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PubMed2001

Mediation in a family-directed program for prevention of adolescent tobacco and alcohol use.

BACKGROUND: Family Matters is a universal intervention designed to prevent adolescent tobacco and alcohol use through involvement of family members and by targeting family risk factors for tobacco and alcohol use. Previously reported findings suggest that the program reduced the prevalence of both adolescent smoking and drinking in the 12 months after program completion. This paper reports analyses conducted to identify the mediators through which the program influenced adolescent smoking and drinking. METHODS: One thousand fourteen adolescents ages 12 to 14 years and their families, identified by random-digit dialing, were entered into a randomized trial. Adolescents and their parents provided data by telephone for measuring mediator and behavioral variables at baseline, 3 months, and 12 months after program completion. Repeated-measures logistic regression with generalized estimating equations was used to assess mediation processes. RESULTS: The program resulted in statistically significant changes in several substance-specific aspects of the family, such as rule setting about tobacco and alcohol use. However, the intermediate family effects did not account for the program effects on adolescent behavior. CONCLUSIONS: The variables hypothesized to explain program effects were not identified by direct empirical examination.

Adolescent↗
PubMed1998

Accuracy characteristics of throwing as a result of maximum force effort.

Fitts' law predicts the accuracy of movement to a target decreases as the velocity of the movement increases. This speed-accuracy tradeoff has been examined under numerous conditions. During some tasks, however, increased force to nearly maximal level decreases the variability of the movement (Sherwood & Schmidt, 1980). This condition apparently produced results different from what would be predicted by Fitts' law. The purpose of the present study was to examine the effects of maximal force on dart throwing accuracy and variability. 54 subject were categorized into groups based upon their experience with dart throwing: Advanced, Intermediate, or Beginners. Each subject performed two sessions of 15 trials. Subjects were instructed to "throw normally" for one session and "throw as hard as you can" for the other session Distances from the target (triple-20 area) on the regulation dart board were measured and recorded after each of three darts was thrown. Average Error and Variable Error were calculated for each condition for each subject. The Average Error and Variable Error were greatest for the Beginner group and least for the Advanced group. For all three experience categories both Average Error and Variable Error were significantly greater when subjects performed with maximal force. The greater average error for the maximal force for all subjects suggested that the speed-accuracy tradeoff applied to this aiming task. The greater variability in accuracy with maximal force suggested a ceiling effect, which reduced variability in previous studies, was not achieved.

Adult↗
PubMed1991

[Short- and intermediate-term angular results of Cüppers retro-equatorial myopexy, with or without additional simultaneous recession].

79 variable esotropias underwent bilateral "Fadenoperations". In the first group, the posterior fixation has been performed alone. In the second series, conventional symmetrical recessions of the medial recti have been performed during the same procedure. Two further additional weakening techniques are compared in the last group: anterior medial tenotomies and the so-called "stretch effect". Concomittant recessions considerably enforced the amount of angle reduction for distance and near without affecting precision, predictibility and stability of the results. Tenotomies and stretching procedures were followed by inconstant results.

Accommodation, Ocular↗
PubMed2004

Impact of CYP2D6 intermediate metabolizer alleles on single-dose desipramine pharmacokinetics.

This study utilized cytochrome P450 2D6 (CYP2D6) genotypes to explain variability of desipramine pharmacokinetics in a cohort of non-poor metabolizer individuals. In an interaction study utilizing desipramine as a probe, genotyping for the CYP2D6*3, *4, *5 and *6 alleles was used to screen out CYP2D6 poor metabolizers. Individuals were categorized according to these and additional alleles (CYP2D6*2, *9, *10, *17, *41 and x2). Genotypes of individuals heterozygous for two or three of *2, *17 and *41 alleles were confirmed by molecular haplotyping. Pharmacokinetic parameters of desipramine were analysed according to CYP2D6 category. Molecular haplotyping was necessary to definitively categorize four of 16 individuals. A subject who had unusually high plasma elimination half-time, exposure and metabolic ratios carried an intermediate metabolizer (IM) *9 allele in combination with a non-functional allele. This combination has a population frequency of less than 1 : 200. Individuals with *1/*1, *1/*2 and *2/*2 genotypes had lower than average plasma elimination half-time, exposure and metabolic ratios. For desipramine, additional genotyping of CYP2D6 IM alleles helped define subgroups of the CYP2D6-positive cohort. This suggests that genotyping for IM alleles will aid in interpretation of clinical trials involving CYP2D6 substrates. Due to the diversity of IM alleles, molecular haplotyping may be necessary to fully characterize CYP2D6 genotype-phenotype relationships.

Alleles↗
PubMed2004

Effects of reboxetine on sleep and nocturnal cardiac autonomic activity in patients with dysthymia.

Antidepressants may have sleep and autonomic side-effects. The acute and long-term effect of reboxetine (2 mg b.i.d.) on sleep and cardiac autonomic activity was compared with that of placebo in a single-blind study. Twelve patients affected by dysthymia underwent four polysomnographic studies at baseline (placebo); at night 3 (reboxetine; acute effect); at night 9 (reboxetine; intermediate-term effect); and at night 122 (reboxetine; chronic effect). After the first administration, reboxetine increased time awake after sleep onset, number of awakenings, percentage of stages 1 and 2 non-rapid eye movement (REM), and reduced the amount of stages 3-4 non-REM, but all these effects disappeared by continuing treatment. However, reboxetine caused a persistent suppression of REM sleep, which was accompanied by an increase of REM sleep latency. The spectral analysis of heart rate variability showed a trend towards an increase in sympathetic activity with both acute and intermediate reboxetine use. Long-term treatment with 4 mg reboxetine does not cause significant changes in cardiac autonomic function.

Adrenergic Uptake Inhibitors↗
PubMed2001

[Influence of experience on intra- and interindividual variability in assessing peripheral endothelial dysfunction with high resolution ultrasound].

UNLABELLED: The non-invasive evaluation of endothelial dysfunction with high-resolution ultrasound has become a widely accepted tool in determination of high-risk subjects for early atherosclerosis. Furthermore it is often used as intermediate outcome in intervention studies. AIM: We examined the influence of examiner experience on intra- and inter-individual variability in the measurement of flow-associated vasodilation (FAD) independent of automated analysis systems. METHOD: FAD was measured on two occasions in 7 and 8 subjects respectively (mean age 32 +/- 3 years) by two investigators after different prior training procedures with a 13 MHz linear transducer (LA14A, ESAOTE Biomedica). RESULTS: The intra-individual variability expressed as median absolute difference in the measurements of FAD was 1.1 % (range from 0.03 % to 3.2 %) for examiner one with an experience of more than 50 FAD measurements through former studies and 2.9 % (range from 1.6 % to 9.2 %) for examiner two with only 10 training examinations under supervision. By a further training period of two months, with an increase of examinations of additional 20 measurements by both examiners, the intra-observer variability could be dropped to 0.9 % (range from 0.03 % to 1.3 %) for examiner two (p = 0.0025) with no significant change for examiner one (median 0.6 % with a range from 0.14 % to 3.7 %). As expected, the inter-individual variability was not influenced by this further training (median 1.0 % with a range of 0.5 % to 3.6 % versus a median of 1.6 % with a range from 0.15 % to 7.5 %). CONCLUSION: 30 training measurements of FAD under supervision should be regarded as minimum requirement for valid determination of endothelial function. The reachable result for the intra-observer variability is thereby within the range of computed analysis systems.

Adult↗
PubMed2001

Anti-titin antibodies in myasthenia gravis: tight association with thymoma and heterogeneity of nonthymoma patients.

BACKGROUND: Titin is the major autoantigen recognized by anti-striated muscle antibodies, which are characteristic of generalized myasthenia gravis (MG). OBJECTIVE: To seek a correlation between anti-titin antibodies and other features of MG patients, including histopathology, age at diagnosis, anti-acetylcholine receptor (anti-AChR), autoantibody titers, and clinical severity. METHODS: A novel, highly specific radioligand assay was performed on a large group of 398 patients with generalized MG. RESULTS: Among thymectomized patients, anti-titin antibodies were present in most patients with thymoma (56/70 [80%]), contrasting with only a minority of patients with thymus atrophy or hyperplasia (17/165 [10%]). They were also present in 64 (41%) of 155 nonthymectomized patients who had a radiologically normal thymus. In these patients and in those who had a histologically normal thymus, anti-titin antibodies were associated with a later age at onset of disease and with intermediate titers of anti-AChR antibodies. After controlling for these 2 variables, disease severity was not significantly influenced by anti-titin antibodies. CONCLUSIONS: Anti-titin antibodies are a sensitive marker of thymoma associated with MG in patients 60 years and younger, justifying the insistent search for a thymoma in MG patients of this age group who have these antibodies. In nonthymoma patients, anti-titin antibodies represent an interesting marker complementary to the anti-AChR antibody titer, identifying a restricted subset of patients. These clinical correlations should prompt further studies to examine the mechanisms leading to the production of anti-titin antibodies.

Adult↗
PubMed2001

Clinicopathologic and prognostic significance of matrilysin expression at the invasive front in human colorectal cancers.

Matrix metalloproteinases (MMPs) have been implicated in tumor progression. Matrilysin, one of the matrix metalloproteinases, is frequently overexpressed in gastrointestinal cancers. The aim of our study was to assess the validity of matrilysin as a prognostic marker of colorectal cancers. Matrilysin expression was immunohistochemically analyzed using formalin-fixed, paraffin-embedded specimens from 113 colorectal cancer patients who had undergone curative surgery. The lumenal surface of neoplastic glands in the superficial layer was apically stained, while the cytoplasm of cancer cells at the invasive front was diffusely stained for matrilysin. Sections with immunostaining signals in more than 30% of carcinoma cells at the invasive front, which were observed in 47 (42%) cases, were judged as being positive for matrilysin. Matrilysin positivity was significantly correlated with the depth of invasion, lymph node metastasis, lymphatic invasion, advanced Dukes' stage and poor outcome. Patients with matrilysin-positive cancer had a significantly shorter overall survival time than those with matrilysin-negative cancer. For patients with intermediate invasive tumor (T2 or T3), only matrilysin was a significant prognostic variable for predicting overall survival in multivariate analysis. Matrilysin expression at the invasive front could be an important marker, predicting an unfavorable prognosis after surgical treatment in patients with colorectal cancer.

Biomarkers, Tumor↗
PubMed2000

Psychosocial factors as predictors of functional status at 1 year in patients with left ventricular dysfunction.

Chronic heart failure patients often experience significant functional impairments. A better understanding of the biopsychosocial correlates of functional status may lead to interventions that improve quality of life in this population. Social isolation, mood disturbance, low socioeconomic status, and non-White ethnicity were evaluated as possible correlates of impaired functional status in 2,992 U.S. patients with left ventricular ejection fractions (LVEFs) </= 35%. Even after controlling for age and clinical characteristics, all of the psychosocial variables examined were significant predictors of risk for experiencing severe limitations in intermediate and social activities of daily living at 1 year, with adjusted odds ratios in the 1.5-2.0 range. The ability of psychosocial characteristics to predict future functional status was also independent of baseline functional status, comorbid medical conditions, and deterioration in heart failure signs and symptoms over the intervening year. These results suggest that psychosocial factors influence patient functional status even in the later phases of cardiac disease.

Activities of Daily Living↗
PubMed2005

Cooperative photochemical reaction mechanism of femtosecond laser-induced photocoloration in spirooxazine microcrystals.

Microcrystalline powders of spirooxazine and spiropyran compounds do not show photocoloration under steady-state illumination, whereas they undergo photochromism on intense femtosecond laser-pulse excitation. We investigated the characteristic mechanism of the crystalline photochromism by studying the photocoloration of spironaphthooxazine (SNO) and its chloro-substituted derivative (Cl-SNO) with our femtosecond diffuse-reflectance spectroscopic system. In particular, femtosecond double-pulse excitation using 390+780-nm pulses and 390+390-nm pulses, with a variable time interval between the two pulses, was applied to reveal an intermediate species involved in the photocoloration. Although 780-nm excitation of an intermediate produced by 390-nm excitation did not lead to isomerization, the 390+390-nm excitation resulted in photocoloration. The yield for SNO decreased on increasing the interval from 40 ps to 5 ns, while that for Cl-SNO was constant. The photocoloration mechanism in the crystalline phase is considered from the viewpoint of the time-dependent density of short-lived transient species, and it is concluded that cooperative interactions of excited states and nonplanar open forms play an important role in femtosecond laser-induced photochromism in these crystals.

Journal Article↗
PubMed1986

Milliwatt carbon dioxide laser and hepatic surgery in mice: surgical technique and pathology.

The milliwatt carbon dioxide laser was used to induce focal lesions and to perform wedge resections in the livers of 75 strain A mice. The procedures were feasible and well tolerated by the mice, with only one postoperative death in the wedge resection group in an early experiment. The hepatic lesions produced by the laser were characterized histologically by an inner area of vaporization, an intermediate area of coagulation necrosis, and an outer rim of cells with variable damage. The lesions healed by fibroblastic proliferation and scar formation with no hepatocytic contribution. The small vessel and bile ductule sealing effect of CO2 laser, together with the sound healing of laser-induced wounds, highlights the usefulness of this modality in liver surgery in general, and suggests its particular application in the treatment of liver trauma and a variety of hepatic focal lesions, neoplastic or otherwise.

Animals↗
PubMed2003

A non-Darwinian role for mutagenesis in stem cell-derived cancers.

It is clear that mutations cause cancer. The implicated mechanism is Darwinism. That is, a stochastic series of mutations is purported to effect the cellular variability upon which natural selection acts to yield increasingly cancer-like intermediates leading ultimately to malignant clones. It is no wonder then that the neoplastic phenotype is considered "alien," having evolved via random unrehearsed events. Neoplasia, however, has also been depicted as something less than foreign, bordering on familiar. This is because cancer shares proliferative and invasive qualities with the native developmental processes of embryogenesis and adult tissue renewal/repair. A question then arises: If key features of malignancy already naturally exist within well-choreographed programs, why reinvent this phenotype via stochastic multistep schemes rather than reactivate it largely en bloc? Indeed, as will be shown, tissues do harbor a malignant potential capable of reactivation. Specifically, this capability is maintained by stem cells (having inherited such from embryonic precursors)-a phenotype controlled by a microenvironment favoring perpetual rearing by (quiescent) stem cells of proliferative progeny for orderly renewal over neoplasia. Accordingly, normally well-sequestered stem cells, when amid carcinogen/mutagen-induced disruption to local surroundings, produce progeny tending by default toward disorderliness (neoplasia) over renewal. Because such tumor-causing mutations act non-cell autonomously, this cancerous state is potentially reversible but subsequent cell-autonomous mutations can impair particular clonal progeny, already cancerous, from regressing. Thus, a scenario wherein mutations (1) de-repress malignancy non-cell autonomously and then (2) slow its reversion cell autonomously, commonly misinterpreted as Darwinian, may constitute a non-Darwinian mechanism for the genesis of cancers that are stem cell derived.

Biological Evolution↗
PubMed1985

Computerized tomographic assessment of graft incorporation after aortic reconstruction.

Computerized tomographic scanning is being used with increasing frequency for the detection of abdominal aortic prosthetic complications. Although computerized tomography remains a very precise method for direct imaging of the retroperitoneal space, the interpretation of a postoperative computerized tomographic scan is limited by the absence of any information on the normal appearance of the routine uncomplicated aortic graft. To study the normal tissue incorporation of aortic grafts, 29 patients were evaluated with periodic postoperative computerized tomographic scans. Seventeen patients had aortoiliac occlusive disease and 12 had aneurysmal disease. No patients who had reoperation were included and all patients had a normal postoperative course. Computerized tomographic scans were obtained in the early (mean 7 days), intermediate (mean 48 days), and late (mean 102 days) postoperative periods. A variable amount of perigraft hematoma was always present on the initial computerized tomographic scan. Perigraft air was seen in only four patients in the early study. Graft incorporation appeared complete in these patients by 48 days, although minimal hematoma persisted in one patient. This study provides baseline data on the appearance and timing of aortic graft incorporation which should facilitate subsequent computerized tomographic detection of aortic graft complications.

Aged↗
PubMed1983

Catecholamine distribution patterns in rat thalamus.

Detailed distribution patterns for norepinephrine and dopamine in rat thalamus were determined by liquid chromatographic assays. The norepinephrine distribution is in good accord with that suggested previously by neuroanatomical tracing techniques. Detailed anterior-posterior concentration profiles for norepinephrine are summarized. An unexpected finding was a strong animal variability in thalamic dopamine content. Thalami were distinguished as having either low, intermediate or extremely high dopamine concentrations.

Animals↗
PubMed1988

Symbolization levels in communicative behaviors of children showing pervasive developmental disorders.

A total of 48 children with severe pervasive developmental disturbance were observed in their communicative behaviors across modalities of language, gesture, play, and drawing. As predicted, levels of symbolization in gesture, play, and drawing were significantly intercorrelated and most strongly correlated with the criterion variable of expressive language. Children who were echolalic showed levels of symbolization intermediate between those of mute children and those with nonecholalic language. The correlation between the expressive language measure and a standardized measure of receptive language for 22 testable children also was significant. The results are discussed in the context of earlier studies of symbol production in verbal samples of disturbed and nonhandicapped children.

Adolescent↗
PubMed2005

The role of curiosity in smoking initiation.

CONTEXT: Although advertising theories have long viewed curiosity as an intermediate goal to encouraging consumption of a product among previous nonusers, this variable is rarely discussed in psychological theories and its role in smoking uptake has not been addressed adequately. DESIGN AND SETTING: Using a longitudinal design, in 1999, we reinterviewed 12- to 15-year-old adolescent never smokers (N=2119; 970 committed never smokers, 1199 susceptible never smokers) 3 years after they responded to a population survey on tobacco use in California. RESULTS: Logistic regression showed curiosity and susceptibility to smoke were independently associated with increased future smoking in all never smokers. Committed never smokers reporting curiosity were more likely to become susceptible by follow-up than those not curious. A multivariate analysis of committed never smokers from the cross-sectional survey identified best friends who smoke and receptivity to tobacco advertising and promotions as associated with curiosity. CONCLUSIONS: Curiosity may be a critical precursor to smoking. Future research on smoking initiation should examine curiosity and investigate factors influencing it.

Adolescent↗
PubMed2000

Differential clinical prognostic classifications in dilated and ischemic advanced heart failure: the EPICAL study.

BACKGROUND: The clinical management of severe congestive heart failure (CHF) should be graded according to the prognosis of each individual patient. Our objective was to elaborate a prognostic rating system for severe CHF. METHODS: The EPICAL program (Epidémiologie de l'Insuffisance Cardiaque Avancée en Lorraine) identified patients with severe CHF defined by hospitalization accompanied by class III/IV dyspnea, edema, or hypertension; an ejection fraction </=30% or a cardiothoracic index >/=60%. Baseline variables were tested in Cox multivariate models. RESULTS: Patients with ischemic heart disease (n = 219) had a lower 1-year survival rate (57.6%) than patients with dilated cardiomyopathy (n = 182) (69. 1%). Multivariate analysis identified 5 prognostic factors for ischemic CHF and 7 for CHF caused by dilated cardiomyopathy. These variables were used to classify patients within prognostic subgroups of good (>75%), intermediate, or poor (</=25%) 1-year survival. CONCLUSION: A score for prognostic prediction was further derived from readily available data to help physicians improve decision making and to assist in clinical trials as a stratification tool.

Adult↗
PubMed2000

Lipid content and energy density of forage fishes from the northern Gulf of Alaska.

Piscivorous predators can experience multi-fold differences in energy intake rates based solely on the types of fishes consumed. We estimated energy density of 1151 fish from 39 species by proximate analysis of lipid, water, ash-free lean dry matter, and ash contents and evaluated factors contributing to variation in composition. Lipid content was the primary determinant of energy density, ranging from 2 to 61% dry mass and resulting in a five-fold difference in energy density of individuals (2.0-10.8 kJg(-1) wet mass). Energy density varied widely within and between species. Schooling pelagic fishes had relatively high or low values, whereas nearshore demersal fishes were intermediate. Pelagic species maturing at a smaller size had higher and more variable energy density than pelagic or nearshore species maturing larger. High-lipid fishes had less water and more protein than low-lipid fishes. In some forage fishes, size, month, reproductive status, or location contributed significantly to intraspecific variation in energy density. Differences in quality are sufficient to potentially affect diet selection of breeding seabirds, especially when transporting food for their young to the nest site.

Journal Article↗