Evaluation of a novel method for grading heart murmur intensity

OBJECTIVE: To determine if heart murmur intensity grading performance can be improved using the heart sounds as an internal reference. METHODS: Single-blind controlled trial of 100 medical students, residents, and pediatric attending physicians at a children's hospital. Groups of 1 to 3 participants were alternately assigned to intervention and control groups, reported their method of grading heart murmur intensity, and then graded the intensity of a random sample of 20 recorded murmurs on a 6-point scale. Before rating another random sample of 20 murmurs, the intervention group was taught a system that uses the heart sounds as an internal reference. Primary outcomes were change in accuracy (percentage correct), interrater agreement (kappa), and consistency (kappa). Subgroup analyses were performed by training level and heart murmur grade. RESULTS: Grading accuracy improved more in the intervention group than the control group (Delta improvement, 5%; 95% confidence interval [CI], -0.1%-10.0%]). This was most pronounced among attending physicians (Delta improvement, 11%; 95% CI, 0.4%-22%) and students (Delta improvement, 12%; 95% CI, 3%-20%) and for grade 2 murmurs (Delta improvement, 20%; 95% CI, 10%-31%). Relatively greater improvements in consistency were observed after the intervention for attending physicians (Delta improvement, 0.17; 95% CI, 0.01-0.32) and grades 2 (Delta improvement, 0.22; 95% CI, 0.09-0.36) and 3 murmurs (Delta improvement, 0.16; 95% CI, 0.05-0.28). CONCLUSIONS: A system that uses the heart sounds as an internal reference for grading heart murmur intensity quickly improves accuracy and consistency for some providers and specific murmurs.     

Adoptive transfer of T cells modified with a humanized chimeric receptor gene inhibits growth of Lewis-Y-expressing tumors in mice

In this study, human T cells were provided with a reactivity against the Lewis-Y (Le(Y)) carbohydrate antigen, which is overexpressed on 70% of epithelial-derived tumors, but not normally recognized by T cells. Antitumor reactivity was achieved by transduction of T cells with a gene encoding a cell-surface chimeric receptor composed of single-chain anti-Le(Y) antibody linked to an enhanced cytoplasmic signaling domain made up of CD28 and CD3-zeta. Importantly, the single-chain antibody was humanized to try to reduce potential problems of human anti-mouse antibody responses in patients receiving chimeric receptor-modified T cells in future clinical trials. T cells expressing the chimeric receptor were demonstrated to secrete cytokines and proliferate in response to receptor ligation and lysed Le(Y+) tumors in vitro. Another aspect of this study was the finding that no activity was observed against normal tissue, as represented by autologous neutrophils that express low levels of Le(Y). Significantly, systemic delivery of anti-Le(Y) T cells dramatically inhibited established s.c. human ovarian OVCAR-3 tumors (a recognized difficult model to treat) in mice. Finally, we demonstrated that anti-Le(Y) T cells preferentially expanded or accumulated in the tumor compared with control empty vector T cells, thereby providing mechanistic insight into the specific antitumor response. This study supports the use of humanized gene-modified T cells as a potential therapy for Le(Y+) malignancies.     

Regression of carotid atherosclerosis by control of morning blood pressure peak in newly diagnosed hypertensive patients

BACKGROUND: Morning blood pressure (BP) peak may be a risk factor for cardiovascular disease. Whether morning BP should be a target of hypertension treatment is not known. We investigated the relationship between morning BP variations, carotid internal-medial thickness (CIMT), circulating inflammatory markers, and sympathetic activity in hypertensive patients with different patterns of morning BP increase at baseline and after antihypertensive treatment. METHODS: One hundred twenty-eight hypertensive patients with morning BP peak (MP+) were compared with 196 hypertensive patients without morning BP peak (MP-). All patients performed 24-h ambulatory BP monitoring, assessment of CIMT, circulating concentration of C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-18 (IL-18), and urinary catecholamines. RESULTS: Compared with MP- patients, MP+ patients had higher CIMT and urinary catecholamine output (P < .001), as well as CRP, IL-6, and IL-18 (P < .001). We randomly assigned 128 drug-naive MP+ patients to either metoprolol or carvedilol, two antihypertensive drugs with different effects on sympathetic activity. The primary outcome was change in CIMT and circulating inflammatory markers at 12 months. Morning BP decreased more among patients in the carvedilol group (P < .001), whereas clinic BP showed a similar decrease in both groups. The CIMT (P < .001), IL-6 (P < .001), IL-18 (P < .001), and CRP (P < .001) decreased more in the carvedilol group than in the metoprolol group. The CIMT regression was observed in 49% of patients in the carvedilol group and 18% of patients in the metoprolol group (P < .01). Reduction in CIMT was directly associated with changes in morning BP. CONCLUSIONS: Higher CIMT and circulating inflammatory markers coexist in hypertensive patients with morning BP peak, and might contribute to their increased cardiovascular risk. Carotid atherosclerosis can be prevented by control of morning BP.     

Henri Ey's neojacksonism and the psychopathology of disintegrated mind

The French psychiatrist Henri Ey developed his organo-dynamic theory of the mind function and consciousness 50 years ago incorporating Hughling Jackson's thinking, along with psychiatric and philosophical theorizations by Janet and Bergson. This model has not received the attention it deserved, but recent advances in neuroscience rekindled interest for Ey's theory. By overcoming the Cartesian mind-body dualism and treating the mind-body unit as an inseparable whole, this model opens the way for the integrated treatment of mental disorders. Ey's conceptualization of consciousness as being simultaneously both synchronous and diachronic anticipates current theories of consciousness (Damasio, Edelman, Mesulam).     

Convection perfusion of glucocerebrosidase for neuronopathic Gaucher's disease

Systemic enzyme replacement for Gaucher's disease has not prevented premature death or severe morbidity in patients with a neuronopathic phenotype, because the enzyme does not cross the blood-brain barrier. We used convection-enhanced delivery for regional distribution of glucocerebrosidase in rat and primate brains and examined its safety and feasibility for neuronopathic Gaucher's disease. Rats underwent intrastriatal infusion and were observed and then sacrificed at 14 hours, 4 days, or 6 weeks. Primates underwent serial magnetic resonance imaging during enzyme perfusion of the right frontal lobe or brainstem, were observed and then sacrificed after infusion completion. Animals underwent histologic and enzymatic tissue analyses. Magnetic resonance imaging revealed perfusion of the primate right frontal lobe or pons with infusate. Enzyme activity was substantially and significantly (p < 0.05) increased in cortex and white matter of the infused frontal lobe and pons compared to control. Immunohistochemistry demonstrated intraneuronal glucocerebrosidase. There was no toxicity. Convection-enhanced delivery can be used to safely perfuse large regions of the brain and brainstem with therapeutic levels of glucocerebrosidase. Patients with neuronopathic Gaucher's disease and similar central nervous system disorders may benefit from this treatment.     

The effects of single and dual sensory loss on symptoms of depression in the elderly

OBJECTIVES: The primary purposes of this study were to determine the effect of dual sensory loss (i.e. combined hearing and vision loss) on depressive symptoms, to determine whether dual sensory loss has an effect on depressive symptoms when controlling for common covariates of depression, and to determine whether persons with dual sensory loss were more likely than those with a single sensory loss to experience depressive symptoms. DESIGN: Secondary analyses of 2001 National Health Interview Survey data. PARTICIPANTS: Nine thousand eight hundred and thirty-two people aged 55 and older residing in the community in the US. MEASUREMENTS: Self-report answers to questions about hearing and vision status, depressive symptoms, health, education level, poverty, social activities, social support, and functional disability (ADL and IADL status). RESULTS: Dual sensory loss had a significant effect on depressive symptoms (OR: 3.2, 95% CI: 2.8-4.0), which was lowered but still significant after controlling for covariates of depression (OR: 2.2, 95% CI: 1.7-2.9). Those with dual sensory loss were not significantly more likely than those with vision loss, but were significantly more likely than those with hearing loss, to experience symptoms of depression. CONCLUSION: Experiencing depressive symptoms is a problem that needs to be addressed with elderly persons with dual sensory loss. Not only is this population more likely to experience these symptoms, because of their sensory losses treatment for them may be problematical. Professionals working with the elderly should be aware of the increased risks of depressive symptoms in those with single or dual sensory loss, and should screen for them. If present, rehabilitation for sensory losses may help decrease them.     

Factor structure and construct validity of the Anxiety Sensitivity Index among island Puerto Ricans

The factor structure and convergent and discriminant validity of the Anxiety Sensitivity Index (ASI) were examined among a sample of 275 island Puerto Ricans. Results from a confirmatory factor analysis (CFA) comparing our data to factor solutions commonly reported as representative of European American and Spanish populations indicated a poor fit. A subsequent exploratory factor analysis (EFA) indicated that a two-factor solution (Factor 1, Anxiety Sensitivity; Factor 2, Emotional Concerns) provided the best fit. Correlations between the ASI and anxiety measures were moderately high providing evidence of convergent validity, while correlations between the ASI and BDI were significantly lower providing evidence of discriminant validity. Scores on all measures were positively correlated with acculturation, suggesting that those who ascribe to more traditional Hispanic culture report elevated anxiety.     

Subjective sleep complaints in pediatric depression: a controlled study and comparison with EEG measures of sleep and waking

OBJECTIVE: Children with major depressive disorder (MDD) often complain of sleep disturbances; however, polysomnographic studies have failed to find objective evidence of these disturbances. This article examines subjective sleep reports of children with MDD and healthy controls focusing on comparing subjective and objective sleep measures. METHOD: Fifty-one subjects with MDD and 42 healthy subjects, 8-17 years old, participated in a comprehensive psychobiologic study including three nights of EEG sleep recording. Each morning, subjects completed a post-sleep form subjectively rating their sleep, which was then compared with their polysomnographic studies. RESULTS: Depressed subjects reported significantly worse sleep on four scales: subjective sleep quality, perceived number of awakenings, estimated minutes awake, and perceived ease of waking. In contrast to these subjective complaints, objective EEG measures indicated no evidence of disturbed sleep in the depressed sample compared to controls. Furthermore, exploratory analyses focusing on the subset of depressed subjects with the greatest subjective sleep disturbance showed, paradoxically, significantly better sleep in terms of the number of EEG awakenings and objective disturbances. CONCLUSIONS: Despite clinical evidence of subjective sleep complaints in depressed children, our EEG measures showed little evidence to indicate an objective basis for these perceptions. These findings raise provocative questions regarding the nature of sleep complaints associated with early-onset depression.     

Manipulating establishing operations to promote initiations toward peers in children with autism

This study examined the effects of manipulating establishing operations on the frequency of initiations of three children with autism toward peers with autism. The EO targeted was deprivation of preferred edibles, and the target initiation was a mand for the preferred snack. A reversal design was used to assess the effects of the EO conditions on frequency of initiations. Results indicated that when the EO was absent, no spontaneous initiations toward the peer occurred. Two participants required training sessions with an adult to transfer initiations toward peers. Once the EO had been established and was present, the participants initiated mands for the snack. Results are discussed in terms of implications for the use of establishing operations in language training for children with autism.     

Factor solution of the BPRS-expanded version in schizophrenic outpatients living in five European countries

RATIONALE: The expanded version of the Brief Psychiatric Rating Scale (BPRS-E) has improved the instrument's coverage and interrater reliability, but there is little knowledge on its subsyndromes. OBJECTIVES: To assess: (1) whether there are common underlying BPRS-E subscales in patients living in different countries and (2) if this is the case, whether these subscales behave the same in all populations and, if not, what are the differences over these populations. METHODS: Data are part of the EPSILON study, a collaborative project carried out in Denmark, England, Holland, Italy and Spain. A random representative sample of 404 adult patients with a ICD-10 diagnosis of schizophrenia who have been in contact with mental health services of a defined catchment area in each site were assessed. Simultaneous component analysis (SCA) was used to find component weights that optimally explain the variance of the variables in different populations simultaneously. RESULTS: Symptom severity differed significantly among the five EPSILON sites in 12 out of 24 BPRS-E items, but a common component solution could be found. It explained 48.8% of the variance and gave four well-interpretable components: manic excitement/disorganization, depression/anxiety, negative and positive symptoms. Each component's internal consistency and intercomponent correlation matrix differed significantly among sites. The four components mean score differed significantly among sites for negative symptoms and depression/anxiety. CONCLUSIONS: In spite of the heterogeneity of symptom's severity in the various countries, the way symptoms cluster in schizophrenia is rather stable cross-culturally. Data demonstrate that to explore schizophrenia a third component, including mania/disorganization items, is necessary beside the positive-negative symptom dimensions. The subscales derived from these analyses can be readily used in clinical trials and epidemiological studies.