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PubMed1991

The social and psychologic factors of bruxism.

Bruxism is a destructive habit that is defined as the nonproductive diurnal or nocturnal clenching or grinding of the teeth. This study investigated whether the combination of physical abnormalities, type A behavior pattern, and the perceived desirability and controllability of life stress are related to bruxism. The subjects for the study were 125 dental patients who were classified as bruxers or nonbruxers by a licensed dentist and who completed two measures, the Jenkins Activity Survey, and a modified version of the Holmes and Rahe Life Events Scale. Regression analyses indicate there is a difference in the separate impact of each variable. Type A behavior and physical abnormalities are significant in a stepwise analysis, while stress is not. Stress appears to be significant only in conjunction with type A behavior, and suggests that the combination of type A behavior, and stress is more predictive of bruxism than either of the individual variables. The linear combination of physical abnormalities, type A behavior, and stress is significant, and suggests that it is the best predictor of bruxism.

Bruxism↗
PubMedDate not supplied

[Material well-being of the province of residence and leisure-time physical inactivity].

OBJECTIVE: To estimate the association between material wellbeing of the province of residence and leisure-time physical inactivity in the Spanish population aged 16 years and older. METHODS: We used data from the Survey on Disabilities, Impairments and Health Status carried out by the Statistical National Institute in 1999. We analyse 24,561 women and 21,133 men. Respondents were classified as inactive if they reported no leisure-time physical activity. The measure of material wellbeing was the per capita income of the province of residence grouped in quartiles. The measure of the association between per capita income and physical inactivity was the odds ratio (OR) estimated from logit multilevel models. RESULTS: Association between per capita income and physical inactivity was observed in people aged 45 years and older. The lower prevalence of physical inactivity was observed in provinces with the higher per capita income. However the higher OR was found in quartile 2 of per capita income, because no significant difference was observed between quartile 4 (richest) and quartile 1 (poorest). After adjusting for socioeconomic characteristics and other individual variables, association remained significant in women and disappeared in men. In women, association between per capita income and physical inactivity was higher in the population group with lower personal income. CONCLUSIONS: Results suggest that physical inactivity in women aged 45 years and older could be related not only with individual characteristics but with the socioeconomic context of the area of residence.

Exercise↗
PubMed2004

The variability of liver graft function and urinary 6beta-hydroxycortisol to cortisol ratio during liver regeneration in liver transplant recipients.

The urinary ratio of 6beta-hydroxycortisol to cortisol (6beta-OHF/F) is considered to be the simplest and most practical method for estimation of hepatic cytochrome P450 3A4 (CYP3A4) activity as a non-invasive marker of human in vivo CYP3A4 activity. However, the inter- and intra-individual variability of the urinary 6beta-OHF/F ratio during liver regeneration and the effect of variability on optimal dose of tacrolimus have not yet been clarified. The objective of this study was to clarify the change in the urinary 6beta-OHF/F ratio during liver regeneration and to determine the effect of the liver graft function on the optimal tacrolimus dose in liver transplant recipients. Two liver transplant recipients (one male and one female) and eight healthy volunteers (five males and three females) were enrolled in this study. Urine samples were collected from the recipients from 08.00 hours for 24 h on post-transplant period, 1-10 and 21-30 days postoperatively. In the healthy volunteers, morning spot urine samples were collected at 08.00 hours. The mean urinary 6beta-OHF/F ratio in the immediate postoperative period was significantly low (p < 0.05). However, a marked difference in the regulation of CYP3A4 activity during liver regeneration was found in the two recipients. A significant correlation was found between the urinary 6beta-OHF/F ratio and the C/D ratio of tacrolimus (R = 0.658, p < 0.05). The urinary 6beta-OHF/F ratio is a useful probe for estimating the variability of CYP3A4 activity in liver transplant recipients in early postoperative phase. Future studies should evaluate the clinical usefulness of the urinary 6beta-OHF/F ratio as a predictor of tacrolimus pharmacokinetics in liver transplantation.

Adult↗
PubMed2005

In vitro and in vivo equivalence studies of alendronate monosodium tablets.

OBJECTIVE: The aim of this study was to test the bioequivalence of two alendronate tablets (CAS 121268-17-5; Marvil 10 and Marvil 70 as test formulations, in short "test"; reference formulation, in short "reference") in vitro and in vivo in healthy adult male subjects and to describe a mode for researching the bisphosphonate oral formulation pharmaceutical quality. METHODS: Two dissolution tests with 10-mg and 70-mg alendronate tablets, a preliminary clinical test with 10-mg tablets (n = 10) and a bioequivalence study with 70-mg tablets (n = 23) were performed. Clinical studies were single-dose, open, cross-over, randomized, including a four-week wash-out period. Alendronate was assessed by HPLC in urine after 6 (UE6) and 24 (UE24) h post-intake. In all the experiments the reference was the one that had proved efficacy and safety in international regulatory clinical trials. RESULTS: The dissolution test showed a comparable release profile between reference and test, of both, the 10-mg and 70-mg tablet, the difference (f1) and similarity (f2) factors being within the acceptance values. The clinical trials showed great variability in urinary recovery, from one third the average figure up to 2-3 fold. The amount recovered with the 70-mg tablet was 11-15 fold higher than with the 10-mg tablets, suggesting higher (test/reference) was found to be 72-122% for UE24, and when analyzed in individuals with apparent steady bone metabolism during the wash-out period (n = 19), it was 86-137%. Both margins are considered acceptable in view of the particular kinetic and dynamic features of bisphosphonates, their very high inter- and intra-individual variability, extremely low absorption, time-changeable bone compartment, high margin of safety and long-term achievable therapeutic benefits. CONCLUSION: Test is bioequivalent to reference.

Alendronate↗
PubMed1993

[BT-PABA/xylose test in the cat?].

The BT-PABA/Xylose test was used in 10 healthy cats and 49 cats with chronic diarrhea. In seven cats the test was performed three times in order to investigate individual variability. There was a statistically significant difference between the control group and the patients in the mean peak concentration of xylose, but no difference between groups of different diseases. The mean peaks of PABA were not significantly different between the control group and the patient group. Due to high individual variation in healthy cats the BT-PABA/Xylose test cannot be considered to be a useful test in feline diagnosis.

4-Aminobenzoic Acid↗
PubMed1994

Variability in the disposition of chlorzoxazone.

Chlorzoxazone is 6-hydroxylated by cytochrome P450 2E1 (CYP 2E1), which bioactivates many toxic and carcinogenic molecules. Seventeen volunteers of varying age, ethnicity, and gender received a 250 mg tablet of chlorzoxazone and their blood and urine were sampled frequently for 8 h. V/F = 42 +/- 21 L and CL/F = 412 +/- 120 mL min-1. Comparison of these values with a study by other investigators using a suspension dosage form suggested that relative Ftablet approximately 0.7. The fraction excreted in the urine as 6-hydroxychlorzoxazone (fe,6-OH) was 0.39 +/- 0.20 and that portion of the total CL accounted for by CYP 2E1-mediated metabolism (CL6-OH) was 163 +/- 95 mL min-1. Thus, while V/F and CL/F varied by factors of less than five, fe,6-OH varied 16-fold and CL6-OH varied 28-fold. These results suggested that there was considerable inter-individual variability in the metabolism of chlorzoxazone to 6-hydroxychlorzoxazone. This variability will significantly affect the construction of physiologically based pharmacokinetic models that use the 6-hydroxylation of chlorzoxazone as a marker for an individual's CYP 2E1 phenotype.

Administration, Oral↗
PubMed1991

Cardiac score. A semiquantitative measure of cardiac involvement that improves prediction of prognosis in systemic sclerosis.

Cardiac involvement, assessed yearly by a semiquantitative cardiac scoring technique (the sum of 2 variables, scored 0 or 1 for left axis deviation, and 0 or 2 for moderate-large pericardial effusion) and outcome at 10 years were evaluated in 90 systemic sclerosis (SSc) patients enrolled in a 3-year prospective drug trial. Higher cardiac scores were associated with decreased survival. The inverse relationship of survival with cardiac score was more significant than the relationship between survival and any of the cardiopulmonary variables individually (P less than 0.0000003). Predicted 6-year survival was 79% in patients with a cardiac score of 0, 51% in those with a score of 1, 15% in those with a score of 2, and 0% in those with a score of 3. We conclude that a simple 2-variable weighted cardiac score, derived from routine electrocardiography and echocardiography, is a useful predictor of survival in patients with SSc, and we propose that the application of this cardiac score be tested in other populations of SSc patients.

Adult↗
PubMed2003

Evaluation of two foot-to-foot bioelectrical impedance analysers to assess body composition in overweight and obese adolescents.

The objective of the present study was to determine the accuracy of two foot-to-foot (FF) bioelectrical impedance analysers (BIA) to assess body composition in overweight and obese adolescents, compared with dual-energy X-ray absorptiometry (DXA) and hand-to-foot (HF) BIA. Body composition was assessed in fifty-three overweight or obese adolescents (BMI 27.9 (SD 4.1) kg/m2; aged 13-16 years) by DXA (Hologic QDR-4500; Hologic Inc., Bedford, MA, USA) and BIA (HF (BIA 101, RJL System, Detroit, IL, USA) and FF (Body Fat Monitor Scale BF-625, Tanita Corporation of America Inc., Arlington Heights, IL, USA; Téfal Bodymaster Vision, Téfal, Rumilly, France)). Bland-Altman tests showed that, compared with DXA, FF-Tanita and FF-Téfal underestimated (P<0.05) fat mass (FM) less than HF-BIA (-1.7 (SD 3.1), -0.7 (SD 5.8) and -2.3 (SD 2.2) kg respectively, P<0.001). However, the limits of agreement between DXA and FF-Tanita or FF-Téfal were much greater than those obtained with HF-BIA (-7.7 and +4.3, - 12.0 and +10.6 v. -2.1 and +6.7 kg respectively). The differences between FM assessed using the FF-Tanita or the FF-Téfal analyser and DXA increased with the waist:hip ratio, and were higher in boys than in girls. The major limiting factor of FF-BIA was the inter-individual variability in FM estimates. In conclusion, FF-BIA and DXA are not interchangeable methods. FF-BIA could be acceptable to assess body composition in large groups of overweight or obese adolescents, but cannot be recommended for body composition assessment in obese subjects because of the large errors in individual estimates.

Absorptiometry, Photon↗
PubMed1975

Analysis of genetic and environmental sources of variation in serum cholesterol in Tecumseh, Michigan. I. Analysis of the frequency distribution for evidence of a genetic polymorphism.

Analyses of serum cholesterol measurements on 4,619 males and 4,730 females residing in the community of Tecumseh, Michigan, were conducted to estimate the contribution of sex, age, temporal variation, and bimodality to determining the normal variation among individuals sampled without regard to their health status. Female values had a higher mean (2.8 mg/100 ml greater) but smaller variance than males when adjusted by polynomial regression to a common age. Positive skew in the frequency distribution for both sexes was removed by natural logarithm (ln) transformation. Age variation accounted for 28.5% and 29.4% of the variance in a ln cholesterol measurement of males and females, respectively. Between 7% and 10% of the variance in a ln cholesterol value was estimated to be attributable to differences between age-adjusted replicate measurements of the same individual. The reduction in individual variability by adjustment for these contributions to variance will allow a more precise evaluation of the relative contribution of alternate genetic hypotheses as explanations for normal variation in cholesterol. Assuming bimodality, approximately one in 1,000 males and one in 1,000 females belong to a second mode of hypercholesterolemic individuals. The locus determining familial hypercholesterolemia is not a major source of normal phenotypic variation in the Tecumseh population.

Adolescent↗
PubMed2006

Implications of genetic polymorphisms in drug transporters for pharmacotherapy.

Drug transporters are increasingly recognized as a key determinant of drug disposition and response. It is now widely appreciated that expression of the ATP-dependent efflux transporter, MDR1 (ABCB1, P-glycoprotein), in organs such as the gastrointestinal tract, liver and kidney significantly alters the extent of drug absorption and excretion. Moreover, expression of MDR1 at the level of the blood-brain barrier limits the entry of many drugs into the central nervous system. Given such an important role of MDR1 in the drug disposition process, it is not surprising to see increasing focus on the role of single nucleotide polymorphisms (SNPs) in this transporter as a potential determinant of interindividual variability in drug disposition and pharmacological response. However, drug transport is often the result of the concerted action of efflux and uptake pumps located both in the basolateral and apical membranes of epithelial cells. A growing list of membrane-spanning proteins involved in the in- or outward transport of a large variety of drugs has been recognized and characterized over the past few years in almost all tissues, including organic anion and cation transporters (OAT, OCT, solute carrier family SLC22A), organic anion transport proteins (OATP, solute carrier family SLCO, formerly SLC21A), and MRPs (ABCCs), other members of the ATP-binding cassette family. We are just beginning to appreciate their role for drug delivery and disposition and the contribution of genetic polymorphisms in these transport proteins to interindividual variability in the efficacy and safety for pharmacotherapy. This review summarizes the consequences of inherited differences in drug transport for pharmacotherapy. With the main focus on ABCB1, an update of recent advances is given and clinically relevant examples are used to illustrate how heritable differential drug transport can help to explain individual variability in drug response. The pharmacogenetics of other transporters is briefly introduced.

ATP-Binding Cassette Transporters↗
PubMedDate not supplied

[A study of some indirect biochemical markers in the evaluation of enzymatic induction caused by antiepileptic drugs].

A comparative study was carried out to examine urinary excretion of D glucaric acid (DGA), g glutamyltransferase (GGT) activity and the concentration of serum bilirubin as enzymatic induction markers in 89 adult patients (56 men and 33 women) who were receiving chronic treatment with phenobarbital, phenytoin, carbamazepine and valproate. As in most cases, these drugs were administered as a polytherapy; drugs doses were expressed in units/day, in accordance with a previously described system of scoring, which would reflect the induction capacity of the combination of drugs administered. We found a high prevalence of results that were above the upper reference limit for urinary DGA (93.2%) and serum GGT (80.6%). Bilirubin and its conjugate and non conjugate fractions were found to offer values that to a large extent matched those of the control group. The levels of the different biochemical variables presented significant correlations with the daily doses of the drugs administered, above all in the case of DGA (r= 0.773, p< 0.001). When we split the data according to sex, the correlations improved in men but were significantly worse in women. This fact could be due to a greater inter individual variability in the response to inducers of the phenobarbital type in female patients. Urinary DGA seems to be a better enzymatic induction marker than GGT and bilirubin and its serum fractions, the value of which appeared to be very limited in these cases. Separating GGT into its isoforms provided no further information of practical interest as regards the enzymatic activity as a whole.

Adult↗
PubMed2005

[Current status of therapeutic drug monitoring for immunosuppressive drugs].

Therapeutic drug monitoring(TDM) is advocate to provide information about the adequacy of a dosing regimen or likelihood of toxicity associated with drug. Such situations include large intra- and inter-individual variabilities in pharmacokinetics; correlation between drug concentrations and toxicity or between concentrations and efficacy; narrow therapeutic interval, meaning toxic symptoms close to concentration with full therapeutic effect; and absence of appropriate parameter to recognize pharmacological effect. Current clinical immunosuppressive regimens consist of combinations of drugs, to allow a reduction in the individual drug doses as a means widening the therapeutic interval and reduction the likelihood of individual drug toxicity. With the recent introduction of new immunosuppressive drugs, there is an unprecedented interest in TDM for immunosuppressive drugs. In this review I discuss the current status of pharmacokinetic monitoring for cyclosporine, tacrolimus and mycophenolate mofetil.

Cyclosporine↗
PubMedDate not supplied

Corticosterone responses of grey-faced petrels (Pterodroma macroptera gouldi) are higher during incubation than during other breeding stages.

We report the results of the first field study examining seasonal changes in corticosterone responses of typically long-lived birds of the order Procellariiformes. In particular, we examined whether grey-faced petrels Pterodroma macroptera gouldi showed changes in circulating baseline corticosterone concentrations and corticosterone responses to a standardized handling protocol across the breeding season. Such changes have been associated with changes in body condition and variations in energy demands on adult birds through the breeding season. During early incubation, males were in significantly better condition than females that had just completed laying, whereas during late incubation, males were in significantly poorer condition than females. In spite of these differences, there was no significant difference in baseline corticosterone concentrations between sexes or among birds at different reproductive stages. However, we detected significant differences in corticosterone responses associated with a standardized handling protocol at different stages through the breeding season. Responses were significantly greater during incubation compared with the prelay period and late chick rearing. Body condition was weakly and negatively correlated with maximum and total integrated corticosterone level, indicating that some of the individual variability in stress corticosterone responses could be explained by variation in body condition. However, the largest stress response occurred during late incubation and was independent of sex, although males were in relatively poor condition and females in relatively good condition. This period coincided with the breeding stage in which energy constraints on individual adults were higher than at other periods of the reproductive cycle and birds may be physiologically primed for extended fasts.

Analysis of Variance↗
PubMed1975

Quantitative evaluation of sensory nerve endings in hypertrophy of labia minora pudendi in women.

The authors studied the types of sensory nerve endings in hypertrophic labia minora pudendi in women aged between 18 and 69. The nervous tissue was impregnated with silver nitrate by Lavrentyev's modification of the Bielschowski-Gross method. The sensory nerve endings were divided into the following groups: free endings and arborizations, spray-like endings, seven types of clew-like nerve endings, and Pacinian corpuscles. It is the clew-like endings that absolutely predominate, they were 2,027 in number. The arborizations and spray-like endings found were 105 in number and only 4 of Pacinian corpuscles were found. As compared with normal labia there are no principal differences among the types of sensory nerve endings. The main difference consists in the rate of occurrence (89.6 as against 57.8) and in the thickness of the capsule, while the nerve clew proper does not grow in diameter. Therefore, we are of theopinion that a more frequent occurrence and larger size of the capsule is associated with local changes in the organ (especially with hypertrophy of the connective tissue). We observed no differences due to age either in the occurrence of the individual types or in the thickness of the capsule. Great individual variability in both directions was seen. The findings corroborated again the rare occurrence of meissner's endings in the labia minora in woman. Therefore it may be assumed that it is rather a random finding and that it is a type of clew-like nerve ending. Finally, we presume that the individually varying rate of occurrence of the nerve endings in the external genitals could also affect general sensitivity in this region, including sexual sensitivity.

Adolescent↗
PubMed2002

Personality change over 40 years of adulthood: hierarchical linear modeling analyses of two longitudinal samples.

Normative personality change over 40 years was shown in 2 longitudinal cohorts with hierarchical linear modeling of California Psychological Inventory data obtained at multiple times between ages 21-75. Although themes of change and the paucity of differences attributable to gender and cohort largely supported findings of multiethnic cross-sectional samples, the authors also found much quadratic change and much individual variability. The form of quadratic change supported predictions about the influence of period of life and social climate as factors in change over the adult years: Scores on Dominance and Independence peaked in the middle age of both cohorts, and scores on Responsibility were lowest during peak years of the culture of individualism. The idea that personality change is most pronounced before age 30 and then reaches a plateau received no support.

Adolescent↗
PubMedDate not supplied

Ex vivo lipopolysaccharide (LPS)-induced TNF-alpha, IL-1beta, IL-6 and PGE2 secretion in whole blood from Type 1 diabetes mellitus patients with or without aggressive periodontitis.

Several studies have demonstrated that diabetes is a risk factor for developing periodontal disease, increasing its prevalence and severity. Furthermore, periodontitis may impair the metabolic control and adequate treatment of diabetic patients. LPS from Gram-negative bacteria penetrates the periodontal tissues and subsequently recruits and activates immune cells. Progression to severe periodontitis with loss of supporting structures is mediated by several factors, including secretion of a broad spectrum of inflammatory and destructive (PGE2). mediators such as cytokines (TNF-alpha, IL-1b and IL-6), chemokines (IL-8) and prostaglandin E2. The aim of this work is to investigate differences in the TNF-a, IL-1b and IL-6 expression and prostaglandin E2 (PGE2) release in blood from diabetic patients with and without aggressive periodontitis (AP) stimulated with lipopolysaccharide (LPS). For this purpose we recruited 29 Type 1 diabetes mellitus (DM) patients, 14 with AP and 15 without AP. Fourteen healthy individuals formed the control group. For cytokine expression and PGE2 secretion, an ex vivo whole blood culture system was used. Cytokines and PGE2 were detected by commercial immunometric assays. A wide range of inter-individual variability in spontaneous and LPS-induced TNF-alpha, IL-1b and IL-6 levels in patient groups and controls was found. The mean of spontaneous and LPS-induced TNF-alpha and IL-1b levels did not differ significantly (p > 0.5) when patients were compared to control individuals. Although not significant, the spontaneous TNF-alpha, IL-1b and IL-6 levels in the group of Type 1 DM with AP were higher than in controls, while in diabetic patients without AP, these values were depressed in comparison with controls. In both groups of patients, the means of LPS-induced IL-6 levels were higher than the controls but the differences observed were not significant (p = 0.07). However, the LPS-induced PGE2 levels varied significantly when all groups were compared (p = 0.007). The means of LPS-induced PGE2 levels for Type 1 diabetic patients with AP (p = 0.0009) and without AP (p = 0.024) were significantly higher than the levels observed for healthy controls. Finally, we conclude that Type 1 diabetic patients with or without AP did not express higher LPS-induced TNF-a, IL-1b and IL-6 levels than controls. However, the PGE2 levels released were significantly higher than those detected in controls.

Adult↗
PubMed1983

Intermale aggression and infanticide in aged C57BL/6J male mice: behavioral deficits are not related to serum testosterone (T) levels and are not recovered by supplemental T.

Healthy aged adult (24-26 months of age) and young adult (2-4 months of age) c57BL/6J male mice were assessed for intermale aggression, pup-killing behavior (infanticide), and circulating levels of testosterone (T). When compared to young adult male mice, aged adult males were highly variable in the exhibition of both androgen-dependent behaviors. Significant numbers of aged males exhibited deficits in aggression and pup-killing while other animals were as behaviorally active as their young male counterparts. Assessment of serum T showed that aging did not produce a reduction in levels of the steroid and individual variability in androgen-dependent behavior of aged males was not related to plasma levels of the hormone. When aged non-aggressive and non-killer males were exposed to supplemental T by way of subcutaneously implanted silastic capsules, circulating levels of the steroid were elevated but T-dependent behavior was not recovered. These findings, in combination with those previously reported for copulatory behavior, indicate that the deficits observed in the androgen-dependent behavior of aged male mice cannot be attributed to a breakdown in the production of testicular androgens. While neural refractoriness to T may account in part for deficits in androgen-dependent behavior of aged males, the variability that is observed in the reproductive behaviors of aged male rodents ultimately may be related to other sources of variation such as the perinatal environment.

Aggression↗
PubMed2001

Processing of neuropeptide Y, galanin, and somatostatin in the cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are two prevalent neurodegenerative disorders for which the causes are unknown, except in rare familial cases. Several changes in neuropeptide levels as measured by radioimmunoassay (RIA) have been observed in these illnesses. Somatostatin (SOM) levels in cerebrospinal fluid (CSF) are consistently decreased in AD and FTD. Neuropeptide Y (NPY) levels are decreased in AD, but normal in FTD. Galanin (GAL) levels increase with the duration of illness in AD patients. The majority of studies of neuropeptides in CSF have not been verified by HPLC. The observed decrease in a neuropeptide level as measured by RIA may therefore reflect an altered synthesis or extracellular processing, resulting in neuropeptide fragments that may or may not be detected by RIA. Matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-MS) has been shown to be a powerful technique in the analysis of biological materials without any pre-treatment, by detecting peptides and proteins at a specific mass-to-charge (m/z) ratio. We studied the processing of the neuropeptides NPY, NPY, SOM and GAL in the cerebrospinal fluid of patients with AD (n = 3), FTD (n = 3) and controls (n = 2) using MALDI-MS. We found that considerable inter-individual variability exists in the rate of neuropeptide metabolism in CSF, as well as the number of peptide fragments formed. Certain patients showed differences in the processing of specific neuropeptides, relative to other patients and controls. This analysis of the metabolic processing of neuropeptides in CSF yielded a large amount of data for each individual studied. Further studies are required to determine the changes in neuropeptide processing that can be associated with AD and FTD. With further investigations using MALDI-MS analysis, it may be possible to identify a neuropeptide fragment or processing enzyme that can be correlated to these disease states.

Alzheimer Disease↗