Search PubMed⌕ Search

Biomedical subjects

J Wells

Publications and source records attributed to J Wells.

At least 19 recordsLinked to original sources
PubMed2005

APOE, vascular pathology, and the AD brain.

OBJECTIVE: To use neuropathologic data to examine the association between APOE genotype and cerebrovascular lesions commonly found in Alzheimer disease (AD), as well as neuritic senile plaque (SP) and neurofibrillary tangle (NFT) burden. METHODS: The sample comprised brains from 96 men and 3 women who fulfilled NIA-Reagan criteria for intermediate to high likelihood of AD. Region-specific and global measures of gross cerebrovascular disease, arteriolosclerosis, white matter lesions, microinfarcts, amyloid angiopathy, neuritic SP, and NFT burden were compared among those who had at least one APOE-epsilon4 vs those who did not. Pairwise rank-order correlations between measures were calculated. The association between APOE epsilon4 status and measures of vascular and AD pathology, adjusting for age at death, sex, brain weight, and Braak stage, were evaluated. RESULTS: APOE-epsilon4 was not associated with gross cerebrovascular pathology. Compared to those who were negative, brains from epsilon4 individuals had a greater degree of small vessel arteriolosclerosis (p = 0.04) and perivascular macrophage infiltration (p = 0.06), but not other markers of small vessel disease or white matter myelin loss. Microinfarcts in the deep nuclei were associated with epsilon4 (p = 0.009), whereas cortical and subcortical microinfarcts were not. There was a trend toward association between APOE genotype and amyloid angiopathy (p = 0.08), and epsilon4 was associated with neuritic SP burden, but not NFT. CONCLUSION: APOE-epsilon4 is associated with small vessel arteriolosclerosis, microinfarcts of the deep nuclei, neuritic senile plaque density, and amyloid angiopathy in patients with autopsy-proven Alzheimer disease (AD). These results suggest a role for epsilon4 in some of the microvascular changes commonly found in AD and are consistent with a potential amyloidogenic role for epsilon4.

Age Factors↗
PubMed2004

Langmuir supercells: a mechanism for sediment resuspension and transport in shallow seas.

Recent measurements at a cabled sea-floor node in 15 meters of water off the coast of New Jersey suggest that Langmuir supercells, Langmuir circulations that achieve vertical scales equal to the water depth under extended storms, are an important mechanism for major sediment resuspension events on the extensive shallow shelves off the eastern U.S. coast. Because sediment resuspension is a prelude to transport, supercell events are a necessary condition for major sediment transport. Such events may also contribute to shelf-sea exchange and to offshore gradation of benthic community structure in shallow seas.

Journal Article↗
PubMed2004

The bioavailability of chemicals in soil for earthworms.

The bioavailability of chemicals to earthworms can be modified dramatically by soil physical/chemical characteristics, yet expressing exposure as total chemical concentrations does not address this problem. In order to understand the effects of modifying factors on bioavailability, one must measure and express chemical bioavailability to earthworms in a consistent, logical manner. This can be accomplished by direct biological measures of bioavailability (e.g., bioaccumulation, critical body residues), indirect biological measures of bioavailability (e.g., biomarkers, reproduction), or indirect chemical measures of bioavailability (e.g., chemical or solid-phase extracts of soil). If indirect chemical measures of bioavailability are to be used, they must be correlated with some biological response. Bioavailability can be incorporated into ecological risk assessment during risk analysis, primarily in the estimation of exposure. However, in order to be used in the site-specific ecological risk assessment of chemicals, effects concentrations must be developed from laboratory toxicity tests based on exposure estimates utilizing techniques that measure the bioavailable fraction of chemicals in soil, not total chemical concentrations.

Animals↗
PubMed2004

Intrathecal fentanyl-induced pruritus during labour: the effect of prophylactic ondansetron.

Fentanyl is commonly used for spinal analgesia during labour but it is associated with a high incidence of pruritus. This randomised, double-blind, placebo-controlled study was performed to evaluate the effect of prophylactic ondansetron on the incidence and severity of pruritus among parturients receiving intrathecal fentanyl as part of combined spinal-epidural analgesia. Seventy-three women were randomised to receive either saline placebo (group P, n = 25), ondansetron 4 mg (group O4, n = 23) or ondansetron 8 mg (group O8, n = 25) intravenously before intrathecal fentanyl 25 micrograms and bupivacaine 2 mg. The incidence and severity of pruritus were measured using a verbal rating and a visual analogue scale, and by the requirement for rescue anti-pruritic medication (naloxone). The overall incidence of pruritus was 95% (group P 100%, group O4 95%, group O8 90%). There were no significant differences between groups for severity of pruritus or requirement for treatment (naloxone given to 45%, 28% and 35% of groups P, O4 and O8 respectively). Secondary outcomes such as the incidence of headache, pain and nausea were not significantly different between groups. We conclude that prophylactic ondansetron 4 or 8 mg intravenously was ineffective in reducing the incidence or severity of intrathecal fentanyl-induced pruritus during labour.

Adult↗
PubMed2004

Glycolytic enzymes associated with the cell surface of Streptococcus pneumoniae are antigenic in humans and elicit protective immune responses in the mouse.

Streptococcus pneumoniae is a leading cause of otitis media, sinusitis, pneumonia, bacteraemia and meningitis worldwide. The drawbacks associated with the limited number of various capsular polysaccharides that can be included in the polysaccharide-based vaccines focuses much attention on pneumococcal proteins as vaccine candidates. We extracted an enriched cell wall fraction from S. pneumoniae WU2. Approximately 150 soluble proteins could be identified by 2D gel electrophoresis. The proteins were screened by 2D-Western blotting using sera that were obtained longitudinally from children attending day-care centres at 18, 30 and 42 months of age and sera from healthy adult volunteers. The proteins were further identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Seventeen proteins were antigenic in children and adults, of which 13 showed an increasing antibody response with age in all eight children analysed. Two immunogenic proteins, fructose-bisphosphate aldolase (FBA) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and a control protein with known low immunogenicity, heat shock protein 70 (DnaK), were expressed in Escherichia coli, purified and used to immunize mice. Mouse antibodies elicited to the recombinant (r) FBA and rGAPDH were cross-reactive with several genetically unrelated strains of different serotypes and conferred protection to respiratory challenge with virulent pneumococci. In addition, the FBA used in this study (NP_345117) does not have a human ortholog and warrants further investigation as a candidate for a pneumococcal vaccine. In conclusion, the immunoproteomics based approach utilized in the present study appears to be a suitable tool for identification of novel S. pneumoniae vaccine candidates.

Adult↗
PubMed2003

Tracheal rupture following endotracheal intubation.

We describe a case of tracheal rupture diagnosed after an apparently routine endotracheal intubation for otherwise uneventful lower abdominal surgery in a 33-year-old woman. Risk factors for tracheal rupture, presenting symptoms and signs, management of tracheal rupture and methods of airway management during the surgical repair of the tracheal laceration are discussed. In this case, "side-by-side" microlaryngoscopy tubes, one endobronchial and the other with the tip in the upper trachea, placed with fibreoptic assistance were used for airway management during the tracheal repair.

Adult↗
PubMed2002

Tetanus immunisation in hypersensitive individuals.

We report on a case of an officer cadet who was inadvertently allowed to commence training with a history suggestive of hypersensitivity to tetanus immunisation and who, eventually, successfully underwent a graduated immunisation regimen. This case combines a search for good evidence with the extraordinary complexities of military medical management and the law. It is a lesson in all three.

Anaphylaxis↗
PubMed2001

Newspaper reporting of screening mammography.

BACKGROUND: Continuing controversy surrounds screening mammography, particularly for women 40 to 49 years of age. Newspapers are potentially important sources of information on this topic, but it is not known whether they provide well-founded and objective information and recommendations. OBJECTIVE: To examine how screening mammography is reported in newspapers. DESIGN: Cross-sectional descriptive study. SETTING: 6 top-circulation U.S. newspapers, 1990 to 1997. MEASUREMENTS: Number of articles about screening mammography, issues covered by the articles, information sources, content and sources of quotes, recommendations cited in articles, and presentation of risks and benefits. RESULTS: The most common theme of newspaper articles about mammography was screening for women 40 to 49 years of age. Thirty-one percent of the articles presented information without citing a source or justification. Quotes and recommendations in the articles were approximately twice as likely to support as to express reservations about mammography for women aged 40 to 49 years. Recommendations changed little over time and rarely reflected changes in recommendations of national organizations. Of the 102 articles describing the benefits of mammography, 95% expressed them in relative terms and 11% expressed them in absolute terms. CONCLUSIONS: Newspapers tended to overrepresent support for screening mammography for women aged 40 to 49 years. Reports would have been improved by identification of all sources for information cited, less reliance on relatively few sources, and discussion of benefits in absolute as well as relative terms. Medical journalism may benefit from identification of standards similar to those used for reporting medical research.

Adult↗
PubMed2001

Experience with urine drug testing by the Correctional Service of Canada.

The Correctional Service of Canada implemented a urine drug-screening program over 10 years ago. The objective of this report is to describe the program and drug test results in this program for 1999. Offenders in Canadian federal correctional institutions and those living in the community on conditional release were subject to urine drug testing. Urine specimens were collected at correctional facilities and shipped by courier to MAXXAM Analytics Inc. laboratory. All urine specimens were analyzed for amphetamines, cannabinoids, cocaine metabolite (benzoylecgonine), opiates, phencyclidine, benzodiazepines, methyl phenidate, meperidine, pentazocine and fluoxetine by immunoassay screening (homogeneous EIA and ELISA assays) followed by GC-MS confirmation. Ethyl alcohol was analyzed when specifically requested. Alternative screening and confirmation methods with lower cut-off values were used, whenever urine specimens were dilute (creatinine <20mg/dl and specific gravity <or=1.003). The number of urine specimens analyzed was 44,722 in 1999 and 6.2% of these specimens were dilute based on creatinine and specific gravity analysis. The positive rate for one or more drugs was 25.5% in 1999. The highest drug positive rates were for cannabinoids (10.7%), morphine (3.2%), cocaine metabolite (3.2%), codeine (2.6%), oxazepam (2.1%), temazepam (1.1%) and ethyl alcohol (1.0%). In correctional institutions (8606 non-dilute specimens analyzed in 1999), 16.4% were positive for cannabinoids, 4.9% positive for codeine and/or morphine and 2.7% positive for oxazepam and/or temazepam. In the 537 dilute specimens collected in institutions, 21% were positive for cannabinoids, 1.3% positive for codeine and/or morphine and 1.3% positive for oxazepam and/or temazepam. In the community setting, 33,928 non-dilute specimens were collected in 1999 (9.0% were positive for cannabinoids and 3.5% positive for cocaine metabolite). In the 1651 dilute specimens collected from offenders in the community in 1999, 12.6% were positive for cannabinoids and 9.5% positive for cocaine metabolite. We conclude that forensic urine drug testing provides an objective measure of drug use by offenders in Canadian federal institutions and those offenders living in the community on conditional release.

Canada↗
PubMed2001

The chromatin structure of the dual c-myc promoter P1/P2 is regulated by separate elements.

The proto-oncogene c-myc is transcribed from a dual promoter P1/P2, with transcription initiation sites 160 base pairs apart. Here we have studied the transcriptional activation of both promoters on chromatin templates. c-myc chromatin was reconstituted on stably transfected, episomal, Epstein-Barr virus-derived vectors in a B cell line. Episomal P1 and P2 promoters showed only basal activity but were strongly inducible by histone deacetylase inhibitors. The effect of promoter mutations on c-myc activity, chromatin structure, and E2F binding was studied. The ME1a1 binding site between P1 and P2 was required for the maintenance of an open chromatin configuration of the dual c-myc promoters. Mutation of this site strongly reduced the sensitivity of the core promoter region of P1/P2 to micrococcal nuclease and prevented binding of polymerase II (pol II) at the P2 promoter. In contrast, mutation of the P2 TATA box also abolished binding of pol II at the P2 promoter but did not affect the chromatin structure of the P1/P2 core promoter region. The E2F binding site adjacent to ME1a1 is required for repression of the P2 promoter but not the P1 promoter, likely by recruitment of histone deacetylase activity. Chromatin precipitation experiments with E2F-specific antibodies revealed binding of E2F-1, E2F-2, and E2F-4 to the E2F site of the c-myc promoter in vivo if the E2F site was intact. Taken together, the analyses support a model with a functional hierarchy for regulatory elements in the c-myc promoter region; binding of proteins to the ME1a1 site provides a nucleosome-free region of chromatin near the P2 start site, binding of E2F results in transcriptional repression without affecting polymerase recruitment, and the TATA box is required for polymerase recruitment.

Base Sequence↗
PubMed2001

HLA-restricted CD8+ cytotoxic T lymphocyte, interferon-gamma, and interleukin-4 responses to respiratory syncytial virus infection in infants and children.

CD8+ cytotoxic T lymphocyte (CTL) activity, interferon (IFN)-gamma, and interleukin (IL)-4 production were evaluated in a blinded manner among respiratory syncytial virus (RSV)-infected newborns and their mothers for 3 epidemic seasons. Most mothers (80%) exhibited RSV-specific CD8+ CTL activity. Twenty (80%) of the 26 infants exhibited significant RSV-specific CTL activity during or after their first RSV season. CTL frequency increased with RSV infection rate, reaching 75% by the end of the third season. Most infants who shed virus (75%) had a medically attended lower respiratory tract disease (LRD). In the first year, RSV-infected infants (virus culture and antibody increase) were more likely to develop CTL activity (10 of 13) than were uninfected infants (1 of 5; P=.02). Infants with CTL activity in the first year were less likely to have an LRD in the second year. CD8+ CTL levels correlated positively with IFN-gamma (P<.001) and inversely with IL-4 (P=.03). Contribution of CD8+ CTL and IFN-gamma in the control of RSV disease in infants and children is implicated.

Adult↗
PubMed2001

Visual risk factors for crash involvement in older drivers with cataract.

BACKGROUND: The Impact of Cataracts on Mobility project has previously demonstrated that older drivers with cataract have an elevated risk of motor vehicle collision. OBJECTIVE: To examine what types of visual impairment serve as a basis of the increased crash risk of older drivers with cataract. METHODS AND DESIGN: A cross-sectional analysis was performed on 274 older drivers with cataract and 103 older drivers free of cataract recruited through 12 eye care clinics for the purposes of the Impact of Cataracts on Mobility project, a prospective study on driving mobility in older adults with cataract. Tests measured visual acuity, contrast sensitivity, and disability glare for each eye separately using habitual distance correction. The dependent variable was involvement in at least 1 state-recorded, at-fault vehicle crash during the 5 years prior to study enrollment. RESULTS: Logistic regression evaluated associations (odds ratios [ORs]) between visual function and crash involvement. Better and worse eye models defined on the basis of visual acuity were developed. Associations between each type of visual function and crash involvement were adjusted for age, sex, driving exposure, cognitive status, and other types of visual function. For both the better and worse eye models, contrast sensitivity was independently associated with crash involvement, whereas visual acuity and disability glare were not. Drivers with a history of crash involvement were 8 times more likely to have a serious contrast sensitivity deficit in the worse eye (defined as a Pelli-Robson score of 1.25 or less) than those who were crash-free (OR = 7.86; 95% confidence interval [CI], 1.55-39.79); this association was weaker for the better eye but still statistically significant (OR = 3.78; 95% CI, 1.15-12.48). Crash-involved drivers were 6 times more likely to have severe contrast sensitivity impairment in both eyes (OR = 5.78; 95% CI, 1.87-17.86) than crash-free drivers. A severe contrast sensitivity deficit in only 1 eye was still significantly associated with crash involvement (OR = 2.70; 95% CI, 1.16-6.51). CONCLUSION: Severe contrast sensitivity impairment due to cataract elevates at-fault crash risk among older drivers, even when present in only 1 eye.

Accidents, Traffic↗
PubMed2001

A serial MR study of cerebral blood flow changes and lesion development following endothelin-1-induced ischemia in rats.

The vasoconstrictive peptide endothelin-1 (ET-1) has been used previously to transiently occlude the middle cerebral artery (MCA) in rats. However, the duration of the resulting reduction in cerebral blood flow (CBF) and the reperfusion characteristics are poorly understood. In this study perfusion and T(2)-weighted MRI were used together with histology to characterize the cerebral perfusion dynamics and lesion development following ET-1 injection. Twenty-two rats received an intracerebral injection of ET-1 adjacent to the MCA. CBF was reduced to 30-50% of control levels, and a significant reduction persisted for 16 h in the cortex and 7 h in the striatum. The lesion size measured by T(2)-weighted imaging at 48 h correlated with the final infarct size measured by histology at 7 d. The sustained reduction in CBF and the gradual development of the ischemic lesion resemble human stroke evolution, suggesting that this model may be useful for evaluating therapeutic agents, particularly when treatment is delayed.

Animals↗
PubMed2001

Timed instrumental activities of daily living tasks: relationship to visual function in older adults.

PURPOSE: To identify instrumental activities of daily living (IADL) tasks whose completion time is related to visual function in older adults. METHODS: Visual function (acuity, contrast sensitivity, and useful field of view) and the time to complete 17 visual tasks of everyday life were measured in a sample of 342 older adults (mean age 71 years, range 56 to 86) recruited from eye clinics. The timed IADL (TIADL) tasks included a variety of visual activities such as reading ingredients on cans of food and instructions on medicine bottles, finding a phone number in a directory, locating items on a crowded shelf and in a drawer, and using a screwdriver. RESULTS: Multiple regression analysis indicated that poorer scores for acuity, contrast sensitivity, and useful field of view were independently associated with longer times to complete visual TIADL tasks, even after adjusting for age, educational level, depression, and general health. Cognitive status also had a significant, independent association with timed task performance. CONCLUSIONS: Older adults' timed performance in everyday tasks is related to various aspects of visual function independent of the influences of other functional and health problems and advanced age. This suggests that TIADL tasks may eventually be useful as performance outcomes in intervention evaluations targeted at reversing vision impairment or minimizing its impact. To understand the relationship between vision impairment and TIADL task performance in older adults, cognitive impairment needs to be taken into account because it has a relatively strong and independent relationship with visual TIADL task performance.

Activities of Daily Living↗