presumably enhanced dopaminergic tone improve the "efficiency" of local circuit processing within the cingulate cortex and thereby its function during AC.

Adult↗
PubMedDate not supplied

[Apnea during sleep and wakefulness in term newborns].

Apneas in the different sleep states are commonly observed in the full-term healthy newborn infant. Central and short apneas prevail whilst apneas greater than 15 sec. are rare; a marked incidence of short apneas (less than 10 sec.) was observed in active sleep, even though apneas are not exclusive of active sleep. There is a strong inter-individual variability of apnea incidence. Apnea incidence in a state is not positively correlated to apnea incidence in different behavioural states: on the contrary there seems to be an opposite correlation between incidence in AS and QS. Apnea occurrence is positively correlated, in individuals, to the periodic breathing percentage. Apneas number and their duration is markedly lowered already in the second month of life. Periodic breathing must be considered a feature of immaturity. Obstructive apneas are less frequent than central apneas: their survey requires sophisticated technics with the aid of simultaneous recording of several breathing parameters. Relationship between central apneas/ obstructive apneas and mixed apneas is not known. Certainly obstructive and mixed apneas occurrence has been underestimated because of technical difficulties deriving from their survey. The meaning of an incidence of short apneas markedly higher than normal in full-term newborn infants is controversial and not clear, individuals with long apneas and subjects with short apneas in excess have been considered infants at SIDS risk. It is not clear whether periodic breathing and apneas depend on a common pathogenesis; the correlation between high incidence of periodic breathing in postnatal period and SIDS risk is still controversial. Few Authors suggest to treat newborn infants with extended apneas in sleep and considerable percentage of periodic breathing with aminophylline. The relation between gastro-oesophageal reflux and apnea has been recently evidenced. Central apneas and obstructive apneas during breast and bottle feeding have also been documented. Differently from pre-term infant apneas, bradycardia, although not exceptional, is not frequent during apneas in full-term newborn infants.

Age Factors↗
PubMed1995

Comparison of measured and FTC-predicted nicotine uptake in smokers.

Cigarette smokers have a wide variety of "tar" and nicotine yields to choose from in the current market, ranging from 0.5 mg "tar" and less than 0.05 mg nicotine to 27 mg "tar" and 1.8 mg nicotine by the Federal Trade Commission (FTC) method. To understand better the relationship between FTC nicotine yields and actual nicotine uptake in smokers, we have studied nicotine uptake in 33 smokers of self-selected products representing four "tar" groupings: 1 mg "tar" (1MG), ultra-low "tar" (ULT), full-flavor low "tar" (FFLT), and full flavor (FF) cigarettes. These cigarette categories had mean FTC nicotine yields of 0.14, 0.49, 0.67, and 1.13 mg/cigarette, respectively. The subjects smoked their usual brand of cigarette ad libitum and provided a 24-h urine sample for total nicotine uptake analysis over a period during which the number of cigarettes smoked was recorded. Nicotine uptake was determined by monitoring urinary nicotine and its metabolites, including the glucuronide conjugates. Daily nicotine uptake was 9.1 +/- 7.3 mg (range 1-21 mg) for 1MG, 19.2 +/- 10.0 mg (range 4-42 mg) for ULT, 21.8 +/- 9.4 mg (range 13-38 mg) for FFLT, and 37.1 +/- 14.4 mg (range 21-60 mg) for FF smokers. On a per cigarette basis, yields were 0.23 +/- 0.11, 0.56 +/- 0.23, 0.60 +/- 0.18, and 1.19 +/- 0.43 mg nicotine, respectively. Although individual variability was fairly large (CVs of 0.39-0.80), means for the different groups showed that lower FTC yield smokers not only absorb less nicotine per 24-h period, but also per cigarette smoked. These data suggest that nicotine uptake is a function of individual smoking behavior within product design limits. We conclude from these data that, while FTC yield cannot precisely predict nicotine uptake for an individual smoker, it is useful in predicting and comparing actual nicotine uptake by smokers who select cigarettes with a particular FTC yield.

Adult↗
PubMed1991

Indomethacin increases the sensitivity of the monocyte migration inhibition assay.

In ophthalmo-immunological investigations only small samples of ocular tissues and fluid are available and assays which are feasible with very small volumes or cell numbers are mandatory. Indomethacin, which is known to augment the immune response both in vivo and in vitro was therefore tested for its effect on the monocyte migration inhibition (MIF) assay using low cell or antigen doses. The sensitivity of the MIF assay may be greatly increased by adding indomethaci during the first step of the assay. Titration of either the antigen dose, the mononuclear cells number or both per assay, resulted in a 10-50-fold increase in sensitivity of the assay, with a broad inter-individual variability. Increasing the sensitivity of the MIF assay with indomethacin has clear advantages with regard to the number of cells required but also confronts us with a new problem: activation of specific cells that circulate at very low frequencies in non-immunized individuals. The enhanced response could be reversed to some extent by adding prostaglandin E2 together with indomethacin to the first step of the assay. Moreover, adding leukotriene B4 to the first step of the assay had an enhancing effect over a limited concentration range. We conclude that in the presence of indomethacin, the MIF assay provides a highly sensitive technique for the demonstration of cellular immune responses in small samples of biological fluids containing very small numbers of antigen-specific lymphocytes.

Cell Migration Inhibition↗
PubMed1994

Micronuclei and 3AB index in X-irradiated human lymphocytes in G0 and G1 phases.

We applied the cytokines-block micronucleus assay to observe the radiobiological response of human lymphocytes after X-ray treatment in the G0 and G1 phases. In addition, we used 3-aminobenzamide (3AB) to measure the 3AB index in the two phases. The experimental results show that at 2 Gy the MN yield and the 3AB index are dependent on the cell phase and show considerable inter-individual variability. The radiation-induced MN frequency obtained for 33 subjects is 0.470 +/- 0.063 for the G0 phase and 0.689 +/- 0.139 for the G1 phase; the 3AB index values are 0.326 +/- 0.144 and 0.067 +/- 0.058 for G0 and G1 phases, respectively. At the individual level, the 3AB index for the G1 phase correlates inversely with the cytogenetic effects observed in that phase. We discuss the possibility of applying the MN test combined with the 3AB index to lymphocytes at different phases to study the individual response to radiation (individual radiosensitivity).

Adult↗
PubMed2005

Responsiveness to cholinesterase inhibitors in Alzheimer's disease: a possible role for the 192 Q/R polymorphism of the PON-1 gene.

Cholinesterase inhibitors (ChEIs) are the most established treatment strategy in Alzheimer's disease (AD). However, the responsiveness to these drugs is widely heterogeneous and the majority of AD subjects do not respond to treatment. Paraoxonase-1 (PON-1) is a potent endogenous ChEI and has been widely studied for its ability to hydrolyze environmental neurotoxins. Serum levels and biological activity of PON-1 display wide inter-individual variability and are strongly influenced by a common polymorphism at position 192 of the PON-1 gene. Here, we evaluated whether this gene variation is associated with differences in the ability of AD subjects to respond to therapy with ChEIs. We found that individuals that respond to ChEIs had a significantly higher frequency of the R allele, compared to non-responders (P<0.05). This study indicates that the 192 Q/R polymorphism of the PON-1 gene might influence responsiveness to ChEIs, with potentially important implications for the treatment of AD. Mutations of genes encoding for endogenous modulators of the cholinergic system should merit further investigation as prognostic indicators of individual response to treatment in AD subjects.

Aged↗
PubMed1995

Venous hemodynamics during impulse foot pumping.

PURPOSE: This study was designed to measure the effect of intermittent pneumatic compression of the plantar venous plexus on popliteal vein (PV) and common femoral vein (CFV) velocities measured by duplex ultrasound scanning. METHODS: Thirty lower limbs in 15 healthy volunteers had venous duplex scanning measurement of PV and CFV velocities before and during foot pumping with an arteriovenous impulse foot pump system. Venous velocities were measured at two pump pressure settings (100 mm Hg, 200 mm Hg) and during two pump impulse durations (short = 1 second, normal = 3 seconds). All limbs were examined with the subjects in the supine position, and then measurements were repeated with subjects in the 15-degree reverse Trendelenburg position. The mean maximum venous velocity (MVV) produced by foot pumping was compared with resting venous velocity at each anatomic location and for each technologic variable. RESULTS: Impulse foot pumping produced a statistically significant increase in MVV in both the PV and the CFV compared with resting velocities. This significant increase was observed for both pressure settings and both impulse durations, and no differences produced by these two individual variables could be detected. The increase in MVV produced by foot pumping was similar for limbs in the supine position and those examined in the reverse Trendelenburg position. The percentage increase in MVV produced by foot pumping was significantly higher in the PV than in the CFV. CONCLUSIONS: Intermittent pneumatic compression of the plantar venous plexus produces measurable increases in venous outflow from the lower limbs of normal subjects. This study seems to justify further evaluation of the effectiveness of this technique for mechanical deep venous thrombosis prophylaxis in selected high-risk patient groups.

Adult↗
PubMed1983

Medical management of obesity. Promoting healthy dieting.

Per capita caloric intake in the United States has not increased significantly in the past 75 years, but energy expenditure has decreased. As a result, average body weight and prevalence of obesity have increased. Paralleling this increase in body weight has been an increase in longevity. Minor obesity, therefore, is not related to increased mortality unless the patient has an underlying disease such as diabetes mellitus, hypertension, or hyperlipemia. Patients with these disorders or with a body weight in excess of 20% of the ideal will benefit most from aggressive therapy for obesity. The team approach to obesity--which may include a physician, nutritionist, psychologist, and physical therapist--has been the most successful. Team members need to understand the difficulties involved in weight loss and the numerous individual variables. A diet should be selected carefully to conform as nearly as possible to the patient's life-style. Regular exercise commensurate with the patient's physical abilities should be encouraged to promote caloric expenditure and to shape the body. Supportive and individualized care with continual motivation is necessary to achieve and maintain weight loss. Of course, the therapy chosen depends upon the risk of morbidity and mortality associated with the degree of obesity.

Appetite↗