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Binding of excess cadmium(II) to Cd7-metallothionein from recombinant mouse Zn7-metallothionein 1. UV-VIS absorption and circular dichroism studies and theoretical location approach by surface accessibility analysis.

A mouse metallotbionein (MT) 1 expression system has been constructed that renders recombinant MT as a high purity Zn-coordinated protein. Spectral changes in absorption and circular dichroism following the addition of up to 7 mol equivalents of Cd2+ to recombinant Zn7-MT showed that it behaves like the native protein. Exposure of Cd7-MT to Cd2+ resulted in further binding of these ions to the protein, although saturation was not achieved on the addition of up to 22 mol equivalents of Cd2+ to Zn7-MT. Spectral data are compatible with a model in which the first four additional Cd2+ ions are bound to Cd7-MT via sulfur atoms, and indicate that no further thiol groups are involved in the binding of the excess Cd(II) over 11. Cd2+ ions bound in excess to Cd7-MT appear to have lower binding constants as exposure of Cdn-MT (n > 7) species to Cbelex-100 retrieved Cd7-MT. Based on the X-ray data, the accessible surface areas of sulfur atoms in Cd5,Zn2-MT 2 were calculated. This led us to propose that the coordination of the first three additional Cd(II) ions to Cd7-MT proceeds by means of S-Met1-O-Met1, S-Cys7-S-Cys13 and S-Cys5-S-Cys26 pairs. Finally, comparison of the behavior of the entire MT with that of the recombinant alpha MT and beta MT subunits indicates that mutual influences may not be negligible.

Animals↗

Partial amino acid sequence of an L-amino acid oxidase from the cyanobacterium Synechococcus PCC6301, cloning and DNA sequence analysis of the aoxA gene.

A novel type of L-amino acid oxidase from Synechococcus PCC6301 was purified and subjected to amino acid sequence analysis. Since the N-terminus of the L-amino acid oxidase protein was not accessible for Edman degradation, the protein was partially hydrolysed and a contiguous sequence of 17 amino acid residues was obtained from an endogenous peptide fragment. Based on the partial peptide sequence two oligonucleotides were designed, which were used as probes in Southern hybridization experiments in order to identify the corresponding aoxA gene. The aoxA gene was isolated from a size-fractionated genomic library of Synechococcus PCC6301 and subsequently sequenced. From the nucleotide sequence (data base accession number Z48565) it can be deduced that the L-amino acid protein consists of 355 amino acid residues resulting in a molar mass of 39.2 kDa. The calculated isoelectric point of the protein is 9.81. The L-amino acid oxidase from Synechococcus PCC6301 shows low homologies to other flavin oxidases/dehydrogenases, especially amine oxidases, but no homologies to other so far sequenced L- or D-amino acid oxidases.

Amino Acid Oxidoreductases↗

Treatment of people with mental illness: a decade-long perspective.

Many believe that managed behavioral health care has been associated with reduced access to care. Data from a variety of sources suggest that access has increased, although patterns of care and locations of treatment have changed. Data from Healthcare for Communities, a nationally representative community survey, show that access to care has not decreased for people with the most serious conditions who were more likely to receive specialty mental health care after 2000. Further, once people enter specialty care, the number of visits appears unrelated to need. The data highlight the urgent need for a greater focus on the quality of care and patient outcomes.

Data Collection↗

Improving young people's access to reproductive health care in rural Zimbabwe.

The aim of this study was to explore ways to improve the accessibility of clinics for young people with reproductive health problems in rural Zimbabwe. This study, which took place in rural Masvingo, was part of a project to develop a comprehensive adolescent reproductive health intervention for Zimbabwean youth. Six focus group discussions were held with secondary school pupils aged 16-19; four focus group discussions were held with nurses. Additionally, 16 community meetings with parents of adolescents were observed. The data were analyzed using the principles of grounded theory: three main categories and several sub-categories emerged from the data. The accessibility of existing services for young people was poor, partly because nurses were reluctant to provide such services due to lack of clarity in legislation and also through fear of condoning adolescent sexual activity. Although the clinical acumen of staff was recognized as sound, service delivery was perceived to be judgemental and lacking in confidentiality and privacy. This reflects the cultural context in which services are delivered. Culturally, adolescents are deemed to be children and as such to have few rights. There is a widely held belief that teaching young people about sex will promote sexual activity. Our findings suggested that staff training should focus on attitudinal rather than medical issues.

Adolescent↗

The HIPAAcratic oath: do no harm to patient data.

Physician executives need to prepare their organizations for the next great system-wide challenge--HIPAA, the Health Insurance Portability and Accountability Act of 1996. Organizations will have to plan for and execute a compliance program with the same vigor and system-wide participation as they did for Y2K. This article provides a brief overview of HIPAA, emphasizing the privacy and security components that will be the biggest challenge for physician executives. Physician leaders must become actively involved in the policymaking process to ensure a balanced approach to protecting the confidentiality of health information, while giving providers optimal access to data to make informed decisions on patient care and management. Ignoring HIPAA is simply not an option.

Computer Security↗

Genomic messaging system language including command extensions for clinical data categories.

This paper, in the area of clinical bioinformatics, highlights relatively efficient means of storing, exchanging, protecting, and searching human and other genomic data, so as to make the data securely accessible to researchers while respecting patient privacy. One important idea is that the GMSL language can be considered as an extension of the way DNA and protein sequences are written so as to carry with them the wishes of the patient in regard to fine-grained consent (as well as retaining the medical experts' cautions, instructions for use, and annotation), and this is carried, whatever environment (e.g., XML) that the data is from or whatever it is going to. At the deepest level, a stream of data expressed in GMSL resembles highly compressed stream of self-checking machine code. For the reader less familiar with the computational aspects, some simple examples illustrate how the raw language looks and works as a raw stream of (interpreted) bytes. The bioinformatics applications are not confined to the clinical domain. This paper completes the initial specification of the language as previously presented and reports on some important extensions including clinical data categories.

Base Sequence↗

A patient follow-up system for stomach cancer.

The concept of PASK (Patient follow-up System of Kyushu University Hospital) has been innovated in order to manage clinical data of patients in the hospital-wide scope over long periods of time by using computers. PASK represents a collection of subsystems, each tuned to a specific disease. For the initial implementation, the subsystem for stomach cancer (STOMAC) was constructed according to the Cancer Center of Kyushu University Hospital project. STOMAC began to work in October 1984 and has proved effective. Using STOMAC, doctors in a clinical section can easily access patient data gained in another section. Besides providing a data reference function, STOMAC automatically gives alarms for abnormalities in clinical examination results, anti-tumor drug dosage, visitation cycles of patients, etc. The database and STOMAC programs are strongly standardized and easily applicable to another specific disease.

Aftercare↗

The prevalence of obesity and undernutrition in Scottish children: growth monitoring within the Child Health Surveillance Programme.

OBJECTIVE: To assess whether anthropometric data, routinely collected as part of the Scottish Child Health Surveillance System (CHSP-PS, pre-school children; CHSP-S, school age children) could provide a means of monitoring/surveillance for obesity and undernutrition at national and health board level. DESIGN: A survey of 15 health boards and both surveillance systems to identify the nature of data collected, format of data, and extent to which data were accessible (e.g., via Information and Statistics Division of the Common Services Agency). Measurements of weight and height collected as part of the CHSP-PS and CHSP-S were extracted from ISD. They were then audited and missing values or implausible values quantified, and degree of dispersion of values used as an index of quality of measurements. SETTING: Health Board Child Health Surveillance Systems and Information and Statistics Division, Edinburgh. RESULTS: Data on height and weight are currently available for 9 health boards for pre-school children and 4 health boards for school age children. This represents coverage of around 80% of the pre-school child population. Analysis of a data extract from the 39-42 month check in 1998/99, used as an example, revealed that 8% of weight and height data were missing, and approximately 1% were implausible measures. Population and health board level estimates of prevalence of obesity and undernutrition were possible and are presented. Data on height and weight are routinely collected in school age children in all health boards, however only four health boards have growth data electronically available via the school CHSP. CONCLUSIONS: Growth data routinely collected as part of child health surveillance for Scotland can be used to estimate population prevalence of undernutrition and obesity. These can in turn be used to monitor trends at local and national level, to monitor achievement in relation to public health targets, identify risk factors and high risk groups, and to follow cohorts over time. We describe a system of surveillance for undernutrition and obesity and identify its strengths and weaknesses.

Adolescent↗

Challenges of change: a qualitative study of chronic care model implementation.

PURPOSE: The Chronic Care Model (CCM) provides a conceptual framework for transforming health care for patients with chronic conditions; however, little is known about how to best design and implement its specifics. One large health care organization that tried to implement the CCM in primary care provided an opportunity to study these issues. METHODS: We conducted a qualitative, comparative case study of 5 of 18 group clinics 18 to 23 months after the implementation began. Built on knowledge of the clinics from a previous study of advanced access implementation, data included in-depth interviews with organizational leaders and varied clinic personnel, observation of clinic care processes, and review of written materials. RESULTS: Relatively small and highly variable care process changes were made during the study period. The change process underwent several marked shifts in strategy when initial efforts failed to achieve much and bore little resemblance to the change process used in the previously successful large-scale implementation of advanced access scheduling. Many barriers were identified, including too many competing priorities, a lack of specificity and agreement about the care process changes desired, and little engagement of physicians. CONCLUSION: These findings highlight specific organizational challenges with health care transformation in the absence of a blueprint more specific than the CCM. Effective models of organizational change and detailed examples of proven, feasible care changes still need to be demonstrated if we are to transform care as called for by the Institute of Medicine.

Ambulatory Care Facilities↗

Managing exacerbations of COPD: room for improvement.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a major cause of hospital admissions. Because of the consequent morbidity, mortality and burden on hospital resources, COPD management guidelines have been formulated. We reviewed 62 consecutive patients with AECOPD admitted from September 1st to December 18th 2000 in St. Vincents University Hospital, Ireland, including 3 months follow-up data, to evaluate the quality of care and in particular to assess the care of such patients by respiratory and non-respiratory physicians. There was a frequent failure to objectively confirm the diagnosis of COPD by spirometry (completed in 39 of the 51 patients who, at admission, had been previously labelled with COPD (76%), and in 53 out of 62 patients (85%) at the end of the study period), or to estimate severity by quantifying the FEV1 as a percentage of the normal predicted range (estimated in only 21 of the 39 patients who had spirometry previously performed (53%)). Those patients managed with input from respiratory physicians were more likely to have their diagnosis of COPD confirmed with spirometry (p < 0.05). They were also more likely to have out-patient follow-up arranged at discharge (p < 0.05). There was a trend towards the more frequent prescribing of oxygen to hypoxic patients in "respiratory" than in "non-respiratory" managed cases (p = 0.182) and a shorter hospital stay (0.1 < p < 0.5). 4 out of 11 severely hypoxaemic patients at admission (PO2 < 7.3kPa) were not screened at discharge for possible long term oxygen therapy (36%). 20 patients received combination antibiotic therapy with no infiltrate on CXR (32%). Pulmonary rehabilitation was offered to 12 patients (19%). 5 out of 18 current smokers had documented smoking cessation advice (28%) and none received smoking cessation pharmacotherapy. Finally we noted that the Hospital In-Patient Enquiry (HIPE) data and casualty department admission books were frequently misleading or medical records unlocatable (in 30 out of 92 cases (33%)). We conclude that the management of AECOPD at St. Vincent's University Hospital is frequently suboptimal, and may be managed better with respiratory physician involvement. In particular, there could be more frequent spirometric confirmation of the diagnosis of COPD, better screening for long term oxygen therapy and more conservative use of antibiotics. Audit is complicated by difficulty accessing relevant data.

Aged↗

Improving performance using indicators. Recent experiences in the United States, the United Kingdom, and Australia.

This article describes recent national performance improvement initiatives in the United States, United Kingdom, and Australia. This comparison is of particular interest because each of these three countries faces similar challenges in delivering health care and improving health. Each has elevated a focus on safety and quality improvement to a national level. Marked differences in the organization and financing of health care across these three countries provide a unique opportunity to compare and contrast approaches. Drawing on the experience of the authors in each of the three countries and publicly available data sources about specific national initiatives, we describe the national context for improvement and outline recent performance improvement initiatives and emerging issues and challenges. Similarities and differences in the current evolution of national performance initiatives are described and conclusions are drawn about challenges that all three countries face, particularly in terms of developing meaningful sets of national indicators of health system performance. The challenges for future work include the importance of information infrastructure, the paucity of accurate and accessible clinical data, the need for effective performance measurement processes at a local level to capture useful data, and the tensions of balancing accountability and improvement agendas for measurement.

Australia↗

A comparison of hypertext and Boolean access to biomedical information.

This study explored which of two modes of access to a biomedical database better supported problem solving in bacteriology. Boolean access, which allowed subjects to frame their queries as combinations of keywords, was compared to hypertext access, which allowed subjects to navigate from one database node to another. The accessible biomedical data were identical across systems. Data were collected from 42 first year medical students, each randomized to the Boolean or hypertext system, before and after their bacteriology course. Subjects worked eight clinical case problems, first using only their personal knowledge and, subsequently, with aid from the database. Database retrievals enabled students to answer questions they could not answer based on personal knowledge only. This effect was greater when personal knowledge of bacteriology was lower. The results also suggest that hypertext was superior to Boolean access in helping subjects identify possible infectious agents in these clinical case problems.

Bacteriology↗

Methodological issues in health care surveys of the Spanish heritage population.

This paper examines national survey data on access to medical care to explore methodological issues associated with conducting health care surveys of Spanish-heritage persons. These include problems of identifying and sampling such groups, achieving respondent cooperation, designing valid interview protocols, and controlling biases that may result from the cultural specificity of the concepts being studied. The findings suggest that more attention should be given to the following in designing health care surveys of Spanish-heritage individuals: cultural and economic heterogeneity of "Spanish-heritage" grouping, validity studies of health care utilization, and yea-saying tendencies related to health care attitude items. Given that there is a paucity of information available on methodological problems associated with health care surveys of Spanish-heritage persons, these analyses should serve to inform researchers of issues to be taken into account in designing such studies and to suggest useful hypotheses to explore in evaluating the validity of social survey data on minority (especially non-English speaking) populations' health care practices.

Adolescent↗

Traditional and new concepts in protein evaluation of feeds: a review.

The purpose of protein evaluation of a diet is to determine its value for meeting amino acid requirements of animals. The early recognition that proteins can be utilized by different efficiency rates has promoted extended research to reveal quality differences and their reasons. A brief historical overview is given in this review about the development of concepts and theories in protein evaluation. Recent developments have focused attention on determination of available quantities of essential amino acids. In vitro chemical assays and dye-binding procedures are relatively fast and provide data without access to animals, however they do not always correlate well with biological estimates. Enzymic digestion methods and microbiological assays for prediction of availability of essential amino acids have the potential for serial determination in quality control, however they are constrained by a lack of information about the availability of peptides liberated and utilized during in vivo digestion of proteins. Animal growth assays and balance experiments can provide valuable estimates of available quantities of essential amino acids. However, the interpretation of data is complicated by the many factors affecting in vivo protein utilization, by the endogenous amino acid excretion and the effects of microflora of the alimentary tract. The search for reliable assays remains a worthwhile objective also in the future.

Amino Acids↗

Permanent vascular access: a nephrologist's view.

Vascular access complications are the greatest cause of morbidity in hemodialysis patients in the United States. Although arteriovenous fistulas have been recommended as the preferred mode of vascular access, recent data indicate that the majority of patients on hemodialysis in the United States have prosthetic graft fistulas. The most frequent complications of prosthetic graft fistulas are thrombosis and stenosis. Hospitalization rates for fistula complications are higher in patients with diabetes mellitus and of black race. Pathogenesis of intimal hyperplasia may include elaboration of platelet-derived growth factor and mechanical endothelial injury. Screening for stenosis and impaired blood flow in fistulas can be carried out with recirculation measurements, venous and intra-access pressure measurements, and Doppler ultrasound. A combination of the techniques is probably the best current strategy for fistula screening and further evaluation. Surgical thrombectomy and fistula revision remain the standard for comparison of newer approaches to management of complications. Percutaneous angioplasty with or without stent placement, thrombolysis, and use of atherectomy devices may play an increasing role in the treatment of complications, although comparative trials of these modalities need to be performed. No satisfactory long-term pharmacologic means of preventing thrombosis, stenosis, or restenosis have been found for graft arteriovenous fistulas. It is hoped that future directions in the field of vascular access placement and management will include better strategies for allowing primary arteriovenous fistula development, advances in graft materials, improved understanding of the pathogenesis of thrombosis and stenosis, and development strategies to prevent complications.

Angioplasty, Balloon↗

Isolation of the epithiospecifier protein from oil-rape (Brassica napus ssp. oleifera) seed and its characterization.

The epithiospecifier protein (ESP) is a myrosinase (MYR) cofactor, which is necessary to drive the MYR-catalyzed hydrolysis of some specific glucosinolates towards the production of cyanoepithioalkanes instead of isothiocyanates and nitriles. ESP was isolated from Brassica napus seeds by anionic exchange and gel filtration chromatography. ESP showed a molecular weight of about 39 kDa and pI 5.3. The amino acid sequence of several tryptic peptides of ESP (accounting for about 50% of the total sequence) made it possible to establish the high similarity (81% identity) with a hypothetical 37 kDa protein (TrEMBL data base accession number Q39104) and several jasmonate-inducible proteins from Arabidopsis thaliana. This observation suggests that ESP is likely to be involved in jasmonate-mediated defence and disease resistance mechanisms.

Amino Acid Sequence↗

In vivo synthesis of ATPase complexes of Propionigenium modestum and Escherichia coli and analysis of their function.

Expression studies of Propionigenium modestum ATPase genes in various combinations with Escherichia coli ATPase genes were performed in the unc deletion mutant strain E. coli DK8. Plasmids containing the whole unc operon from P. modestum were unable to complement the E. coli unc deletion mutant. Although all ATPase subunits were expressed from the plasmids, there was no detectable ATP hydrolysing activity, indicating that the F1 part was not functional. Transformants expressing an E. coli F1-P. modestum F0 hybrid exhibited considerable ATPase activities. Binding of the F1 part to the membrane was very weak, however, and the coupling between ATP hydrolysis and Na+ transport was impaired. After combining the genes for E. coli ATPase subunits alpha, beta, gamma, delta and epsilon and the hydrophilic part of subunit b with P. modestum ATPase subunits a and c and the hydrophobic part of subunit b on a plasmid, a non-functional hybrid ATPase was expressed in E. coli. The ATPase was only loosely bound to the membrane, from which it was solubilized with Triton X-100 and purified. Subunit b and a proteolytic degradation product were the only F0 subunits detectable in the purified enzyme. A stable F0 complex is thus not formed with the hybrid b subunit. The absence of a functional F0 complex was in accord with proton-conduction measurements with bacterial vesicles. The only functional Na(+)-translocating ATPase expressed in E. coli thus far consists of E. coli subunits alpha, beta, gamma and epsilon, and P. modestum subunits delta, a, b and c [Kaim, G. & Dimroth, P. (1993) Eur. J. Biochem. 218, 937-944]. During the cloning conducted in our present study, errors in the sequence entry into the EMBL data bank (accession no. X58461) for the P. modestum ATPase alpha and beta subunits became evident, which are corrected in this paper.

Adenosine Triphosphatases↗

Quality criteria and access characteristics of Web sites: proposal for the design of a health Internet directory.

The increasing volume of information available on the Internet today is a problem for health care professionals who want to access rapidly data of high quality. Usual search engines and directories are not sufficient to satisfy their needs. Moreover, the information published by Web sites is not always guaranteed. Some institutions around the word deal with the definition of a set of criteria for the evaluation of medical Web sites. We base our current work on the technologies we developed previously in order to integrate sources of information of various kinds using the "Unified Medical Language System" knowledge bases. This paper focuses on quality criteria and access characteristics Web sites should satisfy to be registered in a "Health Internet Directory". The design of such a system is proposed and discussed.

Abstracting and Indexing↗