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PubMed1992

Evaluation of two epoxy ether compounds for biocompatible potential.

Bovine arterial tissue exposed to two epoxy ether compounds (Denacol EX-313 and Denacol EX-810) was evaluated for its biocompatible potential by in vitro and in vivo test procedures. The battery of test procedures included percent Inhibition of Cell Growth, Medium Eluate Method (MEM), Agar Overlay (AO), Blood Compatibility, Acute Mouse Systemic Injection, Rabbit Intracutaneous Irritation, Rabbit Subcutaneous Implantation, Guinea Pig Maximization, and Ames Tests. The epoxy exposed tissue was found to be noncytotoxic, nonmutagenic, and biocompatible by the test methods employed. In addition, the maximum concentrations of the unreacted Denacol EX-313 and EX-810 solutions found to demonstrate noncytotoxic reactions by the MEM and AO procedures were identified as 55 and 60 ppm for the MEM and 150 and 200 ppm for the AO procedure, respectively. These studies suggest that Denacol EX-313 and EX-810 are acceptable solutions for the processing of implantable tissue provided the epoxy residuals remain below those levels found to be cytotoxic.

Animals↗
PubMedDate not supplied

The nature and sources of hope: perspectives of family caregivers of people with serious mental illness.

PURPOSE: To explore the importance and meaning of hope for family members of people with mental illness. METHODS: Focused in-depth interviews with 16 family members in Queensland and Tasmania, Australia. FINDINGS: The data confirm the argument that hopefulness appears to be central to a family's coping with the impact of mental illness. Their definitions of hope, descriptions of what they hoped for, and the sources of their hope reflect issues of future orientation, positive expectation, and realism. Families drew their hopefulness from both formal and informal supports, from within and without. CONCLUSIONS: Health professionals need to be respectful of family hopes and aware of the role of hope and time in the process of grief and acceptance. Nurses should be mindful of their capacity to sustain or diminish the hopes of family members.

Adaptation, Psychological↗
PubMed1985

Silicosis in jade workers.

The recent finding of cases of silicosis among jade workers in Hong Kong points to this disease being an occupational hazard. The source was found to be the silica flour that was added in a polishing process. Five cases are described together with the results of environmental investigation in a workplace. In three cases the disease was of early onset, rapidly progressive, and presented the features of galloping silicosis noted in other occupational exposures to silica flour. One patient had massive fibrosis and severe glomerulonephropathy, an association that has also been previously noted. One case showed evidence of active tubercular infection in addition to silicosis and two had healed lesions. Silica concentrations in the workplace during the suepect process were well above accepted threshold limit values.

Adult↗
PubMed2006

Effect of discharge instructions on readmission of hospitalised patients with heart failure: do all of the Joint Commission on Accreditation of Healthcare Organizations heart failure core measures reflect better care?

BACKGROUND: Most nationally standardised quality measures use widely accepted evidence-based processes as their foundation, but the discharge instruction component of the United States standards of Joint Commission on Accreditation of Healthcare Organizations heart failure core measure appears to be based on expert opinion alone. OBJECTIVE: To determine whether documentation of compliance with any or all of the six required discharge instructions is correlated with readmissions to hospital or mortality. RESEARCH DESIGN: A retrospective study at a single tertiary care hospital was conducted on randomly sampled patients hospitalised for heart failure from July 2002 to September 2003. PARTICIPANTS: Applying the Joint Commission on Accreditation of Healthcare Organizations criteria, 782 of 1121 patients were found eligible to receive discharge instructions. Eligibility was determined by age, principal diagnosis codes and discharge status codes. MEASURES: The primary outcome measures are time to death and time to readmission for heart failure or readmission for any cause and time to death. RESULTS: In all, 68% of patients received all instructions, whereas 6% received no instructions. Patients who received all instructions were significantly less likely to be readmitted for any cause (p = 0.003) and for heart failure (p = 0.035) than those who missed at least one type of instruction. Documentation of discharge instructions is correlated with reduced readmission rates. However, there was no association between documentation of discharge instructions and mortality (p = 0.521). CONCLUSIONS: Including discharge instructions among other evidence-based heart failure core measures appears justified.

Academic Medical Centers↗
PubMed2000

Results of a nationwide survey of chest radiography: comparison with results of a previous study.

PURPOSE: To provide public health information by means of measurement of the radiation exposures that patients undergoing chest radiography would receive and to compare the results with those of a similar previous survey. MATERIALS AND METHODS: Surveyed facilities were randomly selected from each state. Patient exposure was evaluated along with film processing, half-value layer, and image quality. Additional information obtained concerned type of equipment, facility work load, radiographic technique, screen-film system, and grid type. RESULTS: Mean entrance air kerma in all facilities was 141 microGy (16.1 mR). Mean kilovoltage in all facilities was 101 kV. In 1994, 140 (90%) of 156 hospitals (vs 71% in 1984) and 92 (58%; nearly double the percentage in 1984) of 159 nonhospital sites were using grids. Scoring with the imaging test tool resulted in a mean spatial resolution of 2.3 cycles per millimeter, and a mean low-contrast sensitivity of about 3%. Two hundred fifty-three (80%) of 315 facilities surveyed were processing film at minimum acceptable performance levels. CONCLUSION: Mean entrance air kerma for all facilities did not substantially change. Although increased grid usage would lead to the expectation of higher measured exposures, this was offset by an increase in the use of faster screen-film combinations.

Health Surveys↗
PubMed2006

Galectin-3 expression is associated with tumor progression and pattern of sun exposure in melanoma.

PURPOSE: Most studies accept a multistep pathogenic process in melanoma that may include the phases of benign nevi and dysplastic nevi, melanoma, and metastatic melanoma. Dysregulation of cellular proliferation and apoptosis is probably involved in melanoma progression and response to therapy. We have studied the expression of galectin-3, a beta-galactoside-binding protein involved in apoptosis, angiogenesis, and cell proliferation, in a large series of melanocytic lesions, and correlated the expression with clinical and histologic features. EXPERIMENTAL DESIGN: Tissue microarray blocks of 94 melanocytic lesions were semiquantitatively evaluated by immunohistochemistry for the cytoplasmic or nuclear expression of galectin-3. RESULTS: Primary and metastatic melanomas expressed galectin-3 at a significantly higher level than nevi in both cytoplasm and nuclei (P<0.0073). There was a significant association between anatomic source (as indirect indication of level of sun-exposure) and cytoplasmic and nuclear expression. Lymph node and visceral metastases had a higher level of expression than s.c. lesions (P<0.004). Interestingly, there was an almost significant finding of worse survival in those patients with lesions showing higher levels of cytoplasmic than nuclear galectin-3 expression (log-rank test, P=0.06). CONCLUSIONS: Melanocytes accumulate galectin-3 with tumor progression, particularly in the nucleus. The strong association of cytoplasmic and nuclear expression in lesions of sun-exposed areas suggests an involvement of UV light in activation of galectin-3.

Biomarkers, Tumor↗
PubMed2002

Dialogue and collaboration: a personal view on laboratory animal welfare developments in general, and on ECVAM's first decade in particular.

A personal view is presented on progress made during the last 25 years in applying the Three Rs (reduction, refinement, replacement) to animal testing in regulatory toxicology, with an emphasis on "good moments" (for example, international workshops on the principles and practical application of the validation process and on regulatory acceptance) and "not-so-good moments" (for example, the time taken to accept alternatives to the LD50 test and to accept in vitro tests for skin absorption as OECD Test Guidelines). The importance of dialogue and cooperation between international coordinating centres and scientific activities at the national level is stressed, as exemplified by the work of ECVAM during its first decade.

Animal Testing Alternatives↗
PubMed2005

An approach to determining applicability domains for QSAR group contribution models: an analysis of SRC KOWWIN.

QSAR model predictions are most reliable if they come from the models applicability domain. The Setubal Workshop report provides a conceptual guidance for defining a (Q)SAR applicability domain. However, an operational definition is necessary for applying this guidance in practice. It should also permit the design of an automatic (computerised) procedure for determining a models applicability domain. This paper attempts to address this need for models that use a large number of descriptors (for example, group contribution-based models). The high dimensionality of these models imposes specific computational restrictions on estimating the interpolation region. The Syracuse Research Corporation KOWWIN model for prediction of the n-octanol/water partition coefficient is analysed as a case study. This is a linear regression model that uses 508 fragment counts and correction factors as descriptors, and is based on the group contribution approach. We conclude that the applicability domain estimation by descriptor ranges, combined with Principal Component rotation as a data pre-processing step, is an acceptable compromise between estimation accuracy and the amount of data in the training set.

Computer Simulation↗
PubMed2003

Household-level technologies to improve the availability and preparation of adequate and safe complementary foods.

Plant-based complementary foods are the main source of nutrients for many young children in developing countries. They may, however, present problems in providing nutritionally adequate and safe diets for older infants and young children. The high starch content leads to low-nutrient diets that are bulky and dense, with high levels of antinutritive factors such as phytates, tannins, lectins, and enzyme inhibitors. Phytates impair mineral bioavailability, lectins interfere with intestinal structure, and enzyme inhibitors inhibit digestive enzymes. In addition, there is often microbial contamination, which leads to diarrhea, growth-faltering, and impaired development, and the presence of chemical contaminants may lead to neurological disease and goiter. The fact that some fruits containing carotenoids are only available seasonally contributes to the vulnerability of children receiving predominantly plant-based diets. Traditional household food technologies have been used for centuries to improve the quality and safety of complementary foods. These include dehulling, peeling, soaking, germination, fermentation, and drying. While modern communities tend to reject these technologies in favor of more convenient fast-food preparations, there is now a resurgence of interest in older technologies as a possible means of improving the quality and safety of complementary foods when the basic diet cannot be changed for economic reasons. This paper describes the biology, safety, practicability, and acceptability of these traditional processes at the household or community level, as well as the gaps in research, so that more effective policies and programs can be implemented to improve the quality and safety of complementary foods.

Biological Availability↗
PubMed2005

Development of a lung slice preparation for recording ion channel activity in alveolar epithelial type I cells.

BACKGROUND: Lung fluid balance in the healthy lung is dependent upon finely regulated vectorial transport of ions across the alveolar epithelium. Classically, the cellular locus of the major ion transport processes has been widely accepted to be the alveolar type II cell. Although evidence is now emerging to suggest that the alveolar type I cell might significantly contribute to the overall ion and fluid homeostasis of the lung, direct assessment of functional ion channels in type I cells has remained elusive. METHODS: Here we describe a development of a lung slice preparation that has allowed positive identification of alveolar type I cells within an intact and viable alveolar epithelium using living cell immunohistochemistry. RESULTS: This technique has allowed, for the first time, single ion channels of identified alveolar type I cells to be recorded using the cell-attached configuration of the patch-clamp technique. CONCLUSION: This exciting new development should facilitate the ascription of function to alveolar type I cells and allow us to integrate this cell type into the general model of alveolar ion and fluid balance in health and disease.

Animals↗
PubMed2005

Mining for diagnostic information in body surface potential maps: a comparison of feature selection techniques.

BACKGROUND: In body surface potential mapping, increased spatial sampling is used to allow more accurate detection of a cardiac abnormality. Although diagnostically superior to more conventional electrocardiographic techniques, the perceived complexity of the Body Surface Potential Map (BSPM) acquisition process has prohibited its acceptance in clinical practice. For this reason there is an interest in striking a compromise between the minimum number of electrocardiographic recording sites required to sample the maximum electrocardiographic information. METHODS: In the current study, several techniques widely used in the domains of data mining and knowledge discovery have been employed to mine for diagnostic information in 192 lead BSPMs. In particular, the Single Variable Classifier (SVC) based filter and Sequential Forward Selection (SFS) based wrapper approaches to feature selection have been implemented and evaluated. Using a set of recordings from 116 subjects, the diagnostic ability of subsets of 3, 6, 9, 12, 24 and 32 electrocardiographic recording sites have been evaluated based on their ability to correctly asses the presence or absence of Myocardial Infarction (MI). RESULTS: It was observed that the wrapper approach, using sequential forward selection and a 5 nearest neighbour classifier, was capable of choosing a set of 24 recording sites that could correctly classify 82.8% of BSPMs. Although the filter method performed slightly less favourably, the performance was comparable with a classification accuracy of 79.3%. In addition, experiments were conducted to show how (a) features chosen using the wrapper approach were specific to the classifier used in the selection model, and (b) lead subsets chosen were not necessarily unique. CONCLUSION: It was concluded that both the filter and wrapper approaches adopted were suitable for guiding the choice of recording sites useful for determining the presence of MI. It should be noted however that in this study recording sites have been suggested on their ability to detect disease and such sites may not be optimal for estimating body surface potential distributions.

Algorithms↗
PubMed2004

Identification of key beta cell gene signaling pathways involved in type 1 diabetes.

In type 1 diabetes, beta cells die through a process of immune-mediated apoptosis. To better understand this process, it has been accepted practice to study beta cell or islet apoptosis in vitro in response to a range of immune stimuli, such as interferon gamma, interleukin-1, nitric oxide or free radicals. In particular, much use has been made of immortalized beta cell lines for such studies, although it is not clear to what extent the behavior of these cell lines might mimic the behavior of normal beta cells in vivo, or freshly isolated beta cells ex vivo. To address this question we compared the gene expression of freshly isolated NOD islets in the presence or absence of insulitis, with previously published data examining either islet or beta cell gene or protein expression in a range of different species and contexts. There was a high correlation between beta cell genes found be to be expressed by mouse and rat islets, by either gene expression or proteomic analysis. There was also a surprisingly high correlation between beta cell genes found be to be expressed by islets exposed to insulitis in vivo and islets stimulated with IFN-gamma and IL-1beta in vitro, suggesting that these two cytokines as produced by the islet infiltrate are important for priming beta cells in vivo. There was a much lower correlation when gene expression was compared between fresh beta cells and beta cell lines, consistent with the view that beta cell lines are very poorly representative of real beta cells. Hence, any results obtained using beta cell lines should be interpreted with great caution when extrapolating to the behavior of real beta cells.

Animals↗
PubMed1998

Stress and the menstrual cycle: relevance of cycle quality in the short- and long-term response to a 5-day endotoxin challenge during the follicular phase in the rhesus monkey.

The notion that stress activates central and peripheral pathways to inhibit the menstrual cycle is well accepted, but the initial processes through which this occurs have not been investigated. This study uses a relevant nonhuman primate model to document the cyclic endocrine effects imposed by a moderate short-term stress episode in the follicular phase. The stress paradigm is a 5-day inflammatory/immune-like challenge produced by the administration of bacterial endotoxin [lipopolysaccharide (LPS)], which, through the release of endogenous cytokines and other mediators, induces a physiopathological response similar to a bacterial infection. LPS was administered iv twice daily for 5 days starting on days 2-8 of the follicular phase. The stress challenge resulted in a significant lengthening of the follicular phase in all monkeys. Two distinct groups were observed. In group 1 (n = 5), the mean (+/- SE) length of the follicular phase in the LPS-treated cycle was significantly increased, from 10.2 +/- 0.2 in control cycle 2 to 30.8 +/- 4.3 days (except in one monkey that had a 4-month amenorrheic interval). In group 2 (n = 5), the length of the follicular phase significantly increased but not to exceed the duration of the LPS treatment (9.7 +/- 1.1 vs. 13.6 +/- 1.2). Estradiol concentrations decreased significantly after LPS in group 1 (34.8 +/- 5.5 vs. 16.2 +/- 6.5 pg/mL) and remained suppressed after the challenge. In group 2, estradiol levels remained stationary throughout the 5-day LPS treatment (26.0 +/- 6.5 vs. 25.6 +/- 3.9). Compared with control values at a similar stage of the follicular phase, most LH and FSH values during LPS treatment were higher than controls. Estradiol and gonadotropin surges were delayed by LPS treatment for a varying length of time according to each grp. Significant differences in integrated luteal progesterone concentrations characterized control cycles of groups 1 and 2 (group 1: 36.5 +/- 1.5, group 2: 47.5 +/- 2.6). In group 1, there were no further effects of LPS on luteal progesterone during the treatment and two post-LPS cycles. In contrast, in group 2, integrated luteal progesterone concentrations were significantly decreased in post-LPS cycle 1 (to 36.0 +/- 4.4). Cortisol significantly increased at hour 3 after each morning LPS injection but the amplitude of the response decreased over the 5-day period. Progesterone increased significantly by hour 3 after the first LPS injection but remained unchanged after subsequent LPS administration. Our data demonstrate that a 5-day inflammatory-like episode during the follicular phase can delay folliculogenesis and that damage to this process is intensified in individuals who already demonstrate a subtle cyclic degradation, in the form of decreased progesterone secretion in the luteal phases preceding the stress episode. Long-term endocrine effects, in the form of decreased luteal secretory activity in the first poststress cycle, are observed in normally cycling individuals, suggesting that inadequacy of the luteal phase may represent the first stage in the damage that a stress episode can inflict upon the normal menstrual cycle.

Animals↗
PubMed1989

Response of parents to learning that their child is homosexual and concern over AIDS: a national study.

This study was a survey of 402 parents of gay and lesbian children from the northeastern, southern, midwestern, and western regions of the United States. Of particular interest was parental response to the knowledge of their child's homosexuality and the AIDS outbreak. Although parents suffered emotional upset upon learning of their children's homosexuality, many progressed through a five-stage grief process that ended with acceptance. Fear of the spread of AIDS, that their offspring might contract AIDS, or that their child might suffer from the backlash related to AIDS were concerns for most parents. Attitudes toward AIDS were not very different between mothers and fathers. However, older parents were more likely to have more positive attitudes toward AIDS than younger parents, and liberal parents were more likely to have a more positive outlook than their conservative counterparts.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Plato's conception of the relations between moral philosophy and medicine.

The first part of this article construes crucial passages from the Platonic dialogues as evidence that Plato takes medicine as a model for moral philosophy and as one of the organizing principles for his writing of the dialogues. The second part reflects upon the significance of one of the most debatable implications of the model: the comparison between health and illness, on the one hand, and moral virtue and moral vice, on the other. It articulates 10 illuminating aspects of this comparison and two potentially serious objections to it. The third part of this article examines what the model implies about the roles of medicine and moral philosophy in the political community and about the natures of doctor-patient and philosopher-interlocutor relationships. It highlights Socrates' criticisms of a kind of politics that covers over moral causes of social disorders by means of Band-Aid legislation, and emphasizes that according to the model, both the doctor and the moral teacher confront agents who must cooperate in the process of reform and accept whatever responsibility they have for their conditions.

Ethics, Medical↗
PubMed2002

Space-bandwidth product enhancement of a monostatic, multiaperture infrared image upconversion ladar receiver incorporating periodically poled liNbO3.

We investigate the space-bandwidth product of a ladar system incorporating an upconversion receiver. After illuminating a target with an eye-safe beam, we direct the return into a piece of periodically poled LiNbO3 where it is upconverted into the visible spectrum and detected with a CCD camera. The theoretical and experimental transfer functions are then found. We show that the angular acceptance of the upconversion process severely limits the receiver field of regard for macroscopic coupling optics. This limitation is overcome with a pair of microlens arrays, and a 43% increase in the system's measured space-bandwidth product is demonstrated.

Journal Article↗
PubMed2005

Factors associated with medication nonadherence in patients with COPD.

STUDY OBJECTIVES: To identify the predictors of medication adherence in patients with COPD and contrast the health beliefs, experiences, and behaviors of COPD patients self-reporting good adherence with those of patients reporting suboptimal adherence to their medications. DESIGN: Cross-sectional self-administered questionnaire. SETTING: Ambulatory care. PARTICIPANTS: Patients with chronic respiratory ailments identified through respiratory support groups and from a pulmonary rehabilitation database. MEASUREMENTS AND RESULTS: A 30-item questionnaire comprising items pertaining to health beliefs, experiences, and behaviors along with a valid self-reported measure of adherence-the medication adherence report scale (MARS)-was administered to 525 ambulatory patients with chronic lung conditions. A total of 276 usable responses were received (52.6%). The mean age of the respondents was 71 years, and there were slightly more male patients (54.4%). COPD was the underlying disease condition in 90.6% of the respondents; two thirds of the respondents had comorbid conditions. The respiratory condition was managed by both general practitioners and respiratory specialists in 61.2% of cases. One third of the respondents self-reported complementary and alternative medicine use. The mean score (+/- SD) on the MARS among the respondents was 23.37 +/- 2.09. One hundred two patients self-reported perfect adherence on the MARS. Differences in knowledge about the illness and treatment, faith in and satisfaction with the treatment and doctors, concerns about the treatment, and intentional and unintentional deviations from the recommended treatment were detected between the adherent and less adherent groups. In multivariate analysis, "I vary my recommended management based on how I am feeling" and "I get confused about my medications" were found to be significant independent predictors of nonadherence. CONCLUSIONS: Patients' acceptance of the disease process and recommended treatment, knowledge about and faith in the treatment, effective patient-clinician interaction, and routinization of drug therapy are critical for optimal medication adherence in patients with COPD.

Aged↗
PubMed2004

Matrix metalloproteinases in the pathogenesis of asthma and COPD: implications for therapy.

While asthma is an inflammatory disorder of the airways involving mediators released from mast cells and eosinophils, inflammation alone is insufficient to explain the chronic nature of the disease. Recent progress in the understanding of disease pathogenesis has revealed that airway remodeling, which is at least in part due to an excess of extracellular matrix (ECM) deposition in the airway wall, plays a significant role in airflow obstruction. Matrix metalloproteinases (MMPs) have been suggested to be the major proteolytic enzymes to induce airway remodeling in asthma and COPD. It has been widely accepted that different inflammatory processes are involved in asthma and COPD with different inflammatory cells, mediators, and responses to treatments. Despite these different processes, airflow obstruction and airway remodeling characterize these two diseases. MMP-2 and -9 have been reported to be involved in the pathogenesis of airway remodeling in both diseases and MMP-12, in addition to these MMPs, in the pathogenesis of COPD. In this review, we discuss the current views on the role of MMPs in the pathogenesis of bronchial asthma and COPD. Anti-MMP therapy could theoretically be useful to prevent airway remodeling in asthma and COPD. However, to date no clinical data are available regarding the efficacy of anti-MMP therapies in the treatment of patients with asthma and COPD.

Asthma↗