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PubMed2006

Alternate structural conformations of Streptococcus pneumoniae hyaluronan lyase: insights into enzyme flexibility and underlying molecular mechanism of action.

Streptococcus pneumoniae hyaluronan lyase is a surface enzyme of this Gram-positive bacterium. The enzyme degrades several biologically important, information-rich linear polymeric glycans: hyaluronan, unsulfated chondroitin, and some chondroitin sulfates. This degradation facilitates spreading of bacteria throughout the host tissues and presumably provides energy and a carbon source for pneumococcal cells. Its beta-elimination catalytic mechanism is an acid/base process termed proton acceptance and donation leading to cleavage of beta-1,4 linkages of the substrates. The degradation of hyaluronan occurs in two stages, initial endolytic cuts are followed by processive exolytic cleavage of one disaccharide at a time. In contrast, the degradation of chondroitins is purely endolytic. Structural studies together with flexibility analyses of two streptococcal enzymes, from S.pneumoniae and Streptococcus agalactiae, allowed for insights into this enzyme's molecular mechanism. Here, two new X-ray crystal structures of the pneumococcal enzyme in novel conformations are reported. These new conformations, complemented by molecular dynamics simulation results, directly confirm the predicted domain motions presumed to facilitate the processive degradative process. One of these new structures resembles the S.agalactiae enzyme conformation, and provides evidence of a uniform mechanistic/dynamic behavior of this protein across different bacteria.

Catalytic Domain↗
PubMed2002

Public participation in life cycle assessment and risk assessment: a shared need.

Life cycle assessment (LCA) and risk assessment are operationally different but share the common purpose of supporting decisions about reducing threats to human welfare. Both analysis methods also involve a complex mixture of science and value judgments reflecting epistemological as well as moral and esthetic values. The inability of risk assessment and LCA to be "value free" has been a source of considerable controversy in both communities. Recognition of the contingent and social nature of human interpretation of the risks and environmental impacts created by public and private decisions has led to an increased appreciation of the importance of involving interested and affected parties in risk characterization. Comparison of the value-based nature of LCA and risk assessment demonstrates the need for participation in LCA. Although the need for participation by affected parties in decision-making processes is gaining acceptance, there is little agreement as to how participation should be structured. Risk assessment and LCA have a shared need for research examining the design and analysis of participation processes appropriate to a given decision context. A proposed framework recommends participation strategies designed to enhance the effectiveness of policy-driven analyses such as risk assessment and LCA based on the level of trust that interested and affected parties have for other policy participants.

Decision Making↗
PubMed1990

[A study to determine the effectiveness of Severance Hospice Home Care Program].

The purpose of this study was to determine whether Severance Hospice Home Care Program was able to meet its objectives. This was done in order to show in detail the effects of hospice home care on the quality of life of terminally ill patients and to provide rationale for setting up more hospice home care programs in korea. The results of the study were as follows: The subjects of the study were 100 terminally ill patients who had died while in the hospice program and 64 family members who were registered with Severance Hospice Home Care Program between march 1988 and Feb. 1990. The nursing needs of these terminally ill patients were assessed by the nursing records of these patients. The need for pain control (82%) was the highest nursing need so far as the physical aspects were concerned. This was followed by poor appetite (37%), 8 dyspnea (34%), nausea and vomiting (30%) in that order of frequency. In regard to spiritual needs, the need for religious support was also high at 72%. Their main psychological symptoms were anxiety and fear (34%). Burn-out was a major problem for 44% of the family members. The psychological process experienced by the terminal ill patients was compared to the dying process, described by Kübler Ross. In comparison of the five stages outlined by kubler Ross with the dying process of the subjects it was found that the subjects not only experienced the five stages but also experienced denial and doubtfulness or denial with acceptance or acceptance with the expectation of a miracle. But rather than acceptance of the dying process, giving up was a frequent end point of the psychological process, of the subjects. However, when the combination of states was observed, most of the patients reached the state of acceptance in the dying process. It was difficult to identify a definite pattern of change in the psychological process of the subjects. Also it was difficult to identify the factors that influenced the psychological process. The symptoms of the terminally ill subjects just before dying, that is, 3-4 days before dying included apparent signs of dying. These were a reduction of intake (77%), reduction of the amount of urination (63%), increase in sleeping time (64%) and acceptance of dying by patients and their families who had been unaccepting before that time (66%). The primary care givers (family member's) degree of satisfaction with the care given to the patient by the hospice was 88.7%.(ABSTRACT TRUNCATED AT 400 WORDS)

Family↗
PubMed2002

Implementation of the 3Rs (refinement, reduction, and replacement): validation and regulatory acceptance considerations for alternative toxicological test methods.

Toxicological testing in the current regulatory environment is steeped in a history of using animals to answer questions about the safety of products to which humans are exposed. That history forms the basis for the testing strategies that have evolved to satisfy the needs of the regulatory bodies that render decisions that affect, for the most part, virtually all phases of premarket product development and evaluation and, to a lesser extent, postmarketing surveillance. Only relatively recently have the levels of awareness of, and responsiveness to, animal welfare issues reached current proportions. That paradigm shift, although sluggish, has nevertheless been progressive. New and alternative toxicological methods for hazard evaluation and risk assessment have now been adopted and are being viewed as a means to address those issues in a manner that considers humane treatment of animals yet maintains scientific credibility and preserves the goal of ensuring human safety. To facilitate this transition, regulatory agencies and regulated industry must work together toward improved approaches. They will need assurance that the methods will be reliable and the results comparable with, or better than, those derived from the current classical methods. That confidence will be a function of the scientific validation and resultant acceptance of any given method. In the United States, to fulfill this need, the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and its operational center, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), have been constituted as prescribed in federal law. Under this mandate, ICCVAM has developed a process and established criteria for the scientific validation and regulatory acceptance of new and alternative methods. The role of ICCVAM in the validation and acceptance process and the criteria instituted toward that end are described. Also discussed are the participation of the US Food and Drug Administration (FDA) in the ICCVAM process and that agency's approach to the application and implementation of ICCVAM-recommended methods.

Animal Testing Alternatives↗
PubMed2001

The mechanism and design of sequencing batch reactor systems for nutrient removal--the state of the art.

The Sequencing Batch Reactor (SBR) process for carbon and nutrient removal is subject to extensive research, and it is finding a wider application in full-scale installations. Despite the growing popularity, however, a widely accepted approach to process analysis and modeling, a unified design basis, and even a common terminology are still lacking; this situation is now regarded as the major obstacle hindering broader practical application of the SBR. In this paper a rational dimensioning approach is proposed for nutrient removal SBRs based on scientific information on process stoichiometry and modelling, also emphasizing practical constraints in design and operation.

Biodegradation, Environmental↗
PubMed2003

Benign prostatic hyperplasia: from A - Z.

The management of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia over the last decade underwent many changes. The introduction of many medical options including alpha blockers and 5 alpha reductase inhibitors provided alternatives to what used to be surgery or "watchful waiting". Alpha blockers evolved over the years from non specific alpha 1, and 2 blockers to alpha 1 selective and then to alpha 1a selective with a wider acceptance due to lack of need to titrate and a better safety profile. 5 alpha reductase inhibitor (finasteride) passed through a lot of changes from being the first medication directed at treating the disease process to less acceptance because of time to response and early data supporting no added benefit when combined to alpha blockers for a short period. Longer studies now demonstrate a benefit to combination causing a reduction of progression parameters and an advantage over 4 years in reducing endpoints, namely acute urinary retention and surgery. Surgical options have also undergone many changes over the last decade with introduction of minimally invasive options as well as the introduction of new energy sources to reduce complications and allow for management of larger glands such as Holmium laser enucleation of the prostate or the use of bipolar loops. The journey has been long and exciting and we are sure Ernie Ramsey enjoyed being in the forefront of the evolution.

5-alpha Reductase Inhibitors↗
PubMed1992

Atherosclerosis--where are we heading?

Aim of this review is, to analyse the current knowledge of the pathogenesis of atherosclerosis from the viewpoint of a clinical cardiologists. All the current ideas about the pathogenesis of atherosclerosis have been derived from the theories of three pathologists. The first was Rokitanski 1852, his theory was somewhat modified by Virchow 1856 and revitalised and modified again by Ross in 1986. All current theories however are based on the term response to injury leading to accelerated atherosclerosis. Following the classification of Stary et al. and the suggestions of the report of the Committee on Vascular Lesions of the Council of Arteriosclerosis the early lesions (Stary class I and II) should be renamed as normal vascular adaptation to physical or chemical causes. These causes include not only shears stress or turbulences due to increased blood pressure but also hypercholesterolemia and certain changes of plasma protein content. The classification of Fuster et al. is mainly dependent on a mechanical injury to the arterial wall induced by the interventional cardiologist. Thus far, it seems questionable, if such a response to injury is indeed the leading mechanism ultimately resulting in advanced arteriosclerosis. In view of the multifactorial processes involved in the pathogenesis of either adaptation or then accelerated arteriosclerosis we have to admit, that our insight is still limited. Thus far, the only lesson to be learned for practising clinicians is that we have to accept that the process of normal adaptation of the vascular arterial wall to the abnormal development of a clinical significant lesion is dynamic and is not well characterized by the response-to-injury theory. We do know that even in the stage of acute coronary syndromes lesion changes are unpredictable. This coincides with the finding from the experimental laboratory that lesion growth is episodic and a result of different stages of activity of the involved cell types and growth factors. Thus, we should avoid looking only for certain stages but rather accept that this is 1. a normal adaptative alteration of the arterial wall which might 2. result in accelerated atherosclerosis due to genetic determination of smooth muscle cells and accumulation of a variety of growth factors.

Animals↗
PubMed2004

[Could we trust clinical statistics from data banks of the National Health Service (NHS)?].

Can we accept the statistics provided by the Ministry of Health, which uses large computerized databases? Through MEDECHO, the Ministry provides to hospital managers, reports cards on different interventions. These reports compare different hospitals performances. Surgeons involved in the process hesitate to accept this information. Using the results of the performance of cholecystectomy provided by this system (Gr: A), we compared the same cohort (1 April-31 December 1996 = 346 cholecystectomies) but using specific criteria determined as relevant to our surgeons (Gr: B). The rate of complication gives a crude aftermath and no attempt was used to adjust for severity. The MEDECHO data are adjusted for severity. The global rate of complications is similar Gr: A 11%, Gr: B 12%. Major complication rate for pulmonary embolism, hemorrhage and biliary duct trauma are identical. The rate of surgical site infection is higher in Gr: B (5% vs. 2%). The patients are seen in the outpatient clinic and these observations are not included by the analytical system unless the patient has been readmitted. For our hospital, the MEDECHO data are valid and reliable even though they underestimated the wound infection rate. These results could be explained by an appropriate interpretation of the code system by the archivist and by the surgeons' precision to complete the summary sheet of hospitalization. We can conclude that these data can be used as a means to evaluate the quality of outcome of a surgical service.

Canada↗
PubMed2004

[Grounded theory approach to health care of older adults at a doctorless farm village].

PURPOSE: The purpose of this study was to explore how older adults kept their health good at a doctorless farm village. METHOD: Data was collected through in-depth interviews with 32 participants who were over 65 years old and analyzed in terms of Strauss and Corbin's (1990) grounded theory methodology. RESULT: The Core Category of health care of older adults was identified as "enduring physical changes by themselves". The process of this could be divided into 4 stages : the stage of bearing, the stage of managing daily living activities, the stage of passively collecting information and the stage of minimally utilizing health care services. Older adults accepted the aging process positively but health sources limitation passively, so they managed daily living activities and used natural food for health. In addition, they collected information related to health care and used health care services minimally. CONCLUSION: We found that participants managed their health passively because of negative attitudes toward active health behaviors of older adults by themselves and the difficulty of access to health care services. Therefore, various community health services for older adults need to be developed to empower older adults in the community.

Aged↗
PubMed2000

Radiologists' preferences for digital mammographic display. The International Digital Mammography Development Group.

PURPOSE: To determine the preferences of radiologists among eight different image processing algorithms applied to digital mammograms obtained for screening and diagnostic imaging tasks. MATERIALS AND METHODS: Twenty-eight images representing histologically proved masses or calcifications were obtained by using three clinically available digital mammographic units. Images were processed and printed on film by using manual intensity windowing, histogram-based intensity windowing, mixture model intensity windowing, peripheral equalization, multiscale image contrast amplification (MUSICA), contrast-limited adaptive histogram equalization, Trex processing, and unsharp masking. Twelve radiologists compared the processed digital images with screen-film mammograms obtained in the same patient for breast cancer screening and breast lesion diagnosis. RESULTS: For the screening task, screen-film mammograms were preferred to all digital presentations, but the acceptability of images processed with Trex and MUSICA algorithms were not significantly different. All printed digital images were preferred to screen-film radiographs in the diagnosis of masses; mammograms processed with unsharp masking were significantly preferred. For the diagnosis of calcifications, no processed digital mammogram was preferred to screen-film mammograms. CONCLUSION: When digital mammograms were preferred to screen-film mammograms, radiologists selected different digital processing algorithms for each of three mammographic reading tasks and for different lesion types. Soft-copy display will eventually allow radiologists to select among these options more easily.

Algorithms↗
PubMed2002

Toxicophores: groups and metabolic routes associated with increased safety risk.

Drugs and chemicals can be metabolized in living organisms in an effort to remove them from the body. During this excretion process, certain chemicals can be transformed into unstable, highly reactive species. This can result in the overwhelming of cellular defense, allowing the reactive metabolite to bind to cellular macromolecules, and leading to abnormal cellular function. It is widely accepted that this process can lead to clinically observed toxicities in the form of idiosyncratic adverse drug reactions. However, it is currently impossible to predict which chemical species will cause these reactions. This review focuses on drugs from which reactive metabolites have been detected and reiterates the need for a more thorough understanding of basic drug metabolism before attempting to relate chemical species formation to biological function.

Animals↗
PubMed1994

Natural mentor relationships among Latina adolescent mothers: psychological adjustment, moderating processes, and the role of early parental acceptance.

Investigated the antecedents, effects, and underlying characteristics of natural mentor relationships in a sample of 54 inner-city, Latina adolescent mothers. Women with mentors reported significantly lower levels of depression and anxiety than those without mentors despite similar levels of stress exposure and overall support resources. Young women with natural mentors were also more satisfied with their support resources and appeared better able to cope effectively with relationship problems. Finally, women with mentors recalled their childhood relationships with their mothers as more accepting. Mentor relationships appear to enhance young women's capacity to benefit from their support resources and offset the effects of relationship problems. Implications for future research and intervention strategies are discussed.

Adaptation, Psychological↗
PubMed1998

Food preservation using ionizing radiation.

Irradiation processing has been researched extensively and is now in use worldwide for many food commodities. Irradiation has been successfully used to reduce pathogenic bacteria, eliminate parasites, decrease postharvest sprouting, and extend the shelf life of fresh perishable foods. Although food irradiation is widely accepted in world food markets, U.S. markets have been slower to accept the idea of irradiated food products. For fruits and vegetables, irradiation is not a cure for shelf life problems; cost and quality problems damage preclude its general use. It appears that the most likely use of irradiation in fruits and vegetables is as an insect control in those commodities for which there is no effective alternative method. For grains such as rice and wheat, irradiation has been used primarily to control insect infestation when insects have been shown to develop resistance to the traditional fumigation methods. Treatment of spices with irradiation doses of 10 kGy has proved to extend shelf life without causing significant changes in sensory or chemical quality. Higher doses that effectively sterilize spices, however, may cause undesirable chemical and sensorial changes. For meat, especially red meat, irradiation is considered a viable alternative in the effort to improve the safety of meat products. With time, the authors believe that economic realities and the technical superiority of irradiation for specific poultry products will lead to public acceptance of the process. Irradiation of seafood products is still being considered for approval by the USFDA, although it is currently used in Asian and European markets, especially for shrimp. It is our belief that scientifically based research in food irradiation and the positive results thereof will also prove economical in the twenty-first century. As we move to a more peaceful world with reduced threat of nuclear holocaust, these valid opinions will prevail and will overshadow the distortions and misinformation generated by the opponents of irradiation.

Animals↗
PubMed2002

Optimization of feeding profile for a fed-batch bioreactor by an evolutionary algorithm.

The optimal feeding profile of a fed batch process was designed by means of an evolutionary algorithm. The algorithm chromosomes include the real-valued parameters of a profile function, defined by previous knowledge. Each chromosome is composed of the parameters that define the feeding profile: the feed rates, the singular arc parameters and the switching times between the profile states. The feed profile design was tested on a fed-batch process simulation. The accepted profiles were smooth and similar to those derived analytically in other studies. Two selection functions, roulette wheel and geometric ranking, were compared. In order to overcome the problem of model mismatches, a novel optimization scheme was carried out. During its operation the process was sampled, the model was updated and the optimization procedure was applied. The on-line optimization showed improvement in the objective function for relatively low sample times. Choosing the sampling frequencies depends on the process dynamics and the time required for the measurements and optimization. Further study on experiments of fed-batch process demonstrated the use of complex, non-differentiable model and produced improved process performances using the optimal feeding profile.

Algorithms↗
PubMedDate not supplied

[New trends in immunosuppressive therapy in patients with kidney transplants].

Following the transplantation of visceral organs, two populations of immunocytes survive which derived from the donor's and the recipient's bone marrow. The rejection process of transplanted organ or graft versus host reaction could result from their mutual stimulation. On the other hand, the immunocytes of the donor and recipient could deny the effects of their MHC antigen disparities directed against each other, to favor the transplant acceptance through the processes of the donor specific tolerance. The spontaneous chimerism has been shown even in patients with the heart or kidney allografts which contain few numbers of donor's passenger lymphocytes. The frequency of chimerism is augmenting more than 1000 times following the combined and simultaneous transplantation of both kidney allograft and donor bone marrow cells. Theoretically, the continuous peroraly giving of high doses of synthetic peptides homologous to immunodominate epitope(s) of the donor MHC molecules could sustain the state of "stable chimerism" with donor immunocytes. This immunosuppressive protocol permits long-term survival of organ (kidney) allograft without diminishing the donor immune system that provokes the present immunosuppressives with non-specific effects.

Graft Rejection↗
PubMed1988

Validation of the pellet coating process used for a new sustained-release theophylline formulation.

Within the scope of the validation process described in this report, the influence of the process parameters on the factors determining the quality of Euphylong pellets during the spraying process is examined. The process is challenged within the meaning of the validation guidelines. Investigations within the scope of product-independent validation of the automated fluid bed coating apparatus (Wurster setup) used here provide the basis for installation qualification and operational qualification as defined by the PIC convention and the GMP guidelines. Within the scope of a classification of risks, potential operating and system errors are examined, giving consideration to the worst case conditions, and the relevance of the "blue book" to the process is discussed. Three critical process parameters (spraying temperature, air velocity and relative humidity) are investigated with respect to their influence on the goal parameter "in-vitro release of the active ingredient after 1 h". Product-related validation of the process is accomplished by means of statistical experimental design (factorial design). Statistical analysis is done using the methods described by Box-Wilson and Yates and by response surface research and grid-search methods via contour plots and isometric graphs. This yields the acceptable range of process parameters with respect to product quality. Finally the differences between validation and optimization are discussed.

Analysis of Variance↗
PubMed1996

Inflammation in EAE: role of chemokine/cytokine expression by resident and infiltrating cells.

Experimental allergic encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system (CNS) which has many clinical and pathological features in common with multiple sclerosis (MS). Comparison of the histopathology of EAE and MS reveals a close similarity suggesting that these two diseases share common pathogenetic mechanisms. Immunologic processes are widely accepted to contribute to the initiation and continuation of the diseases and recent studies have indicated that microglia, astrocytes and the infiltrating immune cells have separate roles in the pathogenesis of the MS lesion. The role of cytokines as important regulatory elements in these immune processes has been well established in EAE and the presence of cytokines in cells at the edge of MS lesions has also been observed. However, the role of chemokines in the initial inflammatory process as well as in the unique demyelinating event associated with MS and EAE has only recently been examined. A few studies have detected the transient presence of selected chemokines at the earliest sign of leukocyte infiltration of CNS tissue and have suggested astrocytes as their cellular source. Based on these studies, chemokines have been postulated as a promising target for future therapy of CNS inflammation. This review summarized the events that occur during the inflammatory process in EAE and discusses the roles of cytokine and chemokine expression by the resident and infiltrating cells participating in the process.

Animals↗
PubMed2006

Ethical issues in pandemic planning.

In the event of an influenza pandemic, many ethical issues will arise in terms of health risks, resource allocation, and management decisions. Planning decisions may be controversial, such as rationing of antivirals, resource allocation (including hospital beds and vaccinations), occupational risk, rostering of staff, responsibilities of health care workers, quarantine measures, and governance issues. A clear ethical framework is needed to enable understanding of the decision-making process and optimise acceptance of decisions by health care workers and other members of an affected community. Planning decisions need to start being examined now, and will require input from a broad group of experts: health care providers, infrastructure managers, lawyers, ethicists, public health physicians, and community members. The process will need to be open, honest and dynamic.

Australia↗