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Biomedical subjects

L McGuire

Publications and source records attributed to L McGuire.

At least 19 recordsLinked to original sources
PubMed2003

The prevalence and spread of Escherichia coli O157:H7 at a commercial beef abattoir.

AIMS: To investigate the prevalence and virulence characteristics of Escherichia coli O157:H7 after a number of beef process operations at a commercial Irish abattoir. METHODS AND RESULTS: Two 12-month studies were carried out. The first study (study 1) examined the prevalence of E. coli O157:H7 at up to six sites on carcasses at eight stages of the dressing, washing, chilling and boning process. The second study (study 2) examined the prevalence of E. coli O157:H7 in bovine faeces and rumen contents post-slaughter and on dressed, washed carcasses. Isolates from both studies were phage-typed and the presence of genes encoding verocytotoxin, enterohaemolysin and intimin production was determined. E. coli O157:H7 was isolated from four of 36 carcasses in study 1. E. coli O157:H7 was detected during hide removal and was detected at multiple carcass sites and multiple process stages, including boning. On two carcasses, contamination was first detected at the bung following its freeing and tying. All isolates from study 1 were phage type (PT) 2, eaeAO157 and ehlyA positive, but were verocytotoxin 1 (VT1) and verocytotoxin 2 (VT2) negative. In study 2, E. coli O157:H7 was isolated from 2.4% of faecal, 0.8% of rumen and 3.2% of carcass samples. In some cases, isolates recovered from the faeces of a particular animal, the resulting carcass and adjacent carcasses on the line had the same phage typing and virulence characteristic profile patterns. All isolates from study 2 were eaeAO157 and ehlyA positive and only one isolate was VT1 and VT2 negative. Most isolates were PT 32. A higher frequency of positive isolations was noted from samples taken during spring and late summer. CONCLUSION: These studies show that in a typical Irish beef abattoir, carcass contamination with E. coli O157:H7 can occur during hide removal and bung tying and this contamination can remain on the carcass during subsequent processing. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides data that is necessary for the understanding of how E. coli O157:H7 contamination of beef occurs.

Abattoirs↗
PubMed2001

Changes in plasma nerve growth factor levels in older adults associated with chronic stress.

Evidence indicates that the actions of nerve growth factor (NGF) reach beyond the nervous system and might modulate immune function. Based on reports that blood NGF rises following the acute stress of parachute jumping, we investigated whether exposure to a chronic stressor, caregiving for a cognitively impaired spouse, could alter the levels of blood NGF. High perceived stress and depression in caregivers (vs. well-matched controls) were associated with elevated blood NGF. These data suggest that exposure to this chronic stressor can alter the concentrations of circulating NGF, and that psychological stress can induce changes in NGF concentrations in older adults.

Aged↗
PubMed2001

Delusions and delusional reasoning.

In 2 studies, delusional participants assigned higher probabilities to narratives of actual delusions than participants with no history of delusions; previously delusional participants did not differ significantly from delusional participants or participants with no history of delusions. In Study 2, the authors found that this reasoning bias was specific to delusions and did not generalize to "neutral" text. Familiarity with the content of the delusion narratives played a mediating role in the estimation of their probability, but delusional status also had a significant, independent effect. These findings are consistent with the Bayesian model of delusion formation proposed by D. R. Hemsley and P. A. Garety (1986), and with R. P. Bentall, P. Kinderman, and S. Kaney's (1994) concept of "emotional saliency." A productive area of future research might be to further determine the elements of "emotional saliency" and their impact on the individual steps of the Bayesian model.

Adult↗
PubMed2001

Long-term caregiving: what happens when it ends?

Data from a longitudinal study were used to examine what happens to caregivers in the years after their cognitively impaired spouse dies. Comparisons of 42 current caregivers, 49 former caregivers, and 52 noncaregivers over a 4-year period showed that former caregivers did not improve on several measures of psychological well-being. Although former caregivers experienced decreases in stress and negative affect, their scores on depression, loneliness, and positive affect did not rebound to levels comparable to noncaregivers and, in fact, remained similar to those of current caregivers up to 3 years after caregiving had ceased. The most consistent predictors of postcaregiving outcomes were social support and intrusive-avoidant thinking about caregiving. The data suggest that some consequences of long-term caregiving may be long-term as well. The needs of former spousal caregivers warrant greater attention both in research and in practice.

Aged↗
PubMed2001

Nonmyeloablative conditioning allows for more rapid T-cell repertoire reconstitution following allogeneic matched unrelated bone marrow transplantation compared to myeloablative approaches.

Nonmyeloablative pretransplantation conditioning regimens have resulted in durable engraftment of allogeneic hematopoietic stem cells. In contrast to conventional fully myeloablative approaches, nonmyeloablative regimens are associated with a marked reduction of morbidity and mortality in the early posttransplantation period. Consequently, such reduced-intensity transplantation approaches can be used in older and frailer patients who would not tolerate fully ablative regimens. However, it is currently unclear how this radically different transplantation strategy affects immunological reconstitution. To address this important issue, we used T-cell receptor Vbeta spectratype analysis to examine the distribution of complementarity-determining region 3 (CDR3)-size bands as a measure of the complexity of the redeveloping T-cell repertoire. For this study, we evaluated the T-cell repertoire of 9 patients receiving T-cell replete, matched unrelated donor transplants following fully ablative or nonmyeloablative conditioning regimens. All 4 of the myeloablative and 2 of the nonmyeloablative patients received bone marrow, whereas 3 other nonmyeloablative patients received peripheral blood stem cells. The results of the spectratype analysis demonstrated that the patients who received nonmyeloablative conditioning together with either bone marrow or peripheral blood stem cells exhibited more rapid reconstitution of T-cell repertoire complexity.

Adult↗
PubMed2000

The envenomation syndrome caused by the Australian Red-bellied Black Snake Pseudechis porphyriacus.

The Australian elapids inject venom which is characteristic of each species; and which cause characteristic and specific envenomation syndromes in human victims of snakebite. Because many of the medically significant Australian elapids look similar, when glimpsed in the field by snakebite victims, defining human envenomation syndromes with secure species identification has been a slow process. Correlations between securely identified species and the human envenomation syndromes which they produce are still evolving. The genus Pseudechis is the most widespread in Australia of the dangerous Australian elapid genera; and P. porphyriacus, the Red-bellied Black Snake, was the first terrestrial Australian elapid to be described and illustrated and the first to be the subject of experimental study. We present here five previously unreported cases of human envenomation in which the species diagnosis is secure. From these and with the perspective of a selected literature review, we describe the full envenomation syndrome of this species. Until the development of the Commonwealth Serum Laboratories' Venom Detection Kit in 1979 and the occasional case report of victims of securely identified species, envenomation syndromes for most Australian snake species have remained indeterminate, because of the lack of professional expertise in the identification of the species involved. Symptoms of the P. porphyriacus envenomation syndrome include those of bite-site pain, nausea and vomiting, generalised pruritus, chest pain, prostration and abnormalities of taste and smell. Signs include local necrosis and scarring of tissue at the bite-site, gross inflammation of surrounding tissues and, at least in one case, epilepsy. Although envenomation by the Red-bellied Black Snake is not lethal in adults, the correct therapy is Tiger Snake antivenom, administered with judgement, taking into account knowledge of the specific envenomation syndrome of this species and the clinical status of the victim.

Adolescent↗
PubMed2000

The relationship between hide cleanliness and bacterial numbers on beef carcasses at a commercial abattoir.

Cattle were visually inspected in the lairage of a commercial abattoir and assigned to a category ranging from 1 (very clean) to 5 (very dirty) depending on the observed cleanliness of the hide. Animals from categories 2, 3 and 5 were slaughtered and total viable counts (TVCs) enumerated at five sites (hock, brisket, cranial back, bung and inside round) on the subsequent carcasses. The TVCs at the hock were significantly higher on category 5 than on category 2 carcasses (P < 0.05). Similarly, TVCs at the brisket were significantly higher on categories 3 and 5 than on category 2 carcasses (P < 0.05). There were no differences in counts among the categories at any of the other sites. The TVCs averaged over the five carcass sites were higher for category 5 than for category 2 carcasses (P < 0.05). The TVCs at the brisket were significantly higher than all other sites (P < 0.01). In general, carcasses from category 2 animals slaughtered in a batch with dirtier animals (categories 3 and 5) did not have higher TVCs than carcasses of category 2 animals slaughtered at the beginning of the day in the absence of dirtier animals. The introduction of improved hygienic practices during the dehiding of category 4 animals resulted in reduced TVCs at the brisket (P < 0.001).

Abattoirs↗
PubMed2000

Cycling safety: injury prevention in Oxford cyclists.

OBJECTIVE: To assess injury prevention measures used by cyclists in Oxford and to detect any differences between wearers and non-wearers of cycling helmets. METHOD: A prospective observational survey of a series of cyclists passing a single point on a busy city road in reduced lighting. Two observers jointly recorded four measures of injury prevention: use of front or rear light, high visibility (reflective or fluorescent) clothing, and cycling helmet. The use of the first three interventions was analysed in relation to helmet use/non-use. RESULTS: A total of 392 cyclists were observed over one hour. Fourteen (3.6%) were observed to use all four studied measures, while 137 (34.9%) used none of them. The frequency of measures observed was: lit front light 190 (48.5%), lit rear light 197 (50.2%), both lights on 163 (41.6%), helmet on 104 (26.5%), and high visibility clothing 39 (9.9%). Despite the helmet using group's smaller size, it contained a significantly higher proportion of cyclists with lit front light (60.6% v 44.1%), lit rear light (61.5% v 46.2%), and high visibility clothing (27.9% v 3.5%), than the non-helmet group (p < or = 0.01). Whereas only 22% of the helmet users had no other observed measures, 47.2% of non-users did so. CONCLUSION: Cycling helmet users were significantly more likely to use collision prevention measures in conditions of reduced visibility. Explanations may include higher levels of risk awareness and greater knowledge of safe cycling practices in the smaller, helmet using group. However, current measures by cyclists in a major cycling centre may be insufficient to prevent collisions and consequent serious injury or death.

Bicycling↗
PubMed1998

Delusions and symptom-consistent violence.

OBJECTIVE: The study examined the extent to which delusions motivate violent behavior among psychiatric patients with a history of delusions. METHODS: Fifty-four psychiatric inpatients identified by hospital staff as having delusions were interviewed about their history of delusions and incidents of violence that were concurrent with delusions. Raters used a 5-point scale to estimate the degree to which each reported incident of violence was motivated by a concurrent delusion. A second set of raters used a 5-point scale to estimate the severity of the violent incidents. RESULTS: Raters' mean estimate indicated overall that violent incidents were probably not motivated by concurrent delusions. However, a significant minority of violent subjects (40 percent) reported at least one violent incident that was judged to be probably or definitely motivated by a concurrent delusion. A smaller subgroup of violent subjects (17.5 percent) reported at least one incident that was judged to be both extremely violent and definitely motivated by a concurrent delusion. CONCLUSIONS: Delusional motivation of violence is rare, but a moderate risk exists that delusions will motivate violence at some time during the course of a violent patient's illness.

Adult↗
PubMed1997

Microbial quality of lamb carcasses during processing and the acridine orange direct count technique (a modified DEFT) for rapid enumeration of total viable counts.

This study was designed to set up a hazard analysis and critical control points (HACCP) system for sheep slaughtering operations at four different plants in Ireland and to determine the differences between plants in terms of microbial contamination. A single carcass area, the abdomen, was examined by swabbing and a microbiological profile was determined at different stages along the slaughter line. The level of contamination was assessed from the total bacteria counts, Enterobacteriaceae and Listeria spp. For the total counts, a modified direct epifluorescent filter technique (acridine orange direct count technique (AODC)) was developed and tested. No significant differences were found among plants in the levels of bacterial contamination. This was observed for all groups of organisms. The rapid direct technique (AODC) was found to be very successful. A correlation coefficient of 0.87 was obtained for this method and the standard plate count. Each test could be carried out in about 10-15 min and could be used to predict the standard plate count.

Abattoirs↗
PubMed1997

Affinity selection and mass spectrometry-based strategies to identify lead compounds in combinatorial libraries.

The screening of diverse libraries of small molecules created by combinatorial synthetic methods is a recent development which has the potential to accelerate the identification of lead compounds in drug discovery. We have developed a direct and rapid method to identify lead compounds in libraries involving affinity selection and mass spectrometry. In our strategy, the receptor or target molecule of interest is used to isolate the active components from the library physically, followed by direct structural identification of the active compounds bound to the target molecule by mass spectrometry. In a drug design strategy, structurally diverse libraries can be used for the initial identification of lead compounds. Once lead compounds have been identified, libraries containing compounds chemically similar to the lead compound can be generated and used to optimize the binding characteristics. These strategies have also been adopted for more detailed studies of protein-ligand interactions.

Binding, Competitive↗
PubMed1997

Mouse fibroblast growth factor 10: cDNA cloning, protein characterization, and regulation of mRNA expression.

Fibroblast growth factor 7 (FGF-7) or keratinocyte growth factor (KGF), is a potent and specific mitogen for epithelial cells. We have recently identified a novel human FGF-7 homologue, named FGF-10. To study the expression of this new FGF family member and its regulation in wound repair, we cloned the mouse FGF-10 (mFGF-10) cDNA. The encoded protein is 92% identical to human FGF-10 and 91% identical to rat FGF-10. When expressed in mammalian 293 cells, the mFGF-10 protein was glycosylated but remained cell- or extracellular matrix-associated. Upon addition of heparin, mFGF-10 protein was released into the media. mRNA encoding mFGF-10 was relatively abundant in lung, skin, brain and heart. In the skin, both FGF-7 and mFGF-10 were expressed in the dermal, but not the epidermal compartment. In contrast to FGF-7, mFGF-10 expression was not induced during cutaneous wound repair. In cultured fibroblasts, expression of mFGF-10 was strongly repressed by transforming growth factor beta and tumor necrosis factor alpha, whereas epidermal growth factor and interleukin-1beta had no effect. These results demonstrate a differential regulation of mFGF-10 and FGF-7 expression in vitro and during the wound healing process.

3T3 Cells↗
PubMed1996

Growth hormone (GH) and insulin-like growth factor I responses after treatments with an orally active GH secretagogue L-163,255 in swine.

L-163,255 is a potent orally active spiropiperidine GH secretagogue. When administered iv or orally, L-163,255 caused GH to be increased in a dose-related manner, with a return to baseline by 90 min. After iv administrations of saline and L-163,255 at 1, 3, and 10 micrograms/kg, GH areas under the curves (GH AUCs) over 120 min were 377 +/- 136, 1151 +/- 413 (P < 0.05), 795 +/- 413 (P = NS), and 1770 +/- 416 ng.min/ml (P < 0.01), and peak GH concentrations were 8 +/- 3, 16 +/- 7 (P = NS), 17 +/- 5 (P = NS), and 43 +/- 12 ng/ml (P < 0.01), respectively. No changes in plasma cortisol concentrations were noted. After oral administrations at 3, 10, and 30 micrograms/kg, GH AUCs over 180 min were 1133 +/- 154, 1246 +/- 129 (P = NS), and 1551 +/- 210 ng.min/ml (P = NS), and peak GH concentrations were 7 +/- 2, 11 +/- 3 (P = NS), and 23 +/- 6 ng/ml (P < 0.01), respectively. After administration in feed, L-163,255 caused a dose-related increase in GH, with an initial peak observed at 60 min for both 30 and 300 micrograms/kg dose groups, and remained elevated above baseline through 180 min for the high dose group only. GH AUCS for 180 min posttreatment were 929 +/- 134 and 1897 +/- 244 ng.min/ml, and peak GH concentrations were 9 +/- 2 and 22 +/- 4 ng/ml for the 30 and 300 micrograms/kg doses prepared in 150 g feed, respectively. When provided in feed ad libitum over the 72-h period, mean plasma insulin-like growth factor I levels increased 15%, 62% (P < 0.01), and 109% (P < 0.01) in the untreated, treated with L-163,255 at 360 ppm, or treated with porcine somatotropin groups, respectively. Repeated iv administration of L-163,255 at 1 mg/kg once daily over 14 days resulted in an initial marked GH response, followed by a much reduced, but significantly elevated, GH response over the saline control values on subsequent treatment days. Repeated iv treatments with L-163,255 also resulted in an elevated insulin-like growth factor I level (approximately 60%) over that in saline controls. Compared to those in saline controls, plasma cortisol concentrations tended to be increased after the initial dose of L-163,255, but no significant increases were noted on days 7 and 14 in the L-163,255 group. The results of these studies indicate that L-163,255 is an orally active GH secretagogue suitable for long term efficacy studies in swine.

Administration, Oral↗
PubMed1996

Mediation by the central nervous system is critical to the in vivo activity of the GH secretagogue L-692,585.

To investigate the effect of hypophyseal transection (HST) on GH secretagogue activity of the non-peptidyl GH secretagogue L-692,585 in the conscious pig, male castrated swine were randomly assigned to either a hypophyseal stalk transection group (HST; n = 3) or to a sham-operated control group (SOC; n = 3). Treatments administered were L-692,585 (100 micrograms/kg), human GH-releasing factor(1-29)NH2 (GRF; 20 micrograms/kg) or L-692,585 (100 micrograms/kg) + GRF (20 micrograms/kg) on days -7 to -3 before surgery and days +3 to +8 after surgery. To evaluate the integrity of the pituitary gland, the animals were challenged with corticotropin-releasing hormone (CRH; 150 micrograms) or GnRH (150 ng/kg) both before and after surgery. Blood was collected from -60 to +180 min post treatment and assayed for GH, cortisol and LH. Before surgery, no significant difference (P > 0.05) in peak GH response (ng/ml) was present between the two groups (SOC vs HST) in response to L-692,585 (101 +/- 12 vs 71 +/- 9) or L-692,585 + GRF (171 +/- 21 vs 174 +/- 21). Only two out of three SOC vs three out of three HST pigs responded to GRF (13 +/- 2 vs 25 +/- 3) resulting in a significant difference between groups. Following surgery, significant differences were present in peak GH response (ng/ml) between SOC and HST groups following L-692,585 (79 +/- 6 vs 13.8 +/- 1.0); however, the response to L-692,585 + GRF was similar (115 +/- 8 vs 94 +/- 7). All animals responded to GRF; however, a significant difference was present between groups due to the magnitude of the responses. Whereas the cortisol responses (ng/ml) to L-692,585 in the SOC and HST groups were similar before surgery, a significant difference was present after surgery (44.4 +/- 6.4 vs 14.6 +/- 2.1). No significant difference was noted between the HST and SOC groups in response to CRH or GnRH either before or after surgery. These results indicated that L-692,585 induced an immediate GH response in the intact animal in contrast to GRF where the GH release was variable. L-692,585 also stimulated an immediate increase in cortisol levels. Transection of the hypophyseal stalk dramatically decreased but did not ablate the GH or cortisol response to L-692,585. Co-administration of L-692,585 + GRF induced an immediate GH response of similar magnitude in the intact and HST animal. We conclude that L-692,585 has a direct but limited action at the level of the pituitary and that an intact hypophyseal stalk is required for a maximal GH and cortisol response. L-692,585 acts with GRF at the level of the pituitary to induce a maximal GH response. These findings suggest that L-692,585 stimulates GH secretion by acting in combination with GRF and interrupting the inhibitory tone of somatostatin on the somatotroph.

Animals↗
PubMed1995

Activity of a novel nonpeptidyl growth hormone secretagogue, L-700,653, in swine.

L-700,653 is a potent nonpeptidyl GH secretagogue consisting of a benzolactam structure: (4'-[[3(R)-[[3-[(2(S),3-dihydroxypropyl) amino]3-methyl-1-oxobutyl]amino]2,3,4,5-tetrahydro-2-oxo-1H-1-benzaze pin- 1-yl]methyl][1,1'-biphenyl]2-carboxamide hydrochloride). When administered sc by a Medi-Jector device at 0, 0.003, 0.01, 0.03, and 0.1 mg/kg BW to male castrated swine (approximately 50 kg BW), L-700,653 stimulated dose-related increases in peak plasma GH concentrations by 20% (P = NS), 150% (P = NS), 250% (P < 0.05), and 340% (P < 0.05), respectively, over the saline vehicle control value (11.3 +/- 6.5 ng/ml) and stimulated increases in GH areas under the curve (AUCs) by 10% (P = NS), 30% (P = NS), 90% (P < 0.05), and 100% (P < 0.01), respectively, over the saline vehicle control value (799 +/- 145 ng/min.ml). After sc administration of L-700, 653, there were no significant changes in plasma LH levels. Subcutaneous dose of 0.03 or 0.1 mg/kg increased plasma cortisol AUCs by 60% (P = NS) and 150% (P < 0.03) over the control value (2461 +/- 935 ng/min.ml) and increased cortisol peaks by 80% (P = NS) and 200% (P < 0.01), respectively, over the control value (38.3 +/- 12.3 ng/ml). Repeated sc administration of L-700,653 (0.03 or 0.1 mg/kg) at 0800, 1400, and 2000 h daily over 3 days consistently increased mean GH peak and GH AUC at each treatment period, with minimal and maximal increases of 40% and 190% in GH peak level at the 0.03 mg/kg dose and 100% and 400% increases in GH peak level at the 0.01 mg/kg dose, respectively. Continuous i.v. infusion of L-700,653, at either 0.01 or 0.1 mg/kg BW.h over a 180-min period, increased GH AUCs by 60% (P = NS) or 470% (P < 0.01) and GH peaks by 190% (P = NS) or 1520% (P < 0.01), respectively, over the control value (589 +/- 313 ng/min.ml; 7.0 +/- 11.1 ng/ml). After a 180- to 300-min saline infusion, an iv bolus dose of 0.1 mg/kg L-700,653 resulted in GH responses inversely proportional to the previous infusion dose, i.e. 0, 0.01, or 0.1 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗