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PubMed2006

Life satisfaction after traumatic brain injury and the World Health Organization model of disability.

OBJECTIVE: To determine which components of the World Health Organization's International Classification of Functioning, Disability, and Health (ICF) are most predictive of global life satisfaction after traumatic brain injury (TBI). DESIGN: Prospective evaluation of 180 individuals enrolled in a TBI model system project site. RESULTS: Multiple regression analysis indicated that the combination of ICF components (body function and structure, activities, and participation) and demographic factors significantly predicted life satisfaction and accounted for 17% of the variance. Participation was the strongest predictor; activities were a significant, but weaker predictor; and body function and structure did not add to the prediction of life satisfaction. Of all the individual variables evaluated, only social integration and productivity were found to be significant, unique predictors. CONCLUSIONS: When considering the effects of various aspects of disabling conditions on the life satisfaction of individuals who have suffered a TBI, restriction of participation in life activities was found to have the greatest impact. Although the model accounted for a significant percentage in the variation of life satisfaction, a large proportion of the predictive picture (>82%) remains unclear. Doubtless, other variables impinge on life satisfaction that would further clarify the complex relationship between disabling conditions and life satisfaction in TBI.

Activities of Daily Living↗
PubMed1998

Ecological and physiological studies on large intestinal bacteria in relation to production of hydrolytic and reductive enzymes involved in formation of genotoxic metabolites.

Several hydrolytic and reductive bacterial enzymes (beta-glucuronidase, GN; beta-glucosidase, GS; arylsulphatase, AS; azoreductase, AR; nitroreductase, NR) involved in production of mutagenic or genotoxic metabolites were measured in human colonic contents. Cell-associated AS and extracellular GS were approximately twice as high in the distal colon compared with the proximal bowel, while AR changed little throughout the gut. Measurements of these enzymes in faeces from seven healthy donors confirmed that the majority were cell-associated, and demonstrated high levels of inter-individual variability. NR decreased four-fold between the proximal and distal colon while extracellular GN was reduced by 50%. Most probable number (MPN) analysis on faeces obtained from six healthy donors showed that counts of intestinal bacteria producing GS and AR were c. 10(10) and 10(11)/g, respectively, in all samples tested. Numbers of GN- and AS-forming organisms were between two and three orders of magnitude lower. Inter-individual carriage rates of bacterial populations synthesising NR were highly variable. Screening of 20 pure cultures of intestinal bacteria, belonging to six different genera, showed that Bacteroides ovatus, in particular, synthesised large amounts of GS, whereas B. fragilis, B. vulgatus and Bifidobacterium pseudolongum formed the highest cell-associated levels of GN. In general, bifidobacteria and Lactobacillus acidophilus did not produce significant amounts of AR. All five clostridia studied (Clostridium bifermentans, C. septicum, C. perfringens, C. sporogenes and C. butyricum) produced NR and AR, as did the bacteroides (B. fragilis, B. ovatus and B. vulgatus). Escherichia coli and C. perfringens formed large amounts of NR. Levels of AS production were invariably low and few of the organisms screened synthesised this enzyme. In-vitro studies investigating the effect of intestinal transit time on enzyme production, in a three-stage (V1-V3) continuous culture model of the colon operated at system retention times (R) of either 31.1 or 68.4 h, showed that specific activities of GS were up to four-fold higher (V3) at R = 31.1 h. Bacteriological analysis demonstrated that representative populations of colonic micro-organisms were maintained in the fermentation system, and indicated that changes in GS activity were not related to numbers of the predominant anaerobic or facultative anaerobic species within the model, but were explainable on the basis of substrate-induced modulation of bacterial metabolism.

Adult↗
PubMed1998

Effects of variability in hepatic clearance on the bioequivalence parameters of a drug and its metabolite: simulations using a pharmacostatistical model.

A semi-physiological pharmacostatistical model was developed and used to study the manner in which intra-individual variability in hepatic clearance is transmitted to the area-under the plasma concentration-time curve from zero to infinity (AUC) of a drug and its metabolite. In order to clarify the effects, the model contained no other sources of variability. As the drug's hepatic extraction ratio increased, the coefficient of variation (CV) of the AUC of the drug increased, whereas that of the metabolite decreased. The AUC of the metabolite increased as the drug's non-hepatic clearance increased. At high extraction ratios, the CV of the AUC of the drug was insensitive to the contributions of other forms of clearance. The results suggest that under certain circumstances, smaller samples sizes could be used in bioequivalence studies for highly variable drugs if the test were based on the metabolite rather than the parent drug.

Area Under Curve↗
PubMed1994

Asbestos bodies in bronchoalveolar lavage fluid in relation to occupational history.

Concentrations of asbestos bodies (AB) were assessed by optical microscopy of 10 ml iron-stained samples and compared with the exposure history acquired by personal interview for 156 patients. Concentrations equalling or exceeding 1 AB/ml were found in 85% of patients who had been heavily exposed to asbestos and only 7% of those who were unlikely to have been exposed. Elevated AB concentrations were observed among primary asbestos, shipyard and construction workers. Smoking was not found to affect the AB concentrations. The use of Papanicolaou-stained cytological Millipore preparations during routine screening was a less sensitive method for the assessment of AB concentrations than that involving iron-stained preparations. The expression of AB concentration as AB/ml or AB/million cells were found to be equally useful indicators of exposure. The correlation between AB concentration and exposure history was greater than in earlier studies on workers exposed to chrysotile. Concentrations exceeding 1 AB/ml were indicative of a nontrivial exposure to asbestos. Despite the observed correlation between AB concentration and exposure history, the individual variability of AB counts, methodological differences and laboratory-bound reference values are important in the interpretation of AB concentrations in bronchoalveolar lavage (BAL) fluid at individual level.

Adult↗
PubMed1999

Dissociation between complement activation, integrin expression and neutropenia during hemodialysis.

Complement activation, neutrophil stimulation, increased cellular adhesiveness, transient leukocyte margination and pulmonary leukostasis take place during hemodialysis with cellulosic dialysis membranes. Several investigators have hypothesized that complement activation is primarily responsible for the acute neutropenia occurring during the early phase of bio-incompatible hemodialysis. We have investigated the relationship between complement activation, levels of expression of CD11b and CD61 integrins on neutrophils and platelets, neutrophil counts and blood gas measurements in patients dialyzed with three types of membranes, known to activate the complement system to a different extent. Polysulfone, cellulose acetate and cuprophane membranes were used subsequently in six patients in a prospective cross-over trial design to reduce inter-individual variability. Increased levels of CD61 and CD11b, as well as neutropenia, were detected regardless of the type of membrane used. We observed a high inter-individual variation with regard to complement activation suggesting varying susceptibility to dialysis membranes. We also report that the kinetics of anaphylatoxin generation were dissociated from those of the upregulation of adhesion molecules, early neutrophil margination and decrease in PaO2 during the first 30 min of hemodialysis. Similar results were obtained with all three types of dialysis membranes. The data strengthen the hypothesis that factors other than complement are involved in the induction of dialysis-related neutropenia and hypoxemia.

Adult↗
PubMed2001

Antigenicity of polyester (Dacron) vascular prostheses in an animal model.

Objectives to investigate the specific humoral immune response to three different polyester (Dacron) prostheses in pigs. Design, materials and methods twenty-four growing pigs were randomly divided into three groups. The infrarenal aorta was replaced by a segment of collagen-impregnated woven polyester prosthesis (low, medium and high porosity). Serum antibodies were detected by modified enzyme immunoassay using non-impregnated prosthesis as the target for the blood samples taken on experimental days 1, 10, 17, 24, 62 and 116 of the 22 pigs followed over the whole observation period. Results significantly enhanced (p <0.05) mean IgG antibody binding against polyester was detected on experimental days 10, 17, 24 and 62 with antibody prevalences of 41%, 41%, 32% and 37%, respectively. Antibody positive pigs were divided into early responders (n =9) and late responders ( n =5) with antibody detection on day 10 and/or 17 vs day 62 and/or 116. No significant differences between the three different prostheses were found. The formation of specific IgG antibodies against polyester in the animals investigated demonstrates a broad individual variability. Conclusions polyester is an antigenic polymer. Specific antibodies, reflecting the inflammatory response, might be not only a parameter for testing biomaterials but also for determining individual bio(in)compatibility for long-term biomaterial function.

Animals↗
PubMedDate not supplied

Biological markers in chromium exposure assessment: confounding variables.

An estimated two million tons of chromate production waste pollution has caused a major environmental and public health concern in Hudson County, New Jersey. As part of an occupational exposure assessment, urinary and red blood cell (RBC) chromium measurements were performed on 52 state employees who worked either near a contaminated site or elsewhere. Samples were collected so as to minimize contamination, and they were analyzed using sensitive techniques. These workers also completed a questionnaire that addressed potentially important third variables. Individual analyses suggested that exercise, drinking beer, past employment in chromium-related occupations, and diabetic status had an important effect on urinary chromium levels. These variables were entered into a regression model and were all found to be significant predictors of urinary chromium level (p less than .10). Some variables were also examined for their influence on RBC chromium level, but none had a measurable effect.

Adult↗
PubMed2005

Alcohol involvement and marital quality in the early years of marriage: a longitudinal growth curve analysis.

BACKGROUND: Previous research suggests that becoming married is associated with declines in drinking. The current study examines two potential influences on newly married husbands' and wives' drinking trajectories, the impact of the partner's drinking and the quality of the marriage. METHODS: Couples (n=592) were assessed at the time of their first marriage, at the first anniversary, and at the second anniversary. Husbands and wives completed separate, self-administered questionnaires at home. Latent growth curve analysis was used to examine husbands' and wives' alcohol use and marital quality trajectories and to test the bi-directional relationships between alcohol involvement and marital quality both within and between couple members. RESULTS: Husbands' and wives' alcohol involvement and marital quality declined over time and there was significant individual variability in these changes over time. Although we failed to find any longitudinal influence of greater alcohol involvement on declines in marital quality or vice versa, individuals' marital quality and alcohol involvement were correlated at the time of marriage and individuals' changes in drinking were significantly associated with changes in their reported marital satisfaction. There were also significant correlations observed between one partner's alcohol involvement slope and the spouse's marital quality slope, indicating that steeper declines in husbands' and wives' drinking were associated with less steep declines in their partner's marital quality. CONCLUSIONS: There is clearly an association between husbands' and wives' alcohol use and marital quality. However, given the absence of longitudinal effects, we cannot discern the temporal precedence of this association. Additional research is needed to more fully understand this complex relationship.

Adult↗
PubMed2005

Time-dependent pharmacokinetics of cyclosporine (Neoral) in de novo renal transplant patients.

PURPOSE: A model for the large scale temporal trend in the oral bioavailability of microemulsion cyclosporine (Neoral) (CsA) is established, with dependence on post-(renal) transplantation day (PTD). METHODS: Twenty de novo adult renal transplant recipients were monitored for CsA administered orally q12 h. A model development group (11 patients, 315 blood concentration samples) was screened at 2 h (C(2); n = 92), 3 h (C(3); n = 56) and at predose troughs (C(min); n = 167) over periods of up to 75 days. The final model was tested in nine patients with C(min) (n = 580) monitored across 4-5 years. The doses varied between 100 and 538 mg with an apparent hyperbolic trend in C(2)/dose vs. PTD. A nonlinear mixed effects modelling (NONMEM) approach was used to obtain population and individual patient one-compartment pharmacokinetic (PK) parameters for oral CsA, which carry implicit the bioavailability (F). RESULTS: In the final PK model (PK-f) the F was modelled via a simple function for the temporal (days) trend of the bioavailability after transplantation as, F(f) = 1-alpha * exp(-lambda * PTD) resulting in a 28% reduction in the unexplained intra-individual variability. The population PK-f parameters were, for apparent clearance [mean, 95% confidence interval (interindividual CV%)] Cl/F(f) = 17.0 (13.8-20.2) L/h (27%), apparent central compartment volume of distribution, V/F(f) = 134 L (108-160) (28%), and lambda = 0.037/day (0.005-0.069) (120%). The absorption rate k(a) and the parameter alpha were approximated iteratively as 4/h and 0.62 respectively. The PK-f was structurally superior to the base model in explaining part of the within subject (occasion) variability and predicting the exposure surrogates C(2) and C(3). Also, the PK-f was better than the base model with Bayesian fitting of individual profiles in that group. CONCLUSION: The PTD-dependent relative bioavailability model provides a rational means of steering dose titration of CsA in de novo renal transplantation patients by removing the large scale PK adjustment signal, either through nomograms or as a Bayesian prior.

Adult↗
PubMed1985

Nature of relapse after surgical mandibular advancement.

Pre-operative, post-operative and follow-up cephalometric records of 16 cases of mandibular retrognathia treated by surgical mandibular advancement were analysed retrospectively. The results showed good mean stability in the mandibular advancement with variable individual relapse. The pre-operative mandibular plane angle, magnitude of the advancement and post-operative increase in the posterior lower face height were the variables chiefly related to relapse. There appeared to be limited control over the posterior segment which was liable to distraction and rotation. The follow-up changes were time linked. Both mechanical and biological factors are postulated to explain the relapse.

Cephalometry↗
PubMed1996

The relation between heavy alcohol use and bar patronage: a latent growth model.

OBJECTIVE: Random effects latent growth (LG) models were used to study the relation between changes in heavy alcohol use and changes in the frequency of bar patronage over a 3-year period. Previous research has identified a close link between alcohol use and bar patronage, but these cross-sectional findings limit inferences about possible temporal ordering. LG models are highlighted and compared with the more traditional but restricted cross-lagged models. METHOD: Three annual measures of heavy alcohol use and frequency of bar patronage were administered to a sample of 3071 adults (62% male) who participated in the National Longitudinal Study of Youch from 1982 to 1984. Background variables included age, gender, ethnicity and marital status. RESULTS: Heavy alcohol use and bar patronage were characterized by negative longitudinal growth trajectories and there was significant individual variability in these changes over time. Changes in heavy alcohol use closely paralleled corresponding changes in bar patronage. Finally, the Time 1 measures of each construct were inversely predictive of subsequent changes over time in the second construct. CONCLUSIONS: These findings suggest that heavy alcohol users tended to continue to patronize bars, and bar patronage tended to encourage continued heavy alcohol use. This relation was particularly strong for singles and males. Compared to more traditional cross-lagged models, LG modeling appears to be a much stronger analytic technique for studying growth over time. It is recommended that LG models be used for future studies of change in alcohol use over time.

Adolescent↗
PubMed1997

Optimisation of the prescription for trans-tibial (TT) amputees.

The great diversity of prosthetic mechanisms available nowadays leads to the question of which type of artificial foot would be the most advisable for a particular person. To answer correctly, it is necessary to establish, in an objective way, the performance of each type of prosthetic mechanism. This knowledge is obtained by means of the study of the subject-prosthesis interaction, both in static and dynamic conditions. This paper, based on the analysis of 8 trans-tibial (TT) amputees, presents a quantitative method for the study of human gait which allows the determination of the influence of four different prosthetic ankle-foot mechanisms (SACH, Single-axis, Greissinger and Dynamic) on gait. To do this, 1341 gait trials at different cadences were analysed (383 with normal subjects and 958 with amputees, using the four prosthetic feet under study). From all the variables available for study only those which offered interpretable clinical information were chosen for analysis. A total of 18 variables (kinetic, kinematic and time-related) were selected. A covariance analysis (ANOVA) of these variables was made, which showed that the factors influencing TT amputee gait were, in order of importance, cadence and leg studied (sound or prosthetic), inter-individual variability and, finally, the prosthetic mechanism used. When looking at the performance during gait of the 4 prosthetic mechanisms studied it can be observed that there are similarities in the kinetic study between SACH and Dynamic feet on one hand and Single-axis and Greissinger feet on the other. These results seem to support the classification criteria of articulated and non-articulated prosthetic mechanisms.

Adult↗
PubMed2002

Latent structure of quantitative dermatoglyphic traits of middle Dalmatia (Croatia).

The latent structure of quantitative dermatoglyphic traits has been analyzed from the population in Middle Dalmatia: islands of Brac, Hvar and Korcula, peninsula of Peljesac and Makarska coastal region. We analyzed 18 variables from fingers and palms, and principal component analysis was performed. In males, we extracted 4 factors for the islands Brac and Korcula, 5 factors for the island of Hvar and Peljesac peninsula and 6 factors for Makarska coastal region. In females we extracted 4 factors for the island of Korcula, 5 factors for the island of Brac, Hvar and Peljesac peninsula, 6 factors for the Makarska region. The total variance in males varies for 4 factors, from 64.19% to 70.71% (for all factors from 68.88% to 75.80%). In females, for 4 factors the total variance was from 57.03% to 66.87% (for all factors from 66.87% to 76.13%). In all population groups on the first factor all finger dermatoglyphics were extracted, while on the other factors there is evident variability of a number of factors extracted and variable explanations. The analysis of variables from extracted factors might give us information about similarities and differences between the groups concerning the latent structure, and also the differences and inter-individual variability in females in comparison to the males. This study provides an insight into the effects of population structure and microevolution on quantitative variation.

Adult↗
PubMed1993

[Selected parameters of hemolymph biochemistry in two growth classes of the snail Planorbarius corneus (L.), regarding infection of the pulmonary cavity with Chaetogaster limnaei limnaei baer (Oligochaeta: naididae)].

We have proved highly significant differences in glucose concentration and activity of alpha-amylase in haemolymph of two growth classes of Planorbarius corneus with width of shell smaller and equal or greater than 20 mm, respectively. Both these parameters were higher and were characterized by greater range of individual variability in snails with smaller width of shell. Any differences in levels of total protein and haemoglobin in haemolymph of these animals, in comparison with adult individuals, were not observed. Effect of infection of the pulmonary cavity of investigated snails with Chaetogaster limnaei limnaei on the examined parameters was not ascertained.

Animals↗
PubMed2001

Variability in vocal and behavioural responses to visual isolation between full-sibling families of beef calves.

In order to assess the value of vocal response as an indicator of welfare in cattle, it is necessary to investigate factors which influence vocal behaviour of individuals, that are independent of the specific environmental conditions to which they are exposed. The effect of parental differences, sex, age and weight on vocal responses of calves to visual isolation were examined. The relationship between vocal response and the amount of body movement during isolation were also evaluated.Seventeen full-sibling families of beef calves (N=130) were created by breeding five sires with 13 superovulated dams. Embryos were transferred into unrelated cows, which reared the calves to weaning age. Vocal response of calves and body movement were measured on four occasions, while they were visually isolated for 1min on a single animal scale platform. The first two observations were made on the day of weaning (mean age 166 days) and the following day. At the third and fourth observations their average ages were 278 and 350 days, respectively. On the four occasions 33.3, 34.8, 27.8 and 38.6% of calves, respectively, vocalized. Both sire and family had a significant influence on the number of vocalizations and acoustic properties of the sounds. Electronically-measured movement while on the scale was also influenced by sire and family, but there was no relationship between vocal responses and body movement. There was a tendency (P=0.08) for older and therefore heavier calves to produce longer vocalizations. In the final observing session, age and weight were positively correlated with fundamental frequency and the sound pressure level at the frequency of greatest intensity, and negatively correlated with the loudest harmonic. At the last two observations, significantly more heifer calves than bull calves vocalized. There was little difference between the acoustic properties of heifers' and bulls' vocalizations.The considerable individual variability in vocal response within a group of identically-treated calves is partly due to parental genetic influences that are independent of rearing and early experience. Other endogenous characteristics such as sex, age and weight also influence vocal response. But there is no clear relationship between individual temperament (as assessed by the amount of body movement during isolation) and characteristics of vocal response.

Journal Article↗
PubMed1985

Benzodiazepines, the popular minor tranquilizers: dynamics of effect on driving skills.

The adverse effects of minor tranquilizers, and more specifically benzodiazepines, on psychomotor and cognitive performance have been documented repeatedly over the years, and epidemiological studies have provided sufficient evidence of their role in traffic accidents. These studies indicate that drug plasma level (DPL) is insufficiently correlated with impairment and that other factors need to be considered in determining the impairment vulnerability. This report reviews several sources of individual variability, particularly as they relate to differential impairment effects. These sources, which include such factors as acute peak effects, acute tolerance, chronic tolerance, benzodiazepine receptor affinity and individual sensitivity, need to be examined before quantification of DPL is introduced as a criterion for driving under the influence. Behavioral testing itself may become the critical means of assessing drug- and/or drug with alcohol-induced driving impairment if acceptable standardized procedures can be developed. Attention is drawn to the rapid onset of impairment associated with acute effects of more lipid soluble drugs. The discussion of impairment of benzodiazepines should be seen in the perspective of their relative overall safety compared to other drugs used as minor tranquilizers.

Accidents, Traffic↗
PubMed1983

Prognostic assessment of patients with coronary artery disease by exercise testing.

To assess whether exercise testing could help predict cardiac mortality, we analyzed 14 exercise and 10 clinical variables in 292 patients treated medically, who underwent treadmill exercise testing and cardiac catheterization and were followed annually for a mean of 2.5 years. None of the individual variables could accurately predict subsequent cardiac mortality with predictive values ranging from 6% to 44%. Combinations of variables were then analyzed in the subset of 113 patients with multivessel coronary disease. A high-risk subgroup (n = 59) consisting of patients with either severe exercise ischemia (greater than or equal to 2 mm ST depression lasting greater than or equal to 5 minutes involving greater than or equal to 3 leads) or left ventricular dysfunction (treadmill time less than or equal to 3 minutes, S3 gallop, or cardiac enlargement) had a mortality of 20%; this was significantly greater (p less than 0.01) than a low-risk subgroup (n = 54) with neither severe exercise ischemia nor left ventricular dysfunction whose mortality was 2%. We conclude that combining clinical and exercise variables to distinguish high- and low-risk subgroups of patients with similar coronary anatomy is useful in predicting cardiac mortality.

Adult↗
PubMed1992

CSF corticotropin releasing hormone, somatostatin, and thyrotropin releasing hormone in schizophrenia.

Cerebrospinal fluid (CSF) corticotropin releasing hormone (CRH), somatostatin (SRIF), and thyrotropin releasing hormone (TRH) were measured by specific radioimmunoassay methods in 86 patients who met DSM-III-R criteria for schizophrenia or schizophreniform disorder and in 30 neurologic controls. The multivariate CSF peptide concentration was significantly different in patients compared with controls, but none of the individual variable differences reached statistical significance when analyzed separately. There were no significant CSF neuropeptide differences among patients with various schizophrenic subtypes. Neither global severity of illness nor individual symptoms were correlated with CSF neuropeptide concentrations. Although schizophrenic patients showed a pattern of mildly lower SRIF and TRH levels in their CSF, together with a weak tendency for higher CSF CRH values, these peptide changes did not appear to be specifically related to the core features of schizophrenia.

Adolescent↗