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Biomedical subjects

C Murphy

Publications and source records attributed to C Murphy.

At least 37 records · Page 2Linked to original sources

Patients' expectations of recovery following stroke: a qualitative study.

PURPOSE: Patients and carers frequently express disappointment with the extent of recovery achieved at the point of discharge from physiotherapy. Research has suggested that high expectations of recovery may be encouraged by physiotherapists. This study examined the information exchanged between physiotherapists and patients in relation to recovery following stroke in order to explore this issue. METHODS: The study comprised in-depth longitudinal case studies of 16 patients with a first incident stroke. Qualitative interviews were conducted with patients and their physiotherapists to explore their understandings and expectations of recovery and of physiotherapy at three time points. Patients were assessed for deficits of movement, function and mood at the same three stages and observations of out-patient sessions were also conducted. Qualitative data were analysed using thematic analysis. The assessment data were analysed using descriptive and comparative statistics. RESULTS: Data indicated deficits of movement improved significantly between the first and third assessments. The qualitative data showed that physiotherapists did not encourage over-optimistic expectations of recovery through the verbal information they provided to patients. Nevertheless patients did maintain high expectations of recovery throughout the three-month post-stroke period. CONCLUSION: Improved communication strategies, informed by an evidence base of recovery, should be used to encourage realistic expectations of physiotherapy without destroying the process of active participation and skill acquisition.

Adult↗

Clinical presentation of inhalational anthrax following bioterrorism exposure: report of 2 surviving patients.

The use of anthrax as a weapon of biological terrorism has moved from theory to reality in recent weeks. Following processing of a letter containing anthrax spores that had been mailed to a US senator, 5 cases of inhalational anthrax have occurred among postal workers employed at a major postal facility in Washington, DC. This report details the clinical presentation, diagnostic workup, and initial therapy of 2 of these patients. The clinical course is in some ways different from what has been described as the classic pattern for inhalational anthrax. One patient developed low-grade fever, chills, cough, and malaise 3 days prior to admission, and then progressive dyspnea and cough productive of blood-tinged sputum on the day of admission. The other patient developed progressively worsening headache of 3 days' duration, along with nausea, chills, and night sweats, but no respiratory symptoms, on the day of admission. Both patients had abnormal findings on chest radiographs. Non-contrast-enhanced computed tomography of the chest showing mediastinal adenopathy led to a presumptive diagnosis of inhalational anthrax in both cases. The diagnoses were confirmed by blood cultures and polymerase chain reaction testing. Treatment with antibiotics, including intravenous ciprofloxacin, rifampin, and clindamycin, and supportive therapy appears to have slowed the progression of inhalational anthrax and has resulted to date in survival.

Anthrax↗

Patients' health-related quality of life and utilities associated with different stages of amyotrophic lateral sclerosis.

OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a devastating disease that has serious consequences in terms of impairments and disabilities, which are expected to impact on health-related quality of life (HRQL). The aim of the present study was to assess self-reported health status and HRQL, as well as patients' own valuation of their present health state in a sample of patients with different levels of severity of ALS. METHODS: Structured interviews were conducted with 77 patients with different levels of disease severity. Patients completed a disease-specific health status measure (ALSAQ-40), a generic health status measure (EuroQol EQ-5D), visual analogue scale (VAS) rating of current health and a standard gamble (SG) exercise to provide health state utilities for their own health state. RESULTS: The results from the ALSAQ-40 and EQ-5D descriptive system indicate that patients' HRQL decreases systematically with increasing severity of disease. Patients' mean VAS rating of their own health ranged from 0.74 for stage 1 (early) disease severity, to 0.37 for stage 4 (late stage) disease severity. Utilities elicited via SG were systematically higher than VAS scores and ranged from a mean of 0.79 for stage 1 disease severity to a mean of 0.45 for stage 4 disease severity.

Activities of Daily Living↗

Structural features of the Abeta amyloid fibril elucidated by limited proteolysis.

Although the gross morphology of amyloid fibrils is fairly well understood, very little is known about how the constituent polypeptides fold within the amyloid folding motif. In the experiments reported here, we used trypsin and chymotrypsin to conduct limited proteolysis studies on synthetic amyloid fibrils composed of the Alzheimer's disease peptide Abeta(1-40). In both reactions, the extreme N-terminal proteolytic fragment is released from fibrils as rapidly as it is from the Abeta monomer, while other proteolytic fragments are generated much more slowly. Furthermore, aggregated material isolated by centrifugation of intermediate digestion time points from both proteases contains, in addition to full-length material, peptides that possess mature C-termini but truncated N-termini. These data strongly suggest that the N-terminal region of Abeta is not involved in the beta-sheet network of the amyloid fibril, while the C-terminus is essentially completely engaged in protective-presumably beta-sheet-structure. In both digests, release of the extreme N-terminal fragments of Abeta(1-40) reaches plateau values corresponding to about 80% of the total available Abeta. This suggests that there are two classes of peptides in the fibril: while the majority of Abeta molecules have an exposed N-terminus, about 20% of the peptides have an N-terminus that is protected from proteolysis within the fibril structure. The most likely cause of this heterogeneity is the lateral association of protofilaments into the fibril structure, which would be expected to generate a unique environment for those Abeta N-termini located at protofilament packing interfaces and/or in the interior core region between the packed protofilaments. This suggests that the N-terminal region of Abeta, while not directly involved in the beta-sheet network of the fibril, may contribute to fibril stability by participating in protofilament packing.

Amino Acid Sequence↗

Codeposition of apolipoprotein A-IV and transthyretin in senile systemic (ATTR) amyloidosis.

Protein material was extracted from amyloid-rich sections of formalin-fixed and paraffin-embedded heart tissue from an individual with senile systemic amyloidosis, known to contain wild-type transthyretin as major amyloid fibril protein. Amino acid sequence analysis of tryptic peptides of this material revealed in addition to transthyretin sequences, also amino acid sequence corresponding to an N-terminal fragment of apolipoprotein A-IV. In immunohistochemistry, an antiserum to a synthetic apolipoprotein A-IV peptide labeled amyloid specifically. This peptide formed spontaneously amyloid-like fibrils in vitro and enhanced fibril formation from wild-type transthyretin. We conclude that several apolipoproteins, including apolipoprotein A-IV, may be important minor amyloid constituents, promoting fibril formation.

Age Factors↗

Glutamate is a mediator of neurotoxicity in secretions of activated HIV-1-infected macrophages.

We sought to identify neurotoxin(s) secreted by HIV-1-infected mononuclear phagocytes that could contribute to the pathophysiology of HIV-1-associated dementia (HAD). Neurotoxic factors were characterized in batches of conditioned media (CM) from human monocyte-derived macrophages (MDM) infected with HIV-1(ADA) and/or activated with lipopolysaccharide (LPS). All of the neurotoxicity was: present in the <3000-Da fraction; blocked by 5 microM MK801; and not trypsin sensitive or extractable into polar organic solvents. Glutamate measured in CM accounted for all neurotoxic effects observed from HIV/LPS CM in astrocyte-poor neuronal cultures and may contribute to the pathophysiology of HIV-1-associated dementia.

AIDS Dementia Complex↗

Interferon gamma and prostaglandin in BSE-infected cattle.

Suspect field cases of BSE infection (displaying clinical signs) were examined for possible alterations of cytokine/autacoid plasma levels and were compared to control cases (not displaying clinical signs of BSE infection). Interferon gamma (IFN-gamma) plasma levels were demonstrated as being elevated in all suspected field cases of BSE infection (irrespective of BSE status; determined via postmortem histopathological examination). We demonstrated that plasma IFN-gamma levels were significantly (P<0.005) higher in suspect cases of BSE infection than in control cases. BSE-positive prostaglandin-E(2), (PGE(2)) plasma levels were demonstrated as being elevated 1.25-fold above BSE-negative cases and 2.22-fold above control cases. No significant (P>0.5) increase in PGE(2)plasma levels was recorded between BSE-positive and -negative. IFN-gamma and PGE(2)plasma levels were examined using commercially available ELISA assay. The results presented in this publication are the first demonstration of alteration in immune state in animals with BSE.

Animals↗

A short-term inpatient program for agitated demented nursing home residents.

OBJECTIVE: This case series describes the various contributors of disruptive behavior in demented nursing home residents and outlines the necessary steps to identify and treat them. DESIGN: Evaluation of overall clinical improvement and agitation at discharge from the hospital and at follow-up. SETTING: Nursing home residents consecutively admitted to the geriatric psychiatry service of a psychiatric university hospital in the New York metropolitan area. PATIENTS: 15 elderly demented nursing home residents with agitation. MEASURES: Overall clinical improvement was assessed with the 'global assessment of functioning scale'. Agitation was evaluated with the 'brief agitation rating scale' and the 'nursing home scale for agitation'. Medication side-effects were measured with the 'Simpson-Angus scale' and the 'abnormal involuntary movement scale'. RESULTS: The patients showed significantly more overall clinical improvement at discharge compared with admission. Additionally, agitation scores were significantly lower at discharge and at follow-up compared with admission. CONCLUSION: A comprehensive medical and neurological assessment, an accurate identification of comorbid psychopathology, evaluation of drug toxicity, and a thorough history of psychotropic medication trials are essential steps for a successful treatment.

Activities of Daily Living↗

Age-related changes in olfactory processing detected with olfactory event-related brain potentials using velopharyngeal closure and natural breathing.

Previous olfactory event-related potential (OERP) studies often employed the Velopharyngeal Closure (VC) method, which prevents respiratory air flow in the nose during odor presentation. However, the use of VC has limited the application of OERPs to populations able to perform this artificial breathing technique. The present study investigated the effects of Natural Breathing (NB) in comparison to VC on OERP latency and amplitude in young (mean age: 24 years) and elderly (mean age: 71 years) adults. OERPs were recorded from three midline scalp electrodes (Fz, Cz, Pz) for 15 trials in each breathing condition with an interstimulus interval of 3.5 min, using amyl-acetate as stimulus. Subjects were asked to report perceived stimulus intensity. A thermistor placed inside one nostril monitored nasal respiration and performance of VC. In the NB condition, subjects were instructed to breathe normally through mouth and nose, while stimulus presentation occurred during inspiration. In both breathing conditions, elderly subjects showed significantly smaller N1-P2 and N1-P3 interpeak amplitudes and longer latencies for N1, P2, P3 than younger subjects. VC generated significantly larger N1-P2 amplitudes across all electrode sites, whereas Natural Breathing produced a trend towards shorter P3 latencies. No significant interaction was found between age and breathing technique. The present investigation showed that the OERP is a sensitive measure for detecting age-related changes in olfactory function regardless of breathing technique.

Adult↗

Characterization of protein C receptor expression in monocytes.

Many sequelae associated with endotoxaemic-induced shock result from excessive production of the cytokine mediators, tumour necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1) and IL-6 from lipopolysaccharide (LPS)-activated monocytes. Protein C (PC)/activated protein C (APC) has potent cytokine-modifying properties and is protective in animal models and human clinical trials of sepsis. The precise mechanism by which this anti-inflammatory response is achieved remains unknown; however, the recently described endothelial protein C receptor (EPCR) appears to be essential for this function. The pivotal role that monocytes play in the pathophysiology of septic shock led us to investigate the possible expression of a protein C receptor on the monocyte membrane. We used similarity algorithms to screen human sequence databases for paralogues of the EPCR but found none. However, using reverse transcription-polymerase chain reaction (RT-PCR), we detected an mRNA transcribed in primary human monocytes and THP1 cells that was identical to human EPCR mRNA. We also used immunocytochemical analysis to demonstrate the expression of a protein C receptor on the surface of monocytes encoded by the same gene as EPCR. These results confirm a new member of the protein C pathway involving primary monocytes. Further characterization will be necessary to compare and contrast its biological properties with those of EPCR.

Blood Coagulation Factors↗

Dual function of rhoD in vesicular movement and cell motility.

The trafficking of intracellular membranes requires the coordination of membrane-cytoskeletal interactions. Rab proteins are key players in the regulation of vesicular transport, while Rho family members control actin-dependent cell functions. We have previously identified a rho protein, rhoD, which is localized to the plasma membrane and early endosomes. When overexpressed, rhoD alters the actin cytoskeleton and plays an important role in endosome organization. We found that a rhoD mutant exerts its effect on early endosome dynamics through an inhibition in organelle motility. In these studies, the effect of rhoD on endosome dynamics was evaluated in the presence of a constitutively active, GTPase-deficient mutant of rab5, rab5Q79L. As rab5Q79L itself stimulates endosome motility, rhoD might counteract this stimulation, without itself exerting any effect in the absence of rab5 activation. We have now addressed this issue by investigating the effect of rhoD in the absence of co-expressed rab5. We find that rhoDG26V alone alters vesicular dynamics. Vesicular movement, in particular the endocytic/recycling circuit, is altered during processes such as cell motility. Due to the participation of vesicular motility and cytoskeletal rearrangements in cell movement and the involvement of rhoD in both, we have addressed the role of rhoD in this process and have found that rhoDG26V inhibits endothelial cell motility.

Actin Cytoskeleton↗

fMRI activation in response to odorants orally delivered in aqueous solutions.

During food intake flavor perception results from simultaneous stimulation of the gustatory, olfactory and trigeminal systems. Olfactory stimulation occurs mainly through the retronasal pathway and the resulting perception is often interpreted as a taste perception, thus leading to the well-known sensory confusion between taste and olfaction. The present experiment was designed to study, with functional magnetic resonance imaging (fMRI), the cortical representation of olfactory perception in humans in response to retronasal stimulation by odorants delivered in aqueous solution. Psychophysical evaluation confirmed that the stimuli acted as pure olfactory stimuli through the retronasal pathway and did not present any taste component. Results showed activation in all brain regions previously described with neuroimaging techniques using olfactory stimulation with an odorized air flow. Piriform and orbitofrontal cortex were found activated as well as the hippocampal region, the amygdala, the insular lobe, the cingulate gyrus and the cerebellum. These results demonstrate the feasibility of efficiently stimulating the olfactory system in an fMRI scanner through the retronasal pathway with liquids delivered to the oral cavity. The presentation of olfactory stimuli in liquids to the mouth is a realistic model for the study of food-related flavor perception. This stimulation protocol furthermore allows presenting taste and olfactory stimuli separately or combined, thus allowing for direct comparisons between single modality representation, taste or olfaction, and representation of multi-modality mixtures.

Administration, Oral↗

Development of a Canadian standardized protocol for subtyping methicillin-resistant Staphylococcus aureus using pulsed-field gel electrophoresis.

A panel of 24 methicillin-resistant Staphylococcus aureus strains was distributed to 15 laboratories in Canada to evaluate their in-house pulsed-field gel electrophoresis (PFGE) protocols and interpretation criteria. Attempts to compare fingerprint images using computer-aided analysis were not successful due to variability in individual laboratory PFGE protocols. In addition, individual site interpretation of the fingerprint patterns was inadequate, as 7 of 13 sites (54%) made at least one error in interpreting the fingerprints from the panel. A 2-day standardized PFGE protocol (culture to gel image) was developed and distributed to all of the sites. Each site was requested to use the standardized protocol on five strains from the original panel. Thirteen sites submitted gel images for comparisons. The protocol demonstrated excellent reproducibility and allowed interlaboratory comparisons with Molecular Analyst DST software (Bio-Rad) and 1.5% band tolerance.

Bacterial Typing Techniques↗

Executive dysfunction and disability in elderly patients with major depression.

The authors studied 126 elderly patients without dementia and with unipolar major depression. Impairment in instrumental activities of daily living (IADLs) was significantly associated with age (P<0.0001), gender (P<0.001), medical burden (P=0.013), severity of depression (P=0.01), initiation/perseveration (IP; P=0.035), and IP x depression (P=0.029). Depression was associated with IADL impairment mainly in patients with impaired IP. Among the cognitive impairments, IP-only contributed significantly to IADL impairment, whereas attention, construction, conceptualization, and memory did not. Attention to executive function and disability may guide clinical management and lead to development of innovative pharmacological and behavioral interventions.

Activities of Daily Living↗