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PubMed1999

Invertebrates versus vertebrates innate immunity: In the light of evolution.

Invertebrates use a nonadaptive, innate immunity, the expression of germline encoded receptors, to identify the allogeneic and xenogeneic attributes. Vertebrates also have the capacity to express ontogenically related adaptive immunity which is a somatically selected gene rearrangement process. Several commonly accepted generalizations are utilized to explain the enigmatic lack of the adaptive immunity in invertebrates. All point to the primitive nature of the innate immunity and the primitive organization of the body plan and the life history patterns of invertebrates. Seven of the most common generalizations are reviewed and confuted by virtue of a biased literature presentation. Subsequently, three evolutionary puzzles are raised and the accepted paradigm that the vertebrate immunity is pathogenically directed is further challenged. This leads to an alternative idea suggesting that preserving the individuality against the threat of invading conspecific cells might have been the original function of the immune system. This ancient system has been co-opted later on to serve as a defence mechanism against pathogens. The secondary role arose in the form of a multiplicity of newly developed phenomena, one of them being the vertebrate adaptive immunity. This proposal is supported by the fact that vertebrates still exhibit two distinct but common types of naturally occurring transplantation events (natural chimerism) and by a variety of recent studies, providing evidence for the crucial role of the vertebrate's innate immunity in signalling and triggering the acquired effector mechanisms.

Adaptation, Physiological↗
PubMed2003

Embryonic stem-cell research and the moral status of embryos.

Stem-cell research has the potential to significantly advance our knowledge of cell differentiation with the promise of exciting and innovative therapeutic applications for otherwise incurable genetic and degenerative disorders. The issue has been the subject of debate in federal and state parliament as research of embryonic stem cells and their application have come under intense scrutiny. Scientists and medical practitioners are highly skilled in the technical aspects of biomedicine but are decidedly less comfortable with ethics. The place of novel and controversial biomedical technology is commonly left to an ad hoc and complex process whereby social acceptability eventually becomes the final arbiter. Utilitarianism is a popular ethical approach that attempts to weigh all the known and anticipated merits and pitfalls. The scientific background of biomedical professionals, the vast explosion of information, and specialization and subspecialization, have all contributed to a reductionistic view of life and ethics. The 'sanctity of life' doctrine is altogether quite different, as secular and religious advocates appear inflexible and unyielding to the logical propositions of utilitarianism and reductionism or to the consensus of democracy. These four major ethical approaches are discussed with reference to the embryonic stem-cell research debate.

Embryo Research↗
PubMed1989

A double buffy coat method for red cell removal from ABO-incompatible marrow.

Hemolytic reactions caused by transfusion of ABO-incompatible marrow can be ameliorated by either reduction of isohemagglutinins in the recipient or depletion of incompatible red cells from the harvested marrow. This article describes a rapid and reliable method for removal of incompatible marrow red cells on a blood cell processor using a double buffy coat technique. In five allogeneic bone marrow transplants, the maximum value of transfused incompatible red cells was 8.8 ml. There was no evidence of a hemolytic transfusion reaction in any patient. The median cell recovery for nucleated marrow cells and progenitor cells was 77 and 104 percent, respectively. Engraftment occurred at a median of 13 days (range, 11-21 days) after transplantation. The double buffy coat method of red cell depletion is an acceptable method for processing ABO-incompatible marrow.

ABO Blood-Group System↗
PubMed2003

First report of a psychosocial intervention for patients with alcohol-related liver disease undergoing liver transplantation.

Performing transplantations in patients with alcoholic liver disease raises great concerns for both clinicians and lay people, not least because of the fear that relapse back to drinking after the procedure may lead to poor outcomes. Therefore it is important to develop and evaluate new strategies for assessing and supporting such patients. A program of psychosocial intervention was developed to assist patients undergoing transplantation for alcoholic liver disease in coping with their alcohol problems. We describe a feasibility study of its implementation in a group of 20 such patients. This report shows that it is feasible to deliver a time-limited psychological intervention to patients undergoing assessment for liver transplantation. The intervention was readily integrated into the usual transplantation process and was acceptable to both patients and staff. Further research is required to clarify its impact on longer-term outcome measures.

Adult↗
PubMed1999

Evolution of the concept of "extracellular matrix' in the brain.

The question as to whether an extracellular matrix exists between cells in the adult brain has been debated since the end of the last century. In the early years, zones containing neuropil and glial processes were mistakenly believed to represent this substance. But Golgi's discovery of the "perineuronal net" paved the way for future study of the true extracellular matrix. In the 1950s, application of histochemical techniques established the existence of interstitial material between nerve cells. Unfortunately the similarity between the pericellular distribution of this material and Golgi's "pericellular nets" was overlooked. The detection of an extracellular volume fraction in the central nervous system furnished further indirect proof for the existence of an extracellular matrix in the brain. However, the repeated failure of electron microscopy to reveal a substantial space between cell processes undermined the acceptance of the concept of "extracellular matrix" in the central nervous system. Nowadays this concept has, however, been firmly established.

Brain↗
PubMed2000

Hippuric acid as a major excretion product associated with black tea consumption.

1. Nine habitual tea-drinking volunteers were recruited and asked to follow a low-polyphenol and low-caffeine diet for 6 days and to provide daily 24-h urine samples. On day 4 of the experiment strong black tea brewed under standardized conditions was re-introduced to the volunteers' diet. 2. 1H-NMR and HPLC profiling of the urine samples indicated that consumption of black tea (6-10 mugs per day) was associated with a significant (p = 0.00017) increase in hippuric acid excretion relative to control, increasing from 153-512 to 742-1374 mg day(-1). The excretion of substantial amounts of hippuric acid has not previously been associated with black tea consumption. 3. For some volunteers, the quantity of benzoic acid processed exceeded the acceptable daily intake (ADI), but this is not considered to constitute any hazard. 4. A mass-balance analysis indicated that the necessary quantity of benzoic acid could not be obtained from the contents of gallic acid, flavanols, flavonol glycosides and theaflavins in black tea even if 100% transformation was obtained, suggesting that the thearubigins (the major and chemically ill-defined polyphenols of black tea) may be an important source.

Adult↗
PubMed2001

Differences detected in vivo between samples of aflatoxin-contaminated peanut meal, following decontamination by two ammonia-based processes.

A sample of peanut meal, highly contaminated with aflatoxins, has been subjected to decontamination by two commercial ammonia-based processes. The original contaminated and the two decontaminated meals were fed to rats for 90 days. No lesions associated with aflatoxin-induced hepatocarcinogenesis were detected histologically following feeding with the two detoxified meals. There were, however, clear differences between the two meals in respect of growth rates of the rats. In addition, feeding one of the detoxified meals resulted in hepatic abnormalities detected using novel immunohistochemical reagents. Differences between the two detoxified meals were also indicated by the results of studies using meals 'spiked' with [14C]-aflatoxin B1 prior to being subjected to the detoxification processes. The meals differed in the bioavailability of the label. It was concluded that peanut meal where an initial, unacceptable level of contamination with aflatoxins had been reduced by two ammonia-based processes to comparable, acceptable levels, may still have different effects in vivo when incorporated into animal diets.

Aflatoxins↗
PubMedDate not supplied

Utilization of 12-step theme groups in a short-term chemical dependence treatment unit.

At Eagleville Hospital, staff have found that utilizing the theme-group process facilitates patient acceptance of 12-Step programs within a relatively short (three weeks) treatment program. Providing a comprehensive orientation to the 12-Step programs increases the likelihood of patients continuing with 12-Step programs as part of their aftercare programs. As previously noted, this is crucial for continued success and sobriety. It is hoped that this description of the use of 12-Step theme groups as part of a comprehensive treatment program will be of help to others.

Hospitals, Psychiatric↗
PubMed2005

Development of clinical guidelines for the pharmacological management of behavioural disturbance and aggression in people with psychosis.

OBJECTIVE: To describe the process underpinning the development of clinical guidelines for the management of behavioural disturbance in psychosis. METHOD: A structured process was followed, encompassing a literature review, focus groups with key staff, and pilot testing and monitoring of the guidelines in an acute psychiatric setting. RESULTS: The process was well accepted by staff and was found useful in monitoring outcomes in a naturalistic setting. The final guidelines proved safe and effective in the acute setting. CONCLUSIONS: The incorporation of a monitoring system for interventions for the management of behavioural disturbance in acute psychiatric settings is beneficial for staff and patients alike.

Acute Disease↗
PubMed1997

The health care needs of hospitalized patients with AIDS in Taiwan.

The purpose of this study was to investigate and highlight health care needs as perceived by hospitalized patients with AIDS (PWA) in Taiwan. Convenience sampling was used for this study. Subjects were chosen from one of the medical centers in metropolitan Taipei, Taiwan. Criteria for sampling were that subjects be diagnosed with AIDS, hospitalized without complications of neuropathy, psychosis, or dementia, 12 years old or older, and able to speak Mandarin. Sample size was determined by the saturation principle. Eight subjects were interviewed in depth using a semistructured interview guide. These interviews were tape recorded and transcribed. Content analysis was applied to analyze interview data. The double coding percentage agreement was 0.81, and the intercoder percentage agreement was 0.89. Results revealed the most important health care needs associated with these patients included obtaining information about AIDS, protecting privacy, improving the quality and quantity of health care, securing family members' safety and financial security, and accepting the grief process. These findings suggest that the needs of the PWAs must be identified before nursing care is provided. Furthermore, developing a health care need scale is recommended for patients with AIDS to more effectively assess their health care needs.

Acquired Immunodeficiency Syndrome↗
PubMed2006

RankProd: a bioconductor package for detecting differentially expressed genes in meta-analysis.

UNLABELLED: While meta-analysis provides a powerful tool for analyzing microarray experiments by combining data from multiple studies, it presents unique computational challenges. The Bioconductor package RankProd provides a new and intuitive tool for this purpose in detecting differentially expressed genes under two experimental conditions. The package modifies and extends the rank product method proposed by Breitling et al., [(2004) FEBS Lett., 573, 83-92] to integrate multiple microarray studies from different laboratories and/or platforms. It offers several advantages over t-test based methods and accepts pre-processed expression datasets produced from a wide variety of platforms. The significance of the detection is assessed by a non-parametric permutation test, and the associated P-value and false discovery rate (FDR) are included in the output alongside the genes that are detected by user-defined criteria. A visualization plot is provided to view actual expression levels for each gene with estimated significance measurements. AVAILABILITY: RankProd is available at Bioconductor http://www.bioconductor.org. A web-based interface will soon be available at http://cactus.salk.edu/RankProd

Computational Biology↗
PubMed2001

Metabolic radiolabeling: experimental tool or Trojan horse? (35)S-Methionine induces DNA fragmentation and p53-dependent ROS production.

Despite the general assumption that widely used radiolabeled metabolites such as [(35)S]methionine and (3)H-thymidine do not adversely affect or perturb cell function, we and others have shown that such low-energy beta-emitters can cause cell cycle arrest and apoptosis of proliferating cells. The goal of the present study was to elucidate the targets and mechanisms of [(35)S]methionine-induced cellular toxicity. Comet analyses (single-cell electrophoresis) demonstrated dose-dependent DNA fragmentation in rabbit smooth muscle cells within a time frame (1-4 h) well within that of most radiolabeling protocols, whereas fluorescence analyses using a peroxide/hydroperoxide-sensitive dye revealed production of reactive oxygen species (ROS). Although ROS generation was inhibitable by antioxidants, DNA fragmentation was not inhibited and was in fact observed even under hypoxic conditions, suggesting that beta-radiation-induced DNA damage can occur independently of ROS formation. Studies with p53(+/+) and p53(-/-) human colorectal carcinoma cells further demonstrated the dissociation of early DNA damage from ROS formation in that both cell types exhibited DNA fragmentation in response to radiolabeling whereas only the p53(+/+) cells exhibited significant increases in ROS formation, which occurred well after significant DNA damage was observed. These findings demonstrate that metabolically incorporated low-energy beta-emitters such as [(35)S]methionine and (3)H-thymidine can induce DNA damage, thereby initiating cellular responses leading to cell cycle arrest or apoptosis. The results of this study require a reevaluation using low-energy beta-emitters to follow not only experimental protocols in vivo processes, but also acceptable exposure levels of these genotoxic compounds in the workplace and environment.

Animals↗
PubMed2006

Computerized provider order entry: strategies for successful implementation.

An estimated 522,000 serious medication errors can be eliminated in the United States each year through the use of computerized provider order entry. However, the implementation of computerized provider order entry is being slowed down by resistance from clinicians, particularly physicians. Nurses understand the work of physicians and are in a unique position to help overcome their resistance and smoothen the transition to computerized provider order entry. The authors outline the strategies for nurses to increase organizational acceptance during the process of computerized provider order entry implementation.

Attitude of Health Personnel↗
PubMed2006

Interstitial lung disease--the new synergy between radiology and pathology.

In the last 30 years, high-resolution computed tomography (HRCT) has been the major advance in diagnosis of diffuse parenchymal lung disease (DPLD). We review the diagnostic accuracy of HRCT and discuss how the gold standard in diagnosis of DPLD has shifted from histopathological diagnosis in isolation to a multidisciplinary approach. This latter process is now accepted as providing the highest levels of diagnostic accuracy in patients with DPLD and lung biopsy is primarily reserved for cases with atypical clinical or radiological presentations.

Adult↗
PubMed1982

Evaluation of individuals deferred from blood donation for medical reasons.

Modern techniques of blood collection require health screening of donors by non-physicians using general guidelines. Health problems of concern to the donor and possible loss to future donation of actually individuals are inherent in this acceptance and deferral process. Of the 108,908 donors presenting at the bloodmobiles of regional blood center from September 1978 to February 1979, 9,542 were deferred. Of these, 1,203 with possible medical problems other than hepatitis, hypertension, or infectious disease were referred to their physician for further information concerning their suitability as donors. Over 80% had irregular pulses or histories suggestive of potential cardiovascular problems. The purpose of this study was to review the evaluation mechanism. Responses for evaluation were received from only 222 out of 1,203 (18%), and of these all but 29 (13%) were granted full permission to donate. Since only one evaluated individual with pulse or cardiovascular findings of possible significance was under the age of 35 years, this age is a reasonable cutoff for such deferrals. The minimum increase in collections with this change in deferral screening would be over 1,000 units per year in Connecticut, and perhaps 60,000 nationwide.

Adult↗
PubMed1994

Facilitating internalization: the self-determination theory perspective.

Self-determination theory (Deci & Ryan, 1985) posits that (a) people are inherently motivated to internalize the regulation of uninteresting though important activities; (b) there are two different processes through which such internalization can occur, resulting in qualitatively different styles of self-regulation; and (c) the social context influences which internalization process and regulatory style occur. The two types of internalization are introjection, which entails taking in a value or regulatory process but not accepting it as one's own, and integration, through which the regulation is assimilated with one's core sense of self. Introjection results in internally controlling regulation, whereas integration results in self-determination. An experiment supported our hypothesis that three facilitating contextual factors--namely, providing a meaningful rationale, acknowledging the behaver's feelings, and conveying choice--promote internalization, as evidenced by the subsequent self-regulation of behavior. This experiment also supported our expectation that when the social context supports self-determination, integration tends to occur, whereas when the context does not support self-determination, introjection tends to occur.

Female↗
PubMed2005

Stochastically modeling Listeria monocytogenes growth in farm tank milk.

This article presents a Listeria monocytogenes growth model in milk at the farm bulk tank stage. The main objective was to judge the feasibility and value to risk assessors of introducing a complex model, including a complete thermal model, within a microbial quantitative risk assessment scheme. Predictive microbiology models are used under varying temperature conditions to predict bacterial growth. Input distributions are estimated based on data in the literature, when it is available. If not, reasonable assumptions are made for the considered context. Previously published results based on a Bayesian analysis of growth parameters are used. A Monte Carlo simulation that forecasts bacterial growth is the focus of this study. Three scenarios that take account of the variability and uncertainty of growth parameters are compared. The effect of a sophisticated thermal model taking account of continuous variations in milk temperature was tested by comparison with a simplified model where milk temperature was considered as constant. Limited multiplication of bacteria within the farm bulk tank was modeled. The two principal factors influencing bacterial growth were found to be tank thermostat regulation and bacterial population growth parameters. The dilution phenomenon due to the introduction of new milk was the main factor affecting the final bacterial concentration. The results show that a model that assumes constant environmental conditions at an average temperature should be acceptable for this process. This work may constitute a first step toward exposure assessment for L. monocytogenes in milk. In addition, this partly conceptual work provides guidelines for other risk assessments where continuous variation of a parameter needs to be taken into account.

Animals↗
PubMed2006

Characteristics associated with liver graft failure: the concept of a donor risk index.

Transplant physicians and candidates have become increasingly aware that donor characteristics significantly impact liver transplantation outcomes. Although the qualitative effect of individual donor variables are understood, the quantitative risk associated with combinations of characteristics are unclear. Using national data from 1998 to 2002, we developed a quantitative donor risk index. Cox regression models identified seven donor characteristics that independently predicted significantly increased risk of graft failure. Donor age over 40 years (and particularly over 60 years), donation after cardiac death (DCD), and split/partial grafts were strongly associated with graft failure, while African-American race, less height, cerebrovascular accident and 'other' causes of brain death were more modestly but still significantly associated with graft failure. Grafts with an increased donor risk index have been preferentially transplanted into older candidates (>50 years of age) with moderate disease severity (nonstatus 1 with lower model for end-stage liver disease (MELD) scores) and without hepatitis C. Quantitative assessment of the risk of donor liver graft failure using a donor risk index is useful to inform the process of organ acceptance.

Adolescent↗