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Biomedical subjects

J Wells

Publications and source records attributed to J Wells.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Mre11 complex and DNA replication: linkage to E2F and sites of DNA synthesis.

We show that the Mre11 complex associates with E2F family members via the Nbs1 N terminus. This association and Nbs1 phosphorylation are correlated with S-phase checkpoint proficiency, whereas neither is sufficient individually for checkpoint activation. The Nbs1 E2F interaction occurred near the Epstein-Barr virus origin of replication as well as near a chromosomal replication origin in the c-myc promoter region and was restricted to S-phase cells. The Mre11 complex colocalized with PCNA at replication forks throughout S phase, both prior to and coincident with the appearance of nascent DNA. These data suggest that the Mre11 complex suppresses genomic instability through its influence on both the regulation and progression of DNA replication.

Animals↗

The protective effects of hypoxia-induced hypometabolism in the Nautilus.

Specimens of Nautilus pompilius were trapped at depths of 225-300 m off the sunken barrier reef southeast of Port Moresby, Papua New Guinea. Animals transported to the Motupore Island laboratory were acclimated to normal habitat temperatures of 18 degrees C and then cannulated for arterial and venous blood sampling. When animals were forced to undergo a period of progressive hypoxia eventually to encounter ambient partial pressure of oxygen (PO2) levels of approximately 10 mmHg (and corresponding arterial PO2's of approximately 5 mmHg), they responded by lowering their aerobic metabolic rates to 5-10% of those seen in resting normoxic animals. Coincident with this profound metabolic suppression was an overall decrease in activity, with brief periods of jet propulsion punctuating long periods of rest. Below ambient PO2 levels of 30-40 mmHg, ventilatory movements became highly periodic and at the lowest PO2 levels encountered, ventilation occasionally ceased altogether. Cardiac output estimated by the Fick equation decreased during progressive hypoxia by as much as 75 80%, and in the deepest hypometabolic states heart rates slowed to one to two cycles of very low amplitude per minute. By the end of 500 min exposure to ambient PO2 levels of 10 mmHg or less, the anaerobic end products octopine and succinate had increased significantly in adductor muscle and heart, respectively. Increased concentrations of octopine in adductor muscle apparently contributed to a small intracellular acidosis and to the development of a combined respiratory and metabolic acidosis in the extracellular compartment. On the other hand, increases in succinate in heart muscle occurred in the absence of any change in cardiac pHi. Taken together, we estimate that these anaerobic end products would make up less than 2% of the energy deficit arising from the decrease in aerobic metabolism. Thus, metabolic suppression is combined with a massive downregulation of systemic O2 delivery to match metabolic supply to demand.

Acid-Base Equilibrium↗

Development and evaluation of an interactive CD-ROM refusal skills program to prevent youth substance use: "refuse to use".

An interactive CD-ROM program designed to reduce adolescent substance use was developed and evaluated. The program uses video vignettes to teach refusal skills and socially acceptable responses to substance use situations, specifically offers of marijuana. In a randomized pretest-to-posttest experiment with 74 public school students from six classes in three high schools, significant changes were observed at posttest on (1) the adolescent's personal efficacy to refuse the offer of marijuana, (2) the adolescent's intention to refuse marijuana if offered, and (3) the adolescent's perceptions of the social norms associated with substance use and the importance of respecting another's decision to refuse a drug offer. In addition, adolescents in the treatment condition were able to recall approximately 50% of the portrayed refusal strategies. Findings are discussed with regard to the potential benefits of an interactive multimedia approach for conducting substance use interventions.

Adolescent↗

A heterogeneous outbreak of Enterobacter cloacae and Serratia marcescens infections in a surgical intensive care unit.

OBJECTIVE: To investigate an outbreak of invasive disease due to Enterobacter cloacae and Serratia marcescens in a surgical intensive care unit (ICU). DESIGN: Pulsed-field gel electrophoresis (PFGE) analysis of restriction fragments was used to characterize the outbreak isolate genotypes. A retrospective cohort study of surgical ICU patients was conducted to identify risk factors associated with invasive disease. Unit staffing data were analyzed to compare staffing levels during the outbreak to those prior to and following the outbreak. SETTING: An urban hospital in San Francisco, California. PATIENTS: During the outbreak period, December 1997 through January 1998, there were 52 patients with a minimum ICU stay of > or = 72 hours. Of these, 10 patients fit our case definition of recovery of E. cloacae or S. marcescens from a sterile site. RESULTS: PFGE analysis revealed a highly heterogeneous population of isolates. Bivariate analysis of patient-related risk factors revealed duration of central lines, respiratory colonization, being a burn patient, and the use of gentamicin or nafcillin to be significantly associated with invasive disease. Both respiratory colonization and duration of central lines remained statistically significant in a multivariate analysis. Staffing data suggested a temporal correlation between understaffing and the outbreak period. CONCLUSIONS: Molecular epidemiological techniques provided a rapid means of ruling out a point source or significant cross-contamination as modes of transmission. In this setting, patient-related risk factors, such as respiratory colonization and duration of central lines, may provide a focus for heightened surveillance, infection control measures, and empirical therapy during outbreaks caused by common nosocomial pathogens. In addition, understaffing of nurses may have played a role in this outbreak, highlighting the importance of monitoring staffing levels.

Cohort Studies↗

Target gene specificity of E2F and pocket protein family members in living cells.

E2F-mediated transcription is thought to involve binding of an E2F-pocket protein complex to promoters in the G(0) phase of the cell cycle and release of the pocket protein in late G(1), followed by release of E2F in S phase. We have tested this model by monitoring protein-DNA interactions in living cells using a formaldehyde cross-linking and immunoprecipitation assay. We find that E2F target genes are bound by distinct E2F-pocket protein complexes which change as cells progress through the cell cycle. We also find that certain E2F target gene promoters are bound by pocket proteins when such promoters are transcriptionally active. Our data indicate that the current model applies only to certain E2F target genes and suggest that Rb family members may regulate transcription in both G(0) and S phases. Finally, we find that a given promoter can be bound by one of several different E2F-pocket protein complexes at a given time in the cell cycle, suggesting that cell cycle-regulated transcription is a stochastic, not a predetermined, process.

3T3 Cells↗

Randomised trial of iodine intake and thyroid status in preterm infants.

BACKGROUND: Low levels of circulating thyroid hormones have been associated with poorer general and neurodevelopmental outcome in preterm babies and it has been speculated that the association is causal. Low levels of circulating thyroid hormone have been reported after inadequate intake of iodine in preterm infants being fed milk formula. AIM: To investigate whether increased iodine intake from supplemented preterm formula would improve thyroid hormone levels in preterm babies (this study) and hence improve neurodevelopmental status (planned subsequent study). METHOD: A total of 121 preterm infants were entered into a randomised controlled trial of standard (68 microg/l) versus increased (272 microg/l) iodine in preterm formula. RESULTS: The two groups were comparable at recruitment. No evidence of an effect of the intervention on thyroid hormone levels was seen up to 41 weeks after conception. CONCLUSION: Calls for increased iodine content of preterm infant formulas are not justified by this study.

Female↗

The long-term performance of DXA bone densitometers.

Long-term performance of a bone mass measuring device is an important criterion when considering the purchase of such equipment and has been regarded as an important feature of dual X-ray absorptiometry (DXA). The performance of a 6-year-old bone densitometer, the Lunar DPX alpha, which has undertaken 1500 scans annually over this period, was assessed. The short-term coefficient of variation calculated from 15 measurements with repositioning on a single day, using the Lunar aluminium phantom, was 0.242%. Long-term precision, also calculated by the coefficient of variation, was 0.548%. The manufacturer's quality control (QC) procedure was performed daily and allowed the machine to be used except on 15 occasions when bone density measurements could be acquired after rebooting. However, a 2.2% shift in phantom values occurred in July 1996 owing to a photomultiplier tube failure, but this did not produce a failure in the Lunar QC. The optical disc drive was replaced in July 1997. The machine failed to back up on six occasions over the last 2 years owing to software corruption and the acquired femur data were not saved on seven occasions owing to overloading of the memory buffer. In conclusion, expected hardware failure and minor software problems have occurred. We were concerned that the manufacturer's QC failed to detect a 2% shift in the phantom bone mineral density values and recommend regular measurements of the Lunar aluminum phantom in addition to the daily QC measurement of the tissue-equivalent block. We were nevertheless impressed by the long-term stability and reproducibility of the Lunar DPX alpha.

Absorptiometry, Photon↗

Stop fake beer.

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Adolescent↗