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Biomedical subjects

J E Edwards

Publications and source records attributed to J E Edwards.

At least 19 recordsLinked to original sources

Time in lairage needed by pigs to recover from the stress of transport.

Two experiments were carried out in which a total of 602 pigs were slaughtered after being held in lairage for periods ranging from less than one hour to 21 hours. In the first experiment the pigs were handled under ideal conditions and slaughtered at the University of Bristol slaughterhouse; in the second the pigs were killed at a commercial plant. Blood samples collected at exsanguination were analysed for indices of stress. There were no consistent effects of time in lairage on the levels of lactate and creatine phosphokinase. Plasma cortisol and beta-endorphin levels were reduced by lairage for three hours or more in the first experiment and cortisol was reduced by lairage for two hours or more in the second; beta-endorphin was not measured in the second experiment. A period of rest in lairage allowed the pigs to recover from transport and the associated handling and the recovery appeared to be complete within two to three hours.

Animals

Influence of width and bends on the ease of movement of pigs along races.

Pigs could be moved along a race 120 cm wide more quickly than along a race 45 cm wide. The presence of a bend with an angle of 45 degrees slowed their progress by about 10 per cent, a bend of 90 degrees or 120 degrees slowed them by 19 per cent and a 180 degrees bend slowed them by 44 per cent. There was little evidence of any interaction between the effects of width and angle of bend; the effect of a sharp bend could not be compensated for by increased width. The pigs became accustomed to the races and moved more quickly in later runs.

Animal Husbandry

Response of newly hatched chicks to inanition.

Newly hatched chicks were kept for up to 48 hours without food and water and compared with a control group of chicks given access to food and water within six hours of hatching. The deprived chicks progressively lost body water and developed increases in plasma total protein concentration consistent with a decrease in plasma volume. They demonstrated a stronger motivation to drink and drank more when offered water, suggesting that they had become dehydrated. There was evidence, however, that normally access to food was necessary to initiate drinking. The deprived chicks continued to rely on fat metabolism to supply their energy needs whereas the fed birds showed rapid reductions in circulating levels of beta-hydroxybutyrate and increases in plasma glucose and liver glycogen concentrations, indicating a change to carbohydrate-orientated energy metabolism. The deprived chicks lost weight at an average of 0.14 g/hour and weighed 16.5 g less than the fed chicks after 48 hours.

3-Hydroxybutyric Acid

Candida albicans adherence to endothelial cells.

Mechanisms of adherence to vascular endothelial cells by microorganisms on a molecular level can be elucidated by using monoclonal antibodies, purified cell wall constituents, and receptor analogues. Since these agents are expensive and available in limited quantities, a microsystem for probing adherence mechanisms to these cells has become essential. We studied techniques to accurately quantify the adherence of L-[35S]methionine-labeled Candida albicans to human umbilical vein endothelial cells in a 96-well microtiter plate system while avoiding specific problems related to Candida coadherence and avid binding to plastic. The endothelial cells were grown on a collagen matrix in individually detachable microwells enabling the determination of the number of adherent organisms from radioactive counts of the entire well. This procedure has the critically important advantage of obviating the need to remove adherent Candida from the wells. Expressing adherence to endothelial cell monolayers as the percentage of total organisms added to each well significantly decreases the variability of the assay.

Antibodies, Monoclonal

Pulmonary circulation in pulmonary atresia associated with the asplenia cardiac syndrome.

OBJECTIVE: The goal of this study was to determine the patterns of the pulmonary circulation in patients with pulmonary atresia and asplenia. BACKGROUND: The asplenic cardiac syndromes characteristically have complex cardiac anomalies including pulmonary stenosis or atresia. Definition of the pulmonary artery circulation and pulmonary venous connections is needed for consideration of surgical procedures. METHODS: In 35 patients, the sources of pulmonary blood flow, anatomic features of pulmonary arteries and pulmonary venous connections were determined from angiograms or autopsy specimens. RESULTS: The main pulmonary artery was absent or hypoplastic in 91% of patients; most had a ductus arteriosus. The right and left pulmonary arteries were confluent in 90% and usually of normal size (right 71%, left 63%). Total anomalous pulmonary venous connections were present in 38%. CONCLUSIONS: The anatomic features of the pulmonary arteries in pulmonary atresia associated with the asplenic cardiac syndrome are usually favorable for palliative surgical procedures. Total anomalous pulmonary venous connection may exist as a complicating factor.

Child

Longer journeys to processing plants are associated with higher mortality in broiler chickens.

1. The number of broilers recorded as dead on arrival (DOA) in 1113 journeys to a poultry processing plant was related to the length of the journeys. The average journey time was 3.3 h and the maximum recorded was 9 h. 2. Overall, 0.194% of 3.2 million birds were DOA. Mortality was higher for journeys which took longer. For journeys lasting less than 4 h the incidence of dead birds was 0.156%; for longer journeys the incidence was 0.283%. 3. There was some evidence that it was time of journey, rather than distance travelled, that was more important in determining mortality.

Animals

Current strategies for treating invasive candidiasis: emphasis on infections in nonneutropenic patients.

The increasing incidence of nosocomial candidal infections is a pivotal problem for patients who do not have neutropenia. In contrast with previous principles, candidemia--even in nonneutropenic patients--should be treated with systemic antifungal agents except in rare circumstances. Amphotericin B remains the agent of choice for treatment of hematogenously disseminated candidiasis and for candidemia, although the optimal dosage and duration of this therapy are poorly defined. Therapy with fluconazole is an alternative for patients who are intolerant to amphotericin B; the efficacy of fluconazole compared with that of amphotericin B in hematogenous candidal infections is unknown but is currently being evaluated. Removal of prosthetic devices that are infected with Candida is necessary in nearly all instances to cure the infection. Similarly, removal of an indwelling catheter whose use is associated with candidemia, as opposed to leaving the catheter in place during antifungal therapy, may increase survival rates of patients and lower their rates of complication. Antifungal prophylaxis may be useful for patients who are undergoing transplantation of an organ.

Amphotericin B

Profile of alopecia areata: a questionnaire analysis of patient and family.

Eight hundred patients with alopecia areata (AA) responded to a detailed questionnaire that was compiled, distributed, and analyzed by Help Alopecia International Research, Inc. (HAIR). Among those responding, 28% were men and 72% were women. Fifty percent had localized alopecia, 30% had alopecia totalis, and 20% had alopecia universalis. Forty-eight percent developed their initial onset before the age of 20. A very strong family history of 42% was found. There were 333 additional family members with AA. Many patients and relatives had concurrent atopic diseases (seasonal rhinitis, bronchial asthma, and atopic dermatitis). Associated autoimmune diseases including vitiligo, thyroid disease, and collagen vascular disease in patients and relatives appeared consistent with previous reports. Insulin dependent diabetes mellitus (IDDM) was not increased in patients but greatly increased in relatives. Additional analysis suggests a genetic association between the two diseases where expression of AA may prevent the development of IDDM.

Alopecia Areata

Modulation of interactions of Candida albicans and endothelial cells by fluconazole and amphotericin B.

Using an in vitro model of intravascular infection, we examined the effects of exposure to subinhibitory concentrations of fluconazole and amphotericin B on the ability of Candida albicans to adhere to and damage human umbilical vein endothelial cells. Incubation of the organisms for 18 h in 0.5x the MICs of fluconazole and amphotericin B inhibited endothelial cell adherence by 22 and 91%, respectively (P less than 0.001 for each drug). Candida-induced endothelial cell injury was also decreased by exposing the organisms to the antifungal drugs while in contact with the endothelial cells. Fluconazole inhibited damage by approximately 50% at concentrations ranging from 0.25x to 5x the MIC (P less than 0.01 for each concentration). Exposure to amphotericin B at 0.5x the MIC completely blocked the ability of the organisms to injure endothelial cells. The capacities of the antifungal agents to inhibit endothelial cell injury paralleled their abilities to suppress candidal germination. Organisms exposed to up to 5x the MIC of fluconazole had diminished, but still detectable, germ tube production and elongation, whereas incubation in 0.5x the MIC of amphotericin B completely abrogated germination. In addition to their direct effects on the growth of C. albicans, fluconazole and amphotericin B may decrease the ability of the fungus to disseminate hematogenously by inhibiting the organisms' capacity to adhere to and injure endothelial cells.

Amphotericin B

Cell extracts of Candida albicans block adherence of the organisms to endothelial cells.

Cell extracts of Candida albicans were fractionated by concanavalin A affinity chromatography. Eluted mannosylated proteins (fraction II) and nonbinding, nonmannosylated proteins (fraction I) were collected and assayed directly for inhibition of adherence of C. albicans to endothelium. Fraction II blocked blastospore adherence to endothelial cells. Fraction I blocked both blastospore and germ tube adherence to endothelial cells. Monoclonal antibody OKM-1 (anti-CR3) and an anti-C. albicans monoclonal antibody, CA-A (anti-CR2), reacted in Western blots with proteins from fraction I, suggesting the presence of the CR2- and CR3-like proteins that have been previously identified on C. albicans germ tubes.

Adhesiveness

Susceptibility testing of Cryptococcus neoformans: a microdilution technique.

We studied a series of test conditions in a microtiter system to define the optimal method for determining the susceptibility of Cryptococcus neoformans to antifungal agents. Twenty-one isolates of C. neoformans were grown for 24 or 48 h in four chemically defined media: yeast nitrogen base (BYNB 7); RPMI 1640; synthetic amino acid medium--fungal (SAAMF), buffered at pH 7.0 to select the medium that best supported growth of this fastidious yeast; and yeast nitrogen base, pH 5.4 (YNB 5.4). Maximum growth of C. neoformans, at 35 degrees C, was obtained in YNB 5.4, with the next highest growth levels in BYNB 7, SAAMF, and RPMI. Growth at 24 h was uniformly poor in all media and lacked reproducibility. In contrast, incubation for 48 h gave adequate growth with low standard deviations, and 48 h was selected as the optimal incubation period for this study. Comparison of the relationship between growth kinetics and initial inoculum size for eight cryptococcal isolates showed that 10(4) cells per ml yielded optimal growth in BYNB 7 and YNB 5.4, whereas 10(5) cells per ml was optimal in RPMI and SAAMF. Furthermore, variation of inocula from 10(3) to 10(5) cells per ml showed small but significant inoculum effects in determining MICs of fluconazole, amphotericin B, and flucytosine for C. neoformans. Therefore, 10(4) cells per ml was chosen as the optimal inoculum for susceptibility testing in this study. Mean MICs of fluconazole, amphotericin B, and flucytosine for 21 crytococcal isolates in RPMI and BYNB 7 were low (for example, fluconazole had mean MICs of 1.2 and 1.3 micrograms/ml in RPMI and BYNB 7, respectively) and differed significantly from medium to medium. In contrast, the MICs obtained in SAAMF were significantly higher (e.g., fluconazole had a mean MIC of 2.2 micrograms/ml). Variance in MICs was large with fluconazole and flucytosine but small with amphotericin B, irrespective of the medium used. A microtiter system employing BYNB 7 as the medium, 48 h as the incubation period, and 10(4) cells per ml as the final inoculum is a simple, accurate, and reproducible method for the testing of C. neoformans susceptibility to fluconazole, amphotericin B, and flucytosine.

AIDS-Related Opportunistic Infections

Right ventricular dysplasia: morphological findings in 13 cases.

OBJECTIVE: To characterize the pathological features of right ventricular dysplasia (RVD). DESIGN: Retrospective morphological case study. SETTING: Three referral-based university medical centres. PATIENTS: Thirteen subjects (one female) aged 16 to 55 years including 10 necropsy hearts from sudden deaths out of hospital, one explant heart and two partial right ventricular resections from patients with intractable ventricular tachycardia. MAIN RESULTS: Most hearts showed hypertrophy and localized or generalized dilatation of the right ventricle. Transillumination revealed myocardial thinning of variable configuration usually conforming to regions of dilatation. Common sites of involvement were apex, infundibular region and posterobasal wall. Histologically, focal or extensive segments of right ventricular myocardium were absent or replaced. Three patterns were found: right ventricle markedly thinned, epicardium and endocardium contiguous, virtually no intervening tissue; wall normal thickness or thinned, myocardium almost totally replaced by fat; and wall normal or thin, myocardium largely replaced by fat with scattered residual myocardial cells and fibrous tissue (the predominant pattern). Endocardial fibrosis was present in eight cases and focal mononuclear cell infiltrates in 10. Electron microscopy in two cases showed nonspecific findings. CONCLUSIONS: RVD has gross and microscopic features which permit its recognition. While a majority of cases are likely congenital (genetic or acquired in utero), the possibility of postnatally acquired conditions (inflammatory, toxic, ischemic) inducing RVD must be explored. The incidence and importance of RVD as a cause of sudden death can only be assessed by continued systematic and detailed studies of patients with recurrent ventricular tachycardia and of hearts, especially from sudden death victims. Although uncommon, RVD should be considered in the differential diagnosis of arrhythmia and sudden death by both clinicians and pathologists.

Adolescent

Effect of the angle of slope on the ease with which pigs negotiate loading ramps.

In experiments to investigate the time taken by pigs to negotiate ramps with different slopes it was found that they ascended with greater facility than they descended. Between 0 degrees and 20 degrees, the slope appeared to have little effect on the time taken to ascend or descend. Above 20 degrees the time taken to ascend increased linearly. The relationship between the time taken to descend and the slope above 20 degrees was biphasic with times increasing substantially above 35 degrees. There were also differences between the times taken on different days but no evidence of habituation. Pigs took longer to climb steeper ramps with wider spaces between cleats but there was no significant effect on the time taken to descend.

Animals

Candida albicans stimulates endothelial cell eicosanoid production.

The response of human umbilical vein endothelial cells to invasion by Candida species was examined in vitro. Live Candida albicans caused significant endothelial release of eicosanoids, mainly prostaglandins. Since prostaglandin I2 (PGI2) is an important prostaglandin produced by endothelial cells, factors influencing its release were studied. The ability of different strains and species of Candida to induce endothelial PGI2 release was closely related to their capacity to injure the endothelium (r = .99). C. albicans was the only species tested that either stimulated PGI2 release or damaged the endothelial cells; only this organism possessed detectable phospholipase activity. Candida glabrata and Candida tropicalis had no phospholipase activity and neither increased PGI2 release nor caused significant endothelial damage. Close proximity with germinated C. albicans was required for endothelial injury and PGI2 release. The ability of C. albicans to stimulate endothelial cells may have important implications in regulating neutrophil activities against organisms that interact with endothelial cells.

Arachidonic Acid

Comparison of fluconazole and amphotericin B for treatment of disseminated candidiasis and endophthalmitis in rabbits.

We compared the efficacy of intravenous fluconazole (80 mg/kg of body weight per day) with that of amphotericin B (1 mg/kg/day) for the long-term treatment of endophthalmitis in rabbits with disseminated candidiasis. After 17 days of therapy, fluconazole decreased the fungal colony counts of the choroid-retinas significantly more than did the saline control (P less than 0.05); however, after 24 days of fluconazole therapy, this treatment effect was lost and fluconazole was no more effective than saline. In contrast, treatment for 24 days with amphotericin B reduced the vitreous and choroid-retina fungal colony counts significantly more than either fluconazole or saline (P less than 0.05 for both treatment groups). After 17 days of therapy, indirect ophthalmoscopy revealed less severe eye involvement in both antifungal treatment groups than in saline controls; however, this difference reached statistical significance only for the amphotericin B-treated rabbits (P less than 0.05). Also, there was a trend towards worsening eye lesions, as seen by indirect ophthalmoscopy, in the fluconazole-treated rabbits after 24 days of therapy, which roughly paralleled the quantitative culture results. Despite the presence of negative choroid-retina cultures, some rabbits in all treatment groups had persistently visible eye lesions, indicating that ophthalmoscopic resolution of Candida endophthalmitis may lag behind lesion sterilization. Amphotericin B was superior to fluconazole in the treatment of Candida endophthalmitis in this model.

Amphotericin B