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Biomedical subjects

S Ramsey

Publications and source records attributed to S Ramsey.

At least 19 recordsLinked to original sources

The longitudinal relationship between circulating concentrations of C-reactive protein, interleukin-6 and interleukin-10 in patients undergoing resection for renal cancer.

The systemic inflammatory response, as evidenced by elevated circulating concentrations of C-reactive protein, is a stage-independent prognostic factor in patients undergoing curative nephrectomy for localised renal cancer. However, it is not clear whether the systemic inflammatory response arises from the tumour per se or as a result of an impaired immune cytokine response. The aim of the present study was to examine C-reactive protein, interleukin-6 and interleukin-10 concentrations before and following curative resection of renal cancer. Sixty-four patients with malignant renal disease and 12 with benign disease, undergoing resection were studied. Preoperatively, a blood sample was collected for routine laboratory analysis with a further sample stored before analysis of interleukin-6 and interleukin-10 using an enzyme-linked immunosorbent assay (ELISA) technique. The blood sampling procedure and analyses were repeated at approximately 3 months following resection. Circulating concentrations of both interleukin-6 and interleukin (P< or =0.01) were higher and a greater proportion were elevated (P<0.05) in malignant compared with benign disease. The renal cancer patients were grouped according to whether they had evidence of a systemic inflammatory response. In the inflammatory group T stage was higher (P<0.01), both interleukin-6 and interleukin-10 concentrations were higher (P<0.001) and elevated (P<0.10) compared with the non-inflammatory group. Tumour volume was weakly correlated with C-reactive protein (r(2)=0.20, P=0.002), interleukin-6 (r(2)=0.20, P=0.002) and interleukin-10 (r(2)=0.24, P=0.001). Following nephrectomy the proportion of patients with elevated C-reactive protein, interleukin-6 and interleukin-10 concentrations did not alter significantly. An elevated preoperative C-reactive protein was associated with increased tumour stage, interleukin-6 and interleukin-10 concentrations. However, resection of the primary tumour did not appear to be associated with significant normalisation of circulating concentrations of C-reactive protein, interleukin-6 or interleukin-10. Therefore, the presence of systemic inflammatory response is unlikely to be solely be determined by the tumour itself, but may be as a result of an impaired immune cytokine response in patients with renal cancer.

Analysis of Variance↗

Survey of the prevalence, diagnosis and treatment of dermatological conditions in small animals in general practice.

A survey was made of the prevalence, diagnosis and treatment of dermatological conditions in small animals in general practice in the UK. Out of 3707 small animal consultations in general practice that were observed and recorded, 795 (21.4 per cent) involved animals that had a dermatological problem. In dogs and exotic species, pruritus was the most common presenting sign, accounting for 30 to 40 per cent of the dermatological consultations. In cats, cutaneous swellings were the most common presentation (36 per cent). A diagnosis or recommendation for treatment was made on the basis of the presenting clinical signs and physical examination alone in 576 (72 per cent) of the cases, and various diagnostic tests were performed in the other cases. In dogs, parasitic infestations, bacterial infections and neoplasia accounted for the majority of the diagnoses. In cats, parasites and bacterial infections were the most common. In exotic species, parasites accounted for over 80 per cent of the dermatological diagnoses. In dogs, the most common final diagnoses were otitis, pyoderma, anal sac impaction, flea infestation and atopic dermatitis. In cats, abscesses, flea infestation, and otitis were the most common diagnoses. In exotic species, the most common diagnosis was an unspecified mite infestation. Systemic antibiotics were prescribed in 196 cases (25 per cent), systemic glucocorticoids were prescribed in 162 cases (20 per cent) and treatment with an ectoparasiticide was prescribed in 167 cases (21 per cent).

Animals↗

Transcriptional noise and cellular heterogeneity in mammalian macrophages.

Transcriptional noise is known to play a crucial role in heterogeneity in bacteria and yeast. Mammalian macrophages are known to exhibit cell-to-cell variation in their responses to pathogens, but the source of this heterogeneity is not known. We have developed a detailed stochastic model of gene expression that takes into account scaling effects due to cell size and genome complexity. We report the results of applying this model to simulating gene expression variability in mammalian macrophages, demonstrating a possible molecular basis for heterogeneity in macrophage signalling responses. We note that the nature of predicted transcriptional noise in macrophages is different from that in yeast and bacteria. Some molecular interactions in yeast and bacteria are thought to have evolved to minimize the effects of the high-frequency noise observed in these species. Transcriptional noise in macrophages results in slow changes to gene expression levels and would not require the type of spike-filtering circuits observed in yeast and bacteria.

Animals↗

The relationship between the preoperative systemic inflammatory response and cancer-specific survival in patients undergoing potentially curative resection for renal clear cell cancer.

The relationship between tumour stage, grade (Fuhrman), performance status (ECOG), a combined score (UCLA Integrated Staging System, UISS), systemic inflammatory response (elevated C-reactive protein concentration), and cancer-specific survival was examined in patients undergoing potentially curative resection for renal clear cell cancer (n=100). On univariate survival analysis, sex (P=0.050), tumour stage (P=0.001), Fuhrman grade (P<0.001), UISS (P<0.001), C-reactive protein (P=0.002) were significant predictors of survival. On multivariate analysis with sex, UISS and C-reactive protein entered as covariates, only UISS (HR 2.70, 95% CI 1.00-7.30, P=0.050) and C-reactive protein (HR 4.00, 95% CI 1.21-13.31, P=0.024) were significant independent predictors of survival. The presence of a preoperative systemic inflammatory response predicts poor cancer-specific survival in patients who have undergone potentially curative resection for renal clear cell cancer.

C-Reactive Protein↗

The Adults with Incapacity (Scotland) Act--Who knows? Who cares?

UNLABELLED: The Adults with Incapacity (Scotland) Act 2000 provides new guidelines on obtaining consent for adults who are incapable of providing informed consent. This article surveys current practice of health workers when obtaining consent from such individuals, and the results are compared to the Incapacity Act and local guidelines. The survey results suggest that practice of the guidelines is variable and often legally inadequate. AIMS: To quantify awareness and practical application of the Adults with Incapacity (Scotland) Act in surgical wards in a central Glasgow teaching hospital, 2 years after the Act's introduction. METHODS: An interviewer led anonymous questionnaire was presented to all degree educated staff encountered on random visits to acute and elective surgical and orthopaedic wards in a split site teaching hospital. RESULTS: 17 out of 50 staff approached (34%) had not heard of the Adults with Incapacity Act. There was a significantly higher level of awareness amongst staff based on acute wards (85%) when compared with those from elective wards (54%) (p < 0.05, chi-square) There was a complete absence offormal training in using the Act and knowledge was sometimes inaccurate or incorrect. Most staff that had heard of the Act could suggest causes of incapacity, but some included physical disability. There was a persistence of the belief that a relative can consentfor an incapable adult patient, and this was expressed by some of the staff despite knowledge of the Act. CONCLUSIONS: This study shows that a significant number of ward staff have no knowledge of the Act; and understanding is variable amongst staff who have heard of it. The Adults with Incapacity (Scotland) Act 2000 is a unique piece of legislation to protect the interests of incapable patients, and doctors treating them; but is of no use if medical and nursing staff are unaware of its existence.

Adult↗

Implementation of ALARA radiation protection on the ISS through polyethylene shielding augmentation of the Service Module Crew Quarters.

With 5-7 month long duration missions at 51.6 degrees inclination in Low Earth Orbit, the ionizing radiation levels to which International Space Station (ISS) crewmembers are exposed will be the highest planned occupational exposures in the world. Even with the expectation that regulatory dose limits will not be exceeded during a single tour of duty aboard the ISS, the "as low as reasonably achievable" (ALARA) precept requires that radiological risks be minimized when possible through a dose optimization process. Judicious placement of efficient shielding materials in locations where crewmembers sleep, rest, or work is an important means for implementing ALARA for spaceflight. Polyethylene (CnHn) is a relatively inexpensive, stable, and, with a low atomic number, an effective shielding material that has been certified for use aboard the ISS. Several designs for placement of slabs or walls of polyethylene have been evaluated for radiation exposure reduction in the Crew Quarters (CQ) of the Zvezda (Star) Service Module. Optimization of shield designs relies on accurate characterization of the expected primary and secondary particle environment and modeling of the predicted radiobiological responses of critical organs and tissues. Results of the studies shown herein indicate that 20% or more reduction in equivalent dose to the CQ occupant is achievable. These results suggest that shielding design and risk analysis are necessary measures for reducing long-term radiological risks to ISS inhabitants and for meeting legal ALARA requirements. Verification of shield concepts requires results from specific designs to be compared with onboard dosimetry.

Astronauts↗

Evolution of 'design' principles in biochemical networks.

Computer modelling and simulation are commonly used to analyse engineered systems. Biological systems differ in that they often cannot be accurately characterised, so simulations are far from exact. Nonetheless, we argue in this paper that evolution results in recurring, dynamic organisational principles in biological systems, and that simulation can help to identify them and analyse their dynamic properties. As a specific example, we present a dynamic model of the galactose utilisation pathway in yeast, and highlight several features of the model that embody such 'design principles'.

Adaptation, Physiological↗

Parameter solicitation for planning cost effectiveness studies with dichotomous outcomes.

When economic endpoints are included alongside clinical effectiveness measures in randomized clinical trials (RCT), they are summarized together by the incremental cost effectiveness ratio (ICER). Adding economic endpoints to an RCT complicates the planning of experiments because investigators must now solicit their beliefs about costs, but even more challenging, they must also specify their association with effectiveness. Solicitation of correlations between costs and effects can be unintuitive, and so potentially highly inaccurate. This is unfortunate because power is highly sensitive to the association between costs and effects. Mis-specification in this association may lead to substantially underpowered or overpowered studies. We show that when clinical effectiveness measures are dichotomous, specification of the correlation between costs and effects can be avoided by instead describing their association with a mixture model. This representation leads to simple and highly intuitive parameter specifications. It may also be used to generate realistic raw data that can be used to evaluate experiment power with simulation. We give particular attention to evaluating and interpreting power when Fieller's theorem method (FTM) is used to calculate confidence for, and test hypotheses about, the ICER. Data from a previously published clinical trial are used to demonstrate the use of this new method to calculate sample size for a cost effectiveness study.

Cost-Benefit Analysis↗

Healthcare charges and use in commercially insured children enrolled in managed care health plans in Washington State.

OBJECTIVE: To determine the relative importance of enrollee, physician, medical group, and healthcare plan characteristics as determinants of healthcare use and expenditures in commercially insured children < 18 years of age enrolled in managed care health plans. We focused on the effects of age and benefit level, the two most important predictors of cost and utilization in our study of adults. METHODS: This study included 67,432 commercially insured children who were between 1 and 18 years of age, and were cared for by 790 primary care physicians, who practiced in 60 medical care groups in Washington State. Plan enrollment and utilization data for 1994 were linked to a survey of medical care groups contracting with three managed care health plans. Benefit level for each enrollee was defined as low, medium, or high and was based on cost sharing by the health plan for hospitalization, outpatient care, and emergency department services. The three outcome measures included estimated total per member per year charges, number of ambulatory visits, and hospital days. RESULTS: In multivariate analysis, enrollee age was the most important determinant of total charges, with younger children incurring higher charges and utilization. For children 5 years and younger, mean total per member per year charges were $617 in the low-benefit category and $878 in the high category (p < .0001). These differences were less apparent for children 6-12 years ($355 versus $420, p = .012), and were not statistically significant for children 13 years and older ($503 versus $552, p = .14). The annual number of visits increased with benefit level for children of all ages. CONCLUSIONS: Enrollee age and benefit level were the most important determinants of healthcare use and expenditures in children enrolled in managed care health plans.

Adolescent↗

Primary care physician compensation method in medical groups: does it influence the use and cost of health services for enrollees in managed care organizations?

CONTEXT: Growth of at-risk managed care contracts between health plans and medical groups has been well documented, but less is known about the nature of financial incentives within those medical groups or their effects on health care utilization. OBJECTIVE: To test whether utilization and cost of health services per enrollee were influenced independently by the compensation method of the enrollee's primary care physician. DESIGN: Survey of medical groups contracting with selected managed care health plans, linked to 1994 plan enrollment and utilization data for adult enrollees. SETTING: Medical groups, major managed care health plans, and their patients/enrollees in the state of Washington. STUDY PARTICIPANTS: Sixty medical groups in Washington, 865 primary care physicians (internal medicine, pediatrics, family practice, or general practice) from those groups and affiliated with 1 or more of 4 managed care health plans, and 200 931 adult plan enrollees. INTERVENTION: The effect of method of primary care physician's compensation on the utilization and cost of health services was analyzed by weighted least squares and random effects regression. MAIN OUTCOME MEASURES: Total visits, hospital days, and per member per year estimated costs. RESULTS: Compensation method was not significantly (P>.30) related to utilization and cost in any multivariate analyses. Patient age (P<.001), female gender (P<.001), and plan benefit level (P<.001) were significantly positively related to visits, hospital days, and per member per year costs. The primary care physician's age was significantly negatively related (P<.001) to all 3 dependent measures. CONCLUSIONS: Compensation method was not significantly related to use and cost of health services per person. Enrollee, physician, and health plan benefit factors were the prime determinants of utilization and cost of health services.

Capitation Fee↗

Recruiting adults with osteoarthritis into an aquatic exercise class: strategies for a statewide intervention.

OBJECTIVE: Although research suggests that regular exercise can be helpful in reducing the dysfunction and discomfort of osteoarthritis, promoting exercise among older adults within this population is neither straightforward nor easily accomplished. This article describes the various methods, and their relative success rates, that were employed to recruit older adults throughout the state of Washington into an aquatic exercise program. METHODS: Strategies included a recruitment letter distributed to Arthritis Foundation (AF) members in Washington state, local media news coverage, physician referrals, and advertisements in local papers and newsletters. RESULTS: The most successful methods for enrolling participants were through the AF recruitment letters and local television coverage. The AF recruitment letter was the most expensive method of generating responses, while the television coverage was the least expensive. CONCLUSIONS: Collaborating with a well-reputed community-based organization and capitalizing on available publicity resources are important strategies researchers can use to gain access to a difficult and geographically dispersed population.

Advertising↗

Physician compensation models in medical group practice.

This article examines physician compensation models in medical groups and the factors affecting physician compensation and their impact on individual physician behavior and group practice performance. Four categories of physician compensation models are identified: (1) production-based compensation, (2) salary, (3) group-based compensation unrelated to individual physician productivity, and (4) capitation-based compensation. The statistics and the economic incentives of different compensation methods are presented. Finally, the impacts on health resources consumption, charges in medical group procedures for utilization and care management, and quality of care are discussed.

Economic Competition↗

Modulation of osteoblast behaviour by tenascin.

The extracellular matrix protein tenascin is secreted by osteoblasts but absent from mineralized bone matrix. The current study was undertaken to test the hypothesis that tenascin regulates osteoblast behaviour. Three osteoblast-like cell lines UMR-106, ROS-17/2.8 (rat) and SAOS-2 (human) were used to investigate the role of tenascin in osteoblast morphology, differentiation and proliferation. Two of three cell lines adhered specifically to tenascin, remaining round and failing to spread. Tenascin as a substratum stimulated alkaline phosphatase activity (a marker of osteoblast differentiation) in two of three cell lines. Moreover, anti-tenascin in the medium caused a reduction in alkaline phosphatase levels in all three cell lines. Anti-tenascin also inhibited collagen synthesis, an important osteoblast function. Since it seemed possible that tenascin may exert its effects on cell function through its ability to cause cell rounding, the ability of cell shape change alone to influence alkaline phosphatase levels was investigated. Cells were incubated in the presence of cytochalasin D and alkaline phosphatase levels assayed. Alkaline phosphatase activity was not elevated by cytochalasin D treatment, indicating that cell rounding alone is insufficient to mimic the effect of tenascin. Anti-tenascin caused a slight increase in proliferation of SAOS-2 cells, indicating that tenascin is itself inhibitory. In ROS 17/2.8 and UMR-106 cells, in contrast, proliferation was inhibited by anti-tenascin. The results presented here indicate that tenascin is able to stimulate osteoblastic differentiation and that endogenous tenascin helps to maintain the functional state of cultured osteoblast-like cells.

Alkaline Phosphatase↗

Closed-captioned television presentation speed and vocabulary.

This study summarizes an extensive research project on closed-captioned television. Caption data were recorded from 205 television programs. Both roll-up and pop-on captions were analyzed. In the first part of the study, captions were edited to remove commercials and then processed by computer to get caption speed data. Caption rates among program types varied considerably. The average caption speed for all programs was 141 words per minute, with program extremes of 74 and 231 words per minute. The second part of the study determined the amount of editing being done to program scripts. Ten-minute segments from two different shows in each of 13 program categories were analyzed by comparing the caption script to the program audio. The percentage of script edited out ranged from 0% (in instances of verbatim captioning) to 19%. In the third part of the study, commonly used words in captioning and their frequency of appearance were analyzed. All words from all the programs in the study were combined into one large computer file. This file, which contained 834,726 words, was sorted and found to contain 16,102 unique words.

Humans↗

Expression of tenascin in joint-associated tissues during development and postnatal growth.

The extracellular matrix protein, tenascin, is selectively expressed in a variety of connective tissues during development. In this study, the distribution of tenascin in tissues contributing to the knee joint during embryonic development and postnatal growth in the rat has been investigated by immunohistochemistry. In recently formed embryonic knee joints, tenascin expression was abundant in the territorial matrix of superficial articular cartilage. Site of attachment of cruciate and patellar ligaments to cartilage were strongly stained; staining of ligaments weakened with distance from the attachment site. In rapidly growing 4-wk-old rats, tenascin was present in a fine line on the surface of articular cartilage, but at 10 wk of age tenascin staining was absent from most of the articular surface. In postnatal rats, there was strong tenascin staining of the synovial lining, but not of subintimal tissue. Cruciate ligaments were histologically fibrocartilaginous in 4 and 10-wk-old rats; within these ligaments strong pericellular tenascin staining was seen in association with rounded chondrocyte-like cells. Tenascin was absent from the cartilaginous growth plates of 4 and 10-wk-old rats, but intense tenascin staining was seen at the junction between epiphyseal bone and growth plate. Within the metaphysis, tenascin staining on bone surfaces increased with distance from the hypertrophic chondrocytes. Osteocytes within epiphyseal trabecular bone were strongly stained for tenascin, whereas those in the metaphysis were mostly unstained. The results presented here demonstrate that tenascin expression in joint-associated tissues changes markedly with cell type and stage of differentiation.

Animals↗

Proposal to reimburse occupational medicine disease and injury claims through third party health insurance.

The current system of compensation for the medical costs of occupational illnesses and injuries, a component of health insurance coverage for most workers in the United States, has recently come under scrutiny in the national health care reform debate. The cost of treatment of these conditions is significant, and there exist numerous disincentives for physicians and patients to use the workers' compensation system. Physicians who treat workers with occupationally related diseases may find compensation for a condition is disputed at the same time that it is excluded from payment by third party insurance coverage, leaving the patient selectively uninsured for at least some medical care services. In addition, most workers' compensation programs have been designed in a way that discourages efficient resource use by providers and claimants. We propose allowing health care providers to bill third party health insurers for all care, including work-related diseases and injuries. Insurers, in turn, would bill workers' compensation programs for associated treatment costs. The potential advantages of such a system include reductions in inefficiency and unfair burdens placed on providers and patients, in reporting bias, and in administrative costs balanced against the risks of insurers excluding workers in high risk occupations from obtaining low cost health insurance and shifting away from employers the administrative burden for workers' compensation.

Accidents, Occupational↗