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Biomedical subjects

K Murray

Publications and source records attributed to K Murray.

At least 37 records · Page 2Linked to original sources
PubMed2001

Unusual presentation of thoracic Pneumocystis carinii infection in a patient with acquired immunodeficiency syndrome.

Pleura-based masses and hilar adenopathy were seen on a chest radiograph of a patient with acquired immunodeficiency syndrome who had a history of Pneumocystis carinii infection. The differential diagnosis of such a presentation is discussed in light of atypical and extrapulmonary manifestations of P. carinii infection in a patient receiving prophylaxis with dapsone.

AIDS-Related Opportunistic Infections↗
PubMed2001

Relationship between change in balance and self-reported handicap after vestibular rehabilitation therapy.

BACKGROUND AND PURPOSE: Dizziness and balance problems are two commonly reported symptoms of vestibular system disease, with subsequent alterations in lifestyle and reports of physical, functional and emotional handicap. Vestibular rehabilitation therapy (VRT) was developed to improve the functional status of patients with vestibular dysfunction. The aim of the present study was to investigate the relationship between change in balance performance and change in self-rated handicap after a four-week home exercise programme in 16 subjects with chronic vestibular disease. METHOD: Before and after the treatment intervention, balance was tested by use of a Smart Balance Master (SBM) system (Neurocom International, Clackamas, OR, USA) and self-rated handicap was measured by use of the Dizziness Handicap Inventory (DHI). RESULTS: Significant improvement was observed in both the SBM (p < 0.001) and DHI (p = 0.003) scores over the testing period. A moderately strong negative correlation existed between change in SBM and DHI scores (Spearman's r = -0.6). Further analysis using the DHI subscales indicated, however, that the emotional component showed no significant change over time, and a poor correlation with change in balance scores (Spearman's r = -0.39). CONCLUSIONS: These results indicate that a home-based exercise programme can significantly improve balance abilities in people with chronic vestibular dysfunction, but that outcomes may be enhanced by addressing the emotional issues associated with their disability.

Adult↗
PubMed2001

Evaluating a telemedicine system to assist in the management of dermatology referrals.

BACKGROUND: Teledermatology systems fall into two categories: live video or store-and-forward. In the former, video-conferencing equipment is used to connect a patient with a remote consultant. This method has been evaluated as an aid to dermatology, but it is expensive both in terms of capital and running costs. Video consultations are generally longer than conventional ones and harder to schedule. Some authors have considered store-and-forward as an alternative to live video: instead of a consultation, specialists could make a rapid inspection of a transmitted still image. OBJECTIVES: A study was conducted to evaluate the role of telemedicine in the dermatology outpatients department of a district general hospital (Whittington Hospital NHS Trust, London, U.K.). METHODS: One hundred and ninety-four patients were seen by one of two consultant dermatologists. A nurse used a video camera to store digital images of each patient's problem and compiled a history from the GP's referral letter. The images were reviewed 13 months later by both dermatologists; they recorded a provisional diagnosis and an assessment of how urgent an appointment would have been made given the information provided by the system. A third consultant graded the level of agreement between the telemedicine diagnoses and the face-to-face consultations. RESULTS: High levels of agreement were found between the diagnoses of the dermatologists using the system to inspect images and those of the dermatologist who saw the patients (77%). Consultants using the system recommended fewer urgent appointments (32% compared with 64%) and felt that in 31% of cases the patient did not need to be seen. In 15% of these cases (5% of the total), however, their diagnosis differed significantly from that of the consultant who saw the patient. Had the system been in use, 14% of patients conventionally assigned a non-urgent appointment would have been seen urgently. CONCLUSIONS: The images allowed a reasonably accurate diagnosis. The software was not reliable (six cases could not be viewed), or easy to use (it took approximately an hour to view 20 cases) but an improved version could be used in triaging outpatient appointments.

Correspondence as Topic↗
PubMed2001

Autologous stem cell transplantation for paediatric-onset polyarteritis nodosa: changes in autoimmune phenotype in the context of reduced diversity of the T- and B-cell repertoires, and evidence for reversion from the CD45RO(+) to RA(+) phenotype.

We have studied immune reconstitution in a patient with paediatric-onset polyarteritis nodosa treated with high-dose immunosuppressive agents followed by stem cell rescue. The patient developed several new autoimmune phenomena over the 18 months after immunosuppression and stem cell rescue. Flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR) heteroduplex and isotype-specific RT-PCR analysis of immunoglobulin expression showed that the T- and B-cell repertoires were highly restricted in the first few months after treatment. The dominant T-cell clones seen after reconstitution were persistently expanded, were different from those which could be demonstrated before autologous stem cell transplantation, and were in the CD8(+) population. Our data also show that 12 months after treatment these expanded T-cell clones were within the CD45RA(+) population, suggesting that reversion from the CD45RO(+) to the CD45RA(+) phenotype had occurred in vivo.

Adult↗
PubMed2000

Validation of the RTOG recursive partitioning analysis (RPA) classification for brain metastases.

PURPOSE: The Radiation Therapy Oncology Group (RTOG) previously developed three prognostic classes for brain metastases using recursive partitioning analysis (RPA) of a large database. These classes were based on Karnofsky performance status (KPS), primary tumor status, presence of extracranial system metastases, and age. An analysis of RTOG 91-04, a randomized study comparing two dose-fractionation schemes with a comparison to the established RTOG database, was considered important to validate the RPA classes. METHODS AND MATERIALS: A total of 445 patients were randomized on RTOG 91-04, a Phase III study of accelerated hyperfractionation versus accelerated fractionation. No difference was observed between the two treatment arms with respect to survival. Four hundred thirty-two patients were included in this analysis. The majority of the patients were under age 65, had KPS 70-80, primary tumor controlled, and brain-only metastases. The initial RPA had three classes, but only patients in RPA Classes I and II were eligible for RTOG 91-04. RESULTS: For RPA Class I, the median survival time was 6. 2 months and 7.1 months for 91-04 and the database, respectively. The 1-year survival was 29% for 91-04 versus 32% for the database. There was no significant difference in the two survival distributions (p = 0.72). For RPA Class II, the median survival time was 3.8 months for 91-04 versus 4.2 months for the database. The 1-year survival was 12% and 16% for 91-04 and the database, respectively (p = 0.22). CONCLUSION: This analysis indicates that the RPA classes are valid and reliable for historical comparisons. Both the RTOG and other clinical trial organizers should currently utilize this RPA classification as a stratification factor for clinical trials.

Age Factors↗
PubMed2000

Bronchopulmonary and mediastinal leishmaniasis: an unusual clinical presentation of Leishmania donovani infection.

We describe a case of unusual leishmaniasis in a Sudanese man with a history of progressively enlarging granulomatous mediastinal lymphadenopathy, worsening hemoptysis, and an intense mucosal granulomatous inflammatory response in the large bronchi. Leishmania donovani DNA was detected in bronchial biopsies by polymerase chain reaction. This is a novel description of human leishmanial infection in an immunocompetent patient involving this anatomical site. The patient's condition improved clinically, spirometrically, and radiologically after a course of treatment with amphotericin B. The cell-mediated immune response was analyzed before, during, and after successful antileishmanial chemotherapy.

Adult↗
PubMed2000

Biochemical and compositional analyses of recombinant lecithin:cholesterol acyltransferase (LCAT) obtained from a hepatic source.

Lecithin:cholesterol acyltransferase (LCAT) is an important plasma glycoprotein which plays a central role in lipid metabolism. This protein is responsible for generation of cholesteryl esters in plasma and it has been proposed to play a pivotal role in the reverse cholesterol transport pathway. Structural and functional studies of LCAT have employed various expression systems for production of recombinant LCAT (rLCAT). However, recent studies have shown some differences in the oligosaccharide structure and composition of rLCAT. In this study, we have generated a new hepatic based expression system using McArdle-RH7777 (Mc-7777) cells to produce a recombinant protein most similar to human plasma LCAT. The expressed glycoprotein was compared to the LCAT expressed in previously characterized baby hamster kidney (BHK) cells. Both proteins were compared on the basis of their carbohydrate structure and composition as well as their functional properties. Although the functional properties of both glycoproteins were similar, the carbohydrate structure was significantly different. While BHK-LCAT contained bi-, tri-, and tetraantennary structures, Mc-7777 LCAT presented only biantennary oligosaccharide structures. The difference in glycosylation pattern of rLCAT from Mc-7777 and BHK cells underlines the importance of appropriate expression system, both in vivo and in vitro.

Animals↗
PubMed2000

On a roll: the process of initiation and cessation of problem gambling among adolescents.

As gambling becomes more accessible and acceptable in society, problems associated with gambling and gaming have begun to affect ever increasing numbers of adolescents. Although restricted from most forms of gambling by law, many adolescents are finding a path into problem gambling. Some are becoming compulsive gamblers early in their gambling career, facing a future filled with consequences and problems. Understanding the pathway or process by which these adolescents become engaged in gambling behavior and how they can extricate themselves from this addictive behavior can enhance the efficiency and effectiveness of our interventions. This article offers a perspective on the initiation and cessation of compulsive gambling using the basic elements of the process of intentional behavior change outlined in the Stages of Change from the Transtheoretical Model. The process of initiation of a problematic behavior is similar to the process of modification or cessation of a problematic behavior in terms of these stages of change. With adolescents it is important to distinguish between the process of initiation, which has implications for prevention of gambling problems, and the process of cessation, which often necessitates the assistance of treatment. Creating interventions that parallel the process of change offers the potential for personalizing and potentiating efforts to reduce the prevalence and consequences associated with compulsive or pathological and problem gambling. Application of this model to gambling behavior offers a heuristic that is intriguing and requires substantiation through rigorous research.

Journal Article↗
PubMed2000

Continuous postoperative catheter irrigation is not necessary for the treatment of suppurative flexor tenosynovitis.

The records of 75 patients admitted with pyogenic flexor tenosynovitis at two academic centers were reviewed. The functional outcomes of patients who received intraoperative irrigation only (n = 20) and those that had both intraoperative irrigation and continuous postoperative irrigation (n = 55) were compared. There were no statistically significant differences between the outcomes in the two groups.

Adolescent↗
PubMed2000

Social and gender variation in the prevalence, presentation and general practitioner provisional diagnosis of chest pain.

OBJECTIVES: To describe the prevalence of Rose angina and non-exertional chest pain in men and women in socioeconomically contrasting areas; to describe the proportions of men and women who present with the symptom of chest pain and who receive a provisional general practitioner diagnosis of coronary heart disease; to assess the effects of gender and deprivation. DESIGN: Two random general population samples in socially contrasting areas were surveyed using the Rose angina questionnaire: the case notes of people identified with chest pain were reviewed. SETTING: Glasgow conurbation. PARTICIPANTS: 1107 men and women, aged 45-64, with chest pain. OUTCOME MEASURES: Prevalence of Rose angina and non-exertional chest pain; the proportions who had presented with chest pain and received a general practitioner's provisional diagnosis of coronary heart disease. RESULTS: There was no difference between social groups in the prevalence of all chest pain but a greater proportion of those in deprived groups had Rose angina and a greater proportion of these had the more severe grade. The proportion of people who had presented with chest pain was higher among socioeconomically deprived groups but there was no difference in the proportions receiving a general practitioner provisional diagnosis of coronary heart disease. Men were more likely to present with chest pain than women and were more likely to receive a provisional general practitioner diagnosis of coronary heart disease. CONCLUSIONS: No evidence was found of social differences in patient presentation or general practitioner diagnosis that might explain reported variations in uptake of cardiology services. In contrast, gender variation may originate in part from differences in patient presentation and general practitioner diagnosis. Further investigation of socioeconomic variations in uptake of cardiology services should focus later in the care pathway, on general practitioner referral patterns and clinical decisions taken in secondary care.

Age Distribution↗
PubMed2000

For the love of the children: the coming out process for lesbian and gay parents and stepparents.

This research investigated the coming out decision and process for 23 lesbian and gay custodial stepfamilies. We argue that lesbian and gay stepfamilies represent a unique type of family, distinct from heterosexual stepfamilies and from lesbian and gay families who have children within the context of a lesbian or gay relationship. The coming out process is one developmental challenge that distinguishes lesbian and gay stepfamilies from these other types. Through interviews with both lesbian and gay parents and stepparents we explored their coming out process to significant others: the children, families of origin and ex-spouses. We discuss those factors influencing the decision and the consequences that developed in light of these decisions. Findings show that the coming out process for lesbian and gay co-parents is a flexible and familial one, primarily influenced by and centered around the needs of the children.

Decision Making↗
PubMed2000

Why are growth factors important in oligodendrocyte physiology?

Recent studies in chicken, rodents and transgenic mice have provided new insight on the nature of factors essential to oligodendrocyte development. Here we first review how sonic hedgehog (shh) graded signalling induces emergence of oligodendrocytes in the embryonic spinal cord from birds to man. We then discuss the way in which thyroid hormone successively signals different thyroid receptors to control fate determination, growth and differentiation in the oligodendrocyte lineage. Platelet-derived growth factor (PDGF) is a potent regulator of oligodendrocyte progenitor (OP) migration and proliferation, while insulin-like growth factor 1 (IGF-1) acts both on neurons and myelin-forming cells to promote myelination. The balance between OP proliferation and differentiation appears to be controlled by different sets of growth factors locally synthesized in the central nervous system (CNS) as well as glutamate. In experimental models of multiple sclerosis (MS), the neuregulin isoform glial growth factor 2, IGF-1 and some neurotrophins can promote remyelination after an episode of inflammatory demyelination. A future challenge is to determine how to induce multipotential neural precursors to generate migratory OP and enhance the remyelination process in the adult CNS.

Animals↗
PubMed2000

Pharmacokinetics, pharmacodynamics, allometry, and dose selection of rPSGL-Ig for phase I trial.

rPSGL-Ig is a recombinant, soluble, and chimeric form of P-selectin glycoprotein ligand-1, which is developed as an antagonist to P-selectin. Allometric and pharmacokinetic/pharmacodynamic modeling was used to select doses for human clinical trials. Pharmacokinetic parameters of rPSGL-Ig such as clearance (CL), volume of distribution (Vc), and t(1/2) across animal species are well described by power functions with body weight as an independent variable. The power functions for CL, Vc, and t(1/2) were CL = 0.37. W(0.93) ml/h (r(2) = 0.94), Vc = 45.0.W(1.064) ml (r(2) = 0.988), and t(1/2) = 190.W(0.159) h (r(2) = 0.75), respectively. These functions provide a means to predict pharmacokinetics of rPSGL-Ig in humans. For a 70-kg human, the values of CL, Vc, and t(1/2) are predicted to be 19.9 ml/h, 4138 ml, and 15.5 days, respectively. The predicted pharmacokinetics in humans is used in conjunction with pharmacological data to estimate appropriate doses for clinical trials. The doses that may provide potential effects in humans range from 0.13 to 4.7 mg/kg. The predicted doses produce concentrations above those that are associated with efficacy in animal disease models and, maintain concentrations above the EC(50) of in vitro binding between rPSGL-Ig and stimulated human platelets. Hence, rPSGL-Ig in clinical trials may provide therapeutic activities for P-selectin-mediated diseases.

Algorithms↗
PubMed2000

Electrodermal activity and temperament in preschool children.

This study had two objectives: To examine poorly understood patterns of young children's electrodermal reactivity and to test the hypothesis that this reactivity reflects individual differences in the behavioral inhibition system (BIS). We recorded skin conductance responses (SCRs) from 92 4-year-old children during a laboratory session that encompassed physiological and psychological stimuli. Physiological stimuli (breaths), moderately loud to loud sounds (expected and unexpected) and, to a lesser extent, stimuli with psychological significance elicited clear SCRs. Induction of psychological conflict and exposure to emotional film clips for the most part did not elicit increases in skin conductance (SC). Children's temperament dimensions of fearfulness and effortful (or inhibitory) control--two components of the BIS--were assessed using robust observational batteries at age 2 and 4 years. The theoretically expected correlations between overall SC lability (reflecting SC levels) and both dimensions of temperament were significant, albeit modest and limited to the contemporaneous measures at age 4.

Arousal↗
PubMed1999

Two distinct segments of the hepatitis B virus surface antigen contribute synergistically to its association with the viral core particles.

The long surface antigen polypeptide (L-HBsAg) of hepatitis B virus (HBV) is believed to mediate contact between the virus envelope and nucleocapsid protein (HBcAg). The N and C termini of L-HBsAg were shortened progressively in order to define the minimum contiguous sequence of amino acids that contains the residues necessary for association with HBcAg. The resulting mutants were expressed in rabbit reticulocyte lysates and their interaction with HBcAg was examined with an immunoprecipitation assay and an equilibrium binding assay in solution to give relative dissociation constants. Binding of HBcAg particles by L-HBsAg displayed two widely differing dissociation constants, indicating two distinct binding sites between the molecules. The two distinct sites, one located between residues 24 and 191 and the other between residues 191 and 322 of L-HBsAg, contribute synergistically to high-affinity binding to HBcAg, but disruption of either of these segments resulted in a much weaker interaction showing only one dissociation constant. Inhibition of the interaction by peptides that bind to the tips of the nucleocapsid spikes differentiated contacts in HBcAg for the two binding domains in L-HBsAg and implied that the amino-terminal binding domain contacts the tips of the HBcAg spikes. Analysis of specific single amino acid mutants of L-HBsAg showed that Arg92 played an important role in the interaction.

Animals↗
PubMed1999

The core antigen of hepatitis B virus as a carrier for immunogenic peptides.

The core antigen of hepatitis B virus (HBcAg) made in Escherichia coli yields particles that closely resemble the viral nucleocapsid. Extensive modifications can be made to the primary structure of HBcAg without impairing particle assembly. This enables other peptide sequences, including very long sequences, to be added, substituted, or inserted into the nucleocapsid subunit while retaining the ability to form highly immunogenic particles. These also retain the T cell epitopes of HBcAg and constitute powerful delivery systems for a diverse range of immunogenic epitopes and have significant potential for development of multicomponent vaccines.

Animals↗
PubMed1998

Peptides that block hepatitis B virus assembly: analysis by cryomicroscopy, mutagenesis and transfection.

Peptides selected to bind to hepatitis B virus (HBV) core protein block interaction with the long viral surface antigen (L-HBsAg) in vitro. High resolution electron cryomicroscopy showed that one such peptide binds at the tips of the spikes of the core protein shell. The peptides contain two basic residues; changing either of two acidic residues at the spike tip to an alanine greatly reduced the binding affinity. Transfection of hepatoma cells with a replication-competent HBV plasmid gave significantly reduced production of virus in the presence of peptide, in a dose-dependent manner. These experiments show that the interaction of L-HBsAg with core particles is critical for HBV assembly, and give proof of principle for its disruption in vivo by small molecules.

Antiviral Agents↗