Characterization and prognostic impact of ACTBL2-positive tumor-infiltrating leukocytes in epithelial ovarian cancer.

Actin beta-like 2 (ACTBL2) was recently identified as a new mediator of migration in ovarian cancer cells. Yet, its impact on tumor-infiltrating and thus migrating leukocytes (TILs) remains to date unknown. This study characterizes the subset of ACTBL2-expressing TILs in epithelial ovarian cancer (EOC) and elucidates their prognostic influence on the overall survival of EOC patients with special regard to different histological subtypes. Comprehensive immunohistochemical analyses of Tissue-Microarrays of 156 ovarian cancer patients revealed, that a tumor infiltration by ACTBL2-positive leukocytes was significantly associated with an improved overall survival (OS) (61.2 vs. 34.4 months; p = 0.006) and was identified as an independent prognostic factor (HR = 0.556; p = 0.038). This significant survival benefit was particularly evident in patients with low-grade serous carcinoma (OS: median not reached vs. 15.6 months, p < 0.001; HR = 0.058, p = 0.018). In the present cohort, ACTBL2-positive TILs were mainly composed of CD44-positive cytotoxic T-cells (CD8+) and macrophages (CD68+), as depicted by double-immunofluorescence and various immunohistochemical serial staining. Our results provide significant evidence of the prognostic impact and cellular composition of ACTBL2-expressing TILs in EOC. Complementary studies are required to analyze the underlying molecular mechanisms of ACTBL2 as a marker for activated migrating leukocytes and to further characterize its immunological impact on ovarian carcinogenesis.

Expression pattern and prognostic potential of histamine receptors in epithelial ovarian cancer.

PURPOSE: Despite recent advances in the treatment of ovarian cancer (OC), long-term remissions remain scarce. For a targeted approach, prognostic markers are indispensable for predicting survival and treatment response. Given their association with multiple hallmarks of cancer, histamine receptors (HR) are emerging as promising candidates. Here, we investigate their expression pattern and prognostic value in OC. METHODS: Specimens of 156 epithelial OC patients were collected during cytoreductive surgery at the Department of Obstetrics and Gynecology, LMU, between 1990 and 2002 and combined in a tissue microarray. Immunohistochemical staining of the HR H1, H2, H3 and H4 was quantified by an immunoreactive score and linked with clinico-pathological data by Spearman's correlation. Via ROC curve analysis, optimal cut-off values for potential prognostic markers were defined. Overall survival (OS) was visualized in Kaplan-Maier curves and significances determined by log-rank testing. A Cox regression model was applied for multivariate analysis. RESULTS: HR H3 and H4 expression was restricted to the cytosol of OC cells, while H1 was also present in the nucleus. A significant association between HR H1, H3 and H4 expression with several clinico-pathological parameters was revealed. In addition, HR H1 and H3 expression correlated positively, HR H4 expression negatively with OS. In addition, HR H3 was identified as independent prognostic marker for OS. HR H2 expression had no prognostic value. CONCLUSIONS: HR H1, H3 and H4 could serve as potential predictors for OS of OC patients. Further research is warranted to elucidate their pathophysiologic role and their predictive and therapeutic potential in OC.

The willingness of UK adults with intellectual disabilities to take COVID-19 vaccines.

BACKGROUND: Given the much greater COVID-19 mortality risk experienced by people with intellectual disabilities (ID), understanding the willingness of people with ID to take a COVID-19 vaccine is a major public health issue. METHOD: In December 2020 to February 2021, across the United Kingdom, 621 adults with ID were interviewed remotely and 348 family carers or support workers of adults with ID with greater needs completed an online survey, including a question on willingness to take a COVID-19 vaccine if offered. RESULTS: Eighty-seven per cent of interviewees with ID were willing to take a COVID-19 vaccine, with willingness associated with white ethnicity, having already had a flu vaccine, gaining information about COVID-19 from television but not from social media, and knowing COVID-19 social restrictions rules. A percentage of 81.7% of surveyed carers of adults with ID with greater needs reported that the person would be willing to take a COVID-19 vaccine, with willingness associated with white ethnicity, having a health condition of concern in the context of COVID-19, having had a flu vaccine, being close to someone who had died due to COVID-19, and having shielded at some point during the pandemic. CONCLUSIONS: Reported willingness to take the COVID-19 vaccine is high among adults with ID in the United Kingdom, with factors associated with willingness having clear implications for public health policy and practice.

Relationship between pubertal testicular ultrasonographic evaluation and future reproductive performance potential in Piétrain boars.

New ways of predicting sperm quality and output performance in young artificial insemination (AI) boars are important for breeding companies to ensure that the pubertal boars delivered to the AI studs have a high chance of meeting minimum quality standards to be used for insemination and therewith dissemination of desirable characteristics. The aim of the current study was to characterize the testicular development of 218 pubertal Piétrain boars (Line 408, Pig Improvement Company) to identify traits with predictable characteristics relative to their sperm quality as an adult AI boar. Scrotum, testes and epididymis were examined ultrasonographically at day (d) 100 (on-test) and 170 (off-test) followed by a computer-assisted grayscale analysis (GSA). Over the test period, paired testicular volume increased 7.3-fold from 22.7 ± 10.8 cm3 to 166.6 ± 62.2 cm3. The right testis was significantly (P = 0.014) larger than the left one at the off-test. Based on the sperm quality (ejaculate volume, sperm concentration, total sperm number, morphologically abnormal sperm and total sperm motility at day 3 of semen storage), 82.11% (n = 179) of the boars were classified as "productive" boars. These boars had a significantly (P = 0.039) larger paired testicular volume than "non-productive" boars (45.9 ± 19.9 cm3vs. 38.5 ± 12.6 cm3) at the on-test. For the right testis at on-test, significant differences for the standard deviation of mean gray value (P = 0.022), area under the curve (P = 0.004) and mean gradient value (GRAD, P = 0.030) regarding the future sperm production capacity (SPC) were shown. At off-test, there was a significant difference for minimum gray value (MIN GV, P = 0.003) and mean gray value (P = 0.001) related to SPC. To find SPC related cut-off values for GSA data, a two segmental non-linear regression analysis was carried out indicating breakpoints for GRAD ≥12 and MIN GV ≥ 40 for boars with low SPC. Off-test boars with MIN GV ≥ 40 showed a 2.4 higher risk to display low SPC (Odds ratio = 2.4 [1.1, 5.4]; P = 0.024). The results may enable breeding companies to include new sperm quality associated traits in their boar testing and selection programs.

Prediction of Stent-Retriever Thrombectomy Outcomes by Dynamic Multidetector CT Angiography in Patients with Acute Carotid T or MCA Occlusions.

BACKGROUND AND PURPOSE: The selection of patients for endovascular therapy is an important issue in stroke imaging. The aim of this study was to determine the predictive value of 3 different dynamic CT angiography parameters, occlusion length, collateralization extent, and time delay to maximum enhancement, for latest generation of stent retriever thrombectomy recanalization outcomes in patients with acute ischemic stroke. MATERIALS AND METHODS: In this study, subjects were selected from an initial cohort of 2059 consecutive patients who had undergone multiparametric CT, including whole-brain CT perfusion. We included all patients with a complete occlusion of the M1 segment of the MCA or the carotid T and subsequent intra-arterial stent retriever thrombectomy. Dynamic CT angiography was reconstructed from whole-brain CT perfusion raw datasets. Angiographic outcome was scored by using the modified TICI scale; and clinical outcome, by using the modified Rankin Scale. Logistic regression analyses were performed to determine independent predictors of a favorable angiographic (mTICI = 3) and clinical outcome (mRS ≤2). RESULTS: Sixty-nine patients (mean age, 68 ± 14 years; 46% men) were included for statistical analysis. In the regression analysis, a short occlusion length was an independent predictor of favorable angiographic outcome (OR, 0.41; P < .05). Both collateralization grade (OR, 1.00; P > .05) and time delay to peak enhancement (OR, 0.90; P > .05) failed to predict a favorable angiographic outcome. None of the dynamic CT angiography predictors were significantly associated with clinical outcome on discharge (OR, 0.664-1.011; P = .330-.953) or at 90 days (OR, 0.779-1.016; P = .130-.845). CONCLUSIONS: A short occlusion length as determined by dynamic CT angiography is an independent predictor of a favorable angiographic outcome of stent retriever thrombectomy in patients with ischemic stroke.

Strategies of collateral blood flow assessment in ischemic stroke: prediction of the follow-up infarct volume in conventional and dynamic CTA.

BACKGROUND AND PURPOSE: Collateral blood flow is an important prognostic marker in the acute stroke situation but approaches for assessment vary widely. Our aim was to compare strategies of collateral blood flow assessment in dynamic and conventional CTA in their ability to predict the follow-up infarction volume. MATERIALS AND METHODS: We retrospectively included all patients with an M1 occlusion from an existing cohort of 1912 consecutive patients who underwent initial multimodal stroke CT and follow-up MR imaging or nonenhanced CT. Collateralization was assessed in both conventional CT angiography and dynamic CT angiography by using 3 different collateral grading scores and segmentation of the volume of hypoattenuation. Arterial, arteriovenous, and venous phases were reconstructed for dynamic CT angiography, and all collateral scores and the volume of hypoattenuation were individually assessed for all phases. Different grading systems were compared by using the Bayesian information criterion calculated for multivariate regression analyses (Bayesian information criterion difference = 2-6, "positive"; Bayesian information criterion difference = 6-10, "strong"; Bayesian information criterion difference = >10, "very strong"). RESULTS: One hundred thirty-six patients (mean age, 70.4 years; male sex, 41.2%) were included. In the multivariate analysis, models containing the volume of hypoattenuation showed a significantly better model fit than models containing any of the 3 collateral grading scores in conventional CT angiography (Bayesian information criterion difference = >10) and dynamic CT angiography (Bayesian information criterion difference = >10). All grading systems showed the best model fit in the arteriovenous phase. For the volume of hypoattenuation, model fit was significantly higher for models containing the volume of hypoattenuation as assessed in the arteriovenous phase of dynamic CT angiography compared with the venous phase (Bayesian information criterion difference = 6.2) and the arterial phase of dynamic CT angiography (Bayesian information criterion difference = >10) and in comparison with conventional CT angiography (Bayesian information criterion difference = >10). CONCLUSIONS: The use of dynamic CT angiography within the arteriovenous phase by using quantification of the volume of hypoattenuation is the superior technique for assessment of collateralization among the tested approaches.

Person-centred reviews as a mechanism for planning the post-school transition of young people with intellectual disability.

BACKGROUND: Person-centred planning has played a key role in the transformation of intellectual disabilities services for more than a decade. The literature has identified clear advantages for service users when service delivery is planned around the individual rather than the user is made to fit into service structures. Researchers however have pointed out that there is a lack of evidence that person-centred planning positively influences outcomes for users. METHOD: Our study examined the application of person-centred planning during transition for young people with intellectual disabilities. We investigated the nature and content of 44 person-centred reviews of transition planning for this population in a local authority in the UK. We carried out a documentary analysis of all person-centred plans and conducted telephone interviews with all families participating in the programme. We focused on the issue of attendance at review meetings and what was discussed during the meetings. RESULTS: Analysis of the data shows an increase in the participation of young people and carers at review meetings and a significant shift in topics discussed during the transition planning process compared with previous programmes. However, some of these effects may dissipate once young people are actually leaving school as planning well is not synonymous with having an improved range of placement options. CONCLUSIONS: The findings suggest that person-centred planning can impact positively on some aspects of transition planning, while it may be too optimistic to expect radical improvement in other area. Key to further improvements is to complement person-centred planning with consistent involvement of all relevant stakeholders in planning for individuals.

Assistive technology, telecare and people with intellectual disabilities: ethical considerations.

Increasingly, commissioners and providers of services for people with intellectual disabilities are turning to assistive technology and telecare as a potential solution to the problem of the increased demand for services, brought about by an expanding population of people with intellectual disabilities in the context of relatively static or diminishing resources. While there are numerous potential benefits of assistive technology and telecare, both for service providers and service users, there are also a number of ethical issues. The aim of this paper is to raise these issues and to set them within the ethical framework proposed by Beauchamp and Childress. There is a need for a wider debate as a first step in the development of strategies to address the issues raised in the paper.

Do cell surface trafficking impairments account for variable cell surface sodium iodide symporter levels in breast cancer?

The Na(+)/I(-) symporter (NIS) is a transmembrane glycoprotein that mediates iodide uptake into thyroid follicular cells and serves as the molecular basis of radioiodine imaging and therapy for thyroid cancer patients. The finding that NIS protein is present in 80-90% of breast tumors suggests that breast cancer patients may also benefit from NIS-mediated radionuclide imaging and targeted therapy. However, only 17-25% of NIS-positive breast tumors have detectable radionuclide uptake activity. The discrepancy between NIS expression and radionuclide uptake activity is most likely contributed by variable cell surface NIS protein levels. Apart from the prevalent view that NIS cell surface trafficking impairments account for the variability, our current study proposes that differential levels of NIS expression may also account for variable cell surface NIS levels among breast tumors. We address the need to confirm the identity of intracellular NIS staining to reveal the mechanisms underlying variable cell surface NIS levels. In addition, we warrant a quantitative correlation between cell surface NIS levels and radionuclide uptake activity in patients such that the cell surface NIS levels required for radionuclide imaging can be defined and the defects impairing NIS activity can be recognized.

SECM characterization of immobilised enzymes by self-assembled monolayers on titanium dioxide surfaces.

SECM in generator-collector mode was used to detect the presence of immobilised enzymes on titanium dioxide layers which were chemically or electrochemically generated with possible application as chemical sensors and biosensors. Glucose oxidase (GOx) and horseradish peroxidase (HRP) were immobilised by SAM generation using aminopropyltriethoxysilane (APTES) and ascorbic acid. The enzymes were successfully immobilised on two different TiO(2) surfaces. A simple test of durability of the system was made and a model of SAM organisation is presented.

Social relationships in the workplace.

As more workers with disabilities are competitively employed, there are numerous opportunities to form social relationships with their co-workers. Close social relationships are associated with a number of positive outcomes (e.g., happiness, less stress) and should be actively pursued for those individuals desiring them. In this paper, we describe the types of social interactions displayed in work settings employing workers with and without disabilities. We also discuss some of the social problems experienced by some workers with disabilities. Finally, we describe two general categories of intervention strategies that have been used to impact social relationships: (a) strategies that involve changing the social behaviors of workers with disabilities, and (b) natural support strategies. The results from these strategies are discussed, and future areas of research are described. MRDD Research Reviews 7:128-133, 2001.

The mtaA gene of the myxothiazol biosynthetic gene cluster from Stigmatella aurantiaca DW4/3-1 encodes a phosphopantetheinyl transferase that activates polyketide synthases and polypeptide synthetases.

Myxothiazol is synthesized by the myxobacterium Stigmatella aurantiaca DW4/3-1 via a combined polyketide synthase/polypeptide synthetase. The biosynthesis of this secondary metabolite is also dependent on the gene product of mtaA. The deduced amino acid sequence of mtaA shows similarity to 4'-phosphopantetheinyl transferases (4'-PP transferase). This points to an enzyme activity that converts inactive forms of the acyl carrier protein domains of polyketide synthetases (PKSs) and/or the peptidyl carrier protein domains of nonribosomal polypeptide synthetases (NRPSs) of the myxothiazol synthetase complex to their corresponding holo-forms. Heterologous co-expression of MtaA with an acyl carrier protein domain of the myxothiazol synthetase was performed in Escherichia coli. The proposed function as a 4'-PP transferase was confirmed and emphasizes the significance of MtaA for the formation of a catalytically active myxothiazol synthetase complex. Additionally, it is shown that MtaA has a relaxed substrate specificity: it processes an aryl carrier protein domain derived from the enterobactin synthetase of E. coli (ArCP) as well as a peptidyl carrier protein domain from a polypeptide synthetase of yet unknown function from Sorangium cellulosum. Therefore, MtaA should be a useful tool for activating heterologously expressed PKS and NRPS systems.

How residents spend their nights on call.

PURPOSE: Night call is a significant part of residents' education, but little information about their night-call activities is available. This study recorded residents' activities during night-call rotations on internal medicine and pediatrics wards. METHOD: In June and July 1997, on-call pediatrics and internal medicine residents at an urban academic medical center were accompanied by trained observers on the general wards between the hours of 7 PM and 7 AM. The types and duration of activities were recorded. RESULTS: Residents were observed for 106 nights. Internal medicine and pediatrics residents spent their time similarly. They spent 5.3 hours and 5.7 hours per night, respectively, on "basic" activities such as eating, resting, chatting, and sleeping, and an average of 2.6 hours and 2.2 hours, respectively, on chart review and documentation. In both programs, discussing the case with team members averaged 1.5 hours per night and use of the computer averaged slightly more than half an hour. Internal medicine residents spent approximately 1.5 hours on patients' history and physical examinations while pediatrics residents spent 1.3 hours. With each new patient, internal medicine residents spent an average of 19.7 minutes and pediatrics residents spent 16.5 minutes. The only significant difference between the two groups of residents was that the pediatrics residents spent more time per night on procedures than did the internal medicine residents (37 minutes versus 14 minutes, p < 0.01). CONCLUSIONS: Residents from both programs spent a surprising amount of time each night on chart review and documentation. In fact, they spent more time with charts than with patients. Whether this activity truly contributes to residents' education or improved patients' outcomes is not clear.

Identification of an L-dopa decarboxylase gene from Sorangium cellulosum So ce90.

During a screening program intended to identify genes encoding enzymes typical for secondary metabolism in Sorangium cellulosum So ce90, an aromatic amino acid decarboxylase gene (ddc) was detected. Expression of ddc in Escherichia coli and subsequent enzyme assays with cell-free extracts confirmed the proposed function derived from amino acid sequence comparisons. In contrast to other aromatic amino acid decarboxylases of eukaryotic origin, the S. cellulosum Ddc converted only L-dihydroxy phenylalanine. This is the first report of a gene encoding an L-dihydroxy phenylalanine decarboxylase in bacteria.

Characterization of atherosclerosis in LDL receptor knockout mice: macrophage accumulation correlates with rapid and sustained expression of aortic MCP-1/JE.

Atherosclerosis and the expression of monocyte chemoattractant protein-1 (MCP-1) were quantified in low density lipoprotein receptor knockout (LDLR KO) mice fed 1.25% cholesterol (study #1) or 0.2% cholesterol (study #2). In study #1 plasma total cholesterols leveled-off at 1800 mg/dl whereas plasma triglycerides remained low. In en face specimens of the aortic root and arch, intimal foam cells plus extracellular lipid particles accumulated and by 8 weeks the fatty streak surface area had rapidly expanded at both sites. In study #2, total cholesterols averaged 400 mg/dl and fatty streaks were 2-3-fold smaller compared to those in study #1. In study #3, LDLR KO mice were fed chow or 1.25% cholesterol, and immunostaining demonstrated a few Mac-2-positive intimal macrophages in mice fed chow, and during the first 10 weeks of hypercholesterolemia the number of intimal macrophages increased continuously. In chow-fed mice (0 weeks) there was little MCP-1 in the aorta. After 2 days of hypercholesterolemia intimal macrophages stained for MCP-1, and during the next 10 weeks recently recruited arterial macrophages also expressed MCP-1. Macrophage accumulation was highly correlated with MCP-1 expression. In study #4, feeding LDLR KO mice 1.25% cholesterol for 6 months produced atherosclerotic plaques at both sites and they contained a fibrous cap of smooth muscle cells, macrophage-foam cells, connective tissue and cholesterol crystals. In summary, LDLR KO mice fed cholesterol develop fatty streaks that transform into fibrous plaques. Hypercholesterolemia rapidly triggers MCP-1 expression in resident intimal macrophages, which is followed by the accumulation of more macrophages that also express MCP-1, suggesting that this chemokine may both initiate and amplify monocyte recruitment to the artery wall during early atherogenesis.

Strategic planning and progress under the All Wales Strategy: reflecting the perceptions of stakeholders.

Nominated representatives from the various stakeholder interests, i.e. social services, health, education, voluntary organizations, parent groups and self-advocacy groups, involved in the implementation of the All Wales Strategy for the development of services for people with intellectual disability were interviewed 2 years after the end of the initial 10-year phase. Interviewees were asked to reflect on the strengths and weaknesses of policy implementation, including: changing priorities, planning arrangements, agency roles, central guidance and financial mechanisms, consumer participation, and the impact of more recent policy or structural developments. Despite recognition of the leadership of the Welsh Office, the shift in thinking achieved, the developments made in joint agency collaboration and in consumer participation in planning, and an increasing competence to plan effectively over time, the overriding perception was that more could have been made of the opportunity afforded by the clearest and best resourced central government policy within the UK in this area. At the heart of this judgement lay concerns about pragmatic rather than strategic planning, a failure to link annual service developments to a final comprehensive end point and a related failure to integrate planning to meet community needs with hospital resettlement Factors which may have contributed to these weaknesses are discussed, as are lessons for subsequent community care policy.

New lessons for combinatorial biosynthesis from myxobacteria. The myxothiazol biosynthetic gene cluster of Stigmatella aurantiaca DW4/3-1.

The biosynthetic mta gene cluster responsible for myxothiazol formation from the fruiting body forming myxobacterium Stigmatella aurantiaca DW4/3-1 was sequenced and analyzed. Myxothiazol, an inhibitor of the electron transport via the bc(1)-complex of the respiratory chain, is biosynthesized by a unique combination of several polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS), which are activated by the 4'-phosphopantetheinyl transferase MtaA. Genomic replacement of a fragment of mtaB and insertion of a kanamycin resistance gene into mtaA both impaired myxothiazol synthesis. Genes mtaC and mtaD encode the enzymes for bis-thiazol(ine) formation and chain extension on one pure NRPS (MtaC) and on a unique combination of PKS and NRPS (MtaD). The genes mtaE and mtaF encode PKSs including peptide fragments with homology to methyltransferases. These methyltransferase modules are assumed to be necessary for the formation of the proposed methoxy- and beta-methoxy-acrylate intermediates of myxothiazol biosynthesis. The last gene of the cluster, mtaG, again resembles a NRPS and provides insight into the mechanism of the formation of the terminal amide of myxothiazol. The carbon backbone of an amino acid added to the myxothiazol-acid is assumed to be removed via an unprecedented module with homology to monooxygenases within MtaG.

Metabolic diversity in myxobacteria: identification of the myxalamid and the stigmatellin biosynthetic gene cluster of Stigmatella aurantiaca Sg a15 and a combined polyketide-(poly)peptide gene cluster from the epothilone producing strain Sorangium cellulosum So ce90.

Myxobacterial strains producing polyketides (PKs) assumed to be biosynthesized by a type I polyketide synthase (PKS) were analysed. Myxobacteria also produce a variety of polypeptides (PP) and PKs with incorporated amino acids ('mixed PK-PP'). In order to be able to identify the biosynthetic gene clusters for these metabolites a PCR based approach has been developed to clone ketosynthase (KS) domains of PKS genes from these organisms. Conserved regions of peptide synthetases of the non-ribosomal type (NRPS) were also amplified via PCR. KS fragments from Stigmatella aurantiaca Sg a15 were used for chromosomal gene inactivation experiments resulting in a series of mutants including such that were unable to produce stigmatellins and myxalamids. A NRPS fragment and PKS fragments from Sorangium cellulosum So ce90 were used to identify cosmids hybridizing with both types of probes from a genomic library. Both a NRPS and a PKS fragment were cloned and sequenced from a relatively short restriction fragment of one of these cosmids. The method described here should be very useful to clone and identify PKS, NRPS and mixed PKS-NRPS from myxobacteria in general and thereby open opportunities to use the biochemical diversity of these bacteria for genetic engineering and combinatorial biosynthesis.

Enhanced reduction of atherosclerosis in hamsters treated with pravastatin and captopril: ACE in atheromas provides cellular targets for captopril.

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase and angiotensin-converting enzyme (ACE) reduce experimental atherosclerosis by different mechanisms. To determine whether dual-drug therapy additively retards the progression of early lesions, control hyperlipidemic hamsters were compared with those treated with pravastatin, captopril, and pravastatin plus captopril. After 8 weeks of treatment, pravastatin (34 mg/kg/day) reduced plasma total cholesterol and triglycerides by 41 and 84%, respectively, whereas captopril (100 mg/kg/day) reduced normal blood pressure by 21%. The combination of pravastatin and captopril (33 and 100 mg/kg/day) decreased plasma total cholesterol and triglycerides by 44 and 84%, and blood pressure was decreased by 14%. In the aortic arch, pravastatin reduced macrophage-foam cell size and fatty streak area by 21 and 31%, respectively, whereas captopril decreased macrophage-foam cell number and fatty streak area by 34 and 35%. Pravastatin plus captopril decreased macrophage-foam cell number, foam cell size, and fatty streak area by 38, 24, and 67%. ACE inhibitors were previously reported to retard atherosclerosis without affecting blood pressure, suggesting that these agents acted on the artery wall. Therefore the expression of arterial ACE was determined in normal and atherosclerotic hamster aortas. ACE messenger RNA (mRNA) and protein were detected in endothelial cells, intimal macrophage-foam cells and medial smooth-muscle cells of atherosclerotic arteries indicating an upregulation of ACE expression with hyperlipidemia and atherosclerosis. In conclusion, dual-therapy with pravastatin and captopril produced an additive reduction in fatty streak area compared with either drug alone and suggested that atherogenesis can be retarded beyond the level achieved with monotherapy. The presence of ACE in endothelial cells and intimal macrophage-foam cells provides cellular targets for captopril to directly modify the formation of early atherosclerotic lesions.

Staff:staff and staff:client reliability of the Schalock & Keith (1993) Quality of Life Questionnaire.

A small-scale study of the inter-rater and staff:client reliability of the Schalock & Keith (1993) Quality of Life Questionnaire (QOL-Q) was conducted. Whilst the sample size was small and the QOL-Q achieved an acceptable overall level of reliability, the study replicated the pattern of low staff:client concordance and staff overestimation of the independence and autonomy of clients reported by Reiter & Bendov (1996). The results are briefly discussed in the context of the ongoing debate about the utility of proxy response in the literature.