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PubMedDate not supplied

The relationship between hostility and beta-adrenergic receptor physiology in health young males.

OBJECTIVE: We examined the relationship between hostility and mononuclear leukocyte (MNL) beta-adrenergic receptor function in a sample of young healthy males. METHOD: Thirty subjects were selected for having scored above 20 (N = 11) and below 14 (N = 19) on the Cook-Medley Hostility (Ho) scale. MNL beta-adrenergic receptor function was characterized in terms of receptor density (Bmax) and ligand-binding affinity (Kd) in homogenized cells, and intracellular cyclic adenosine monophosphate (cAMP) responses to saline, isoproterenol, and forskolin in whole cells. Subjects also completed the Multidimensional Anger Inventory (MAI), which assesses dimensions of anger. RESULTS: Relative to men with low Ho scores, men with Ho scores above 20 showed lower receptor number and greater forskolin-stimulated cAMP. Moreover, high hostile men reported a greater frequency of anger, longer duration of anger, more frequent brooding, and a hostile outlook. CONCLUSIONS: These data indicate that adrenergic receptor down-regulation is associated with hostility. This association may be linked to hostile persons' propensity for excessive and prolonged neuroendocrine responses to either psychological stressors or the experience of chronic stress associated with frequent and prolonged bouts of anger.

Adolescent↗

PubMed1993

Rheumatoid arthritis: evaluation of wrist extensor tendons with clinical examination versus MR imaging--a preliminary report.

To determine whether magnetic resonance (MR) imaging can improve assessment of the extensor tendons of the wrist and their propensity to rupture, the dorsal tendons in 23 wrists in 20 patients with rheumatoid arthritis were clinically assessed and then examined with MR imaging. Clinical and MR imaging evaluations were performed blindly and independently. The six extensor tendon compartments were assessed with MR imaging for presence of pannus, synovial effusion, and tendon involvement or rupture. Clinical scores of systemic disease, dorsal tendon sheath swelling, and risk of tendon rupture ranged from 0 to 3 in each category; the overall score was not associated with any MR imaging category. Clinical assessment of enlargement of the dorsal tendon sheath and clinical risk of rupture correlated poorly with findings on MR images. All eight wrists with clinically minimal risk of rupture had pannus, effusions, and tendon involvement on MR images; the findings were similar in the wrists with moderate (grade 2) risk of rupture. MR imaging depicts involvement of the dorsal tendon sheath and dorsal tendons that cannot be assessed with other radiologic or clinical means.

Adult↗

PubMed2026

Evaluating a Genome-Wide Polygenic Score for Handgrip Strength and Its Interplay with Leisure-Time Physical Activity Across the IGEMS Twin Cohorts.

PURPOSE: Polygenic scores (PGSs) may help assess genetic predisposition to multifactorial traits. We examined whether age, sex, and leisure-time physical activity (LTPA) modify the association between a PGS for handgrip strength (HGS) and measured HGS in older adults. METHODS: PGS for HGS (PGS hgs) , based on Pan-UK Biobank genome-wide association study data, was calculated for 5103 participants (aged 40-96; 44% women) from eight twin cohorts in Denmark, Sweden, Australia, the United States, and Finland within the IGEMS consortium. Sex-standardized HGS and self-reported LTPA were assessed cross-sectionally. Linear mixed models estimated associations between PGS hgs and HGS, including interactions with age, country, and LTPA, as well as an association between PGS hgs and LTPA. Fixed-effect within-pair models were conducted to assess environmental contributions. RESULTS: Higher PGS hgs was associated with greater HGS (β = 2.14, SE = 0.15, P < 0.001), explaining 4.6% of HGS variance overall, with modest variation across countries. In sex-stratified models, PGS hgs explained 5.2% of the variance in females and 4.3% in males. No statistically significant interaction with age was found. A significant PGS hgs × LTPA interaction (β = -0.034, P = 0.013) indicated that the association between LTPA and HGS was more pronounced among individuals with lower PGS hgs . The within-pair models offered limited support for the independent environmental impact of LTPA. CONCLUSIONS: The PGS hgs was associated with measured HGS in the meta-analysis, highlighting the potential of PGSs to capture individual differences in strength-related traits across populations. The association of PGS hgs with HGS was moderated by LTPA, such that the beneficial impact of LTPA on HGS was greater among individuals with a lower genetic propensity for HGS.

Humans↗

PubMed1998

CD44 splice variants as prognostic markers in colorectal cancer.

BACKGROUND: Splice variants of CD44 play a causal role in the metastatic spread of pancreatic carcinoma in the rat. In previous studies we have shown that homologues of these CD44 isoforms (CD44v6) are overexpressed during colorectal tumorigenesis in man and that CD44v6 overexpression is associated with an unfavorable prognosis in this disease. In the present study we have assessed the prognostic significance of CD44 variants containing exon v5. In addition, we have used a panel of different antibodies against CD44v6 and applied a combined scoring system to improve its value as prognosticator. METHODS: Expression of CD44 variants was studied by immunohistochemistry on frozen tissue sections, and the prognostic value of the CD44 variant expression was assessed using univariate and multivariate analysis. RESULTS: Our studies show that expression of CD44v6, but not CD44v5, has significant prognostic value. Analysis of CD44v6 expression by means of a combined scoring system, on the basis of a panel of three different monoclonal antibodies (mAbs), makes CD44v6 a highly significant prognostic marker that is independent of Dukes stage, tumor grade, or tumor localization. CONCLUSION: Assessment of CD44v6 expression by a combination of mAbs yields an independent prognosticator that may be of value in identifying patients with a high propensity to develop distant metastasis.

Adult↗

PubMed2005

A comparison of two double-injection techniques for peribulbar block analgesia: infero-temporal plus supero-medial vs. infero-temporal plus medial-percaruncular.

BACKGROUND: Combinations of infero-temporal and either supero-nasal ('inferior-superior') or medial percaruncular ('inferior-medial') injections are popular double-injection techniques for establishing peribulbar block analgesia. This study compared the efficacy of these two techniques in achieving ocular and lid akinesia. METHODS: One hundred patients were randomized to receive inferior-superior or inferior-medial injections in a study in which injectate, injectate volumes, 5-min ocular akinesia scoring (0-8), lid scoring (0-2) and supplemental injection protocols were standardized. The numbers of supplemental injections required at each observation period and the total volume of injectate required to produce ocular and lid akinesia were compared. RESULTS: The two test groups were demographically similar. The inferior-medial combination achieved greater ocular akinesia than the inferior-superior combination 5 min after the initial injections (mean score +/- standard deviation of 1.74 +/- 1.86 vs. 2.66 +/- 2.39; P < 0.05), with a reduced requirement for supplementary injections (3 vs. 23 supplementary injections; P < 0.025). The inferior-superior technique achieved greater lid akinesia at 5 min than the inferior-medial technique (mean score +/- standard deviation of 0.7 +/- 0.9 vs. 0.3 +/- 0.58; P < 0.005). A medial subconjunctival hemorrhage occurred in one patient in the inferior-medial group. CONCLUSION: Compared with the inferior-superior technique, the inferior-medial combination achieved more rapid ocular akinesia with less need for supplementation, but induced less efficient lid akinesia and had a propensity to cause iatrogenic subconjunctival hemorrhage. The latter complication is considered by our surgeons to be a contraindication to the inferior-medial technique in patients undergoing trabeculectomy.

Aged↗

PubMed1978

Rorschach human movement responses of acting-out and withdrawn adolescents.

Rorschach human movement responses of 20 male and 20 female acting-out and withdrawn adolescents were scored according to flexor/extensor/blocked categories. Comparison of the two groups showed: (a) All subjects produced more extensor M than the other two M categories, (b) Acting-out adolescents produced more extensor M than the withdrawn subjects, (c) The two groups did not differ in number of flexor or blocked M. Extensor M seems to tap a propensity for acting-out, while flexor and blocked M do not differentiate the two groups of children.

Acting Out↗

PubMed2004

A new approach to prediction of short-range conformational propensities in proteins.

MOTIVATION: Knowledge-based potentials are valuable tools for protein structure modeling and evaluation of the quality of the structure prediction obtained by a variety of methods. Potentials of such type could be significantly enhanced by a proper exploitation of the evolutionary information encoded in related protein sequences. The new potentials could be valuable components of threading algorithms, ab-initio protein structure prediction, comparative modeling and structure modeling based on fragmentary experimental data. RESULTS: A new potential for scoring local protein geometry is designed and evaluated. The approach is based on the similarity of short protein fragments measured by an alignment of their sequence profiles. Sequence specificity of the resulting energy function has been compared with the specificity of simpler potentials using gapless threading and the ability to predict specific geometry of protein fragments. Significant improvement in threading sensitivity and in the ability to generate sequence-specific protein-like conformations has been achieved.

Algorithms↗

PubMed2001

An alpha1-antitrypsin enhancer polymorphism is a genetic modifier of pulmonary outcome in cystic fibrosis.

Lung disease is the direct cause of death in over 90% of cystic fibrosis (CF) patients. Excess neutrophil elastase is an important determinant of pulmonary disease in CF. alpha1-antitrypsin (AAT), also known as alpha1-proteinase inhibitor (alpha1PI) is a major modulator of elastase activity. We investigated the hypothesis that an enhancer polymorphism in the AAT gene would contribute to pulmonary prognosis in CF. Respiratory function, chest X-ray scores, bacterial colonisation and infective exacerbation were assessed to evaluate pulmonary disease severity in the CF group. Sixteen patients were found to have the 1237A allele, and 108 the more frequent G allele. Contrary to expectation, the patients with the 1237A allele were found to have better indices of pulmonary disease progression than those without, as indicated by less change in X-ray score (1237A: 0.2+/-0.1; 1237G: 1.2+/-0.1; P = 0.002) and fewer infective exacerbations (1237A: 2.8+/-0.6; 1237G: 4.6+/-0.3; P = 0.03) over the preceding 2 years. Also, a higher proportion of the 1237A (25%) than the 1237G (6.5%) were not colonised by Pseudomonas Aeruginosa (P = 0.04). Prospective monitoring of infections for a further 2 years confirmed a lesser propensity to infection in patients with the 1237A allele. These trends were also observed in a tightly matched sub-set of CF genotypes of similar age and sex, thus confirming that these effects were independent of the CF genotype. These results indicate that this AAT enhancer polymorphism is associated with better pulmonary prognosis in CF. Though the number of CF patients with the polymorphism is small, and these data need to be confirmed in larger studies, they suggest that a cautious approach should perhaps be taken to treatment of CF patients with supplemental AAT.

Adolescent↗

PubMed2006

Interaction-based evaluation of the propensity for amyloid formation with cross-beta structure.

In order to reveal the requirements for amino acid sequences prone to form amyloid fibrils, a novel prediction method based on the original structural model of amyloids was developed. As a working hypothesis, two fundamental conditions were introduced into the design of the present system for the evaluation of the propensity for amyloidogenicity. The first of these two conditions was to ensure that the hydrophobic and hydrogen-bonding interactions between residues on neighboring antiparallel beta-strands were formed along a fibril axis. The other condition was that the hydrophobic interacting residues appeared on both faces of the protofibril, which gave line-matching interactions. Most peptides with sequences exhibiting high scores, as evaluated by this method, were found to easily form amyloids with the aid of a turn-inducing structure designed as a connection of two beta-strands. On the other hand, peptides with low-scoring native sequences and those modified by an internal residue-residue exchange (the latter yielding a null score) did not lead to amyloid formation. These data demonstrated the validity of this method for the prediction of amyloid structures. Moreover, the present study provided support for the proposed model of the essential structure associated with the above working hypothesis. The predicted high-scoring regions were in good agreement with the putative amyloid core regions reported thus far.

Amyloid↗

PubMed2001

Impact of the physician's participatory style in asthma outcomes and patient satisfaction.

OBJECTIVES: To identify factors associated with asthma patients' perceptions of the propensity of pulmonologists to involve them in treatment decision-making, and its association with asthma outcomes. DESIGN: Cross-sectional observational study performed from June 1995 to December 1997. SETTING: Pulmonary unit of a university teaching hospital. PATIENTS: Adult patients with asthma (n = 128). MEASUREMENTS AND RESULTS: By patient self-report, mean physician's participatory decision-making (PDM) style score was 72 (maximum 100, 95% CI 65, 79). PDM scores were significantly correlated (P < .0001) with the duration of clinic visits (r = .63), patient satisfaction (r = .53), duration of tenure of doctor-patient relationship (r = .37), and formal education (r = .22, P = .023). Significantly higher PDM style scores were reported when visits lasted longer than 20 minutes and when a patient had a >6-month relationship with a particular doctor. PDM scores were also significantly correlated with possession of a written asthma action plan (r = .54, P < .0001), days affected by asthma (r = .36, P = .0001), asthma symptoms (r = .23, P = .017), and preferences for autonomy in asthma management decisions (r = .28, P = .0035). Those with PDM scores <50 reported significantly lower quality of life for all domains of a disease-specific instrument and the Short-Form 36 health survey version 1.0. In multiple regression analysis, PDM style was associated with the length of the office visit and the duration of tenure of the physician-patient relationship (R2 = 0.47, P = .0009). The adjusted odds ratio, per standard deviation decrease in PDM scores, for an asthma hospitalization was 2.0 (95% CI 1.2, 3.2) and for rehospitalization was 2.5 (95% CI 1.2, 4.2). CONCLUSIONS: Patients' report of their physician's PDM style is significantly associated with health-related quality of life, work disability, and recent need for acute health services. Organizational factors, specifically longer visits and more time seeing a particular physician, are independently associated with more participatory visits. This has significant policy implications for asthma management.

Adolescent↗

PubMed1988

Hypermobility in hallux valgus.

Hypermobility has been implicated as one of the etiological components in common foot problems such as hallux valgus but has not been substantiated by experimental data. Twenty patients with symptomatic untreated hallux valgus and 20 controls were evaluated with a simple hypermobility scoring system. A statistically significant correlation was found to reveal that female patients aged 20 to 40 yr with symptomatic hallux valgus have a mild generalized hypermobility when compared to a similar group of control patients. The presence of such ligamentous laxity would seem to support the need for bony correction in such patients as soft tissue procedures would have a greater propensity for malalignment due to the underlying hypermobility in combination with everyday environmental stresses of trauma and overuse.

Adult↗

PubMed1988

The association of health with stressful life changes, social supports, and coping.

Cross-sectional associations of social stressors, social supports, and coping strategies with health status were explored in a self-selected sample of 157 white adults. Using a mailed questionnaire, stressful life changes were assessed by a 40-item version of the Social Readjustment Rating Scale, social supports were measured by a 13-item index, and health status was assessed by the 63-item Duke-UNC Health Profile (DUHP). Responses to a recent stressful event were categorized by method of coping and by focus of coping. In a multivariate analysis controlling for the effects of age, gender, and education level, higher 12 month life change score was related to lower composite DUHP score. The use of active-cognitive coping was directly associated and the use of avoidance-coping was inversely associated with health status. When interaction terms were included in the multivariate analysis, avoidance-coping potentiated the adverse health effect of stressors and weak social supports potentiated the harmful effect of avoidance-coping on health. The findings suggest that the propensity to engage in avoidant behavior in response to a stressful experience is associated with health impairment, particularly when social supports are weak.

Adaptation, Psychological↗

PubMed2002

The effect of quetiapine on psychosis and motor function in parkinsonian patients with and without dementia.

Recently, several small studies have indicated that quetiapine may be useful in the treatment of drug-induced psychosis in patients with PD. However, there have been questions related to atypical antipsychotic therapy and patient selection and how that may affect response and tolerability, especially worsening of the motor symptoms of PD. In particular, the presence or absence of dementia seems to be important. The aim of this study was to evaluate the effect of quetiapine on psychosis and motor symptoms in PD patients with and without dementia. A retrospective record review of patient responses to quetiapine was conducted. Response of psychosis was assessed through patient and caregiver interviews. Motor symptom change in relation to this therapy was assessed by patient and caregiver interviews and completion of the motor portion of the Unified Parkinson's Disease Rating Scale (UPDRSm). Analysis was performed by comparing psychosis and motor feature measures from before and after therapy for the group as a whole and for demented and nondemented subgroups, using nonparametric tests and Fisher's exact test. Forty-three consecutively treated PD patients were evaluated. The mean dose of quetiapine was 54 mg per day and the duration of therapy was 10 months. Eighty-one percent of patients demonstrated partial or complete amelioration of psychosis. Five patients (13%) experienced a worsening of PD motor symptoms, which was corroborated by changes seen in UPDRSm. When the group was examined as a whole, no significant change in UPDRSm score was noted. When demented (n = 20) and nondemented (n = 19) patients were compared, improvement in psychosis occurred in similar numbers of patients, but a significant difference in the numbers of patients who experienced a worsening of motor symptoms was seen (P < 0.02, Fisher's exact test). All five patients who complained of motor worsening were in the demented group. UPDRSm score after therapy tended to be worse in the demented group (P = 0.55, Mann-Whitney U test). There was no significant change in the levodopa dose. Approximately 80% of patients chose to continue therapy. We conclude that quetiapine is effective in improving psychosis in approximately 80% of PD patients both with and without dementia. Patients with dementia seem to have a higher propensity for worsening of motor symptoms.

Aged↗

PubMed2000

Evaluation and management of common running injuries.

Adults who run for sport or for pleasure often present to their primary care physician with musculoskeletal complaints. Rapid diagnosis and conservative management of common running injuries and referral of patients with injuries that have a propensity for morbidity, such as femoral neck stress fractures, are reviewed. Careful evaluation of the patient's running program and physical therapy are important components of management.

Adult↗

PubMed2000

From amino acid landscape to protein landscape: analysis of genetic codes in terms of fitness landscape.

Assigning the values of a certain physicochemical property for individual amino acids to the corresponding codons, we can make an amino acid property "landscape" on a four valued three dimensional sequence space from a genetic code table. Eleven property landscapes made from the standard genetic code (SGC) were analyzed. The evaluation of correlation for each landscape is done by theta value, which represents the ratio of the mean slope (as an additive term) to the degree of roughness (as a nonadditive term). The theta-values for hydropathy indices, polarity, specific heat, and beta-sheet propensity were considerably large with respect to SGC. This implies that the additivity of the contribution from each letter holds for these properties. To clarify the meaning of the so-called mutational robustness of SGC, we next examined correlations between the amino acid property and the actual "site fitnesses" of a protein. The site fitnesses were derived from a set of binding preference scores of amino acid residues at every site in MHC class I molecule binding peptides (Udaka et al. in press). We found that the SGC's theta value for an amino acid property is correlated with the significance of the property in the protein function. Adaptive walk simulation on fitness (= affinity) landscapes in a base sequence space for these model peptides confirmed better evolvability due to the introduction of SGC.

Amino Acids↗

PubMed1999

Lack of efficacy of the 5-HT3 receptor antagonist granisetron in the treatment of acute neuroleptic-induced akathisia.

The specific mechanism underlying the apparent involvement of the serotonergic (5-HT) system in the pathophysiology of extrapyramidal side-effects, particularly neuroleptic-induced akathisia (NIA), remains unknown. We hypothesized that the 5-HT3 receptor subtype may play a role in the light of the moderate-to-high affinity to this receptor of some of the atypical antipsychotic agents which have a low propensity to cause akathisia, as well as our earlier findings with the 5-HT2/5-HT3 antagonist mianserin. In an open-label pilot study, we administered the selective 5-HT3 antagonist granisetron (fixed dose, 2 mg/day) for 4 days to 10 neuroleptic-treated patients with acute NIA. Three patients discontinued granisetron because of a lack of response. The remainder showed no significant change in score on the Barnes Akathisia Scale during the trial. NIA symptoms remained unchanged or worsened in five patients (71.4%) and improved to a certain degree in only two. It seems that the 5-HT3 subtype of serotonergic receptor is not involved in the development of NIA, and 5-HT3 antagonists are ineffective in the serotonin-related pharmacotherapy of NIA.

Acute Disease↗

PubMed2000

Lack of seasonal mood change in the Icelandic population: results of a cross-sectional study.

OBJECTIVE: The prevalence of seasonal affective disorder-as measured by the Seasonal Pattern Assessment Questionnaire-has been found to be unexpectedly low among Icelanders. The aim of this cross-sectional study was to measure seasonal variations in the prevalence of anxiety and depression among Icelanders assessed with the Hospital Anxiety and Depression Questionnaire. METHOD: Four 1, 000-person cohorts, age 20-70 years, selected at random from the Icelandic National Register, were sent the Hospital Anxiety and Depression Scale by mail in either January, April, July, or October. Only responses from the 4-week period after each mailing were considered in the subsequent analysis. RESULTS: The mean anxiety and depression scores in winter were not higher than those in summer for either sex. There was no significant difference between winter and summer in rates of actual or borderline cases of anxiety or depression or for the two categories combined. CONCLUSIONS: This lack of seasonality in anxiety and depression is in sharp contrast to findings from similar cross-sectional studies and may reflect the low propensity for seasonal affective disorder that has been described in the Icelandic population.

Adult↗

PubMed2001

Bipolar sensation seeking is associated with a propensity to abuse rather than to temperamental characteristics.

OBJECTIVE: As some temperament profiles may be markers of genetic vulnerability traits, we aimed to compare sensation seeking in euthymic bipolar patients and in controls. METHODS: One hundred ninety-four patients fulfilling DSM-IV diagnostic criteria for bipolar disorders (BP), 81% of whom presented type I BP, and 95 controls were included in this study. Euthymia was assessed using both the MADRS and Bech mania scales. Subjects were evaluated using the French abbreviated form of Zuckerman's Sensation Seeking Scale (SSS), which provide a total score (TS) and four subscores: Thrill and Adventure Seeking (TAS), Experience Seeking (ES), Disinhibition (Dis), and Boredom Susceptibility (BS). RESULTS: SSS total score differed significantly between men (17.2 +/- 0.5) and women (15.3 +/- 0.6) (P = 0.02) and all the subscores were negatively correlated with age. On adjustment for sex and age, we found that bipolar patients had a high Dis score (P = 0.003). However, if the same analysis was performed with a lifetime history of alcohol abuse or dependence as a covariable, no such difference was found (P = 0.436). The SSS demonstrated a high degree of test-retest reliability (ICC = 0.91). CONCLUSION: These results suggest that sensation seeking assessed with the SSS is not a temperament characteristic associated with bipolar disorders but is instead linked to a tendency towards alcohol abuse.

Adult↗