Screening mammography re-evaluated.
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Age Distribution↗
Biomedical subjects
S Moss
Publications and source records attributed to S Moss.
Evaluation of primary prevention initiatives for skin cancer: a review from a UK perspective.
To ensure effective primary prevention of skin cancer, aimed at changing behaviour in the sun, and ultimately at reducing the incidence and mortality rates from skin cancer, sufficient information needs to be known about the relationship between sun exposure and skin cancer, the effectiveness of sun protection measures, and the acceptability and uptake of protective measures by the general public. This review specifically addresses the quality and outcome of studies designed to evaluate the impact of primary prevention initiatives in the U.K. Four main areas of concern are highlighted: (i) teenage behaviour in the sun is difficult to change; (ii) fashion, in part, dictates adult and adolescent behaviour in the sun; (iii) there are practical problems related to response rates, follow-up and interpretation of self-reported behaviour; and (iv) a strategy for primary prevention in the U.K. may be falsely based on the experience and results of Australian and American programmes. Standardized methods for monitoring general population behaviour are needed in the U.K. Evaluation of interventions targeting specific groups, especially parents and young children, and the relative costs of different strategies should be reported. Primary prevention messages and strategies should be adapted to the type of ultraviolet radiation exposure experienced, and the overall low risk of melanoma, while addressing controversies on the health effects of sun exposure and sun screens.
Adolescent↗
Interleukin 10-induced thrombocytopenia in normal healthy adult volunteers: evidence for decreased platelet production.
Recombinant human interleukin 10 (rhuIL-10) inhibits the production of proinflammatory cytokines and has shown promise in the treatment of inflammatory bowel disease. Clinical trials have been accompanied by a reversible decline in platelet counts. We conducted a randomized, double-blinded, placebo-controlled, parallel group trial in 12 healthy volunteers to investigate the aetiology of rhuIL-10-induced thrombocytopenia. Eight volunteers received 8 microg/kg/d of rhuIL-10 subcutaneously, while four subjects received a placebo alone for 10 d. A reversible decline in the platelet counts from a mean of 275 x 10(9)/l to 164 x 10(9)/l was observed in the IL-10-treated cohort (P = 0.012). A fall in the haemoglobin mean levels was also observed in the IL-10-treated cohort from 13.7 to 11.7 g/dl (P = 0.011). No significant change was observed in the bone marrow cellularity or myeloid/erythroid ratio or in the number of megakaryocytes per high-powered field (HPF). A fall was observed in the number of megakaryocyte colony-forming units (CFU-MKs) after the administration of IL-10 compared with those receiving the placebo (P = 0.068). No difference in the change in granulocyte-macrophage CFUs (CFU-GMs), mixed lineage CFUs (CFU-GEMMs) or erythroid burst-forming units (BFU-Es) was observed when comparing the IL-10- vs. placebo-treated groups (P > 0.465). Serum cytokine levels of thrombopoietin (TPO). IL-6 and granulocyte-macrophage colony stimulating factor (GM-CSF) were not decreased following IL-10 administration. In fact, both TPO and GM-CSF appeared to be slightly increased in the serum. All subjects underwent In111-labelled platelet survival studies with liver/spleen scans to assess splenic sequestration prior to and then on day 7 of treatment. A significant reduction in splenic sequestration of platelets (P =0.012) was observed in the IL-10-treated group, but not in the placebo-treated subjects.
Adult↗
Mental health services for people with intellectual disability: a conceptual framework.
The present paper discusses the application of the 'matrix model' to mental health services for people with intellectual disability. There is great variability between the service models in this area, which makes comparisons and conclusions difficult. The present model facilitates the breaking down of these complexities into understandable parts so that future directions for research, service planning and delivery can be logical, coherent and evidence-based.
Evidence-Based Medicine↗
BIOMED-MEROPE project: service provision for adults with intellectual disability: a European comparison.
The aim of the present paper is to describe and compare services for adults with intellectual disability (ID) and mental health needs in five European countries: Austria, England, Greece, Ireland and Spain. A framework and structure for collecting information about service provision was designed. This information was collected through a mixture of interviews with service providers, questionnaires and a review of the research literature within each country. Information was collected on historical context, policy, legislation, assessment, treatment and the structure of services for people with ID and mental health problems. Overall, the needs of those with additional mental health needs have not been specifically addressed at a national level with perhaps the exception of England and Ireland, although there are still gaps in services in these nations. Normalization has been adopted in each of the five countries, and there are moves toward deinstitutionalization, integration and inclusion. Families and self-advocacy groups have grown. The pace of this change varies between and even within countries. The main findings of the study include: unclear policy, trends for legislative changes, increased prevalence of mental health problems, inadequate generic service provision, a need for specialist mental health services, a need for improved interconnections of services, and a need for training developments. Policy and legislation in the five European countries under consideration tend to separate the disability aspects of people with ID from their mental health needs. Consequently, the service needs of this group remain largely invisible. This might be a direct reflection of policy clarity and legislation, or could be the result of a failure to implement existing guidelines. This has a detrimental effect on the lives of people with ID, and their families and carers.
Adult↗
Feasibility of targeted early detection for melanoma: a population-based screening study.
The feasibility of targeted screening for cutaneous malignant melanoma in the UK using a postal questionnaire and invitation to screening by a consultant dermatologist was investigated in a population based cross-sectional survey. A total of 1600 people aged 25-69 years, stratified by the social deprivation score of wards within one general practice, were randomly selected from a population of 8000.1227 (77%) returned the questionnaire and 896 (56%) attended the screening clinic. Uptake was lower for men (P<0.001), those aged under 50 (P<0.001), people from deprived areas (P<0.001) and skin types III and IV (men only, P<0.001). Twenty per cent of women and 10% of men felt nervous about attending the clinic, but only 4% were worried by the questionnaire. The level of agreement between the self- and dermatologist's assessments of risk factors was best for hair colour (Kappa = 0.67, sensitivity 73% and specificity 98%). People tended to under-report their level of risk. Over 95% knew about at least one major sign, but 54% reported incorrect signs of melanoma. Targeted screening for melanoma in the UK will be hampered by difficulties in accurately identifying the target population. Strategies to improve skin self-awareness rather than screening should be developed and evaluated.
Adult↗
A comprehensive program to improve safety for pregnant women and fetuses in motor vehicle crashes: a preliminary report.
OBJECTIVE: A program was developed to study the mechanisms of abruptio placentae and pregnancy loss caused by motor vehicle crashes. The results were intended to be used to develop strategies to improve protection of the fetus in this setting. STUDY DESIGN: Four integrated projects were conducted: (1) seated anthropometric measurements and belt fit determination during pregnancy, (2) development of new models of traumatic abruptio placentae, (3) investigations of crashes involving pregnant women, and (4) the development of the second-generation pregnant crash dummy from these data and others. RESULTS: Twenty-two different pregnant subjects in five different height groups underwent serial measurements of abdominal surface contours, seat belt fit, and distances between the subjects and various landmarks in the automobile interior with a laboratory-designed "automobile seat" (seating buck). The abdomen was significantly closer to the steering wheel in the shorter stature group than among the taller women. Beginning at approximately 20 weeks' gestation the fundus of the uterus was above the lower rim of the steering wheel. Lap belts fit properly over the anterior superior iliac spine throughout gestation, but the lap belt overlapped the uterus in the midsagittal plane. Two separate mechanisms for traumatic abruptio placentae were tested: shear failure and tensile failure. In the shear failure model large circumferential strains in the uterine wall induce a shear strain across the uteroplacental interface, and the model predicts placental separation at a mean circumferential strain of -58% +/- 8%. By means of finite-element modeling, it was demonstrated that tensile failure might also be a mechanism that causes abruptio placentae during rapid deceleration of the uterus. Crash investigations were performed in 43 cases involving pregnant women beyond 20 weeks' gestation. There were a total of 8 fetal losses and 8 major complications (fetal survival with abruptio placentae, direct fetal injury, or preterm delivery before 34 weeks' as a result of the accident). The best predictors of fetal loss or adverse outcome were impact severity and proper seat belt use. With these newly acquired data a second-generation crash dummy, known as the Maternal Anthropomorphic Measurement Apparatus version 2b (MAMA-2b), is being developed. It incorporates strain gauges in the fundal region of the fluid-filled uterus plus pressure transducers in both the anterior and posterior uterus. Criteria are being developed to associate the likelihood of abruptio placentae with measurements from these instruments that correspond to the two major hypothesized mechanisms of abruptio placentae. CONCLUSION: An improved understanding of the elements of automobile crashes that cause fetal loss and other major pregnancy complications has been gained through this series of investigations.
Abdomen↗
Intranodal hemangioma of the oral soft tissues: a case report of a rare entity with review of the literature.
The presentation of a primary vascular tumor in a lymph node is a rare occurrence. Only 16 documented cases have been reported to date, with none described in the oral soft tissues. This case report presents the first occurrence of an intra-nodal hemangioma of the oral soft tissue in an 11-year-old girl. A review of the literature is also presented.
Child↗
The unreliability of clinical measures of muscle tone: implications for stroke therapy.
BACKGROUND: the central tenet of the neurofacilitatory approach to stroke therapy is that muscle tone needs to be normal before normal movement can occur. A reliable clinical measure of the full spectrum of muscle tone is needed to test: (i) the purported relationship between muscle tone, other motor impairments and disability, and (ii) the effectiveness of stroke therapy to restore movement. AIM: the purpose of the study was to test the inter-rater reliability of clinical categorization of muscle tone (spastic/normal/flaccid) and also a visual analogue scale with anchor points of 'lowest tone possible' (score 0) and 'highest tone possible' (score 100). METHODS: four independent raters assessed tone of elbow flexors and knee extensors of 14 stroke rehabilitation inpatients using the categorical scale. Six independent raters assessed tone of elbow flexors and knee extensors of 25 chronic stroke patients and two healthy volunteers using the visual analogue scale. All assessment orders were randomized. RESULTS: both scales were unreliable, with K coefficients for the categorical scale ranging from -0.046 to 0.56 for the categorical scale, and intra-class correlation coefficients for the visual analogue scale of 0.595 for elbow flexors and 0.451 for knee extensors. Assessment order effects for the visual analogue scale were non-significant for elbow flexors (P= 0.545) and knee extensors (P= 0.911). CONCLUSIONS: these results, and those of earlier studies, suggest that clinical measures of muscle tone are consistently unreliable. Systematic investigation of the therapy rationale for planning and evaluating treatment is required before relevant clinical measures can be developed.
Humans↗
An audit of psychiatric case notes in relation to antipsychotic medication and information giving.
This paper reports upon a Welsh Office funded "clinical effectiveness" project. The project aimed to produce evidence-based practice guidelines for depot neuroleptic medication. An audit was conducted to establish current practice regarding the provision of illness and treatment specific information to out-patients and their informal carers. Sixty-five patients' case-notes, under the care of a single community mental health team were examined for evidence of the type, nature and frequency of information given to patients receiving typical depot neuroleptic medications. Service guidelines were produced and are presented.
Antipsychotic Agents↗
Is targeted early detection for melanoma feasible? Self assessments of risk and attitudes to screening.
OBJECTIVES: To study the feasibility of developing targeted screening for those at high risk of melanoma by examining how attitudes relate to (a) acceptance of an invitation for a free skin check and (b) self assessed and clinically assessed risk factors for developing cutaneous melanoma. DESIGN: A population based cross sectional survey. SETTING: A general practice with a broad mix of socioeconomic groups in one district health authority. SUBJECTS: A total of 1600 subjects aged 25-69 years stratified using the social deprivation score of wards were randomly selected from a population of 8000; 77% (1227) returned the questionnaire and 56% (896) attended for screening. MAIN OUTCOME MEASURES: Questionnaire measures of confidence in own ability to self assess risk factors for melanoma, attitudes to seeking medical help for skin abnormalities, and self assessment of relative risk of developing melanoma. RESULTS: Clinic attenders were less confident in their ability to self assess risk factors (p<0.005), more favourable towards seeking help (p<0.001), and more pessimistic about developing melanoma (p<0.001) than non-attenders. Those from more affluent wards were more willing to seek help (p<0.001). Those clinically assessed as at higher risk were more pessimistic about developing melanoma (p<0.001) but clinical assessments were inconsistently related to help seeking attitudes and self assessment confidence. CONCLUSIONS: Barriers to the uptake of screening included greater optimism about not developing melanoma, confidence in self assessment, and reluctance to seek professional help. Such reluctance was greater in more deprived social groups. Targeting screening at high risk groups cannot depend on self identification and self referral.
Attitude to Health↗
Psychiatric symptoms in adults with learning disability and challenging behaviour.
BACKGROUND: In people with learning disability one of the most frequent reasons for psychiatric referral is challenging behaviour. AIMS: To determine what proportion of people with challenging behaviour actually have psychiatric symptoms. METHOD: Using an instrument specifically designed for use by informants, a sample of 320 people with administratively defined learning disability, with and without challenging behaviour, was surveyed for the presence of psychiatric symptoms. RESULTS: Increasing severity of challenging behaviour was associated with increased prevalence of psychiatric symptoms, depression showing the most marked association. Anxiety symptoms were associated with the presence of self-injurious behaviour. CONCLUSIONS: There is clearly the potential for reducing challenging behaviour by improved identification and treatment of coexisting psychiatric disorders. The possibility of modifying diagnostic criteria for depression in people with learning disability, by including aspects of challenging behaviour, merits attention.
Adolescent↗
Calcium/calmodulin-dependent phosphorylation and activation of human Cdc25-C at the G2/M phase transition in HeLa cells.
The human tyrosine phosphatase (p54(cdc25-c)) is activated by phosphorylation at mitosis entry. The phosphorylated p54(cdc25-c) in turn activates the p34-cyclin B protein kinase and triggers mitosis. Although the active p34-cyclin B protein kinase can itself phosphorylate and activate p54(cdc25-c), we have investigated the possibility that other kinases may initially trigger the phosphorylation and activation of p54(cdc25-c). We have examined the effects of the calcium/calmodulin-dependent protein kinase (CaM kinase II) on p54(cdc25-c). Our in vitro experiments show that CaM kinase II can phosphorylate p54(cdc25-c) and increase its phosphatase activity by 2.5-3-fold. Treatment of a synchronous population of HeLa cells with KN-93 (a water-soluble inhibitor of CaM kinase II) or the microinjection of AC3-I (a specific peptide inhibitor of CaM kinase II) results in a cell cycle block in G2 phase. In the KN-93-arrested cells, p54(cdc25-c) is not phosphorylated, p34(cdc2) remains tyrosine phosphorylated, and there is no increase in histone H1 kinase activity. Our data suggest that a calcium-calmodulin-dependent step may be involved in the initial activation of p54(cdc25-c).
Benzylamines↗
A trial to study the effect on breast cancer mortality of annual mammographic screening in women starting at age 40. Trial Steering Group.
OBJECTIVE: Although there is clear evidence from randomised trials of the effectiveness of mammographic screening in women over 50 in reducing mortality from breast cancer, the benefit of screening in younger women remains less certain. This paper describes a randomised controlled trial in progress to study the effect on breast cancer mortality of annual mammographic screening of women starting at age 40-41. SETTING: Screening centres of the NHS Breast Screening Programme. METHODS: In 1991 a national multicentre randomised controlled trial was set up by the United Kingdom Coordinating Committee on Cancer Research (UKCCCR). This trial (the "age" trial) aims at recruiting 195,000 women aged 40-41 such that 65,000 form a study group and the remaining 130,000 a control group. Women in the study group are invited for annual screening by mammography, and become eligible for the National Health Service Breast Screening Programme (NHSBSP) after age 50. Those in the control group are not offered any additional services, but will also join the national programme after age 50. All malignant breast histology in trial women is recorded. ANALYSIS: The principal method of evaluation will be the comparison of cumulative breast cancer mortality rates in the study and control groups; interim analyses of prognostic factors of breast cancers will also be possible. Additional NHS screening costs incurred owing to lowering the age of screening will be assessed as part of an economic evaluation. The amount of unscheduled screening occurring in the control group of the trial will also be assessed.
Adult↗
Oxidized LDL can induce macrophage survival, DNA synthesis, and enhanced proliferative response to CSF-1 and GM-CSF.
Modification of low density lipoprotein (LDL), eg, by oxidation, has been proposed as being important for the formation of foam cells and therefore for the development of atherosclerotic plaques. There are a number of reports showing that macrophage-derived foam cells can proliferate in both human and animal lesions, particularly in the early phase of the disease and possibly involving macrophage-colony stimulating factor (M-CSF, or CSF-1). We studied the in vitro effects of oxidized LDL (ox-LDL) on murine bone marrow-derived macrophages (BMMs), a cell population with a high proliferative capacity in vitro in response to CSF-1 and a dependence for survival on the presence of this growth factor. We report here that treatment of BMMs with low doses of ox-LDL, but not with native LDL, led to cell survival, DNA synthesis, and an enhanced response to the proliferative actions of CSF-1 and granulocyte macrophage-CSF (GM-CSF); the effects were dependent on the degree of LDL oxidation. For CSF-1, a synergistic effect was noticeable at suboptimal doses. The effect of ox-LDL occurred even in the absence of endogenous CSF-1 or GM-CSF. Our findings suggest that ox-LDL, and possibly other modified forms of LDL, could maintain macrophage (and foam cell) survival and therefore lengthen their tenure in a plaque; the modified LDL could also cause local macrophage proliferation or "prime" them so that they could proliferate better in response to CSF-1 (and GM-CSF) concentrations that may be present in the atheroma.
Animals↗
Trial of mammography in women under 50 is ethical.
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Age Factors↗
Routine invitation of women aged 65-69 for breast cancer screening: results of first year of pilot study.
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Aged↗
Human monoclonal antibodies specific to hepatitis B virus generated in a human/mouse radiation chimera: the Trimera system.
An approach to develop fully human monoclonal antibodies in a human/mouse radiation chimera, the Trimera system, is described. In this system, functional human lymphocytes are engrafted in normal strains of mice which are rendered immuno-incompetent by lethal total body irradiation followed by radioprotection with severe combined immunodeficient (SCID) mouse bone marrow. Following transplantation, human lymphocytes colonize murine lymphatic organs and secrete human immunoglobulins. We have established this system as a tool to develop fully human monoclonal antibodies, and applied it for the generation of monoclonal antibodies specific for hepatitis B virus surface antigen. A strong memory response to hepatitis B surface antigen was elicited in Trimera engrafted with lymphocytes from human donors positive for antibodies to hepatitis B surface antigen. The human specific antibody fraction in the Trimera was 10(2)-10(3)-fold higher as compared with that found in the donors. Spleens were harvested from Trimera mice showing high specific-antibody titres and cells were fused to a human-mouse heteromyeloma fusion partner. Several stable hybridoma clones were isolated and characterized. These hybridomas produce high-affinity, IgG, anti-hepatitis B surface antigen antibodies demonstrating the potential of the Trimera system for generating fully human monoclonal antibodies. The biological function and the neutralizing activity of these antibodies are currently being tested.
Amino Acid Sequence↗