Search PubMed⌕ Search

Biomedical subjects

C Murphy

Publications and source records attributed to C Murphy.

At least 55 records · Page 3Linked to original sources
PubMed2000

Clinical study and literature review of nasal irrigation.

OBJECTIVES/HYPOTHESIS: Nasal disease, including chronic rhinosinusitis and allergic rhinitis, is a significant source of morbidity. Nasal irrigation has been used as an adjunctive treatment of sinonasal disease. However, despite an abundance of anecdotal reports, there has been little statistical evidence to support its efficacy. The objective of this study was to determine the efficacy of the use of pulsatile hypertonic saline nasal irrigation in the treatment of sinonasal disease. STUDY DESIGN: A prospective controlled clinical study. METHODS: Two hundred eleven patients from the University of California, San Diego (San Diego, CA) Nasal Dysfunction Clinic with sinonasal disease (including allergic rhinitis, aging rhinitis, atrophic rhinitis, and postnasal drip) and 20 disease-free control subjects were enrolled. Patients irrigated their nasal cavities using hypertonic saline delivered by a Water Pik device using a commercially available nasal adapter twice daily for 3 to 6 weeks. Patients rated nasal disease-specific symptoms and completed a self-administered quality of well-being questionnaire before intervention and at follow-up. RESULTS: Patients who used nasal irrigation for the treatment of sinonasal disease experienced statistically significant improvements in 23 of the 30 nasal symptoms queried. Improvement was also measured in the global assessment of health status using the Quality of Well-Being scale. CONCLUSIONS: Nasal irrigation is effective in improving symptoms and the health status of patients with sinonasal disease.

Humans↗
PubMed2000

Sinonasal disease and olfactory impairment in HIV disease: endoscopic sinus surgery and outcome measures.

OBJECTIVES: To investigate the effects of ESS (ESS) on olfactory impairment, disease-specific symptoms, and general quality of well-being In HIV+ patients with sinonasal disease. STUDY DESIGN: Study 1: Nasal cytology, rhinomanometry, nasal examination including endoscopy, disease-specific sinonasal symptoms, olfactory threshold sensitivity, and odor identification testing were performed before and after ESS in HIV+ patients with sinonasal complaints. Study 2: Quality of well-being was assessed before and after ESS in HIV+ patients with sinonasal complaints and controls. RESULTS: Significant olfactory sensitivity loss persisted for patients with chronic sinusitis after ESS, suggesting that the impairment in these patients may be due to viral disease rather than inflammation. Significant improvement in other disease-specific symptom scores (nasal obstruction, nasal congestion, headache, sinus pain, etc.) and results of the general quality of well-being assessment showed ESS to be beneficial in the extended health management of HIV illness. CONCLUSIONS: The current study indicated both olfactory dysfunction and subjective negative symptoms in HIV+ patients with chronic sinusitis. Although olfactory dysfunction remained, ESS was successful in providing marked alleviation of symptomatology in HIV+ patients with chronic sinusitis. The results support ESS as an appropriate treatment option for HIV+ patients with chronic sinusitis.

Adult↗
PubMed2000

Phenotypic differences between African and white patients with motor neuron disease: a case-control study.

There is increasing evidence that race may affect the phenotype in some neurodegenerative diseases. To investigate this in motor neuron disease a retrospective case-control study has been carried out on 15 negroid African and 45 white patients with the disease seen over 8 years. Each African was compared with three age and sex matched white patients with motor neuron disease. There were no statistically significant differences in age of onset or the mean duration of disease in the two groups. The chance of presenting with the "flail arm" variant of motor neuron disease was four times as high in the African group than the white group (odds ratio 4.33, p=0. 05, 95% confidence interval 0.99-18.92). Although no overall differences in survival were seen between the two groups, in those with the flail arm variant, four out of the six African patients had died whereas all six white arm patients were alive at the censoring date of 1 January 1999 (median follow up 38.5 months). It is concluded that race may influence the phenotype and progression of motor neuron disease.

Africa↗
PubMed2000

Activated protein C inhibits tumor necrosis factor and macrophage migration inhibitory factor production in monocytes.

The precise regulatory mechanisms of amplification and downregulation of the pro- and anti-inflammatory cytokines in the inflammatory response have not been fully delineated. Although activated protein C (APC) and its precursor protein C (PC) have recently been reported to be promising therapeutic agents in the management of meningococcal sepsis, direct evidence for the anti-inflammatory effect remains scarce. We report that APC inhibits in vitro the release of tumor necrosis factor (TNF) and macrophage migration inhibitory factor (MIF), two known cytokine mediators of bacterial septic shock, from lipopolysaccharide (LPS)-stimulated human monocytes. The THP-1 monocytic cell line, when stimulated with LPS and concomitant APC, exhibited a marked reduction in the release of TNF and MIF protein in a concentration-dependent manner compared to cells stimulated with LPS alone. This effect was observed only when incubations were performed in serum-free media, but not in the presence of 1-10% serum. Serum-mediated inhibition could only be overcome by increasing APC concentrations to far beyond physiological levels, suggesting the presence of endogenous serum-derived APC inhibitors. Inhibition of MIF release by APC was found to be independent of TNF, as stimulation of MIF release by LPS was unaltered in the presence of anti-TNF antibodies. Our data confirm that the suggested anti-inflammatory properties of APC are due to direct inhibition of the release of the pro-inflammatory monokine TNF, and imply that the anti-inflammatory action of APC is also mediated via inhibition of MIF release.

Cell Line↗
PubMed1999

Thermodynamic instability of human lambda 6 light chains: correlation with fibrillogenicity.

Certain types of human light chains have the propensity to deposit pathologically as amyloid fibrils as evidenced by the preferential association of monoclonal lambda 6 proteins with AL amyloidosis. However, the molecular features that render such proteins amyloidogenic have not been elucidated. Based upon the demonstrated relationship between the thermodynamic stability of light chains and their propensity to aggregate in vitro, we have initiated studies where the thermodynamic properties and fibrillogenic potential of two recombinant (r) V lambda 6 molecules were compared. The first protein was generated from cDNA cloned from marrow-derived plasma cells from a patient (Wil) who had AL amyloidosis and renal amyloid deposits; the second was from a patient (Jto) with multiple myeloma in whom the lambda 6 protein was deposited not as amyloid but in the form of renal tubular casts. The thermodynamic stabilities of rV lambda 6Wil and -Jto were determined from chaotropic and thermal denaturation studies. Based upon the Delta GH2O, Delta H, Delta G25 degrees C, Tm, and Cm values, the rV lambda 6Wil was less stable than its nonamyloidogenic counterpart, rV lambda 6Jto. Measurement of fibril formation using a novel in vitro fibril forming assay demonstrated that although both rV lambda 6 proteins formed fibrils in vitro, Wil had a shorter lag time and exhibited faster kinetics under physiologic conditions. Comparative amino acid sequence analyses of these two components and other lambda 6 amyloid-associated light chains revealed that the Jto protein had certain primary structural features that we posit contributed to its increased stability and thus rendered this protein nonamyloidogenic. Our studies provide the first evidence that stabilizing interactions within the V L domain can influence the kinetics of light chain fibrillogenicity.

Amino Acid Sequence↗
PubMed1999

Oligomeric complexes link Rab5 effectors with NSF and drive membrane fusion via interactions between EEA1 and syntaxin 13.

SNAREs and Rab GTPases cooperate in vesicle transport through a mechanism yet poorly understood. We now demonstrate that the Rab5 effectors EEA1 and Rabaptin-5/Rabex-5 exist on the membrane in high molecular weight oligomers, which also contain NSF. Oligomeric assembly is modulated by the ATPase activity of NSF. Syntaxin 13, the t-SNARE required for endosome fusion, is transiently incorporated into the large oligomers via direct interactions with EEA1. This interaction is required to drive fusion, since both dominant-negative EEA1 and synthetic peptides encoding the FYVE Zn2+ finger hinder the interaction and block fusion. We propose a novel mechanism whereby oligomeric EEA1 and NSF mediate the local activation of syntaxin 13 upon membrane tethering and, by analogy with viral fusion proteins, coordinate the assembly of a fusion pore.

Adenosine Triphosphatases↗
PubMed1999

T lymphocytes induce endothelial cell matrix metalloproteinase expression by a CD40L-dependent mechanism: implications for tubule formation.

Neovascularization frequently accompanies chronic immune responses characterized by T cell infiltration and activation. Angiogenesis requires endothelial cells (ECs) to penetrate extracellular matrix, a process that involves matrix metalloproteinases (MMPs). We report here that activated human T cells mediate contact-dependent expression of MMPs in ECs through CD40/CD40 ligand signaling. Ligation of CD40 on ECs induced de novo expression of gelatinase B (MMP-9), increased interstitial collagenase (MMP-1) and stromelysin (MMP-3), and activated gelatinase A (MMP-2). Recombinant human CD40L induced expression of MMPs by human vascular ECs to a greater extent than did maximally effective concentrations of interleukin-1beta or tumor necrosis factor-alpha. Moreover, activation of human vascular ECs through CD40 induced tube formation in a three-dimensional fibrin matrix gel assay, an effect antagonized by a MMP inhibitor. These results demonstrated that activation of ECs by interaction with T cells induced synthesis and release of MMPs and promoted an angiogenic function of ECs via CD40L-CD40 signaling. As vascular cells at the sites of chronic inflammation, such as atherosclerotic plaques, express CD40 and its ligand, our findings suggest that ligation of CD40 on ECs can mediate aspects of vascular remodeling and neovessel formation during atherogenesis and other chronic immune reactions.

CD40 Antigens↗
PubMed1999

Measuring outcomes in children's rehabilitation: a decision protocol.

OBJECTIVE: To develop and test the feasibility and clinical utility of a computerized self-directed software program designed to enable service providers in children's rehabilitation to make decisions about the most appropriate outcome measures to use in client and program evaluation. DESIGN: A before-and-after design was used to test the feasibility and initial impact of the decision-making outcome software in improving knowledge and use of clinical outcome measures. SETTING: A children's rehabilitation center in a city of 50,000. PARTICIPANTS: All service providers in the children's rehabilitation center. Disciplines represented included early childhood education, occupational therapy, physical therapy, speech and language pathology, audiology, social work, and psychology. INTERVENTION: Using a conceptual framework based on the International Classification of Impairment, Disability, and Handicap (ICIDH), an outcome measurement decision-making protocol was developed. The decision-making protocol was computerized in an educational software program with an attached database of critically appraised measures. Participants learned about outcome measures through the program and selected outcome measures that met their specifications. The computer software was tested for feasibility in the children's rehabilitation center for 6 months. OUTCOME MEASURES: Knowledge and use of clinical outcome measures were determined before and after the feasibility testing using a survey of all service providers currently at the centre and audits of 30 randomly selected rehabilitation records (at pretest, posttest, and follow-up). RESULTS: Service providers indicated that the outcomes software was easy to follow and believed that the use of the ICIDH framework helped them in making decisions about selecting outcome measures. Results of the survey indicated that there were significant changes in the service providers' level of comfort with selecting measures and knowing what measures were available. Use of outcome measures as identified through the audit did not change. CONCLUSIONS: The "All About Outcomes" software is clinically useful. Further research should evaluate whether using the software affects the use of outcome measures in clinical practice.

Child↗
PubMed1999

Loss of olfactory function in dementing disease.

Alzheimer's (AD) patients show neuropathological changes in areas of the brain central to olfactory processing, suggesting the theoretical importance and potential diagnostic utility of investigating functional changes in olfaction in these patients. Persons with Down's Syndrome who live to the fourth decade develop neuropathological changes in the brain similar to those found in AD. A series of investigations have been conducted to assess olfaction function in both patients with Alzheimer's disease and persons with Down's Syndrome. Functional testing included olfactory threshold, odor identification, odor similarity judgements, odor recognition memory, odor recall, odor fluency. Both Alzheimer's patients and persons with Down's Syndrome showed significant impairment in olfactory function, with some measures showing more impairment than others in the early stages of the disease process. Longitudinal investigation of several of the measures indicated decreased function over time consonant with falling DRS scores. Normal controls who tested positive for the APOE4 allele showed impaired odor identification compared to those who were allele negative. Patients with Huntington's Disease showed olfactory functional impairments, although the degree of impairment differed from the cortical dementias for some of these tasks. The sensitivity and specificity of these assessments will be discussed in relation to analogous assessments in other sensory modalities.

Alzheimer Disease↗
PubMed1999

A demonstration of classical conditioning of the human eyeblink to an olfactory stimulus.

While acquisition of the eyeblink conditioned response to a variety of stimuli has been widely studied, it has yet to be established that humans will demonstrate a conditioned response to an olfactory stimulus. In this study we present data to show that humans will demonstrate a classically conditioned eyeblink response to an olfactory stimulus. Ten participants were tested in a delay conditioning procedure with an olfactory stimulus presented in a heated, humidified stream of air via an olfactometer, allowing the precise control over stimulus duration necessary for delay conditioning. Trials on which odor alone was presented were administered to four additional participants. Establishing that humans will demonstrate an eyeblink conditioned response to an olfactory stimulus will allow further exploration of the pathways involved in classical conditioning and associative learning, as well as an analysis of conditioning pathways across sensory modalities.

Adult↗
PubMed1999

Normal aging and odor intensity effects on the olfactory event-related potential.

Olfactory event-related potentials (OERPs) were recorded in 14 young and 14 older adults, with odor strength of isoamyl acetate manipulated to assess olfactory stimulus intensity. Young participants produced significantly larger N1/P2, N2/P3 amplitudes and shorter N1, P2 and N2 latencies than older participants. Medium- and high-odor concentrations elicited significantly shorter P2 and N2 latencies than the lowest concentration for both age groups. Odor concentration appears to affect the speed of olfactory stimulus information processing regardless of age.

Adult↗
PubMed1999

Individuals with Down's syndrome demonstrate abnormal olfactory event-related potentials.

OBJECTIVE: Recent research has demonstrated that individuals with Down's syndrome (DS) develop plaques and tangles in the brain similar to people with Alzheimer's disease. As a result, they show increased dementia and decreased olfactory functioning compared to healthy individuals. The olfactory event-related potential (OERP) has been used as an objective quantitative measure of olfactory functioning in normal and clinical populations. The present study investigated the utility of the latency and amplitude of the OERP components in examining olfactory dysfunction in DS individuals. METHODS: OERPs were recorded monopolarly at the Fz, Cz and Pz electrode sites, using amyl acetate at a 60 s inter-stimulus interval, from individuals with DS (mean age 26.0 years) and age-matched normal controls. Participants were screened for nasal health and odor thresholds were assessed. Dementia was assessed using the dementia rating scale (DRS). RESULTS: Results indicate that DS subjects have significantly longer latencies in the sensory (N1, P2, and N2) and cognitive (P3) components of the OERP than normal controls. Odor threshold was significantly associated with sensory OERP components. In addition, DS subjects with a higher level of dementia showed significantly longer P3 latencies than those with lower dementia levels. CONCLUSIONS: The study suggests that the OERP may be a useful measure of olfactory dysfunction in DS which may precede developing dementia in this population.

Adult↗
PubMed1999

Olfactory P3 in young and older adults.

Olfactory event-related potentials (OERPs) were recorded monopolarly at the Fz, Cz, and Pz electrode sites in 16 young adults and 16 older adults to assess aging effects on the olfactory P3. Amyl acetate was used to elicit the OERPs, with an intertrial interval of 45 s. Young adults produced significantly larger P3 amplitudes and shorter P3 peak latencies than older adults. The olfactory P3 response appears to be sensitive to age-related changes in the olfactory system and may reflect cognitive slowing in the central nervous system.

Adult↗
PubMed1999

Odor detection, learning, and memory in Huntington's disease.

We compared 7 mildly affected Huntington's disease (HD) patients to 7 age- and education-matched healthy controls (NC) on an odor detection test, the California Odor Learning Test, and the California Verbal Learning Test. Results demonstrated that odor detection sensitivity, but not group membership, accounted for significant variance in total olfactory learning. Both groups learned fewer items in the olfactory modality compared to the verbal modality, but retained a similar amount following a delay. No group differences were demonstrated for verbal recognition discriminability, but the HD group demonstrated significantly impaired odor recognition discriminability. Finally, odor detection provided excellent classification sensitivity and specificity between the patients and controls, suggesting that olfactory testing may provide a sensitive measure of the early disease process in HD.

Cognition Disorders↗
PubMed1999

The 20% rule: a simple, instantaneous radioactivity measurement defines cure and allows elimination of frozen sections and hormone assays during parathyroidectomy.

BACKGROUND: Although primary hyperparathyroidism is a physiologic disease, surgeons rely on anatomical characteristics (gross and histologic) to determine appropriate operative decisions. After the development of radioguided parathyroidectomy, we hypothesized that the amount of radioactivity contained within resected tissue would be the only information needed to establish the nature of the tissue and to determine a cure for the disease. METHODS: A total of 1290 tissue specimens were obtained from 345 patients who had sporadic primary hyperparathyroidism. Ex-vivo radioactivity, in counts per second, was measured in parathyroid and other tissues within 3.5 hours of sestamibi injection. Background radioactivity was measured after tissue excision, and ratios were calculated. RESULTS: Lymph nodes, normal parathyroids, and fat never contained more than 2.2% of background radioactivity, whereas thyroid and hyperplastic parathyroids contained 5.5% and 7.5%, respectively, and never more than 16%. In contrast, adenomas contained 59% +/- 9% of background radioactivity (P < .000001 vs all other tissues), with a range of 18% to 136%. CONCLUSIONS: Radioactive ratios are an instantaneous measure of metabolic activity, thereby determining parathyroid function. Any excised tissue containing more than 20% of background radioactivity in a patient with a positive sestamibi scan result is a solitary parathyroid adenoma. This alleviates the need to identify other glands, obtain frozen sections, or measure serum parathyroid hormone levels intraoperatively.

Adenoma↗