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Biomedical subjects

T Grant

Publications and source records attributed to T Grant.

At least 19 recordsLinked to original sources

Effect of bacterial invasion of macrophages on the outcome of assays to assess bacterium-macrophage interactions.

In vitro assays to quantify killing of bacteria by macrophages provide useful insights into host-pathogen relations. In the present study, we used strains of Yersinia enterocolitica and Escherichia coli which varied in their ability to invade mammalian cells to evaluate these assays. The results showed that 30 min and 24 h after incubation with murine bone marrow-derived macrophages, strains of Y. enterocolitica and E. coli which expressed invasin (an outer membrane protein which allows bacteria to penetrate mammalian cells) achieved significantly greater numbers in macrophages than otherwise isogenic bacteria which lacked this protein (P < 0.01). When the 24-h data were corrected for the number of bacteria ingested by macrophages initially, the differences between invasin-positive and -negative bacteria were no longer evident (P> 0.2). This study has shown (1) that invasin-mediated penetration of macrophages by bacteria is not associated with enhanced intracellular survival, and (2) that invasion of macrophages by bacteria may influence the interpretation of assays for bactericidal capacity unless allowance is made for the number of bacteria ingested during the early phase of the assay.

Animals

Normal variability of postural measures: implications for the reliability of relative balance performance outcomes.

The reliability of outcome measures obtained using the Balance Master and the limits of stability in anterior, posterior, and lateral directions were evaluated in 70 healthy subjects aged 20 to 32 years. Data relating to static sway and the ability to shift the centre of gravity to preset targets were collected on three occasions one week apart. The centre of gravity position and limits of stability were determined over three trials and data converted from a relative reference system to absolute displacements from vertical. Intraclass correlation coefficients revealed fair to poor reliability of static and dynamic sway measures (coefficients < or = 0.55) and excellent reliability of limits of stability measures and the position of the centre of gravity (coefficients > or = 0.75). The variability in outcome measures from tests which do not maximally challenge the postural control system may be a hallmark of normal balance performance. Further, the intersubject variation in resting centre of gravity position and in limits of stability supports the use of absolute performance measures as the interpretive value of data expressed relative to standard norms is limited.

Adult

Identification of virulence-associated characteristics in clinical isolates of Yersinia enterocolitica lacking classical virulence markers.

Yersinia enterocolitica is an important enteric pathogen which has well-defined virulence determinants that allow the bacteria to become established in their hosts and overcome host defenses. A number of strains obtained from patients with diarrhea, however, lack these genes. Accordingly, the mechanisms by which they cause disease are uncertain. Most of these isolates belong to biotype 1A. Strains of this biotype are also frequently isolated from a variety of nonclinical sources, such as food, soil, water, and healthy animals, and there is evidence that some of these strains are avirulent. In this study we investigated 111 strains of Y. enterocolitica biotype 1A, 79 from symptomatic humans and 32 from nonclinical sources, for virulence-associated characteristics. DNA hybridization studies showed that none of the strains carried sequences homologous with pYV, the approximately 70-kb Yersinia virulence plasmid. Some strains hybridized with DNA probes for one of the following chromosomal virulence-associated genes: ail (7.2%), myfA (11.7%), ystA (0.9%), and ystB (85%). In addition, 33 strains (29.7%) produced an enterotoxin that was reactive in infant mice. However, the frequencies of these virulence-associated properties in clinical and nonclinical isolates were similar. Clinical isolates invaded HEp-2 cells and Chinese hamster ovary cells to a significantly greater extent than nonclinical strains (P < or = 0.002). In addition, clinical strains colonized the intestinal tracts of perorally inoculated mice for significantly longer periods than nonclinical isolates (P < or = 0.01). Light and electron microscopic examination of tissue culture cells incubated with invasive yersiniae revealed that the bacteria invaded selected cells in large numbers but spared others, suggesting that biotype-1A strains of Y. enterocolitica may invade cells by a novel mechanism. These results indicate that some clinical isolates of Y. enterocolitica which lack classical virulence markers may be able to cause disease via virulence mechanisms which differ from those previously characterized in enteropathogenic Yersinia species.

Animals

Contact lens induced peripheral ulcers during hydrogel contact lens wear.

PURPOSE: Ulcerative keratitis is the most serious adverse response associated with contact lens wear. However, some reports of microbial keratitis in the literature may refer to a less severe form of corneal ulceration, which we have termed contact lens induced peripheral ulcers (CLPU). METHODS: We present details of 11 cases of CLPU which occurred in clinical trials at our research unit. RESULTS: CLPU episodes are characterized by a single, small (< 2 mm diameter) circular lesion in the corneal mid-periphery or periphery, involving a focal loss of the full thickness of the epithelium associated with subepithelial stromal infiltrates. Patient symptoms may include ocular irritation, pain, photophobia, and lacrimation. They are usually associated with the use of hydrogel extended wear contact lenses. The lesions are self-limiting, typically healing within 7 days without treatment. After resolution, a small circular scar remains, which does not affect vision because of its peripheral location. The etiology of CLPU is unclear. In our studies, the incidence of CLPU was similar in conventional (2.9% per patient year) and disposable (2.0% per patient year) hydrogel extended wear, but lower during intermittent extended wear (1.6% per patient year); only one case occurred during daily wear (< 0.5% per patient year). CONCLUSIONS: A conservative approach to patient management of all suspected cases of corneal ulceration is encouraged. However, we suggest that future reports of ulcerative keratitis associated with various lens types and wearing schedules should differentiate between potentially devastating microbial keratitis and the relatively innocuous peripheral ulceration described in this paper.

Adult

Gram-negative bacteria can induce contact lens related acute red eye (CLARE) responses.

PURPOSE: Twelve volunteers participated in a study designed to measure the overnight corneal edema response with a variety of hydrogel contact lenses. During the study four subjects (5 eyes) experienced a contact lens related acute red eye (CLARE) reaction, which manifested as severe ocular pain, photophobia, corneal infiltration, and conjunctival hyperemia. An additional five subjects (7 eyes) developed corneal infiltrates only. Twelve eyes (of 9 subjects) showed no response. METHODS AND RESULTS: Upon microbiological examination of the contact lenses and storage solutions, gram-negative bacteria were isolated in large amounts. The bacteria were identified as Serratia marcescens, Pseudomonas putida, and Pseudomonas aeruginosa. Significantly greater numbers of bacteria were isolated from contact lenses of subjects who experienced CLARE than from the other subjects (P = 0.005) and from the contact lenses of subjects who experienced an adverse reaction (CLARE or infiltrates) than from the other subjects (P < 0.001). The contaminating bacteria are thought to have been introduced to the lens storage vials as a result of lens handling and subsequent failure to disinfect lenses. CONCLUSIONS: This study draws attention to the possible contribution of contaminated lenses and storage cases in contact lens related acute inflammation and specifically implicates gram-negative bacteria, in particular Pseudomonas spp. and Serratia spp., in the inducement of acute inflammatory reactions such as CLARE.

Acute Disease

Effect of acute ethanol ingestion on orthostatic vital signs.

STUDY OBJECTIVE: To determine the effect of acute ethanol intoxication on the results of orthostatic tilt testing. DESIGN: Prospective, randomized crossover study. Subjects received ethanol (1.1 gm/kg) or an equal volume of water added to nonalcoholic beer. Orthostatic vital signs, ethanol concentration, and relative volume status were checked initially and hourly for 8 hours. PARTICIPANTS: Twenty healthy human volunteers, 10 men, and 10 women. RESULTS: Peak ethanol concentration was 116 +/- 18 mg/dL (mean +/- SD) 1 hour after ingestion. ANOVA for repeated measures revealed a significant difference in orthostatic pulse change and relative volume deficit between the ethanol and placebo groups (P < .05). Post hoc testing revealed significant differences between the two groups at two, five, seven and eight hours post ingestion for pulse change, and two to eight hours for volume status (Bonferroni's corrected t test, P < .0055). At 2 and 5 to 8 hours, there were significantly more positive tilt tests (+/- 30 beat/minute increase) in the ethanol group than in the placebo group (P < .05). Starting at 2 hours, the ethanol group had a statistically significant relative fluid deficit averaging .5 L by 3 hours. There was no difference in postural blood pressure changes between the two groups. CONCLUSION: In healthy volunteers, ethanol intoxication resulted in exaggerated postural pulse changes and in a greater proportion of positive orthostatic tilt test results than in a placebo group. These changes were accompanied by significant relative fluid deficits.

Adult

Cocaine exposure during pregnancy: improving assessment with radioimmunoassay of maternal hair.

OBJECTIVE: To compare radioimmunoassay of postpartum maternal hair samples with a structured maternal interview for the detection of cocaine use during pregnancy. METHODS: Radioimmunoassay of hair samples obtained postpartum was compared with self-report of cocaine use obtained by confidential, structured interviews of 405 postpartum women. RESULTS: Cocaine or benzoylecgonine was detected in the hair samples of 129 of the 148 women (87%) who reported using cocaine at least once during pregnancy. Thirty-six of 257 women (14%) who reported that they had used no cocaine during pregnancy had positive hair tests. Positive hair assay with negative self-report was significantly more common among women who were unmarried (P = .001), African-American (P < .001), and multiparous (P = .035). CONCLUSIONS: Hair analysis is a valuable complement to maternal self-report by interview. The methods used together provide a useful clinical and research technique yielding a comprehensive estimate of gestational cocaine exposure. Either method alone may result in misclassification of gestational cocaine exposure.

Adult

Injury prevention instruction in the emergency department.

STUDY OBJECTIVE: To describe preventable pediatric injuries and the proportion receiving documented injury prevention instruction by emergency department personnel. DESIGN: Retrospective chart review. SETTING: A rural Level I trauma center. TYPES OF PARTICIPANTS: All injured children aged birth through 15 years presenting to our hospital from January 1, 1987, through December 31, 1987. MEASUREMENTS AND MAIN RESULTS: During the study period, 1,449 injuries presented to the trauma center. Motor vehicle crashes caused the largest number of preventable injuries (71), although the proportion of preventable injuries was higher among poisonings, burns, and pedestrian-automobile collisions. Among the 1,313 patients available to ED personnel at discharge, injury prevention instruction was indicated in 27% of cases but documented in the medical record in only 3%. ED personnel were more likely to document instruction for preventing poisoning than other causes of injury. CONCLUSION: Most preventable pediatric injuries treated and released by ED personnel do not receive documented injury prevention instruction.

Adolescent

CCLRU standards for success of daily and extended wear contact lenses.

Success in contact lens wear is often judged on the basis of patient "survival" rather than the achievement of satisfactory performance based on specific criteria. In 1971, Sarver and Harris defined a series of standards for successful polymethyl methacrylate (PMMA) lens wear which incorporated criteria for wearing time, comfort, vision, ocular tissue changes, and patient appearance. In this paper we propose a revision of these criteria based on current understanding of the ocular response to contact lens wear. These revised CCLRU (Cornea and Contact Lens Research Unit) standards for success are intended as realistic performance objectives, and can be applied in clinical trials to evaluate and compare the clinical performance of present and future rigid and soft contact lenses, worn for daily and extended wear.

Contact Lenses

Microwave irradiation and soft contact lens parameters.

We evaluated the effect of repeated microwave irradiation on soft contact lens parameters to determine if microwave disinfection affects soft lens polymers or parameters. Ten factory-sealed lenses from each of the four FDA categories were placed in Ciba AOsept cases which were filled with 13 ml of sterile unpreserved saline. The cases were placed in a 10-cm diameter circle on the rotating plate of a standard 2450 MHz 650 W microwave oven and exposed to repeated 5-min cycles of microwave irradiation. The lens parameters, including back vertex power, back optic zone radius, diameter, thickness and water content, were measured over a period of 200 cycles to simulate over 6 months of daily disinfection. The postirradiation measurements were compared to baseline measurements taken before microwave exposure. We found statistically significant changes in many lens parameters, but all were small and few were clinically significant. These findings indicate that microwave disinfection does not have a clinically significant effect on the parameters of most unworn soft contact lenses. Further studies are needed to determine the long-term effects of microwave disinfection on worn soft contact lenses.

Contact Lenses, Hydrophilic

Comparative visual performance of three presbyopic contact lens corrections.

We compared the visual performance of a soft diffractive (DIFF) bifocal contact lens, a near center (CN) concentric bifocal design, and monovision (MV), using a comprehensive vision testing protocol. Fifteen presbyopic subjects who were successfully wearing DIFF bifocal contact lenses participated in the study. Of the three systems tested, MV provided best visual acuity at distance and near; less than one line of acuity was lost relative to best spectacle acuity under all lighting and contrast conditions, and there was less disturbance of a point source of light. Both bifocal corrections gave similar visual acuity performance, with more lines of acuity lost relative to spectacles at near compared to distance. However, the concentric bifocal induced more ghosting at near than the other two systems. Stereopsis was compromised at distance with MV correction, but all systems performed worse than spectacles at near. An understanding of the strengths and weaknesses of presbyopic contact lens options allows the clinician to improve management of the presbyope who wishes to wear contact lenses.

Contact Lenses, Hydrophilic

Interest of presbyopes in contact lens correction and their success with monovision.

The presbyopic population is seen as a large potential source of contact lens wearers. The aims of this study were: (1) to estimate the percentage of presbyopes interested in contact lenses, (2) to ascertain the success of interested presbyopes with monovision correction, and (3) to determine the percentage willing to continue wearing monovision lenses after 1 month's trial. Seven practitioners in Sydney surveyed consecutive presbyopes attending their practices about their interest in contact lenses. Of the 1133 presbyopes surveyed, 314 (28%) were interested in trying monovision lenses. A total of 72 patients were subsequently fitted with monovision in high water content hydrogel form. After 1 month, 46 of these patients (64%) were still wearing the lenses, and 39 (54%) expressed willingness to continue with monovision correction. The major reasons for discontinuation from lens wear during the 1-month trial were inadequate vision and difficulty in lens handling.

Adult

Twelve-month success rates with a hydrogel diffractive bifocal contact lens.

In this study we assessed success rates over 12 months with a hydrogel diffractive bifocal contact lens. A total of 108 presbyopes were fitted with lenses, and after 12 months 46% were still wearing the lenses. Subjects with previous presbyopic lens-wearing experience achieved greater success (58% of those fitted) than neophyte lens wearers (33% of those fitted, and 17% of all neophyte presbyopes initially expressing an interest in contact lenses before screening). More neophytes failed for nonvision-related reasons than experienced subjects (31% vs. 12% of those fitted). Consequently, when nonvision-related failures were excluded from the calculation of success rates, 59% of those fitted with lenses (49% of neophytes and 66% of experienced subjects) were still wearing the lenses at 12 months. Most discontinuations from lens wear occurred in the first month of the study, the major reason for discontinuation being poor near vision (blur and/or ghosting; 47% of discontinuations).

Aged

Clinical performance of two opaque, tinted soft contact lenses.

Comfort, visual acuity, visual fields, daytime corneal edema and corneal staining were evaluated on 22 subjects wearing opaque tinted and non-opaque control hydrogel lenses. CooperVision Permaflex Mystique (38% polymacon) and Wesley-Jessen Durasoft 3 Colors (55% phemfilcon A) opaque lenses were compared to non-opaque lenses from the same manufacturers (CooperVision CV Classic and Wesley-Jessen Durasoft 3). Subjects were randomly assigned one type of opaque lens and one clear lens on each of two days, and two opaque lenses on another day. All lenses yielded similar results in terms of comfort, visual acuity, visual fields and corneal staining. The only visual problem with the opaque lenses was the reporting of "haziness" (usually peripheral) in 72 percent of Mystique and 59 percent of Durasoft 3 Colors trials. The greatest daytime corneal edema, 4.7 percent, occurred with the Mystique lens compared with 2.7 percent with CV Classic and 1.8 percent and 1.7 percent with the opaque and clear Durasoft 3 lenses respectively. These levels of edema were associated with a 40 percent incidence of striae with Mystique (17/43), 14 percent with the CV Classic (3/21 eyes), 5 percent with Durasoft 3 clear (1/22 eyes) and 2 percent with Durasoft 3 opaque lenses (1/44 eyes). Corneal swelling correlated with the measured Dk/L of the lenses. The Durasoft 3 Colors lens was the opaque tinted lens of choice based primarily on corneal physiology.

Adult