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J Lucas

Publications and source records attributed to J Lucas.

At least 19 recordsLinked to original sources
PubMed2006

LPS induces translocation of TLR4 in amniotic epithelium.

Toll-like receptor 4 (TLR4) mediates lipopolysaccharide (LPS) induced immune responses, which may contribute to preterm labor associated with intraamniotic gram-negative bacterial infections. The study objective was to investigate gestational age and LPS-induced changes in TLR4 subcellular localization within amniotic epithelium, the first line of host defense against intraamniotic bacteria. TLR4 localization in amniotic epithelium was assessed using immunohistochemistry on 24 placentas of different gestational ages: first trimester (n=6), second trimester (n=6), and third trimester (n=12). Immunofluorescence was used to determine TLR4 localization following ex vivo LPS stimulation of amnion from women undergoing cesarean section without labor at term. TLR4 was expressed in the cytoplasm of amniotic epithelium starting at 9weeks with apical polarization by 25weeks gestation. TLR4 localization to the basal membrane was significantly associated with chorioamnionitis (p=0.01). After LPS stimulation, TLR4 was expressed sequentially within the apical membrane, cytoplasm, and finally in the basal cellular compartment. This suggests that TLR4 expression in amniotic epithelium is poised to monitor amniotic fluid for pathogens. TLR4 translocation to the basal membrane may decrease LPS signaling early in an infection, but allow the amniotic epithelium to remain competent to invasive or intracellular bacteria.

Amnion↗
PubMed2005

Cardiovascular phenotyping of fetal mice by noninvasive high-frequency ultrasound facilitates recovery of ENU-induced mutations causing congenital cardiac and extracardiac defects.

As part of a large-scale noninvasive fetal ultrasound screen to recover ethylnitrosourea (ENU)-induced mutations causing congenital heart defects in mice, we established a high-throughput ultrasound scanning strategy for interrogating fetal mice in utero utilizing three orthogonal imaging planes defined by the fetus' vertebral column and body axes, structures readily seen by ultrasound. This contrasts with the difficulty of acquiring clinical ultrasound imaging planes which are defined by the fetal heart. By use of the three orthogonal imaging planes for two-dimensional (2D) imaging together with color flow, spectral Doppler, and M-mode imaging, all of the major elements of the heart can be evaluated. In this manner, 10,091 ENU-mutagenized mouse fetuses were ultrasound scanned between embryonic days 12.5 and 19.5, with 324 fetuses found to die prenatally and 425 exhibiting cardiovascular defects. Further analysis by necropsy and histology showed heart defects that included conotruncal anomalies, obstructive lesions, and shunt lesions as well as other complex heart diseases. Ultrasound imaging also identified craniofacial/head defects and body wall closure defects, which necropsy revealed as encephalocele, holoprosencephaly, omphalocele, or gastroschisis. Genome scanning mapped one ENU-induced mutation associated with persistence truncus arteriosus and holoprosencephaly to mouse chromosome 2, while another mutation associated with cardiac defects and omphalocele was mapped to mouse chromosome 17. These studies show the efficacy of this novel ultrasound scanning strategy for noninvasive ultrasound phenotyping to facilitate the recovery of ENU-induced mutations causing congenital heart defects and other extracardiac anomalies.

Abnormalities, Multiple↗
PubMed2005

Effects of once-weekly oral alendronate on bone in children on glucocorticoid treatment.

OBJECTIVES: To determine the effects of once-weekly oral alendronate on indices of bone size, density and resorption in children with chronic illness being treated with glucocorticoids. METHODS: Twenty-two children with chronic illness treated with prednisone were randomized to receive 1 year's treatment with either once-weekly oral placebo or alendronate (1-2 mg/kg body weight) in a double-blind study. The main outcome measures were changes in lumbar spine and femoral shaft size and volumetric density (measured by dual energy X-ray absorptiometry) and N-telopeptide excretion (a marker of bone resorption). RESULTS: Once-weekly alendronate was well tolerated, and there were no major adverse events. In both groups bone size and bone mineral content increased through growth. Volumetric bone density of the lumbar spine increased significantly in the alendronate group (P = 0.013), but not in the placebo group. There were no differences between the groups in growth in the cortical width of the femoral shaft, but the cross-sectional moment of inertia per unit length-a derived estimate of mechanical strength-increased significantly in the alendronate group (P = 0.014) but not in the placebo group. Urine N-telopeptide excretion was suppressed significantly in the alendronate group (P = 0.007) but not in the placebo group. Height velocity was positively correlated with changes in both lumbar spine area and the total width of the femoral shaft (P = 0.015, P = 0.026, respectively). CONCLUSION: Once-weekly oral alendronate is well tolerated, suppresses bone resorption and may improve volumetric bone density at the lumbar spine and mechanical strength of the femoral shaft in children with chronic illness taking glucocorticoids. It does not affect bone growth. Larger controlled studies are needed to determine if these changes translate into reduced fracture incidence or greater peak bone mass. This study highlights the importance of differentiating between changes in bone size and changes in volumetric bone density in assessing bone in children, and also having control subjects in intervention studies.

Administration, Oral↗
PubMed2005

Safety Climate Survey: reliability of results from a multicenter ICU survey.

BACKGROUND: It is important to understand the clinical properties of instruments used to measure patient safety before they are used in the setting of an intensive care unit (ICU). METHODS: The Safety Climate Survey (SCSu), an instrument endorsed by the Institute for Healthcare Improvement, the Safety Culture Scale (SCSc), and the Safety Climate Mean (SCM), a subset of seven items from the SCSu, were administered in four Canadian university affiliated ICUs. All staff including nurses, allied healthcare professionals, non-clinical staff, intensivists, and managers were invited to participate in the cross sectional survey. RESULTS: The response rate was 74% (313/426). The internal consistency of the SCSu and SCSc was 0.86 and 0.80, respectively, while the SCM performed poorly at 0.51. Because of poor internal consistency, no further analysis of the SCM was therefore performed. Test-retest reliability of the SCSu and SCSc was 0.92. Out of a maximum score of 5, the mean (SD) scores of the SCSu and SCSc were 3.4 (0.6) and 3.4 (0.7), respectively. No differences were noted between the three medical-surgical and one cardiovascular ICU. Managers perceived a significantly more positive safety climate than other staff, as measured by the SCSu and SCSc. These results need to be interpreted cautiously because of the small number of management participants. CONCLUSIONS: Of the three instruments, the SCSu and SCSc appear to be measuring one construct and are sufficiently reliable. Future research should examine the properties of patient safety instruments in other ICUs, including responsiveness to change, to ensure that they are valid outcome measures for patient safety initiatives.

Canada↗
PubMed2003

Actinomyces infection in a dog with pulmonary carcinoma.

Thoracic actinomycosis was diagnosed by bacterial isolation in a dog with a history of chronic productive cough, weight loss, pyrexia and a pulmonary mass lesion on radiography. Therapy with amoxycillin and clindamycin did not significantly improve the patient's condition and euthanasia was performed during exploratory thoracotomy. Histological examination of the affected lung lobes revealed the presence of peribronchiolar adenocarcinoma. Actinomycosis has been reported to co-exist with pulmonary neoplasia in humans and may mask the presence of malignancy.

Actinomyces↗
PubMed2003

In situ sensing of volatile organic compounds in groundwater: first field tests of a mid-infrared fiber-optic sensing system.

A prototype mid-infrared sensor system for the determination of volatile organic pollutants in groundwater was developed and tested under real-world conditions. The sensor comprises a portable Fourier transform infrared spectrometer, coupled to the sensor head via mid-infrared transparent silver halide fiber-optic cables. A 10 cm unclad middle section of the 6-m-long fiber is coated with ethylene propylene copolymer in order to enrich the analytes within the penetration depth of the evanescent field protruding from the fiber sensor head. A mixture of tetrachloroethylene, dichlorobenzene, diethyl phthalate, and xylene isomers at concentrations in the low ppm region was investigated qualitatively and quantitatively in an artificial aquifer system filled with Munich gravel. This simulated real-world site at a pilot scale enables in situ studies of the sensor response and spreading of the pollutants injected into the system with controlled groundwater flow. The sensor head was immersed into a monitoring well of the aquifer system at a distance of 1 m downstream of the sample inlet and at a depth of 30 cm. Within one hour, the analytes were clearly identified in the fingerprint region of the IR spectrum (1300 to 700 cm(-1)). The results have been validated by head-space gas chromatography, using samples collected during the field measurement. Five out of six analytes could be discriminated simultaneously; for two of the analytes the quantitative results are in agreement with the reference analysis.

Equipment Design↗
PubMed2003

[Pelviperitonitis and intestinal occlusion: two unusual cold-knife conisation complications].

Complications associated with cold-knife conization are mainly hemorrhage, genital and urinary infections. We presented two cases of accidental posterior colpotomy with Douglas pouch wound initially unnoticed at the time of the cold-knife conization, and secondary complicated by a pelviperitonitis for the first case and by an incarceration of the bowel loop in the vaginal wound for the second case.

Adult↗
PubMed2002

European Union-funded research on probiotics, prebiotics and new foods.

At the beginning of 1999, the European Commission launched the Fifth Framework Programme for Research, Technological Development and Demonstration (1998-2002), which has been conceived to help solve problems and to respond to major socio-economic challenges facing the European Union. Within its thematic programme 'Quality of life and management of living resources', Key Action 1 covers the subject 'Food, nutrition and health' with a total budget of 290 million euro. The key action concentrates on consumer needs, the competitiveness of the European food industry, the role of nutrition in health and well-being, and the safety and integrity of the food supply. Within this framework, research on probiotics, prebiotics and new foods is an important focus of the funding activities of the European Commission at present and in future.

Antioxidants↗
PubMed2001

Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity.

Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC(50) = 30 nM), several additional analogues were prepared. Optimization of the C-4 anilino group of 1a led to 1c, which contains a 2,4-dichloro-5-methoxy-substituted aniline. Replacement of the methoxy group at C-7 of 1c with a 3-(morpholin-4-yl)propoxy group provided 2c, resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c with other trisubstituted anilines at C-4 were also potent Src inhibitors, and the propoxy group of 2c was preferred over ethoxy, butoxy, or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a, which had an IC(50) of 1.2 nM in the Src enzymatic assay, an IC(50) of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a, which had higher 1 and 4 h plasma levels than 2c, effectively inhibited tumor growth in xenograft models.

Animals↗
PubMed2001

Lipogranulomatous conjunctivitis: clinical findings from 21 eyes in 13 cats.

OBJECTIVE: The clinical and, where available, histologic features of lesions fitting a previous description of lipogranulomatous conjunctivitis were reviewed retrospectively from a series of cats. ANIMALS STUDIES: Thirteen cats (21 eyes) with lesions consistent with a diagnosis of lipogranulomatous conjunctivitis were seen over a 4-year period in a referral practice in southern Australia. Affected cats ranged in age from 6 to 16 years (mean 11.2 +/- 3.6 years). RESULTS: Twelve cats were domestic shorthair or longhair cats and one was a British shorthair cat. Five cats were white, four were bicolor, two were orange tabby and two were dilute orange tabby. Lesions were always found in the palpebral conjunctiva, adjacent to the eyelid margin. They affected upper eyelids only in five cases, and upper plus lower eyelids in eight cases. Lesions were bilateral in eight cases. Lesions were excised in eight cases, with resolution of associated irritation and no signs of lesion recurrence during a 4- to 21-month follow-up period. SUMMARY: Histologic features of tissues excised from surgically treated cases were consistent with a previous report of lipogranulomatous conjunctivitis and with descriptions of chalazia. A possible role of actinic radiation in the etiopathogenesis of lesions is discussed.

Animals↗
PubMed2001

Outcome of adolescent trauma admitted to an adult surgical intensive care unit versus a pediatric intensive care unit.

BACKGROUND: Institutional protocol designates the adult trauma service as the primary manager of all adolescent traumas (age 14-18 years) unless admission to the pediatric intensive care unit (PICU) occurs. In the PICU, primary care becomes the responsibility of the pediatric intensivist, with trauma service as a consultant. The purpose of this study was to identify differences in the management of adolescent trauma between the pediatric intensivist in the PICU, and the adult trauma team in the surgical intensive care unit (SICU). METHODS: From January 1993 to January 1998, the medical records of all adolescent trauma patients requiring intensive care unit (ICU) management were reviewed. Depending on bed availability, patients younger than 16 were admitted to the PICU, and those 16 or older to the SICU. Demographic data obtained were age, sex, race, mechanism of injury, length of stay (LOS), ICU length of stay, days on mechanical ventilation, intubation, tracheotomy, intracranial pressure monitor, and Swan-Ganz catheter placement. Home discharge, rehabilitation placement, and death were recorded. Morbidity was measured using Injury Severity Score methodology, Pediatric Trauma Score, and Pediatric Risk of Mortality. RESULTS: One hundred nine completed records were reviewed (SICU, n = 58; PICU, n = 51). There was no statistical difference in sex, race, mechanism of injury, ICU LOS, tracheotomy, and intracranial pressure monitor placements. There was no difference in morbidity, as measured by Injury Severity Score, Pediatric Trauma Score, and Pediatric Risk of Mortality score or in outcome measurements (death, rehabilitation placement). SICU patients were older (SICU, 16.9 +/- 1.0 years; PICU, 15.4 +/- 1.0 years; p < or = 0.1 Mann-Whitney U test), more likely to be intubated (SICU, n = 42; PICU, n = 24; p < or = 0.05 Fisher's exact test), more likely to have pulmonary artery catheter placement (SICU, n = 7; PICU, n = 0), and had longer LOS (SICU, 12.2 +/- 10.6; PICU, 9.8 +/- 14.1; p < or = 0.03 Mann-Whitney U test). CONCLUSION: Adolescent trauma patients admitted to the PICU were less likely to be intubated or have a Swan-Ganz catheter placed. They had decreased LOS and days of mechanical ventilation. There was no difference in outcome measurements.

Adolescent↗
PubMed2001

Genetic variations in human G protein-coupled receptors: implications for drug therapy.

Numerous genes encode G protein-coupled receptors (GPCRs)-a main molecular target for drug therapy. Estimates indicate that the human genome contains approximately 600 GPCR genes. This article addresses therapeutic implications of sequence variations in GPCR genes. A number of inactivating and activating receptor mutations have been shown to cause a variety of (mostly rare) genetic disorders. However, pharmacogenetic and pharmacogenomic studies on GPCRs are scarce, and therapeutic relevance of variant receptor alleles often remains unclear. Confounding factors in assessing the therapeutic relevance of variant GPCR alleles include 1) interaction of a single drug with multiple closely related receptors, 2) poorly defined binding pockets that can accommodate drug ligands in different orientations or at alternative receptor domains, 3) possibility of multiple receptor conformations with distinct functions, and 4) multiple signaling pathways engaged by a single receptor. For example, antischizophrenic drugs bind to numerous receptors, several of which might be relevant to therapeutic outcome. Without knowing accurately what role a given receptor subtype plays in clinical outcome and how a sequence variation affects drug-induced signal transduction, we cannot predict the therapeutic relevance of a receptor variant. Genome-wide association studies with single nucleotide polymorphisms could identify critical target receptors for disease susceptibility and drug efficacy or toxicity.

Drug Therapy↗
PubMed2001

[Laparoscopic promontofixation feasibility study in 44 patients].

OBJECTIVE: To evaluate the feasibility of laparoscopic promontofixation. MATERIAL: and methods. Forty patients between 1993 and 1999 were scheduled for a laparoscopic promontofixation. Fifteen of these patientes had a previous cure of prolapse with recurrence. Three patients had a "universal jointcervix" syndrome (Masters and Allen). RESULTS: We observed no recurrence of the prolapse after an average follow-up of 18.6 months. The peroperatoire complication rate is 9%, and the postoperative complication rate is 9% too. 4.5% of the patients had to undergo a laparotomy. CONCLUSION: Laparoscopic promontofixation is feasible with good results in the cure of genital prolapse. Laparoscopy is performing the same procedure as the open technique with the advantages of the minimal invasive surgery.

Adult↗