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PubMed2003

Individuality: the barrier to optimal immunosuppression.

Immunosuppressive therapy aims to protect transplanted organs from host responses. Individuals have unique repertoires of responses to foreign antigens and toxic reactions to immunosuppressants; the former determining the type or intensity of rejection reactions and the latter influencing the severity of iatrogenic effects. Because existing agents target molecules that are widely distributed in tissues, new strategies must selectively block lymphoid cells only, disrupt alloresponses but not innate immune responses, interact synergistically with other agents, facilitate the homeostatic process that naturally leads to graft acceptance and ideally only interrupt donor-specific responses. Approaches presently under investigation aim to alter cell trafficking, or selectively deviate the maturation of antigen-presenting cells or inhibit lymphocyte-activation cascades - events that are crucial to rejection responses.

Animals↗
PubMed2001

Sepsis begins at the interface of pathogen and host.

To the modern mind, the term 'sepsis' conjures up images of microbes. It is easy to forget that the word predates any understanding of the microbial origins of infectious disease. Derived from the Greek 'sepsios' (rotten), sepsis denotes decay: a phenomenon that humans once regarded as a mysterious though inevitable natural process. A living organism does not accept decay passively. Virtually all multicellular life forms are capable of resisting infection through the generation of a vigorous immune response. In mammals, the response is so stereotypic that it has come to define sepsis itself: it is often called the 'septic syndrome'. Our current understanding of the innate immune system is deeply rooted in the study of sepsis. The chain of events linking infection to tissue injury and cardiovascular collapse is not obvious, and affirmation of the concept required three major discoveries. First, the septic syndrome was found to be caused by toxic products of microbes. Secondly, these toxic substances were found to be toxic because of their propensity to activate cells of the innate immune system, prompting cytokine production. Thirdly, the activating events initiated by microbial toxins were traced to members of an ancient family of defensive molecules, versions of which operate in virtually all multicellular life forms. In mammals, proteins of this family are now known as Toll-like receptors. They represent a point of direct contact, and first contact, between a pathogen and the host immune system.

Animals↗
PubMed2003

Clinical nurses' response to an environment of health care reform and organizational restructuring.

BACKGROUND: Clinical nurses at the crux of health care service delivery experienced radical organizational restructuring during the 1990s in Australia. Despite the implications organizational restructuring has for patient care delivery, clinical nurses continue to lack presence in policy decision-making processes. AIMS: The aim of this paper is to provide an explanation for clinicians' undisputed acceptance of change. This will be performed by examining the process of organizational restructuring across three analytical levels -- the macro, meso and micro; identifying the consequences of restructuring for clinical nurses' performance; and evaluating organizational restructuring using a micro-political theoretical framework. FINDINGS: Utilizing Hoyle's (1988) micro-political theory, it would appear that clinical nurses are functioning within a paradigm of maintenance. In order to provide quality patient care, effective resource use and preservation of the status quo are prioritized. CONCLUSION: Successful change outcomes are dependent on clinical nurses' performance. Whether nurses are politically inactive as a result of poor communication, as a consequence of the structural change environment or because their energy is devoted to achieving a balance between organizational imperatives and their personal commitment to patient care requires further investigation.

Attitude of Health Personnel↗
PubMed2003

How is medical decision-making shared? The case of haemophilia patients and doctors: the aftermath of the infected blood affair in France.

OBJECTIVE: This article looks at how users and doctors in France have rethought the question of shared decision-making in the clinical field of haemophilia following a major crisis - that of the infected blood affair. DESIGN: We did a qualitative survey based on semi-structured interviews in three regions of France. SETTING AND PARTICIPANTS: The interviews covered 31 clinical doctors of haemophilia and 31 users: 21 adult males with severe haemophilia (21/31), infected (14/21) or not (7/21) with HIV, the infected wife of one of the latter (1/31) and nine parents of young patients with severe haemophilia (9/31), either HIV positive (6/9) or negative (3/9). RESULTS AND CONCLUSIONS: The results show the infected blood affair to be a major individual and collective ordeal. It has caused users and doctors to rethink their roles within clinical relationships and to develop new ways of sharing medical decision-making. Prior to the crisis, the dominant model was based upon a distinction between the medical aspect, governed by the doctors, and the psychosocial aspect, which involved the patients and their families. Since the crisis, medicoscientific knowledge has been shared between users and doctors. This general trend nevertheless permits the existence of different patient, family and doctor profiles which in turn correspond to different notions of what a clinical decision should be. Some users remain attached to the idea of complementarity between doctors and patients (new partnership model), whilst others put doctors and patients on an equal footing (negotiation model). On the doctors' side, whilst some still prefer the initial model for therapeutic decision-making, the majority have reassessed their perceptions and viewpoints. A certain number believe that decisions should be made by both doctor and patient in accordance with scientific procedures (decision-making controlled by scientific standards) or regulatory procedures (decision-making controlled by legal standards). Yet others feel that multiple points of view are acceptable within the decision-making process (decision-making model as interactivity).

Adult↗
PubMed2003

Direct demonstration of nitric oxide formation in organs of rabbits treated by transdermal glyceryl trinitrate using an in vivo spin trapping technique.

Glyceryl trinitrate (GTN) is commonly delivered by a patch for the treatment of angina pectoris. The idea is now generally accepted that GTN requires a biotransformation process that activates the drug, in particular through nitric oxide (NO) generation. However, the pharmacokinetics of NO delivery from GTN still remains obscure. The objective of this study was to assess GTN-derived NO formation in vascular tissues and organs in rabbit given GTN patches. NO levels were evaluated in rabbits after 3 h of treatment with a 10 mg GTN patch (GTN group; n = 7) or a placebo patch (CTL; n = 7). Nitrosylhaemoglobin (HbNO) was evaluated by electron spin resonance (ESR) spectroscopy in red cell suspension. In vivo spin trapping technique using FeMGD as a spin trap, associated with ESR was used to quantify NO in tissues. The NO-spin trap complex, which is a relatively stable product, has been measured in several tissues. The ESR spectrum corresponding to HbNO was not found in red cell of GTN or CTL rabbits. The spectrum corresponding to the NO-spin trap complex was observed in all analysed tissues of CTL rabbits. The signal was significantly increased in liver, renal medulla, heart left ventricle and spleen of GTN-treated rabbits, and to a lesser extent in right ventricle and lung. No difference was shown between NO-spin trap levels measured in aorta or inferior vena cava from GTN or CTL rabbits. These data suggest that GTN patch treatment induced NO release, and that tissue-specific differences in transdermal GTN-derived NO exist. The GTN-NO pathway appears to be largely involved in organs such as the liver, kidney and heart.

Administration, Cutaneous↗
PubMed2003

Barriers to accessing low vision services.

AIM: To investigate barriers to accessing low vision services in Australia. METHODS: Adults with a vision impairment (<6/12 in the better eye and/or significant visual field defect), who were current patients at the Royal Victorian Eye and Ear Hospital (RVEEH), were interviewed. The questions investigated self-perceived vision difficulties, duration of vision loss and satisfaction with vision and also examined issues of awareness of low vision services and referral to services. Focus groups were also conducted with vision impaired (<6/12 in the better eye) patients from the RVEEH, listeners of the Radio for the Print Handicapped and peer workers at Vision Australia Foundation. The discussions were recorded and transcribed. RESULTS: The questionnaire revealed that referral to low vision services was associated with a greater degree of vision loss (p = 0.002) and a greater self-perception of low vision (p = 0.005) but that referral was not associated with satisfaction (p = 0.144) or difficulties related to vision (p = 0.169). Participants with mild and moderate vision impairment each reported similar levels of difficulties with daily activities and satisfaction with their vision (p > 0.05). However, there was a significant difference in the level of difficulties experienced with daily activities between those with mild-moderate and severe vision impairment (p < 0.05). The participants of the focus groups identified barriers to accessing low vision services related to awareness of services among the general public and eye care professionals, understanding of low vision and the services available, acceptance of low vision, the referral process, and transport. CONCLUSION: In addition to the expected difficulties with lack of awareness of services by people with low vision, many people do not understand what the services provide and do not identify themselves as having low vision. Knowledge of these barriers, from the perspective of people with low vision, can now be used to guide the development and content of future health-promotion campaigns.

Activities of Daily Living↗
PubMed1998

Survival of fresh human platelets in a rabbit model as traced by flow cytometry.

BACKGROUND: In the event of hemorrhage and blood loss, platelets play a vital role in the coagulation process. However, there are currently no acceptable protocols for long-term storage of platelets. As a first step toward testing the efficacy of stored platelets or platelet substitutes in vivo, a flow cytometric technique was developed to detect human platelets in rabbit blood. STUDY DESIGN AND METHODS: Human platelets were transfused to rabbits whose reticuloendothelial system was inhibited by the administration of ethyl palmitate. Because human and rabbit platelets display surface molecules with different epitopes, human platelets were selectively labeled with antibodies specific for glycoprotein IX (CD42a). As this antibody does not label rabbit platelets, it allows discrimination of human from rabbit platelets in samples of rabbit blood containing both types of platelets. RESULTS: Survival of human platelets in rabbits was monitored by flow cytometry and fluorescence microscopy in blood drawn at various times after the platelet transfusion. Fresh human platelets transfused to untreated control rabbits (n = 3) were removed from circulation within 10 minutes of the completion of the transfusion. Fresh platelets (1 day old) transfused to rabbits treated with ethyl palmitate (n = 5) survived for 24 hours with an average half-life of 8.6 hours. In contrast, 8-day-old platelets were cleared from the circulation sooner with an average half-life of 2.9 hours (n = 4). CONCLUSION: This report describes a rapid and efficient method of assessing the survival of human platelets in a rabbit model using flow cytometry. This technique will enable the monitoring in rabbits of human platelets prepared by various preservation protocols.

Animals↗
PubMed1976

Accreditation of occupational health programs: development and validation of criteria.

Defined standards and a mechanism for evaluation of performance can help promote new and improve existing occupational health programs. Criteria must be based on sound principles, be comprehensive, discriminating and attainable. They should apply to small and large establishments with varying hazards. A successful program requires a multi-disciplinary effort involving physicians, nurses, industrial hygienists, health physicists, safety professionals, managers, technicians and labor. Assessment by on-site peer review is necessary. The criteria and process for their use must be accepted by the professions, labor and management. The Occupational Health/Safety Programs Accreditation Commission plans to use the document entitled Standards, Interpretations and Audit Criteria for Performance of Occupational Health Programs in its accreditation activities. The development and validation of this document and its use are described.

Accreditation↗
PubMedDate not supplied

Discriminability of load heaviness: implications for the psychophysical approach to manual lifting.

The main objective of this study was to investigate human ability to discriminate between different levels of load heaviness in manual lifting. Twelve male college students participated in the laboratory experiment. Twenty-eight sequences of five boxes that weighed from 5 to 64 lbs (2.27-29.1 kg) were used. The subjects were asked to arrange boxes in each sequence in order of the perceived (increasing or decreasing) heaviness, i.e., from lightest to the heaviest box, or from heaviest to the lightest box. The subjects were also asked to assign linguistic descriptors of perceived load heaviness to each box in the sequence, and to indicate the confidence levels regarding correctness of the assigned box order and assignment of linguistic values. The independent variables included magnitude of weight and load differential between the successive weights in a sequence. The number of sequential ordering errors, assignment of linguistic variables, and estimated confidence levels were highly dependent on the load differential and weight range. It was concluded that in order to assure reliable results of the psychophysical approach to determining the values of maximum acceptable weight of lift, the adjustment process for male subjects should require using small weights of at least 4 lbs (1.8 kg) to be added or removed from the lifted box. The results of this study also suggest that the error rate in load discriminability can be controlled below the 10% level, if the relative difference in weight between successive boxes lifted is at least 12%. Given the above findings, it is suggested that usefulness of some of the recommendations for setting safe limits for manual lifting tasks, which were reached based on the psychophysical approach and broadly reported in the past, may need to be carefully re-examined. Finally, this study showed that the Weber fraction for load heaviness over the range of lifted weights from 8.6 to 29.1 kg is between 0.03 and 0.04.

Biomechanical Phenomena↗
PubMed2006

Sexual identity development among gay, lesbian, and bisexual youths: consistency and change over time.

A longitudinal report of 156 gay, lesbian, and bisexual youths examined changes in sexual identity over time. Fifty-seven percent of the youths remained consistently self-identified as gay/lesbian, 18% transited from bisexual to gay/lesbian, and 15% consistently identified as bisexual over time. Although youths who consistently identified as gay/lesbian did not differ from other youths on time since experiencing sexual developmental milestones, they reported current sexual orientation and sexual behaviors that were more same-sex centered and they scored higher on aspects of the identity integration process (e.g., more certain, comfortable, and accepting of their same-sex sexuality, more involved in gay-related social activities, more possessing of positive attitudes toward homosexuality, and more comfortable with others knowing about their sexuality) than youths who transited to a gay/lesbian identity and youths who consistently identified as bisexual. Contrary to the hypothesis that females are more sexually fluid than males, female youths were less likely to change identities than male youths. The finding that youths who transited to a gay/lesbian identity differed from consistently gay/lesbian youths suggests that identity integration continues after the adoption of a gay/lesbian sexual identity.

Adolescent↗
PubMed1993

Nutrition and hydration in the terminally ill cancer patient: the nurse's role in helping patients and families cope.

Cancer patients and their family members must cope with multiple losses as the disease progresses. The loss of ability to eat and drink is a real and perceived harbinger of the ultimate loss: death. While health care professionals know that these physiologic changes are a normal part of the dying process, families are rarely able to accept them easily. Because these losses have such profound emotional, spiritual, and physical ramifications, it is important that staff be prepared to provide appropriate support and information to patients and families. The suggestions posed in this article may be utilized by all members of the interdisciplinary team.

Adaptation, Psychological↗
PubMed1979

The use of sand substitution to solve the free silica problem in foundry atmospheres.

Field tests were carried out to compare the air quailty in a gray iron foundry before and after changing the molding material from the standard silica based sand to the mineral olivine. Olivine is a magnesium iron silicate (Mg, Fe) SiO4 which occurs in nature and contains little or no free silica. Data were collected using standard OSHA approved methods to determine the total dust and the respirable limit for the alpha-quartz particle loading levels. Additional samples were taken using a cascade impactor and filter tape samplers. The foundry was surveyed once before the substitution of olivine and three times after the changeover. The study demonstrates that the partial substitution of olivine can reduce the concentration of free silica to acceptable health levels. However, contamination from processes using silica sand must be controlled.

Air Pollutants↗
PubMedDate not supplied

A risk analysis approach to selecting respiratory protection against airborne pathogens used for bioterrorism.

The authors present a quantitative risk analysis approach to estimating infection risk due to airborne pathogens exhibiting relatively large infectious dose values. The method is applied to hypothetical scenarios involving airborne spores of Bacillus anthracis. The method combines the estimated parameters for exposure intensity, the pathogen dose-response relationship, and respirator penetration values (if respiratory protection is used). Because knowledge of the true parameter values will be uncertain, an uncertainty analysis is an essential part of the process. Given a specified value for acceptable infection risk, the method permits choosing a respirator that sufficiently reduces exposure to meet the acceptable risk criterion. A strength of the risk analysis approach is its transparency, in that the model structure and data inputs are explicitly identified. Further, risk analysis informs the expert judgment that must typically be applied in selecting respiratory protection against airborne pathogens.

Anthrax↗
PubMed1998

The activity of differentiation factors induces apoptosis in polyomavirus large T-expressing myoblasts.

It is commonly accepted that pathways that regulate proliferation/differentiation processes, if altered in their normal interplay, can lead to the induction of programmed cell death. In a previous work we reported that Polyoma virus Large Tumor antigen (PyLT) interferes with in vitro terminal differentiation of skeletal myoblasts by binding and inactivating the retinoblastoma antioncogene product. This inhibition occurs after the activation of some early steps of the myogenic program. In the present work we report that myoblasts expressing wild-type PyLT, when subjected to differentiation stimuli, undergo cell death and that this cell death can be defined as apoptosis. Apoptosis in PyLT-expressing myoblasts starts after growth factors removal, is promoted by cell confluence, and is temporally correlated with the expression of early markers of myogenic differentiation. The block of the initial events of myogenesis by transforming growth factor beta or basic fibroblast growth factor prevents PyLT-induced apoptosis, while the acceleration of this process by the overexpression of the muscle-regulatory factor MyoD further increases cell death in this system. MyoD can induce PyLT-expressing myoblasts to accumulate RB, p21, and muscle- specific genes but is unable to induce G0(0) arrest. Several markers of different phases of the cell cycle, such as cyclin A, cdk-2, and cdc-2, fail to be down-regulated, indicating the occurrence of cell cycle progression. It has been frequently suggested that apoptosis can result from an unbalanced cell cycle progression in the presence of a contrasting signal, such as growth factor deprivation. Our data involve differentiation pathways, as a further contrasting signal, in the generation of this conflict during myoblast cell apoptosis.

Animals↗
PubMed1979

The influence of stimulus age and sex on person perception.

College males and females evaluated 25-, 50-, and 75-year-old males and females using a semantic differential. Evaluations became more negative with increasing age of stimulus concept. Males were perceived as more effective and autonomous than females until age 75. Females were perceived as more personally acceptable at all ages. The aging process was perceived as similar for males and females between 25 and 50 but more detrimental to males than to females between 50 and 75. Female Ss evaluated male and female stimulus concepts similarly while male Ss evaluated male stimuli more positively than female stimuli.

Adult↗
PubMed2000

Strand bias in Ig somatic hypermutation is determined by signal sequence within the variable region.

Ig genes undergo hypermutation with a nucleotide preference of A over T for mutation on the coding strand. As only with concomitant strand bias can such nucleotide bias be observed, Ig gene hypermutation is generally accepted as a strand-specific process, for which the mechanistic basis remains unknown. It has previously been shown that different non-Ig sequences replacing the LVJ region of an Ig transgene to various extents are targeted for hypermutation with similar mutation frequencies. However, the nucleotide bias characteristic of Ig hypermutation was not found in two of the three such sequences studied. To test whether it is the DNA sequences of the non-Ig substrates that determine the pattern of nucleotide bias in hypermutation or whether the LVJ sequence may contain element(s) that confer strand bias, we have added back all the replaced LVJ sequences to one of the transgenes, L(kappa)-Vgpt*, that expresses no strand bias in hypermutation and studied the outcome. The results show that the gpt sequence in the presence of the complete LVJ sequence hypermutates differently from the same sequence in L(kappa)-Vgpt* where 84% of the LVJ was replaced. The main difference is the resumption of strand bias characteristic of Ig hypermutation. Thus, whether or not a substrate sequence manifests strand bias in hypermutation is not inherently determined by the substrate DNA sequence. This indicates the presence of special element(s) within the LVJ that confer strand bias.

Animals↗
PubMed2006

Kinetic analysis of ribosome binding process onto mRNA using a quartz-crystal microbalance.

Translation initiation is the most dynamic and important step along a series of protein synthesis processes. In bacteria, it is generally accepted that the 70S ribosome initially dissociates into the 30S and 50S subunit, and then, the 30S ribosomal subunit binds to the Shine-Dargalno (SD) sequence of mRNA. We analyzed binding kinetics of 70S, 50S and 30S ribosomes to the SD sequence by using a mRNA-immobilized 27 MHz quartz-crystal microbalance (QCM). The 70S ribosome was found to bind strongly to the SD sequence as a ratio of 1:1 without dissociation to each subunit from the lateral side, as well as the 30S subunit. The binding constant for 70S increased in the presence of the initiator tRNA, which suggests that the SD and initiator codon of AUG could be also recognized precisely with 70S.

Base Sequence↗
PubMed2000

A clinical approach to complex regional pain syndrome.

The clinical approach to complex regional pain syndrome (CRPS) is complicated by a lack of precision diagnostically, and a lack of evidence-based information for treatment. The vagaries of diagnosis were somewhat improved by the Orlando Conference (1993), where a consensus panel of experts developed a new taxonomy and criteria. Unfortunately the criteria can be based entirely on subjective grounds (patient history), and as such provides a very sensitive but not very specific device. There is some effort in the research community to amend these criteria to make them more specific. We encourage the practicing physician to include as much objective data along with the quasi-objective and subjective information currently used in formulating the diagnosis. This imprecision in diagnostic issues has significantly hampered treatment because it has not led to solid, generalizable, randomized controlled trials. To date there are no substantial scientific trials of any particular therapy or medication in the specific diagnosis of CRPS. Much can be inferred from the work with peripheral neuropathy and central pain. However, it is unlikely that this will be a perfect concordance with best therapy for CRPS. It remains our responsibility to diagnose each patient as best we can, supported by the best possible objective signs and testing. Once the diagnosis is made it is necessary to proceed in a pragmatic empirical way, following the best guidelines available. The guidelines should be considered a "rough sketch" and the key to clinical success will be flexibility, a vast fund of the available knowledge, patience, and compassion. To allow the deficiencies in the science to paralyze the clinical process is therapeutic nihilism, and not acceptable.

Causalgia↗