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Biomedical subjects

G Manley

Publications and source records attributed to G Manley.

At least 19 recordsLinked to original sources
PubMed2001

Hypotension, hypoxia, and head injury: frequency, duration, and consequences.

BACKGROUND: Retrospective studies have suggested an association between systemic hypotension and hypoxia and worsened outcome from traumatic brain injury. Little is known, however, about the frequency and duration of these potentially preventable causes of secondary brain injury. HYPOTHESIS: Early episodes of hypoxia and hypotension occurring during initial resuscitation will have a significant impact on outcome following traumatic brain injury. DESIGN: Prospective cohort study. SETTING: Urban level I trauma center. PATIENTS: Patients with a traumatic brain injury who had a Glasgow Coma Score of 12 or less within the first 24 hours of admission to the hospital and computed tomographic scan results demonstrating intracranial pathologic features. Patients who died in the emergency department were excluded from the study. MAIN OUTCOME MEASURES: Automated blood pressure and pulse oximetry readings were collected prospectively from the time of arrival through initial resuscitation. The number and duration of hypotensive (systolic blood pressure, < or =90 mm Hg) and hypoxic (oxygen saturation, < or =92%) events were analyzed for their association with mortality and neurological outcome. RESULTS: One hundred seven patients met the enrollment criteria (median Glasgow Coma Score, 7). Overall mortality was 43%. Twenty-six patients (24%) had hypotension while in the emergency department, with an average of 1.5 episodes per patient (mean duration, 9.1 minutes). Of these 26 patients with hypotension, 17 (65%) died (P =.01). When the number of hypotensive episodes increased from 1 to 2 or more, the odds ratio for death increased from 2.1 to 8.1. Forty-one patients (38%) had hypoxia, with an average of 2.1 episodes per patient (mean duration, 8.7 minutes). Of these 41 patients with hypoxia, 18 (44%) died (P =.68). CONCLUSIONS: Hypotension, but not hypoxia, occurring in the initial phase of resuscitation is significantly (P =.009) associated with increased mortality following brain injury, even when episodes are relatively short. These prospective data reinforce the need for early continuous monitoring and improved treatment of hypotension in brain-injured patients.

Adolescent↗
PubMed2000

Electropalatography and the Linguagraph system.

This paper describes the technique of electropalatography and the development of Linguagraph, which is a user-friendly, clinical instrument, for measurement of tongue/palate contact, during speech. Linguagraph allows objective assessment of tongue function; appropriate targeting of therapy is therefore possible. Visual feedback is also provided, for therapy, and an objective measurement of outcome is easily obtained. Linguagraph was used, for both therapy and assessment, in a clinical trial. Technical aspects of Linguagraph and of the trial results are presented here. These suggest that the instrument will prove useful in the assessment and management of many speech disorders. Full clinical details of the trial are reported elsewhere.

Adult↗
PubMed2000

Skeletal muscle function and water permeability in aquaporin-4 deficient mice.

It has been proposed that aquaporin-4 (AQP4), a water channel expressed at the plasmalemma of skeletal muscle cells, is important in normal muscle physiology and in the pathophysiology of Duchenne's muscular dystrophy. To test this hypothesis, muscle water permeability and function were compared in wild-type and AQP4 knockout mice. Immunofluorescence and freeze-fracture electron microscopy showed AQP4 protein expression in plasmalemma of fast-twitch skeletal muscle fibers of wild-type mice. Osmotic water permeability was measured in microdissected muscle fibers from the extensor digitorum longus (EDL) and fractionated membrane vesicles from EDL homogenates. With the use of spatial-filtering microscopy to measure osmotically induced volume changes in EDL fibers, half times (t(1/2)) for osmotic equilibration (7.5-8.5 s) were not affected by AQP4 deletion. Stopped-flow light-scattering measurements of osmotically induced volume changes in plasmalemma vesicles also showed no significant differences in water permeability. Similar water permeability, yet approximately 90% decreased AQP4 protein expression was found in EDL from mdx mice that lack dystrophin. Skeletal muscle function was measured by force generation in isolated EDL, treadmill performance time, and in vivo muscle swelling in response to water intoxication. No differences were found in EDL force generation after electrical stimulation [42 +/- 2 (wild-type) vs. 41 +/- 2 (knockout) g/s], treadmill performance time (22 vs. 26 min; 29 m/min, 13 degrees incline), or muscle swelling (2.8 vs. 2.9% increased water content at 90 min after intraperitoneal water infusion). Together these results provide evidence against a significant role of AQP4 in skeletal muscle physiology in mice.

Animals↗
PubMed2000

Going private? Exploring the drift away from the NHS.

The perception that dentistry is being privatised is widespread. A two-phase study was undertaken to investigate the factors influencing dentists' decisions to practise in the public and or private sectors. In phase I a national postal survey of general dental practitioners (n = 1011) explored differences in working practices and experience of NHS and non-NHS work. Survey data were supplemented in phase II by in-depth interviews with four subsamples of dentists in two regions. The survey found that although the majority of dentists continued to treat the majority of their patients within the NHS since the introduction of the 1990 contract patterns of practice have changed. Where private dentistry was increasing, it was regionally variable and arose mainly from concerns with financial security, maintaining quality of work and autonomy. Ideological differences were apparent in relation to differences in practice mix. Those who continued to work in the NHS, because of insufficient demand for private dentistry, did so in order to provide access to treatment and to maintain a reliable source of income and pension rights. Dentists interviewed expressed reluctance in withdrawing from NHS practice. Disillusionment with government policy and recognition of the marginal nature of dental health issues suggests that current trends will continue.

Dental Care↗
PubMed1999

Dentistry. Filling in time.

A national survey of 1,000 dentists revealed an increase in the amount of private work they undertake. Many thought that fees for NHS dentistry compromised quality. A high proportion believed that the government planned to privatize dentistry.

Attitude of Health Personnel↗
PubMed1999

An instrument for the multiparameter assessment of speech.

This paper describes the development of SNORS+, a clinical, user-friendly instrument for measurement of the articulators during speech. The design criteria for the instrument were based upon a wide-ranging review of current practice and available techniques. SNORS+ allows objective assessment of the function and co-ordination of key articulators. Appropriate targeting of therapy is therefore possible. Visual feedback is provided, for therapy, and an objective measurement of outcome is easily obtained. Preliminary results are presented. These suggest that the instrument will prove extremely useful in the assessment and management of many speech disorders.

Adult↗
PubMed1999

Private or NHS General Dental Service care in the United Kingdom? A study of public perceptions and experiences.

BACKGROUND: Recent changes in the NHS General Dental Service have led to a reduction in the availability of NHS dental care and increased charges. This study explores public and user views and experiences of NHS and private dental care in the light of these changes. METHODS: The study employed a combination of quantitative and qualitative methods. The first phase involved a postal survey of a random sample of adults on the electoral registers in a county in Southern England, which yielded a response rate of 55 per cent (n = 1506). Follow-up face-to-face interviews were carried out with sub-samples (n = 50) selected from survey respondents. RESULTS: The evidence shows greater satisfaction with certain aspects of private care than with NHS dental care and suggests that the decline in perceived quality of NHS care is less to do with the quality of dental technical skills and more to do with perceived access and availability. However, there was general support for the egalitarian principles associated with NHS dentistry, although payment for dental care by users was acceptable even though dentistry on the NHS was preferred. CONCLUSION: The shift in the balance of NHS and private dental care reflects the interests and preferences of dentists rather than of the public. It suggests, however, that a continued shift towards private practice is a trend that the public will not find acceptable, which might limit the extent of expansion of private practice.

Adult↗
PubMed1999

The quality of general dental care: public and users' perceptions.

BACKGROUND: Systematic evidence about how the public and users perceive and experience the quality of general dental care is in short supply, particularly in light of the recent changes in the general dental service. The study reported here attempted to fill this gap. OBJECTIVES: To identify the criteria the public and users adopt in evaluating the quality of general dental care, and to identify the extent and nature of perceived concerns with general dental care. DESIGN: Postal questionnaires were sent to random samples of adults living in an inner city area (I) and semi-rural area (R) in southern England. Fifty six per cent (1499) in area R and 48% (1388) in area I completed the questionnaire after four mailings. Follow up face-to-face interviews were done with a purposive subsample (n = 50) of responders from the postal survey. MAIN MEASURES: Public/user views about quality of dental care were measured through groups of questions about the importance of and satisfaction with different aspects of dental care (access/availability including cost; facilities; technical skills; and interpersonal care) and a scale (Dentsat) measuring general satisfaction was constructed from questions on different aspects of care. RESULTS: Evaluation of quality of general dental care from the users' point of view hinges on perceived technical skills, particularly pain management. Major dissatisfaction stems from concerns about costs of dental care and privatisation. CONCLUSIONS: The criteria adopted by the public/users to assess general dental care are similar to other areas of health care, apart from the priority placed on technical skills and pain management. However, the major source of decline in satisfaction with the quality of general dental care is the barrier to access created by the rising cost of dental care and the increasing involvement of dentists in private practice. This evidence suggests that the public and users find the drift towards private practice and away from NHS practice a major source of concern.

Consumer Behavior↗
PubMed1998

Detection of Bartonella henselae by polymerase chain reaction in brain tissue of an immunocompromised patient with multiple enhancing lesions. Case report and review of the literature.

The authors report the first DNA-based diagnosis of Bartonella henselae cultured from a brain lesion in a patient with acquired immune deficiency syndrome. This human immunodeficiency virus-infected patient presented with altered mental status, fever, and diabetes insipidus. Magnetic resonance imaging revealed multifocal parenchymal and leptomeningeal involvement, which was confirmed on studies of tissue biopsy samples. Using the polymerase chain reaction and gene sequencing techniques, the authors definitively demonstrated the presence of B. henselae in the brain tissue biopsy specimen.

AIDS-Related Opportunistic Infections↗
PubMed1996

The HuD paraneoplastic protein shares immunogenic regions between PEM/PSN patients and several strains and species of experimental animals.

Patients with small-cell carcinoma of the lung and paraneoplastic encephalomyelitis develop antibodies (anti-Hu) against HuD, a member of a family of neuronal specific RNA-binding proteins, which are also expressed by the tumor. In order to determine if the human HuD paraneoplastic antigen shares immunogenic regions between patients and several strains and species of animals, we immunized animals with HuD and several deletion constructs of this protein. All immunized animals developed high titers of anti-HuD antibodies, comparable to the antibody titers found in paraneoplastic patients. Using immunohistochemistry and Western blot analysis of human and mouse cerebral cortex, the pattern of reactivity of these antibodies could not be differentiated from the human paraneoplastic anti-Hu antibodies. None of the immunized animals developed neurologic symptoms. Western blot analysis of HuD deletion constructs demonstrated that the first and second RNA binding domains were the main immunodominant regions, and that the animal immune response was both strain and species dependent.

Animals↗
PubMed1996

Pitfalls in the diagnosis of autoantibodies associated with paraneoplastic neurologic disease.

We studied the sera of 15 patients with Sjögren's syndrome using the Western blot technique for the presence of anti-Ro and anti-Hu (type 1 antineuronal nuclear autoantibody [ANNA-1]). All sera reacted with Ro-52 protein. Two of the Sjögren sera reacted with 38-kd bands on Western blots of rat cerebellar homogenate, resembling anti-Hu immunoreactivity. However, when reacted with purified human Purkinje cells or purified recombinant HuD protein, none of the sera immunoreacted with the Hu antigens. We recommend the use of either a recombinant Hu protein or the combination of immunohistochemistry and Western blot of purified human neuronal preparations to identify paraneoplastic antibodies. This approach will prevent the unnecessary workup for suspected lung cancer.

Animals↗
PubMed1994

Sera from some patients with antibody-associated paraneoplastic encephalomyelitis/sensory neuronopathy recognize the Ro-52K antigen.

Screening a small cell lung cancer cDNA library with serum from a patient with antibody-associated paraneoplastic sensory neuronopathy (Anti-Hu syndrome) resulted in the isolation of a cDNA clone encoding the Ro-52 kD antigen. The Ro-52 kD antigen is one of the major antigens recognized by the sera of patients with Sjögren's syndrome and systemic lupus erythematosus. Further investigation revealed that the sera of only a small percentage (4%) of patients with the Hu syndrome reacted with Ro-52 kD antigen. The cross-reactivity may result from a domain of high homology between Ro-52 kD and HuD antigen. These results emphasize the necessity of using recombinant antigens whenever possible when assaying for assaying for specific antibodies.

Amino Acid Sequence↗
PubMed1993

Cloning and characterization of a Lambert-Eaton myasthenic syndrome antigen.

Lambert-Eaton myasthenic syndrome is a paraneoplastic neuromuscular disorder in which an immune response directed against a small-cell lung tumor crossreacts with antigens in the neuromuscular junction. To isolate and characterize the antigens, we screened a human fetal brain expression library with a high-titer serum from a patient with Lambert-Eaton myasthenic syndrome. This screening resulted in the isolation of a complementary DNA clone encoding an antigen we call myasthenic syndrome antigen B (MysB). Approximately 43% (3 of 7) of Lambert-Eaton myasthenic syndrome sera specifically recognized MysB fusion protein, whereas none of 34 control sera did. The predicted amino acid sequence of this clone shows a high degree of homology to the beta subunit of calcium channel complexes. The MysB pre-messenger RNA is alternatively spliced to yield 3 forms of the protein differing in the domain between two highly conserved alpha-helical segments.

Antigens↗
PubMed1993

Retrieval and allocation of organs for transplantation: the Michigan experience.

The Organ Procurement Agency of Michigan (OPAM) is now in its twenty-third year of service to the transplant community in Michigan. From a beginning with one coordinator in 1971, it now employs 53 individuals, including 8 laboratory technologists for its own on-site histocompatibility laboratory, a dozen procurement coordinators stationed throughout the state, 6 organ placement coordinators in the main office, 6 screening coordinators who provide around-the-clock coverage at the office, a tissue recovery section, as well as additional finance, education, and administrative support staff. This chapter outlines the history and growth in organ recoveries of the organization. More importantly, the chapter also analyzes the Michigan experience regarding racial distribution of kidneys. While African-Americans comprise 14% of the general population of the state, they comprise 40% of the waiting kidney recipients and only 26% of the actual recipients. Depending upon blood type, average waiting time for a kidney for African-Americans can be up to 4 months longer than for Whites. The analysis attributes this variance primarily to the allocation methodology for kidney distribution, which is largely driven by antigen matching and secondarily to the generally greater frequency and higher degree of blood sensitization among African-Americans, which causes a substantially higher frequency of positive-crossmatch results between potential donor and recipient. The authors conclude that changes in the present allocation system could be made to achieve greater equity for African-American patients, without removing the advantages inherent in transplanting kidneys with closely matched antigens.

ABO Blood-Group System↗
PubMed1992

The fibrinogen anion-binding exosite of thrombin is necessary for induction of rises in intracellular calcium and prostacyclin production in endothelial cells.

Thrombin stimulation of prostacyclin (PGI2) synthesis by cultured human umbilical vein endothelial cells (HUVEC) requires the active site of thrombin and involves rapid and transient rises in cytoplasmic free calcium [Ca2+]i. In this study, we investigated whether or not the anion-binding exosite for fibrinogen recognition of thrombin (which confers certain substrate specificities) is also necessary for the induction of rises in [Ca2+]i and PGI2 production. Thrombin variants which lack either the catalytic site (DIP-alpha-thrombin) or anion-binding exosite (gamma-thrombin) either alone or in combination failed to induce rises in [Ca2+]i or PGI2 production in HUVEC. To further study the role of the anion-binding exosite of thrombin in the activation of HUVEC, COOH-terminal fragments of hirudin were used. This portion of hirudin interacts with the anion-binding exosite of thrombin and inhibits thrombin-induced fibrinogen coagulation while leaving the catalytic activity of thrombin intact. A 21-amino acid COOH-terminal peptide of hirudin (N alpha-acetyldesulfato-hirudin45-65 or Hir45-65) inhibited thrombin-induced (0.5 U/ml) rises in [Ca2+]i and PGI2 production with IC50 of 0.13 and 0.71 microM, respectively. Similar results were obtained using shorter hirudin-derived peptides. Thus, the fibrinogen anion-binding exosite of thrombin is required for alpha-thrombin-induced rises in [Ca2+]i and PGI2 production in HUVEC.

Amino Acid Sequence↗
PubMed1992

Human serum and urine glycosaminoglycans in health and in patients with chronic renal failure.

Quantitation of uronic acid precipitable by cetylpyridinium chloride (CPC) and electrophoretic separation of glycosaminoglycans were performed on sera from patients with chronic renal failure and compared to normal controls. Serum CPC-precipitable uronic acid (CpUA) levels in patients with renal failure were significantly higher (mean 13.7 mg/L, range 7.1-23.6 mg/L) than normal controls (mean 9.6 mg/L, range 5.1-13.9 mg/L) due to increased concentrations of low sulphated chondroitin sulphate. A positive correlation between serum CpUA and creatinine was found in renal failure patients. Urine CpUA excretion was raised in renal failure patients compared to normal controls with an increased excretion of chondroitin sulphate (Ch-S) of reduced electrophoretic mobility. Heparan sulphate (HS), a major glycosaminoglycan in normal urine, was absent from the urine of these patients. The possible origin of urine glycosaminoglycans and the role of the kidney in glycosaminoglycan metabolism are discussed.

Adolescent↗
PubMed1991

HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding domains and is homologous to Elav and Sex-lethal.

A neuronal antigen (HuD) recognized by the sera of patients with antibody-associated paraneoplastic encephalomyelitis has been isolated by screening a lambda cerebellar expression library. The recombinant antigen provides an unambiguous assay for this rare condition associated with small cell lung cancer. The recombinant antigen has been used to identify specific infiltrating lymphocytes in tumors and affected brain tissues of patients with antibody-associated paraneoplastic encephalomyelitis and sensory neuronopathy. HuD mRNA is uniquely expressed in brain tissue. The HuD protein shows a remarkable homology to the Drosophila proteins Elav and Sex-lethal and is likely to play a role in neuron-specific RNA processing.

Amino Acid Sequence↗