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Biomedical subjects

D Gardner

Publications and source records attributed to D Gardner.

At least 37 records · Page 2Linked to original sources

TgPVR21 mice for testing type-3 oral poliovirus vaccines: role of clinical observation and histological examination.

Transgenic mice susceptible to poliovirus (TgPVR mice) have been used to study poliovirus neurovirulence and attenuation. It was shown recently that mouse line TgPVR21 may be a suitable model to evaluate neurovirulence safety of oral poliovirus vaccine. It was important to determine whether TgPVR21 mice are sensitive enough to discriminate between type-3 reference and 'marginal' vaccines, i.e. those that failed the monkey test while containing only slightly increased amounts of neurovirulent revertants at position 472 of the viral genome as measured by a molecular assay MAPREC. Data presented here demonstrate that TgPVR21 mice are not less sensitive than monkeys in the detection of marginal vaccines. In contrast to the monkey neurovirulence test, which is based on histological examination of the CNS, the TgPVR21 mouse neurovirulence test revealed marginal vaccines by simple analysis of clinical signs without requiring a laborious histological examination.

Animals↗

Postural dynamics and the preferred critical boundary for visually guided reaching.

How do people choose an action to satisfy a goal from among the actions that are afforded by the environment? In 3 experiments the action modes used by actors to reach for a block placed at various distances from them were observed. In each experiment, when actors were not restricted in how they could reach for the object, the transition from their reaching using only arm extension to a mode of reaching in which they used the upper torso to lean forward occurred at closer distances than each actor's absolute critical boundary, beyond which the former action was no longer afforded. In Experiments 2 and 3 actors' seated posture was varied so that the effect of postural dynamics on the distance at which actors actually chose to make the transition between action modes, the preferred critical boundary, could be examined. The results are consistent with the proposal that the preferred critical boundary reflects the relative comfort of available modes of reaching.

Adult↗

Cryptosporidiosis outbreak associated with an educational farm holiday.

In April 1995 an outbreak of cryptosporidiosis occurred among 43 schoolchildren and four staff after a week's holiday at a rural farm. A retrospective cohort study found illness to be 3.8 times more likely in those who handled calves and 1.5 times more likely in those who habitually bit their nails or sucked their thumbs. Cryptosporidium oocysts were detected in faecal specimens from six of the 29 pupils and one of the four staff who were ill. Infection occurred in children despite supervised handwashing. The infection hazards of farm visits need more publicity, and further study on the risks of cryptosporidiosis transmission in the farm environment is required to guide preventive measures.

Adult↗

A poliovirus-susceptible transgenic mouse model as a possible replacement for the monkey neurovirulence test of oral poliovirus vaccine.

Two poliovirus-susceptible transgenic mouse (Tg PVR) strains, Tg1 and Tg21, were compared with the monkey test for their sensitivity to neurovirulence of live oral poliovirus vaccine (OPV). Intracerebral (i.c.) and intraspinal (i.s.) routes of inoculation were investigated to determine the most suitable combination of mouse strain and route. Evaluation of the mouse tests was performed using several indicators; clinical score and failure time were selected as the most efficient. Tg1 and Tg21 mice inoculated i.s. with type 2, and Tg21 mice inoculated i.s. with type 3 OPV were determined to be the most appropriate systems, whereas they are shown not to be suitable for type 1 OPV. The sensitivity of each of the two mouse models was at least equal to that of the monkey test, suggesting that these mouse systems might be considered as a potential replacement for the monkey test of OPV. However, more data are needed to establish regulatory criteria of acceptability for vaccine lots tested in Tg PVR mice. This is the first study conducted with Tg PVR mice with all three types of poliovirus vaccine preparations.

Animals↗

Consecutive salmonella outbreaks traced to the same bakery.

Two consecutive community outbreaks of Salmonella enteritidis phage type 4 (PT4) traced to the same bakery occurred in Cardiff, Wales during August-September 1992. In the first outbreak, illness was associated with eating custard slices (odds ratio 23.8, 95% confidence interval 6.5-94.4, P < 0.0001), and in the second, with eating fresh cream cakes (odds ratio 15.8, 95% confidence interval 1.6-374, P = 0.004). Environmental investigations implicated cross-contamination during preparation of the cold-custard mix as the cause of the first outbreak, and inadequate cleaning and disinfection of nozzles used for piping cream in the second outbreak. S. enteritidis PT4 was isolated from fresh cream sponge cake retained by a case and from two fresh cream cakes and four environmental swabs obtained at the bakery. This incident illustrates the hazard of widespread environmental contamination with salmonella and the need for thorough environmental cleansing for any premises implicated in an outbreak of food poisoning.

Adolescent↗

A milk-borne campylobacter outbreak following an educational farm visit.

After a nursery school trip to a dairy farm, 20 (53%) of 38 children and 3 (23%) of 13 adult helpers developed gastrointestinal infection. Campylobacter jejuni was isolated from 15 primary cases and from 3 of 9 secondary household cases. A cohort study of the school party found illness to be associated with drinking raw milk (relative risk 5.4, 95% confidence interval 1.4-20.4, P = 0.001). There was a significant dose response relationship between amount of raw milk consumed and risk of illness (chi 2-test for linear trend 12.1, P = 0.0005) but not with incubation period, severity of symptoms or duration of illness. All 18 human campylobacter isolates were C. jejuni resistotype 02 and either biotype I (number 16) or biotype II (number 2). Campylobacter was also isolated from samples of dairy cattle and bird faeces obtained at the farm but these were of different resisto/biotypes. Educational farm visits have become increasingly popular in recent years and this outbreak illustrates the hazard of exposure to raw milk in this setting.

Adult↗

Tyramine content of previously restricted foods in monoamine oxidase inhibitor diets.

Traditional monoamine oxidase inhibitors (MAOIs) remain an important class of drugs for a variety of psychiatric conditions, including depressive illnesses, anxiety, and eating disorders. It was the objective of this study to refine the MAOI diet by determining the tyramine content of a variety of untested and "controversial" foods that continue to appear on MAOI diet-restricted food lists. A secondary objective of the study was to evaluate the effect of freshness on the tyramine content of some foods. Fifty-one food samples were evaluated for tyramine content by liquid chromatography. Food samples included a selection of sausages, beverages, sliced meat products, including chicken liver, and some fruits, including raspberries, bananas, and banana peels. Foods that were found to have dangerously high concentrations of tyramine (> or = 6 mg/serving) included chicken liver aged 9 days (63.84 mg/30 g), air-dried sausage (7.56 g/30 g), soy sauce (0.941 mg/ml), and sauerkraut (7.75 mg/250 g). Of the foods analyzed in this study, only those with high tyramine content per serving should continue to be absolutely restricted. All other foods are either safe for consumption or safe in moderation. The data provided should be combined with the data from other similar analytical studies to develop a list of foods that should be absolutely restricted. A more accurate list of restricted foods may enhance patient dietary compliance.

Diet Therapy↗

The successful pharmacological treatment of adolescents and young adults with borderline personality disorder: a preliminary open trial of flupenthixol.

Borderline personality disorder is a significantly disabling disturbance often arising in adolescents or young adults. In the absence of demonstrated effective treatments in this population, this open prospective study evaluated the effect of low dose (3 mg per day) flupenthixol in 13 rigorously diagnosed adolescents with borderline personality disorder. Therapeutic outcome over eight weeks of treatment assessed across measures of impulsivity, depression/dysphoria, general psychopathology and global functioning showed significant improvement in all spheres. These findings suggest that low dose flupenthixol may have a role to play in the short-term treatment of this population.

Adolescent↗

Multipurpose practice guideline modules for clinical decision analysis and quality improvement.

This study aimed to measure the loss of information in communication between clinical researchers and information system developers, to design a tool for sharing clinical practice guidelines, and to test the feasibility of this tool in knowledge base development. The analysis of a sample of 101 randomized controlled clinical trials indicated that exact numeric results were published in only 64 percent of the trials. While structured abstracts were associated with improved total quality scores (p0.001), there was no significant improvement in reporting numeric results (p=0.31). Based on the documented loss of information and the needs of various parties involved, the concept of a multipurpose knowledge module was developed for sharing clinical practice recommendations. Such clinical practice guideline modules were applied in developing the knowledge base of a quality feedback expert system (QFES).

Abstracting and Indexing↗

Immunomodulation by metals.

A symposium entitled Immunomodulation by Metals was held at the 32nd Annual Meeting of the Society of Toxicology (SOT) in New Orleans, Louisiana. The symposium was co-sponsored by the Immunotoxicology and Metals Specialty Sections of SOT and was designed to describe the types of adverse immunological reactions which occur in response to environmental and/or occupational exposure to metals. Epidemiological evidence and underlying mechanisms responsible for the observed alterations were also discussed. The following is a summary of each of the individual presentations.

Animals↗

Space exploration and toxicology: a new frontier.

Results of the microbial and immunological studies discussed above clearly illustrate an in-flight or post-flight blunting of the cellular immune mechanism in humans and test animals, coincident with a relative increase in pathogenic microorganisms. This situation predicts an increased incidence of in-flight infectious disease events. To prevent this from occurring, most observers agree that a robust program of preflight and in-flight immunological and microbiological monitoring, combined with an effective countermeasures program, are required for optimally successful long-duration spaceflight.

Animals↗

Hypertensive episode associated with phenelzine and tap beer--a reanalysis of the role of pressor amines in beer.

A case report of a hypertensive crisis resulting from the ingestion of tap beer in a patient on an irreversible monamine oxidase inhibitor (MAOI; phenelzine) stimulated the investigation of different kinds of beer for tyramine concentration. The objective was to determine the tyramine concentration in tap and bottled beers. A total of 98 beer samples (79 different brands of beer) were analyzed by high-performance liquid chromatography for tyramine. Of these 98 beers, 49 were bottled or canned beers and 49 were beers on tap. All of the bottled beers analyzed had safe tyramine concentrations (< or = 10 mg/liter; range, 0 to 3.16 mg/liter) and, thus, do not require restriction in patients receiving MAOIs. Therefore, the consumption of canned or bottled beer, including dealcoholized beer, in moderation (fewer than four bottles or cans; 1.5 liters within a 4-hour period) appears to be safe and does not require restriction in patients receiving MAOIs. Only 4 of 98 beer samples studied were found to have a dangerous (> 10 mg/liter) tyramine concentration, one of which was the index beer. The tyramine concentration in these four beers ranged from 26.34 to 112.91 mg/liter. All four of these beers were tap beers produced by bottom fermentation (lagers) and brewed by a secondary fermentation process. Although we did not find any visible bacterial growth in the tap beers with high tyramine content, this finding does not preclude the possibility that bacterial contamination, bacterial growth, production of tyramine, and eventually bacterial death occurred at some earlier time. Therefore, to err on the side of caution, it is recommended that patients on irreversible MAOIs avoid beers on tap.

Adult↗

Transgenic PVR Tg-1 mice for testing of poliovirus type 3 neurovirulence: comparison with monkey test.

Transgenic mice susceptible to poliovirus were recently produced by two groups of investigators. In this study, we compared the sensitivity of PVR Tg-1 transgenic mice and rhesus monkeys to poliovirus type 3. We found that intracerebrally inoculated Tg-1 mice are able to differentiate wild-type strain from attenuated strains and from a vaccine revertant. However, this mouse system can not discriminate between live poliovirus vaccine lots which passed the intraspinal (i.s.) monkey neurovirulence safety test (WHO) and those that failed. Unlike the monkey test which can detect as failed those vaccine lots which possess above 1% revertants at the 472 (U-->C) position, the test in Tg-1 mice inoculated intracerebrally (i.c.) did not recognize virus preparations containing even three percent revertants. Thus, the PVR Tg-1 i.c. mouse model is suitable for epidemiological and other virological studies, but it does not appear to be useful for neurovirulence testing of live poliovirus vaccines. A solution to the latter may be found in the use of a more sensitive i.s. route of inoculation of PVR Tg mice.

Animals↗

Inhibition of neutral endopeptidase amplifies the effects of endogenous atrial natriuretic peptide on blood pressure and fluid partition.

Neutral endopeptidase (EC 3.4.24.11) is a wide-spread enzyme that degrades atrial natriuretic peptide (ANP). We studied the effects of a potent neutral endopeptidase inhibitor, SQ 28,603, given intravenously (30 mg/kg over 45 min) to anesthetized, bilaterally nephrectomized Sprague-Dawley rats. Infusion of vehicle alone was accompanied by a modest increase, 3.2 +/- 2.2% (mean +/- SE), in mean arterial blood pressure (MAP) and a slight rise in hematocrit (Hct) of 0.9 +/- 0.7%. After administration of SQ 28,603, MAP fell 3.2 +/- 0.5%, and Hct rose 4.9 +/- 0.5%, both significantly different from the changes with vehicle alone; the lesser increase in plasma protein concentration (2.5 +/- 0.4%) suggested an increase in vascular permeability to both plasma protein and fluid similar to that caused by ANP. When SQ 28,603 was given to rats pretreated with rabbit antirat ANP antiserum, blood pressure rose by 3.8 +/- 0.5%, and Hct increased by 1.0 +/- 0.4%, values very similar to those observed with vehicle alone. Inhibition of neutral endopeptidase therefore amplifies the actions of endogenous ANP on blood pressure and fluid partition.

Alanine↗