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Biomedical subjects

A Williams

Publications and source records attributed to A Williams.

At least 19 recordsLinked to original sources

Studies on maternal transmission of scrapie in sheep by embryo transfer.

The technique of embryo transfer was used to investigate the maternal transmission of scrapie in sheep. Embryo donor ewes were experimentally infected with scrapie (all eventually developing the disease) and artificially inseminated six months later with semen from an uninfected scrapie-susceptible ram. Embryos were harvested five and six days after insemination and transferred by laparoscopy, unwashed, into recipient ewes which had been genetically selected for very low susceptibility to scrapie. Six of the 26 lambs born to these recipients developed scrapie.

Animals

A scoring system for lung function tests in infants.

Measurements of thoracic gas volume (TGV), airway resistance (Raw), and airway conductance (Gaw) were calculated in a group of 42 normal infants using a whole-body plethysmograph. Maximum expiratory flow at functional residual capacity was measured in a separate group of 108 normal infants. Using data obtained from these infants the following regression equations were calculated: Gaw (L.s-1.cmH2O) = -0.0475 + 0.00164 x length (cm) square root of TGV (mL1/2) = -3.22 + 0.263 x length (cm) VmaxFRC (mL.s-1) = -173 + 5.2 x length (cm). The standard errors of prediction are a measure of the scatter of individual results from the normal population about the true regression line. They were used to define limits of the normal ranges for these tests of lung function, and to develop a scoring system. This approach is preferable to expressing results as percent predicted, which gives no indication of how likely a measurement is to be within normal limits.

Age Factors

Ultrastructural features of spongiform encephalopathy transmitted to mice from three species of bovidae.

The ultrastructural neuropathology of mice experimentally inoculated with brain tissue of nyala (Tragelaphus angasi; subfamily Bovinae), or kudu (Tragelaphus strepsiceros; subfamily Bovinae) affected with spongiform encephalopathy was compared with that of mice inoculated with brain tissue from cows (Bos taurus; subfamily Bovinae) with bovine spongiform encephalopathy (BSE). As fresh brain tissue was not available for nyala or kudu, formalin-fixed tissues were used for transmission from these species. The effect of formalin fixation was compared with that of fresh brain in mice inoculated with fixed and unfixed brain tissue from cows with BSE. The nature and distribution of the pathological changes were similar irrespective of the source of inoculum or whether the inoculum was from fresh or previously fixed tissue. Vacuolation caused by loss of organelles and swelling was present in dendrites and axon terminals. Vacuoles were also seen as double-membrane-bound and single-membrane-bound structures within myelinated fibres, axon terminals and dendrites. Vacuoles are considered to have more than one morphogenesis but the structure of vacuoles in this study was nevertheless similar to previous descriptions of spongiform change in naturally occurring and experimental scrapie, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome and kuru. Other features of the ultrastructural pathology of the transmissible spongiform encephalopathies including dystrophic neurites and scrapie-associated particles or tubulovesicular bodies were also found in this study. Neuronal autophagy was a conspicuous finding. It is suggested that excess prion protein (PrP) accumulation, or accumulation of the scrapie-associated protease-resistant isoform of PrP, may lead to localised sequestration and phagocytosis of neuronal cytoplasm and ultimately to neuronal loss.

Animals

Transposon mutagenesis in Legionella pneumophila. II.--Mutants exhibiting impaired intracellular growth within cultured macrophages and reduced virulence in vivo.

Transposon Tn5 mutants of L. pneumophila were isolated and screened for loss of virulence-associated characteristics. Three mutants were found with normal ability to produce putative pathogenicity determinants and to be endocytosed by guinea pig alveolar macrophages in vitro but with a greatly reduced ability to multiply within them. These mutants showed considerable loss of virulence in an authentic animal model of the pneumonia.

Animals

Student mental health needs: survey results and implications for service.

In preparation for planning counseling and mental health services at Columbia University, the authors conducted a mental health needs assessment survey that sampled representative numbers of students. Respondents were most concerned about academic and school-related issues, followed by concerns in the area of love relationships. Multiple regression analysis revealed certain subgroups that were more likely to have these concerns and certain health and mental health problems that were significantly associated with these concerns. The study identified serious psychological problems, including suicidal/homicidal thoughts and sexual abuse, and surveyed respondents' treatment preferences. Finally, the authors discuss how the study findings contributed to sharpening and expanding focus on different aspects of program development in the collaboration between mental health and health education.

Adult

Analysis of the contraceptive potential of antibodies against native and deglycosylated porcine ZP3 in vivo and in vitro.

We have undertaken a comparative analysis of the contraceptive activity of antibodies directed against the porcine sperm receptor zona pellucida antigen (ZP3) and its Mr = 32,000 polypeptide core (DGZP-32). The strategies employed for this analysis included the induction of active immunity in a primate, the common marmoset, and an in vitro fertilization protocol involving the use of viable human ova. In both experimental situations, antibodies against ZP3 were shown to exhibit contraceptive activity, leading respectively to the induction of long-term infertility in the primate model and to the complete inhibition of human fertilization in vitro. The in vivo studies also revealed that the induction of high titer antibodies against ZP3 was inevitably associated with the appearance of an ovarian pathology characterized by the progressive depletion of the primordial follicle pool within one to two years. This side effect could not be alleviated by the use of DGZP-32 as antigen since the induction of immunity against this polypeptide was also associated with the eventual appearance of an ovarian pathology identical to that observed with ZP3. Furthermore, the DGZP-32 peptide was less effective than ZP3 in inducing the formation of antibodies capable of inhibiting the fertilization of human ova in vitro. We conclude that significant problems remain with the use of deglycosylated zona peptides for the development of contraceptive vaccines and that their potential will not be realized until the epitopes responsible for the induction of infertility and the primordial follicle depletion have been identified and segregated.

Animals

Demonstration of the intracellular production of tissue-destructive protease by Legionella pneumophila multiplying within guinea-pig and human alveolar macrophages.

The major extracellular enzyme of Legionella pneumophila, a metalloprotease, has been proposed as a pathogenic factor in Legionnaires' disease due to its cytotoxic, tissue-destructive, and phagocyte-inhibitory properties. The relevance of these activities depends on the production of the protease during infection, i.e. by L. pneumophila multiplying intracellularly. In this study, L. pneumophila was demonstrated to produce protease in guinea-pig and human alveolar macrophages infected in vitro. After 24 h infection, approximately 0.1 to 0.2 micrograms of protease per 10(6) bacteria was measured by ELISA in culture supernatants and lysates of the infected cells, whereas no protease could be detected immediately after infection. Immunogold labelling using anti-protease antibody showed the enzyme to be located within phagosomes and distributed throughout the macrophages. Recent observations have shown that this protease could modify host defence mechanisms through inhibition of bacterial killing by neutrophils and monocytes. The intracellular production of the enzyme in infected macrophages demonstrated here further supports a role for the protease in the pathogenesis of Legionnaires' disease.

Animals

Keratan sulphate in rheumatoid arthritis, osteoarthritis, and inflammatory diseases.

Serum concentrations of antigenic keratan sulphate determined by an enzyme linked immunosorbent assay (ELISA) with a monoclonal antibody were studied in patients with rheumatoid arthritis (RA), osteoarthritis, ankylosing spondylitis, other inflammatory diseases, and a large control group of women without arthritis. Mean keratan sulphate concentrations were low in 117 women with RA compared with 227 female control subjects matched for age drawn from a community survey. There were significant correlations between serum keratan sulphate concentrations in patients with RA and serum C reactive protein and the erythrocyte sedimentation rate. Serum keratan sulphate concentrations were also low in 29 men and women with ankylosing spondylitis and 29 patients with arthritis and high concentrations of C reactive protein. In 98 women undergoing an operation for benign breast disease there were decreases in serum keratan sulphate concentrations after the operation which correlated with doses in serum C reactive protein. No differences were found in keratan sulphate concentrations in 137 women with osteoarthritis compared with controls. Within the group with osteoarthritis there were no differences for the various joint groups and there was no obvious correlation with radiographic severity or progression. These findings suggest serum keratan sulphate is unlikely to be useful as a diagnostic marker in osteoarthritis or RA but indicate a role for inflammation in the regulation of cartilage loss.

Acute-Phase Reaction

Cost-effectiveness analysis: is it ethical?

Many clinicians believe that allowing costs to influence clinical decisions is unethical. They are mistaken in this belief, because it cannot be ethical to ignore the adverse consequences upon others of the decisions you make, which is what 'costs' represent. There are, however, some important ethical issues in deciding what costs to count, and how to count them. But these dilemmas are equally strong with respect to what benefits to count and how to count them, some of which expose ethically untenable assumptions about such widely-used clinical criteria as survival rates. One of the advantages of systematic cost-effectiveness analysis is that it exposes these hidden assumptions, and requires explicit judgements to be made about which ethical position is appropriate in a particular policy context. This should have the important incidental benefit of improving the accountability of policy-makers to the community they are serving.

Cost Control

Intergenerational talk and communication with older people.

A program of research conducted within an anti-agism paradigm demonstrates that young people process and respond to the speech of older people in stereotypical ways. Such conclusions result from studies using a variety of research methods. Experimental studies demonstrate that older-sounding speech triggers age schematic responses and that young people tend to use agist strategies of information seeking and compliance gaining from older people, while interactive studies explore how stereotypes and age identities are co-produced by young and old people in conversation. We use lifespan and intercultural perspectives to argue that the communicative patterns we observe in our studies are in some senses and contexts counterproductive in both the long and short term, in that they can reproduce negative attitudes toward aging as well as inhibit successful aging.

Adult

Communication skills training in undergraduate medicine: attitudes and attitude change.

The importance of communication skills training in undergraduate medical education is now widely accepted. However little is known about student attitudes towards their own communication skills and whether their attitudes changes as a result of participating in communication skills courses. The aim of the present study was to identify these attitudes prior to commencing such a course and to further evaluate changes in these attitudes on completion of the course. Results demonstrated an improvement in perceived confidence regarding a number of specific communication skills. The study provides further evidence of the value of such courses in undergraduate medical training.

Attitude

Models of healthcare delivery in cancer pain management.

The delivery of pain management services to patients with cancer varies across healthcare settings. Identification of areas common to successful programs would be helpful to healthcare professionals developing or restructuring their own programs. The delivery of pain management services in six different systems is described with respect to organizational structure, service process, and essential components. Three elements common to successful programs are identified: (1) team effort and coordination, (2) provision of education, and (3) accountability and administrative support. The authors conclude that these three elements are critical to the delivery of pain management services across healthcare settings.

Health Personnel

General practitioners' confidence in diagnosing and managing eye conditions: a survey in south Devon.

In order to open dialogue aimed at increasing eye care in general practice and reduce waiting times for ophthalmic outpatient appointments general practitioners in the Torbay health district were asked about their levels of confidence in ophthalmology as a subject, and in the diagnosis and management of specific eye conditions. They were also asked about ophthalmic equipment available to them, their management policies for 34 specific eye conditions, and their perceived need for further training in this subject. A total of 75% of the general practitioners responded to the questionnaire. Despite more than half of the general practitioners indicating that they did not feel confident with ophthalmology generally, most expressed confidence in diagnosing and managing common eye conditions. Basic equipment for examining the eye was available to most doctors. Referral policies varied considerably, and these have resource implications. Seventy eight per cent of respondents were prepared to take on more eye care in general practice, and over 80% of general practitioners requested informal teaching sessions in ophthalmology. Support must be forthcoming if general practitioners are to provide eye care in general practice.

Clinical Competence

Time-course of medial and intimal thickening in pig venous arterial grafts: relationship to endothelial injury and cholesterol accumulation.

With use of an established model of pig saphenous vein grafts in the carotid artery, the time-course of the following changes was related: (1) medial and intimal size by morphometry of transverse sections, (2) cell number by deoxyribonucleic acid concentration, (3) cell density by deoxyribonucleic acid concentration per milligram wet weight and by counting nuclei in transverse sections, (4) endothelial morphology by scanning electron microscopy, and (5) cholesterol concentration. In the first week after grafting, medial and intimal thickening occurred associated with an increase in cell number. Between 1 and 4 weeks after grafting, further rapid medial and intimal thickening occurred with no further increase in cell number but with a reduction in cell density, which suggested that cell migration, hypertrophy, and the laying down of extracellular matrix were responsible. Between 4 and 39 weeks after grafting, a slower increase in medial and intimal size occurred, associated with a parallel increase in cell number and no further change in cell density. The endothelium of grafts showed only localized abnormalities, including loss of cells and leukocyte adhesion, either 1 or 4 weeks after grafting. Cholesterol concentration was slightly elevated 1 week after grafting but returned to values similar to those in vein by 4 weeks after grafting. Distention to 600 mm Hg during surgical preparation of vein for grafting resulted in lower graft patency after either 1 or 4 weeks and caused significant medial and endothelial injury. Distention did not, however, affect changes in medial or intimal size, deoxyribonucleic acid, or cholesterol concentration caused by grafting. We conclude that three processes contribute to medial and intimal thickening, namely: (1) an initial phase of rapid smooth muscle cell proliferation, (2) smooth muscle cell migration, hypertrophy, and synthesis of extracellular matrix, and (3) a late phase of slower smooth muscle cell proliferation. The incomplete late suppression of smooth muscle cell proliferation occurs despite regeneration of a morphologically intact endothelium and in the absence of progressive cholesterol accumulation.

Anastomosis, Surgical