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Biomedical subjects

S West

Publications and source records attributed to S West.

At least 19 recordsLinked to original sources

Prevention of blindness and priorities for the future.

The impact of visual loss has profound implications for the person affected and society as a whole. The majority of blind people live in developing countries, and generally, their blindness could have been avoided or cured. Given the current predictions that the number of blind people worldwide will roughly double by the year 2020, it is clear that there is no room for complacency. As the world's population increases and as a greater proportion survives into late adulthood, so the number of people with visual loss will inexorably rise. Given the success of programmes in combating the most common causes of blindness (infectious diseases and malnutrition) which generally affect the young, and the projected demographic shift, age-related eye disease will become increasingly prevalent. Effective preventive measures for these diseases can only be established as more is known about their etiology. As the longevity of the world's population increases, the visual requirements at the workplace are also changing. People with low vision may be at a disadvantage in many common activities, and may face unemployment--particularly in technological societies. The definition of blindness needs to be rethought, to ensure that people with "economic" blindness are not forgotten. Efforts should be made to recognize and treat those affected at an early stage, for the benefit of the individual and society.

Aging↗

Effect of low-dose estrogen on hemodynamic response to stress.

OBJECTIVE: To determine the effect of low-dose esterified estrogen on hemodynamic responses at rest and during stress in postmenopausal women, and to compare the changes with those seen with conjugated equine estrogen. DESIGN: Open-label study of esterified estrogen compared with a double-blind, placebo-controlled investigation of conjugated equine estrogen. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Postmenopausal women with normal endometrium, not currently using hormones. INTERVENTION(S): Cardiovascular parameters at rest and in response to stressors were assessed in 11 postmenopausal women before and 6 months after receiving 0.3 mg esterified estrogen. Responses were compared with 42 postmenopausal women randomized to 0.625 mg conjugated equine estrogen or placebo. MAIN OUTCOME MEASURE(S): Changes in mean arterial pressure (MAP) and vascular resistance index from before to after treatment. RESULT(S): At rest, MAP increased 3.3 +/- 1.5 mm Hg (+/-SD) in the placebo group, while declining 2.3 +/- 1.5 mm Hg and 4.8 +/- 1.4 mm Hg, respectively, in the esterified estrogen and conjugated equine estrogen groups after treatment. During mental stressors, MAP dropped significantly in both treatment groups. At rest and during mental stressors, vascular resistance index decreased with estrogen treatment. CONCLUSION(S): Low-dose esterified estrogen improved hemodynamic patterns similar to standard doses of conjugated equine estrogen in postmenopausal women.

Animals↗

A comparison of vertical force and temporal parameters produced by an in-shoe pressure measuring system and a force platform.

OBJECTIVE: To investigate the ability of Pedar in-shoe system to measure vertical force accurately, by comparing it with the Kistler force platform. DESIGN: In vivo experiment in normal subjects. BACKGROUND: It has been suggested Pedar is highly reliable, but absolute accuracy of the system with regard to force measurement has not been comprehensively tested. METHODS: Sampling at 99 Hz, using five healthy subjects, simultaneous data were collected barefoot, and in three types of shoes (Trainers, Oxfords, Slip-on Deck Type). Six variables obtained from the force/time curve from each footstep were compared. RESULTS: The temporal data recorded by Pedar correlated well with that obtained using Kistler, with significant differences only in overall duration of the step in Deck shoes (P < 0.001) and Oxford shoes (P < 0.01), and peak to peak barefoot (P < 0.01). Pedar recorded a lower first peak force and mid-peak force in all cases (P < 0.001). However, the magnitude of the 2nd peak force recorded by both systems was significantly different only in Trainers (P < 0.05) and Oxford shoes (P < 0.001). The impulse data obtained with Oxford shoes was not significantly different, although barefoot, Trainers and Deck shoes were significantly lower (P < 0.001) for Pedar. CONCLUSIONS: In most cases, comparison of data recorded by the two systems provided good evidence for the accuracy and reliability of temporal measurements and second peak force measurements taken with the Pedar in-shoe system. Relevance. In-shoe pressure data provides evidence for clinical decisions if the systems utilised are proven to be valid, repeatable and accurate. Comparison with an established force platform enables some assessment of these factors.

Adult↗

Susceptibility markers in colorectal cancer.

Many susceptibility factors contribute to an individual's risk of developing colorectal cancer. Family history of colorectal cancer (particularly with early age of onset), maleness and increasing age are all factors associated with increasing risk. About three quarters of colorectal cancers are thought to be due to somatic mutations, and both high- and low-penetrance predisposing genes contribute to the remaining quarter of cases. Many of the highly penetrant dominant genes are known, but others remain to be identified. Describing the contribution of individual genes is likely to be very complex, as some modify the impact of other genes and other environmental factors rather than incurring a direct, easily attributable effect. The two dominant predisposing syndromes are familial adenomatous polyposis and Lynch syndrome, the first due to a mutant tumour-suppressor gene APC, and the second due to mutations in a number of genes responsible for mismatch repair in DNA at cell division. Establishing genetic susceptibility for colorectal cancer will soon be possible, and could save lives by allowing targetting of screening and the encouragement of preventive behaviours. However, there will always be a risk of making healthy people "sick" through the identification of predisposing genes, and there are many potential ways by which a gene carrier may be stigmatized by society, insurance companies and employers.

Aged↗

The red eye.

Explore the source record for details and available documents.

Adolescent↗

Mapping of the human CP49 gene and identification of an intragenic polymorphic marker to allow genetic linkage analysis in autosomal dominant congenital cataract.

The CP49 protein is an intermediate filament protein expressed specifically in the lens fibre cells of the lens, where it is an important cytoplasmic structural component. Dominant-negative mutations in other intermediate filament proteins, such as keratins, cause disorders characterised by dense cytoplasmic aggregates in specific cell types. The CP49 gene is therefore a good candidate for dominantly inherited forms of cataract. To allow genetic linkage analysis of families with autosomal dominant cataract with respect to CP49, a highly polymorphic intragenic microsatellite marker for this gene has been developed. In addition, both low and high resolution radiation hybrid mapping of the CP49 gene has been completed, placing it very close to microsatellite marker D3S1290 on human chromosome 3q. Furthermore, using the intragenic CP49 microsatellite, linkage was excluded in four families with genetically uncharacterized forms of autosomal dominant congenital cataract.

Base Sequence↗

A comparison of vertical force and temporal parameters produced by an in-shoe pressure measuring system and a force platform.

OBJECTIVE: To investigate the ability of Pedar in-shoe system to measure vertical force accurately, by comparing it with the Kistler force platform. DESIGN: In vivo experiment in normal subjects. BACKGROUND: It has been suggested Pedar is highly reliable, but absolute accuracy of the system with regard to force measurement has not been comprehensively tested. METHODS: Sampling at 99 Hz, using five healthy subjects, simultaneous data were collected barefoot, and in three types of shoes (Trainers, Oxfords, Slip-on Deck Type). Six variables obtained from the force/time curve from each footstep were compared. RESULTS: The temporal data recorded by Pedar correlated well with that obtained using Kistler, with significant differences only in overall duration of the step in Deck shoes (P<0. 001) and Oxford shoes (P<0.01), and peak to peak barefoot (P<0.01). Pedar recorded a lower first peak force and mid-peak force in all cases (P<0.001). However, the magnitude of the 2nd peak force recorded by both systems was significantly different only in Trainers (P<0.05) and Oxford shoes (P<0.001). The impulse data obtained with Oxford shoes was not significantly different, although barefoot, Trainers and Deck shoes were significantly lower (P<0.001) for Pedar. CONCLUSIONS: In most cases, comparison of data recorded by the two systems provided good evidence for the accuracy and reliability of temporal measurements and second peak force measurements taken with the Pedar in-shoe system. Relevance In-shoe pressure data provides evidence for clinical decisions if the systems utilised are proven to be valid, repeatable and accurate. Comparison with an established force platform enables some assessment of these factors.

Adult↗

Identification of novel genes in late-onset Alzheimer's disease.

Four genes affecting Alzheimer's Disease (AD)(AP, PS1, PS2, and APOE) have been identified and a fifth potential gene localized to chromosome 12. Collectively, these genes explain at most half of the genetic effect in AD. Understanding the genetics of AD is critical to developing new treatments. The quest to find the remaining AD genes led us to undertake a large genomic screen using over 466 families (730 affected sibpairs) in late-onset AD. In conjunction with this increase in power, we initiated several novel approaches to identify potential AD-related genes. This included stratification of the data into an autopsy-confirmed subset of 199 AD families. Each of these targeted analyses resulted in the identification of novel regions containing potential AD genetic risk factors. Our most significant finding was on chromosome 9 in the autopsy-confirmed subset where we obtained an MLS of 4.31. These approaches, together with new methodologies such as conditional linkage analysis, generalized family-based association tests (PDT), and a new generation of genetic markers (SNPs), opens the door for additional AD gene discovery. Such strategies are necessary if we are to understand the subtle and complex threads that, woven together, create the intricate tapestry of AD.

Age of Onset↗

Detection of mutations in mismatch repair genes in Portuguese families with hereditary non-polyposis colorectal cancer (HNPCC) by a multi-method approach.

Mutation searching was performed in the hMSH2 and hMLH1 genes in 20 Portuguese families representing 124 registered affected individuals. Of the 20, 16 fulfilled the classic 'Amsterdam' criteria for HNPCC, whereas the remaining four families satisfied a modified set of criteria. These criteria required a CRC diagnosed before age 50 years and cancers diagnosed in two other relatives within the HNPCC spectrum. A multi-method approach was performed using the protein truncation test (PTT), single strand conformation polymorphism (SSCP) with two different sets of conditions, heteroduplex analysis (HA) and denaturing gradient gel electrophoresis (DGGE). Putative phenotype-genotype correlations were also explored. Ten different germline mutations were identified. Six of these were found in hMLH1 in seven families and four in hMSH2 in four families. SSCP and DGGE had the highest diagnostic yields with the percentage of variants detected above 67% and together HA and PTT had the lowest. No single technique detected all variants. Trends for the absence of extracolonic manifestations were observed in families carrying hMLH1 germline mutations (four of seven in hMLH1 vs one of four in hMSH2). Most of the families with rectal cancer were associated with hMLH1 (six of seven in hMLH1 vs two of four in hMSH2). A multi-technique approach is necessary to identify a high percentage of germline mutations. Seven novel mutations were found in this Portuguese population.

Adaptor Proteins, Signal Transducing↗

Dry eye and dry mouth in the elderly: a population-based assessment.

BACKGROUND: Symptoms of dry eye and dry mouth are common in the elderly and are often debilitating. Previous research on small populations has been inconsistent regarding the contribution to sicca symptoms of autoimmune markers, medication use, and other factors. The objective of this study was to determine the population prevalence of symptoms of dry eye and dry mouth and to evaluate possible risk factors. METHODS: This is a population-based study of 2481 individuals, aged 65 to 84 years, residing in Salisbury, Md, and identified by the Health Care Financing Medicare database. The main outcome measures included information on sicca symptoms, medical history, medication use, and joint examination results collected in a standardized manner. Autoimmune status was assessed in 1200 individuals by measuring antinuclear antibody, rheumatoid factor, and autoantibodies to the soluble nuclear antigens Ro/SS-A and La/SS-B by double immunodiffusion. RESULTS: Approximately 27% of the population reported dry eye or dry mouth symptoms to be present often or all the time and 4.4% reported both. The prevalence of dry mouth (but not dry eye) symptoms increased with age, female sex, and white race. No association of sicca symptoms was found with rheumatoid arthritis, smoking, alcohol consumption, reproductive hormonal status, or the presence of autoantibodies. A strong, dose-response relationship was observed between sicca symptoms and the use of certain medication classes. The proportion of the population prevalence of sicca symptoms attributable to the use of drying medications was estimated at 62% for dry eye and dry mouth and 38% for dry eye or dry mouth symptoms. CONCLUSIONS: Sicca symptoms are common in the elderly, and medication side effects appear to be a major underlying factor. Our results do not indicate an association between autoimmune status and sicca symptoms and do not support immunologic testing in persons with sicca symptoms in the absence of other important systemic features.

Age Factors↗

The quality of life of African American women with breast cancer.

The objectives of this study were to describe the quality of life of African American women with breast cancer and test a model of factors that may affect their quality of life. A stress-coping framework that included person (demographics, current concerns, and optimism), social resources (family functioning), and illness-related factors (symptom distress, medical characteristics), as well as appraisal of illness and quality of life, was used to guide this exploratory, cross-sectional study. Participants included 98 African American women who were approximately 4 years postdiagnosis. The women reported a fairly high quality of life, were generally optimistic, and had effective family functioning. Although symptom distress was generally low, a sizable number of women reported problems with energy loss, sleep disturbances, and pain. The model explained 75% of the variance in quality of life, with appraisal, family functioning, symptom distress, and recurrence status each explaining a significant amount of the variance. Current concerns had an indirect effect on quality of life that was mediated by appraisal. These findings underscore the importance of helping women foster a positive appraisal of their illness, manage current concerns, maintain family functioning, and reduce symptom distress, because each of these factors indirectly or directly affects their quality of life.

Adaptation, Psychological↗

Posterior C1-C2 transarticular screw fixation in the treatment of displaced type II odontoid fractures in the geriatric population--review of seven cases.

BACKGROUND: Seven geriatric patients presented with displaced Type II odontoid fractures. All patients underwent a posterior C1-C2 transarticular fixation between November 1994 and December 1996. Ages ranged between 63 and 88 years. METHODS: Fractures were treated with placement of bilateral transarticular screws, allowing immediate fixation, except in one patient, for whom only a unilateral screw was used. An autograft interspinous strut was also placed, allowing three-point fixation. Mean follow-up was 10.6 months. RESULTS: Six patients received rigid fixation and developed a stable union. One patient died before any follow-up could be obtained. Two other patients died within 1 year of unrelated causes. The remaining four patients remain active and independent. One intraoperative vertebral artery injury was identified. No clinical sequalae were noted. CONCLUSION: Posterior transarticular screw fixation is a reasonable option in treating these controversial fractures. Seven geriatric patients tolerated this surgery well, and were mobilized early, avoiding complications related to external immobilization.

Aged↗

Who participates in population based studies of visual impairment? The Salisbury Eye Evaluation project experience.

PURPOSE: To describe characteristics of respondents and nonrespondents to a home questionnaire and comprehensive clinical examination in a population of elderly Americans. METHODS: The SEE project is a population-based study of age-related eye diseases, visual impairment, and functional status of individuals aged 65 to 84. Potential participants were identified using the Health Care Financing Administration Medicare data base for Salisbury, MD: After sending out an introductory letter, a trained interviewer visited potential participants in their homes, obtained their consent to participate, administered a short screening interview that included questions about their general health and vision, and administered an extensive questionnaire on their diet, medical history, and difficulty performing activities related to vision. The interviewer then scheduled an appointment for the participants to visit a central site for an exam. Potential participants could fall into one of two refusal groups; refusal to take part in the study before the home questionnaire or prior to the clinic visit. RESULTS: The overall response rate for the clinic visit was 65%. Compared to individuals with complete exams, the two groups of refusals were older, less likely to have any college education, more likely to report poor health status, and more likely to need help with Independent Activities of Daily Living (IADL's). Participants with complete home questionnaires that failed to come to the clinic were more likely to have Mini-Mental scores below 25. There were not significant differences by race, gender, or self reported vision status among the three groups. CONCLUSIONS: Population-based studies requiring an in-clinic examination may selectively under-sample those with health and mental difficulties. These differential responses may introduce bias in the study results and need to be addressed when assessing the burden, type and severity of disease in the community. However, self-report of visual status was similar among refusals and participants in this study on vision.

Activities of Daily Living↗

Therapeutic antibody fragments with prolonged in vivo half-lives.

Antibody fragments can be isolated rapidly using techniques such as phage display and can be expressed to high levels in microbial systems. However, to date such antibody fragments have been of limited use for many therapeutic applications because they are rapidly cleared from the body. We present a strategy for the site-specific chemical modification of antibody fragments with polyethylene glycol, which results in the production of antibody fragments with long in vivo half-lives and full retention of antigen-binding properties. This technology should allow more rapid and economical production of therapeutic antibodies for chronic disease therapy.

Animals↗

Characteristics of effective village treatment assistants: the Kongwa Trachoma Project.

PURPOSE: Mass treatment of entire communities with tetracycline eye ointment is one method for treatment of hyperendemic trachoma. Village Treatment Assistants (VTAs) are often recruited to implement mass treatment in their neighborhoods. We determined characteristics of these volunteers that were associated with effective treatment outcomes. METHODS: Three villages received mass treatment with tetracycline ointment daily for four weeks as part of a clinical trial. Community members selected VTAs to administer the ointment. Trachoma status was assessed by grading photographs of the tarsal conjunctiva in a sample of children randomly selected from households in each village. Change in trachoma status was determined from baseline to one month post treatment. VTA performance outcome was "good" if there was improvement in the majority of the children treated by the VTA, "poor" if the majority worsened, and "neutral" if there was neither improvement nor worsening on average. Trained interviewers administered a questionnaire measuring socioeconomic and demographic variables to 82% of all VTAs. RESULTS: A total of 280 VTAs (229 with questionnaire) were evaluated: 36.8% had good outcomes and 12.5% had poor outcomes. Those VTAs with poor outcomes tended to be unmarried females (OR = 11.73) and those who used a bicycle to carry out treatment activities (OR = 4.16). Formal education or prior experience as a health worker were not predictors of performance. CONCLUSION: Community selection and effective, non-formal, training are key components for the use of VTAs in mass treatment campaigns. Prior education or health training does not play a major role in effectiveness. The possible effects of gender roles in the community need to be considered in program design.

Anti-Bacterial Agents↗

Incidence of trichiasis in a cohort of women with and without scarring.

BACKGROUND: Blindness from trachoma is a significant problem for many underdeveloped countries. While active trachoma is common in children, trichiasis, the potentially blinding sequella, develops in adulthood and affects mainly women. Little is known about factors associated with the development of trichiasis. METHODS: The 7-year incidence of trichiasis and its association with ocular chlamydia infection was examined in a cohort of women from a hyperendemic area. A total of 4,932 women 18 years and older, living in 11 villages in Central Tanzania, were examined in 1989. A follow-up examination in 1996 was performed on all women with scars living in six of the 11 villages and on a random sample of women without scars from the same villages. Trachoma was graded clinically, chlamydia infection was ascertained at follow-up using polymerase chain reaction-enzyme immunoassay (PCR-EIA). RESULTS: A total 523 of the women with scars and 503 of the women without scars were re-examined. Forty-eight of the women with scars (incidence, 9.2%) and three of the women without scars (0.6%) developed trichiasis in the 7-year period. Prevalence of chlamydia infection was significantly higher in the group with scars (11.7% versus 7.1%). Trichiasis cases were more likely to be older, and to have chlamydia infection at follow-up odds ratio (95% confidence interval) 2.5 (1.1-5.7). CONCLUSION: The 7-year incidence rate in the population with scars was high, over 1% per year. Ocular chlamydia infection was more common in the group with scars at baseline and was also associated with being a trichiasis case, suggesting the importance of potentially long-term chlamydia infection in the progression to trichiasis. Antibiotic distribution programmes for trachoma control should include women with scars.

Adult↗

Ocular ultraviolet B exposure and lens opacities: a review.

A review of the epidemiological evidence linking cataract and chronic ultraviolet B radiation (UV-B) exposure was carried out. The majority of ecological studies suggest an increased risk of cataract with residence in areas of greater ambient UV-B. Studies which have measured personal ocular exposure to UV-B have found that even low exposures, as encountered in the general populations of developed countries, confer a measurable risk of cortical cataract. There is sufficient evidence of increased risk of cortical lens opacity with ocular exposure to UV-B to warrant public health messages about simple measures to decrease exposure.

Cataract↗