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Biomedical subjects

C Dyson

Publications and source records attributed to C Dyson.

At least 19 recordsLinked to original sources

Immunologic considerations for therapeutic strategies utilizing allogeneic hepatocytes: hepatocyte-expressed membrane-bound major histocompatibility complex class I antigen sensitizes while soluble antigen suppresses the immune response in rats.

Understanding the immunologic effects of hepatocytes is critical because of the potential to use these cells for bioartificial livers, as a vehicle for gene transfer, and as a means to induce donor-specific immunosuppression in organ transplantation. However, this understanding is complicated by the fact that hepatocytes express membrane-bound and soluble forms of major histocompatibility complex (MHC) class I antigen, each with the potential to induce different immune responses. In the present study we first determined the immunologic effect of normal donor-derived hepatocytes in a rat heart transplant model. We then used ex vivo hepatocyte gene transfer to examine the immunologic effects of different forms of hepatocyte-expressed MHC class I antigen. Results showed that intrasplenic injection of purified, donor-strain-specific hepatocytes into recipients primes alloimmunity, as evidenced by acceleration of heart allograft rejection. Interestingly, injection of autologous hepatocytes transfected ex vivo with DNA encoding only membrane-bound donor MHC class I antigen (RT1.A(a)) also accelerated allograft rejection. However, hepatocytes transfected to express only secreted donor MHC antigen prolonged transplant survival. Limiting-dilution analysis of lymphocytes from animals treated with hepatocytes producing only secreted alloantigen showed an antigen-specific reduction in cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) precursors. Further analysis of CTL populations by flow cytometry revealed a relatively high percentage of nonviable cells, implying that soluble antigen promotes allospecific CTL death. In summary, this study suggests that hepatocyte-expressed MHC class I molecules have opposing immunologic effects, with the membrane-bound antigen inducing immunologic sensitization, and the soluble antigen promoting donor-specific immunosuppression.

Animals↗

Infective endocarditis: an epidemiological review of 128 episodes.

OBJECTIVES: The objective was to determine the current epidemiology of infective endocarditis. PATIENTS AND METHODS: All microbiologically positive episodes of infective endocarditis treated at The University Hospital of Wales over a 9-year period from March 1987 to March 1996 was reviewed. Patients originated from the catchment area of The University Hospital of Wales or were referred from other hospitals in Wales. Data extraction was from records held in the Microbiology Department and, whenever possible, from patients' casenotes. The epidemiological parameters were: (1) age and sex of patients; (2) distribution of affected sites; (3) frequency of predisposing risk factors (cardiac and extracardiac); (4) incidence of early prosthetic valve endocarditis; and (5) mortality rates. RESULTS: There were 128 microbiologically positive episodes of endocarditis in 125 patients. The mean age of the population was 53.1 years and the aortic valve was the most frequently involved site of infection (51.6%). A presumed source of infection was identified in 20% if episodes. The commonest predisposing cardiac risk factor in native valve episodes was bicuspid aortic valve (16.7%) but there was no identifiable cardiac risk factor in a much larger proportion (37.7%) of native valve episodes. There was a low incidence (0.6%) of culture positive early prosthetic valve episodes and low mortality rates for both native and prosthetic valve endocarditis (12.3% and 24.5%) in this study. Viridans streptococci were the predominant organisms. In prosthetic valve episodes with onset after the 60th postoperative day but within one postoperative year the identity of the isolate suggested, in most cases, perioperative valve contamination. CONCLUSIONS: The epidemiology of infective endocarditis has undergone significant change. Inability to detect clinically common predisposing lesions, and the frequent absence of any identifiable predisposing cardiac risk factor mean that initial diagnosis is often difficult and demands a high index of suspicion. There was a low incidence of culture positive early prosthetic valve episodes and there were low mortality rates for both native and prosthetic valve endocarditis; these figures suggest improvements in cardiac care. The microbiological evidence indicates that the duration of the postoperative time period used for classifying prosthetic valve endocarditis into 'early' and 'late' episodes should be extended from 60 days to 1 year.

Adolescent↗

The persuasiveness of synthetic speech versus human speech.

Is computer-synthesized speech as persuasive as the human voice when presenting an argument? After completing an attitude pretest, 193 participants were randomly assigned to listen to a persuasive appeal under three conditions: a high-quality synthesized speech system (DECtalk Express), a low-quality synthesized speech system (Monologue), and a tape recording of a human voice. Following the appeal, participants completed a posttest attitude survey and a series of questionnaires designed to assess perceptions of speech qualities, perceptions of the speaker, and perceptions of the message. The human voice was generally perceived more favorably than the computer-synthesized voice, and the speaker was perceived more favorably when the voice was a human voice than when it was computer synthesized. There was, however, no evidence that computerized speech, as compared with the human voice, affected persuasion or perceptions of the message. Actual or potential applications of this research include issues that should be considered when designing synthetic speech systems.

Adult↗

The role of the microbiology laboratory in the investigation of child sexual abuse.

Detection of a sexually transmitted pathogen in a child is suggestive of sexual abuse. Consequently, there are very strong clinical, social and legal reasons for diagnosing sexually transmitted disease in children correctly. Carefully considered protocols should be established for all stages of the microbiological investigation. All procedures, from specimen collection to report generation, should be undertaken to the highest possible standard with appropriate documentation. For the more commonly identified sexually transmitted pathogens in the paediatric population, the gold standard of diagnosis in the microbiology laboratory remains culture in vitro because this method offers maximum specificity. Whenever possible, culture must be followed by appropriate confirmatory tests. This highly exacting approach has significant resource and organisational implications and some tests may have to be centralised. The effective provision of an appropriate service for these cases is dependent on the local laboratory collaborating closely with hospital paediatricians and other microbiology laboratories.

Child↗

Large scale use of ciprofloxacin in the control of a Salmonella outbreak in a hospital for the mentally handicapped.

An outbreak of salmonella food poisoning occurred in a hospital for the mentally handicapped in July 1990. Salmonella enteritidis phage type 4 was identified in 101 patients and eight staff. Standard infection control measures were instituted. Ciprofloxacin was given to all resident patients and to all affected staff. The outbreak was rapidly controlled. There were no new cases after ciprofloxacin was started and there were no clinical relapses. Microbiological relapsers were retreated with ciprofloxacin. A gradual return to normal activity was possible and within two months the hospital was functioning normally. No salmonellae have been identified in the hospital since that time, confirming that the organism was eradicated, rather than just temporarily suppressed.

Ciprofloxacin↗

Association of ocular cataracts with inhaled and oral steroid therapy during long-term treatment of asthma.

BACKGROUND: Posterior subcapsular cataracts (PSCs) have been reported to occur in some asthmatic patients treated with inhaled steroids. METHODS: We studied the associations between the occurrence of PSCs and inhaled and oral steroid therapy in 48 adults in a cross-sectional survey by slit lamp. Accurate records of the patients' long-term usage of these drugs were available: 9.2 +/- 5.2 years for inhaled steroid and 9.1 +/- 9.3 years for prednisone (mean +/- SD). Their current inhaled steroid dosage averaged 1.46 +/- 0.85 mg/day (range, 0 to 3.2 mg/day). RESULTS: Twenty-seven percent of the group had PSCs. The occurrence of PSCs correlated with the current daily dose and duration of prednisone use (p = 0.002 and p = 0.01, respectively), but not with the dose or duration of inhaled steroid treatment. As judged by multiple logistic regression analysis, neither the particular inhaled steroid drug used, nor its daily dose or cumulative dose, nor the additional nonsteroidal risk factors for PSCs also present in some of these patients contributed significantly to their risk of developing PSCs. CONCLUSIONS: The findings do not exclude the possibility that inhaled steroid therapy might lead to PSCs if a person has an exceptionally high inherent susceptibility. However, in the asthmatic population at large, the risk appears negligible, even if high doses of inhaled steroid are administered.

Administration, Inhalation↗

Life threatening Branhamella catarrhalis pneumonia in young infants.

Branhamella catarrhalis is a common nasopharyngeal commensal organism but is also a recognised pathogen. Lower respiratory tract infections caused by this organism have been reported in adults but not, to our knowledge, in otherwise healthy infants. Two infants, born prematurely, suffered near fatal pneumonia. Branhamella catarrhalis was the only microbial pathogen isolated in each case. We suggest that initial antibiotic therapy for severe pneumonia in young infants should be tailored to cover B. catarrhalis infection.

Humans↗

Globular bodies: a primary cause of the opacity in senile and diabetic posterior cortical subcapsular cataracts?

We examined 9 cataracts from maturity onset diabetics and 4 senile posterior subcapsular cataracts by scanning electron microscopy, transmission electron microscopy, immunofluorescence for crystallin proteins and actin, histochemical methods and x-ray diffraction. The cataractous regions contained spherical globules up to 20 mu in diameter, often in a fibrous matrix. Some were extracellular Morgagnian globules, apparently formed by blebbing from the cell surface; others appeared to have been formed intracellularly. The area of globular degeneration was usually 300 mu deep, but had deeper fusiform extensions. Morphological changes in the cell cytoplasm varied according to their depth in the cataract. Electron microscopy showed intracellular and extracellular globules, many of them were bounded by lipid bilayer membranes. Immunofluorescent staining showed that all the globules contained gamma-crystallin; some contained alpha- and beta-crystallins and actin. All the globules contained higher concentrations of cysteine or cystine than the surrounding lens tissue but they did not react to stains for carbohydrate or calcium. X-ray diffraction studies showed that crystalline calcium salts were absent. Globules and cavities averaged 45% of the total area in cross section. Assuming an area of cataract to be 300 micron thick and that globules 1 mu in diameter scattered, while 2--20 mu in diameter reflected light, we calculated that light passing through such a thickness would be reduced by 65%. Thus the globules could account for most of the opacity of the cataractous area. Presumably the fibrous degeneration of the cells causes enough light scattering to account for the remainder of the reduction. Cataract patients complain of decreased visual acuity, a golden halo around objects, and difficulties when driving while facing oncoming traffic at night. These probably result from light scattering. In our previous experiments, globular bodies containing gamma-crystallin were found in cells grown in tissue culture, and blebs with increased acitn content similar to Morgagnian globules were formed in tissue culture by treating differentiated rat lens cells of stage 2 by cytochalasin D (which impaired microfilament function). These results suggest the possibility of simulating in tissue culture the morphological alterations seen in the cataractous cell.

Aged↗

[Malignant glaucoma (author's transl)].

A 35-year-old male, one of three siblings with spherophakia and glaucoma, was treated surgically by aspiration of vitreous through a posterior sclerotomy wound, and air insufflation of the anterior chamber in each eye. Previous peripheral or sector iridectomies were not helpful in contolling the condition. Some improvement was noted with intensive cycloplegic therapy in each eye. In the right eye, one surgical procedure was sufficient to arrest the condition. In the left eye, a sector iridectomy, and three posterior sclerotomies combined with air insufflations of the anterior chamber have been unsuccessful in controlling the pressure. A further sclerotomy with a vitrectomy instrument to remove most of the formed vitreous followed by air insufflation of the anterior chamber is proposed for the uncontrolled eye and if this is not successful in controlling the condition, lens extraction will be carried out.

Adult↗

A clinical study of the autorefractor, an antomatic refracting device.

Four hundred eyes were examined with the Autorefractor, an automatic refracting machine, and the results compared with those found by standard techniques of clinical refraction with and without cycloplegia. Agreement was good for spherical power, cylindrical power and spherical equivalents, but less so for cylinder axes.

Adolescent↗