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Biomedical subjects

K Murphy

Publications and source records attributed to K Murphy.

At least 55 records · Page 3Linked to original sources

Site of facilitation of diaphragm EMG to corticospinal stimulation during inspiration.

The electromyographic response of the diaphragm to (a) transcutaneous electrical stimulation (TCES) of the spinal cord at C5 and above, (b) transcranial magnetic stimulation (TMS) over the motor cortex and (c) transcutaneous electrical stimulation of the phrenic nerve in the neck (TPNS), was recorded in six normal subjects at the antero-lateral chest wall. The compound motor evoked potentials (cMEPs) recorded in response to both TMS and TCES were facilitated to a similar extent during volitional inspiration; this facilitation was greater than any change seen in response to TPNS with inspiration. The results show that facilitation of the response in the diaphragm to TMS during volitional inspiration is due to increased excitability at synapses associated with the spinal motoneurone pool, but they do not exclude a component due to increased higher centre excitability. We conclude that it is unsafe to assign a cortical contribution to 'automatic' inspiration on the sole basis of facilitation of the electromyographic response in the diaphragm to TMS.

Adult

Development, testing, and validation of two scales measuring nursing home management of subjects with mental disorder.

This paper describes the development, testing, and validation of summary scales measuring nursing processes commonly used in caring for elderly nursing home residents with cognitive, mood, and behavior problems, or other markers of mental disorder. Data were obtained from a cross-sectional study of 1017 residents from a proportionate random sample in Delaware nursing facilities, to determine the prevalence of mental disorders and to describe distinguishing characteristics and treatments. An exploratory factor analysis was performed on 11 frequently encountered nursing management strategies as applied to 808 subjects with some indicator of mental disorder. Two factors emerged, which were subsequently conceptualized as separate scales (composed of six and five elements, respectively) that measure the basic approaches termed Encouragement and Control. Alpha reliability levels determined internal consistency for each scale. Cognitive, behavioral, and mood correlates were identified for each scale using multiple regression. Replication and validation were achieved when similar findings were obtained using a random sample of 290 residents at Hebrew Rehabilitation Center for Aged, a 725-bed long-term care facility in Boston. LISREL analyses confirmed the presence of at least two dimensions in behavior management strategies. The identification of these approaches is significant in providing non-pharmacologic and non-restraint alternatives to managing elderly residents with symptom distress.

Aged

Adults with attention deficit hyperactivity disorder: assessment and treatment considerations.

Attention Deficit Hyperactivity Disorder (ADHD) has, historically, been viewed as a childhood disorder which would be outgrown by adulthood. More recent findings have established that the disorder often persists into adult-hood in a significant number of those diagnosed as children. Due to increased awareness and media attention being focused on ADHD in adults, greater numbers of adults are seeking evaluation and treatment for this disorder. The symptoms of ADHD are common to a variety of other psychiatric disorders including learning disabilities, so clinicians need to update their knowledge of assessment, treatment, and differential diagnosis issues regarding this often misunderstood disorder. This article discusses some current methods used in the assessment and treatment of adults with ADHD.

Attention Deficit Disorder with Hyperactivity

Hospice services.

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Alzheimer Disease

Inspiratory coactivation of the genioglossus enlarges retroglossal space in laryngectomized humans.

To investigate the relationship between the electrical activity of the genioglossus (GG-EMG) and associated tongue movement, seven laryngectomized subjects breathing through a tracheal stoma (without pressure or flow change in the upper airway) were studied in the supine position. Tongue movement, with the use of lateral fluoroscopy, and GG-EMG expressed as a percentage of maximum voluntary genioglossal activation were monitored simultaneously during 1) spontaneous inspiration (SI), 2) resistive loaded inspiration (LI), and 3) rapid inspiration (RI). Tongue position during each maneuver was compared with its position during spontaneous expiration. Peak GG-EMG during the three maneuvers was significantly different from each other (SI: 5.4 +/- 1.6, LI: 11.9 +/- 1.8, and RI: 51.6 +/- 9.4 (SE) %, respectively). Associated forward movement of the posterior aspect of the tongue was minimum during SI; however, significant movement was observed during LI, and this was increased during RI. Significant covariance existed between peak GG-EMG and this movement. Genioglossal coactivation with inspiration enlarges the glossopharyngeal airway, particularly in its caudal part. In subjects with intact upper airways, this activation may protect or enhance upper airway patency in an effort-dependent manner.

Aged

Eicosanoids and lipocortin-1 in BAL fluid in asthma: effects of smoking and inhaled glucocorticoids.

Both smoking and asthma are associated with inflammatory changes in the lung, which may be suppressed with the help of exogenous anti-inflammatory drugs or by the endogenous defense system. Lipocortin-1 (LC-1; annexin-1) is an anti-inflammatory protein present in respiratory tract secretions. We report an inverse correlation between extracellular LC-1 concentration and the bronchoconstrictor prostaglandin (PG) D2 [n = 15, Spearman rank correlation coefficient (rS) = -0.597, P < 0.05] in bronchoalveolar lavage fluid (BALF) from allergic asthmatic patients, together with positive correlations between extracellular LC-1 per milliliter BALF and the prostacyclin (PGI2) metabolite 6-keto-PGF1 alpha (n = 15, rS = 0.480, P < 0.05) and between LC-1 per milliliter BALF and concentration of histamine causing a 20% decrease in forced expired volume in 1 s (n = 15, rS = 0.720, P < 0.01) in these subjects. We found no significant difference between the LC-1 concentration in BALF from nonsmoking asthmatic patients who were receiving inhaled glucocorticoid therapy (2 x 100 micrograms beclomethasone 4 times/day for 2.5 yr; median 186 ng LC-1/mg albumin; n = 6) and those who were not (median 126 ng LC-1/mg albumin; n = 12), perhaps because inhaled drugs deposit predominantly in central airways, which are poorly represented in bronchoalveolar lavage. Both asthmatic and healthy volunteers who smoked had higher levels of LC-1 in their BALF than did their nonsmoking counterparts (e.g., asthmatic smokers, median 317 ng LC-1/mg albumin, n = 10; asthmatic nonsmokers, median 162 ng LC-1/mg albumin, n = 18; P < 0.05), perhaps because smokers' lungs contain more alveolar macrophages, cells that release LC-1. We observed a positive correlation between BALF LC-1 and bronchoalveolar lavage cell number (n = 16, rS = 0.821, P < 0.001). Increased extracellular LC-1 may be part of a protective response of the lung to inflammatory insult. Regulation of prostanoid levels might be one mechanism by which LC-1 suppresses inflammation.

6-Ketoprostaglandin F1 alpha

Human cerebral activity with increasing inspiratory force: a study using positron emission tomography.

Human cerebral activity with increasing inspiratory force: a study using positron emission tomography. J. Appl. Physiol. 81(3): 1295-1305, 1996.--The major aim of this study was to use positron emission tomography (PET) to assess dose-dependent effects of inspiratory loads on relative regional cerebral blood flow as an indication of neuronal activation and recruitment. Six normal men underwent H2 15O-PET scanning during unloaded breathing and with external inspiratory loads (generating mouth pressures of -5, -10, and -15 cmH2O); positive-pressure ventilation against relaxed respiratory muscles acted as control. During unloaded breathing, the supplementary motor area was significantly activated. With the addition of the smallest load, activations also occurred in the right premotor area and bilaterally in the superolateral motor cortex (MI) in areas previously shown to be activated with deeper breathing. There was little further change in these areas with greater loads. Additional force-related activations occurred in the inferolateral sensorimotor cortex, parietal cortex, and midbrain/hypothalamus. The results suggest that volitionally induced increases in inspiratory muscle force are achieved via a complex integration of neuronal activations in cortical and subcortical regions associated with motor control.

Adult

Male adolescents' reactions to TV beer advertisements: the effects of sports content and programming context.

OBJECTIVE: This study examines white male adolescent responses to TV beer advertisements with and without sports content and to nonbeer ads when embedded in sports and entertainment programming. METHOD: A total of 72 advertisements and 24 television program excerpts were randomly sampled from national television programming. White male adolescents (N = 157) recruited in a public school system each viewed six ads (one of each of three types of ad embedded in each of two types of programming) comprising the 2 x 2 x 3 factorial, within-subjects, mixed-model (random and fixed effects) experimental design along with an age-level blocking factor and random factors for commercial and program stimuli. Cognitive responses to each ad were content-analyzed. Individual difference variables including alcohol use behavior, sensation-seeking, masculinity and sports involvement were also measured. RESULTS: Subjects showed a consistent preference for beer ads with sports content. A significant three-way interaction between ad type, programming type and junior versus senior high-school age level also indicated that sports programming had an inconsistent effect on responses to beer ads but that nonbeer ads were responded to more positively during sports than during entertainment programming. Other analyses showed that subjects were more cognitively resistant to beer ads than to nonbeer ads. CONCLUSIONS: These results support public and official concerns that sports content in beer ads increase the ads appeal to underage youth. They do not support hypothesized concerns that sports programming might prime adolescents to be more receptive to beer ads. Implications for alcohol education efforts are discussed.

Adolescent

Adolescent counterarguing of TV beer advertisements: evidence for effectiveness of alcohol education and critical viewing discussions.

The pervasiveness of American youth's exposure to alcohol advertising is well-documented, as is the correlational evidence linking such exposure to alcohol-related attitudes, use, and expectancies. While efforts to train young people to resist persuasive appeals are often made in alcohol education programs, little evidence exists concerning the effectiveness of such efforts. The present study (N = 83) found that recency of exposure to alcohol education classes and discussion of alcohol advertising in such classes predicts cognitive resistance (counterarguing) of such advertisements months or even years after class exposure. Age, gender, and ethnicity were statistically controlled. While females tended to counterargue the alcohol advertisements more than did males, there was no statistically significant difference in the impact of education on males and females.

Adolescent

Expansion of 50 CAG/CTG repeats excluded in schizophrenia by application of a highly efficient approach using repeat expansion detection and a PCR screening set.

Studies of the transmission of schizophrenia in families with affected members in several generations have suggested that an expanded trinucleotide repeat mechanism may contribute to the genetic inheritance of this disorder. Using repeat expansion detection (RED), we and others have previously found that the distribution of CAG/CTG repeat size is larger in patients with schizophrenia than in controls. In an attempt to identify the specific expanded CAG/CTG locus or loci associated with schizophrenia, we have now used an approach based on a CAG/CTG PCR screening set combined with RED data. This has allowed us to minimize genotyping while excluding 43 polymorphic autosomal loci and 7 X-chromosomal loci from the screening set as candidates for expansion in schizophrenia with a very high degree of confidence.

Alleles

Linkage, association and mutational analysis of the dopamine D3 receptor gene in schizophrenia.

This study follows the observation of an association between homozygosity of an Mscl polymorphism in exon 1 and schizophrenia, which gives rise to a glycine to serine substitution and may alter the functional properties of the receptor. Alternatively the polymorphism may not itself be of functional significance but may be in linkage disequilibrium with another genetic variant in the coding or regulatory regions. To examine the second possibility we have screened all six exons of DRD3 by single-stranded conformational polymorphism analysis (SSCP) in 36 cases and 36 controls. Our findings suggest that the gene is highly conserved since we found no other mutations which alter protein structure. However we did detect a 5-bp deletion in the 3' intronic sequence flanking exon 5 which occurred in 7-8% of subjects within both case and control samples. A single bp substitution (g to a) in exon 3, which does not alter an amino acid was found in one affected individual. In addition we carried out a linkage study of 24 families multiply affected with schizophrenia and a non-parametric linkage study of 90 affected sibling pairs. These studies give no support for either major or moderate gene effects on schizophrenia susceptibility. Finally we have extended our association sample and observe a non-significant excess of homozygotes for the Mscl polymorphism in the sample overall (chi 2 = 2.09, 1 d.f., P = 0.15). The excess of homozygotes is specific to males (chi 2 = 4.617, 1 d.f., P = 0.032) and not females (chi 2 = 0.243, 1 d.f., NS). When these data are added to our previous published data a highly significant excess of homozygotes is observed in males (chi 2 = 13.766, 1 d.f., P = 0.00021) but not females (chi 2 = 0.606, 1 d.f., NS). In conclusion the accumulated data suggest strongly that genetic variation at the DRD3 locus increases susceptibility of schizophrenia, at least in males. At present the Mscl polymorphism in exon 1 of the gene remains a candidate for bringing about functional change in the receptor but this has not been formally tested. Other coding region polymorphisms have not been detected but it remains possible that variation within the promoter may alter receptor function.

Base Sequence

Hyperpnoea during and immediately after exercise in man: evidence of motor cortical involvement.

1. The neurophysiological basis for the increase in breathing associated with exercise remains obscure. The present study uses positron emission tomography (PET) to measure relative regional cerebral blood flow (rCBF) in order to identify sites of increased neuronal activation during and immediately following exercise. 2. Male volunteers underwent H2(15)O PET scanning during two complementary studies. Firstly, six subjects performed right leg exercise, adequate to increase oxygen uptake 2.5-fold. Secondly, five different subjects were scanned immediately following bicycle exercise (adequate to increase oxygen uptake 5-fold) while breathing was still increased. In each study, as a control, scanning was also performed during matched passive isocapnic positive pressure ventilation; additionally, in the first study, passive right leg movement was performed. 3. Increases in relative rCBF were obtained in each individual and co-registered with their magnetic resonance image of the brain defining individual gyral morphology. 4. During exercise, individual and group analysis revealed significant relative rCBF increases in the left and right superomedial primary motor cortex (the motor cortical 'leg' areas) and also in the left and right superolateral primary motor cortex in areas previously shown to be associated with volitional breathing. After exercise, there was no significant increase in relative rCBF in the superomedial areas but such increases were still present bilaterally in the superolateral areas which had been activated during the exercise. Other relative rCBF increases were also found, both during and after exercise, in cortical and subcortical areas known to be involved in motor control. 5. The results from PET scans during and after exercise, taken together, provide evidence for motor cortical involvement in the exercise-related hyperpnoea in man.

Adult

Heterogeneity of intracellular cytokine synthesis at the single-cell level in polarized T helper 1 and T helper 2 populations.

CD4+ T helper (Th) cells can be classified into different types based on their cytokine profile. Cells with these polarized patterns of cytokine production have been termed Th1 and Th2, and can be distinguished functionally by the production of IFN-gamma and IL-4, respectively. These phenotypes are crucial in determining the type of immune response that develops after antigen priming. There are no surface markers that define them, and cytokine immunoassay or mRNA analysis both have limitations for characterization of single cells. Using immunofluorescent detection of intracellular IFN-gamma and IL-4, we have studied the emergence of Th1 and Th2 cells in response to antigen exposure and the patterns of cytokine synthesis in established T cell clones. IFN-gamma production by Th1 clones was detectable in almost all cells by 4 h, and it continued in most cells for > 24 h. IL-4 production in Th2 cells peaked at 4 h, but declined rapidly. In Th0 cells containing both cytokines, fewer cells produced IFN-gamma, which did not appear until IL-4 synthesis declined. Cocultivation of clones showed no such cross-regulation. Antigen stimulation of transgenic T cells expressing an ovalbumin-specific T cell receptor generated Th2 cells, probably as a result of endogenous IL-4 production. Addition of IL-12 and/or anti-IL-4 caused Th1 cells to develop, while some Th0 cells were seen when IL-12 alone was added. These results show that stimulation in the presence of polarizing stimuli results in cells producing either IFN-gamma or IL-4, but that coproduction can occur in rare cells under defined conditions.

Animals

Evidence for limbic system activation during CO2-stimulated breathing in man.

1. The role of supra-brainstem structures in the ventilatory response to inhaled CO2 is unknown. The present study uses positron emission tomography (PET), with infusion of H2(15)O, to measure changes in relative regional cerebral blood flow (rCBF) in order to identify sites of increased neuronal activation during CO2-stimulated breathing (CO2-SB) in awake man. 2. Five male volunteers were scanned during CO2-SB (mean +/- S.E.M.; end-tidal PCO2, 50.3 +/- 1.7 mmHg; respiratory frequency, 16.4 +/- 2.7 min-1; tidal volume, 1.8 +/- 0.2 l). As control, scans were performed during 'passive' isocapnic (elevated fraction of inspired CO2) positive pressure ventilation (end-tidal PCO2, 38.4 +/- 1.0 mmHg; respiratory frequency, 15.5 +/- 2.2 min-1; tidal volume, 1.6 +/- 0.2 l). With CO2-SB, all subjects reported dyspnoea. 3. The anatomical locations of the increases in relative rCBF (CO2-SB versus control) were obtained using magnetic resonance imaging. 4. Group analysis identified neuronal activation within the upper brainstem, midbrain and hypothalamus, thalamus, hippocampus and parahippocampus, fusiform gyrus, cingulate area, insula, frontal cortex, temporo-occipital cortex and parietal cortex. No neuronal activation was seen within the primary motor cortex (at sites previously shown to be associated with volitional breathing). 5. These results suggest neuronal activation within the limbic system; this activation may be important in the sensory and/or motor respiratory responses to hypercapnia in awake man.

Adult

The brn-2 gene regulates the melanocytic phenotype and tumorigenic potential of human melanoma cells.

The Oct transcription factors N-Oct-3 and N-Oct-5 are differentially expressed in normal melanocytes, melanoma tumors and cell lines. We have cloned the human brn-2 gene and have shown that it encodes both the N-Oct-3 and N-Oct-5 octamer binding activities detected in melanoma cells. The brn-2 genomic locus has been mapped to chromosome 6q16 and although chromosomal aberrations are common in this region in melanoma, no deletion or rearrangement of the brn-2 gene in melanoma cell lines was observed. Sequencing of the entire gene showed that there are no intervening sequences within the open reading frame. Antisense RNA-mediated inhibition of brn-2 gene expression in melanoma cells was associated with a change in morphology and loss of melanocytic and neural crest markers, including the melanocyte transcription factor microphthalmia and the TYRP pigmentation genes. In addition, loss of brn-2 in these cells resulted in the complete loss of ability to form tumors in SCID and nu/nu mice. These results suggest roles for brn-2 in the determination of the melanocytic lineage and in the tumorigenic phenotype of melanoma.

Animals