Background: Arthritis is very common but is not well understood. Actually, “arthritis” is not a single disease; it is an informal way of referring to joint pain or joint disease. There are more than 100 different types of arthritis and related conditions. People of all ages, sexes and races can and do have arthritis, and it is the leading cause of disability in America. More than 50 million adults and 300,000 children have some type of (...) class='Hi'>arthritis. It is most common among women and occurs more frequently as people get older. Common arthritis joint symptoms include swelling, pain, stiffness and decreased range of motion. Symptoms may come and go. They can be mild, moderate or severe. They may stay about the same for years, but may progress or get worse over time. Severe arthritis can result in chronic pain, inability to do daily activities and make it difficult to walk or climb stairs. Arthritis can cause permanent joint changes. These changes may be visible, such as knobby finger joints, but often the damage can only be seen on X-ray. Some types of arthritis also affect the heart, eyes, lungs, kidneys and skin as well as the joints. Objectives: The main goal of this expert system is to get the appropriate diagnosis of disease and the correct treatment and give the appropriate method of treatment through several tips that concern the disease and how to treat it and we will see it through the application on the expert system. Methods: in this paper the design of the proposed Expert System which was produced to help Orthopedist in diagnosing Arthritis disease through its symptoms such as: pain on pressure in a joint , Inflammation indicated by joint swelling, Stiffness especially in the morning , Loss of flexibility of joint, Limited, joint movement, Deformity of the joints , Weight loss and fatigue , Non-specific fever and Crepitus. The proposed expert system presents an overview about Arthritis disease is given, the cause of diseases is outlined and the treatment of disease whenever possible is given out. SL5 Object Expert System language was used for designing and implementing the proposed expert system. Results: The proposed Arthritis disease diagnosis expert system was evaluated by Orthopedics students and they were satisfied with its performance. Conclusions: The Proposed expert system is very useful for Orthopedist, patients with arthritis and newly graduated Orthopedics students. (shrink)

Rheumatoid arthritis (RA) may not be a multifactorial disease; it can be hypothesized that RA is developed through a series of events following a triggering event, which is the emergence of a chemokine for neutrophils in the synovium. IL‐17A, secreted by infiltrated neutrophils, stimulates synoviocytes to produce CCL20, which attracts various CCR6‐expressing cells, including Th17 cells. Monocytes (macrophages) appear after neutrophil infiltration according to the natural course of inflammation and secrete IL‐1β and TNFα. Then, IL‐17A, IL‐1β, and TNFα stimulate (...) synoviocytes to produce CCL20, amplifying the inflammation. Varieties of chemokines secreted by infiltrating cells accumulate in the synovium and induce synoviocyte proliferation by binding to the corresponding G protein‐coupled receptors, thus expanding the synovial tissue. CCL20 in this tissue attracts circulating monocytes that express both CCR6 and receptor activator of NF‐κB (RANK), which differentiate into osteoclasts in the presence of RANKL. In this way, pannus is formed, and bone destruction begins. (shrink)

This chapter focuses on the view that diseases comprise natural kinds and how this view is in conflict with the essentialist picture of natural kinds as championed by Kripke and Putnam. This essentialist depiction of natural kinds contends that in order for a class of entities to be a natural kind, it is required that all and only members of the class instantiate very specific properties that explain the presence of any other properties typically associated with being a member of (...) the kind; these privileged properties constitute the “essence” of the kind. The problem is that the essentialist picture provides only two options, none of which is desirable: satisfy the essentialist desiderata by locating some etiological feature both necessary and sufficient for kind membership, or reject the thought that similarity between disease instances can be understood in terms of natural kinds. (shrink)

Tyler Burge's (1979) famous thought experiment concerning 'arthritis' is commonly assumed to show that all ascriptions of content to beliefs and other attitudes are dependent for their truth upon facts about the agent's social and linguistic environment. It is also commonly claimed that Burge's argument shows that Putnam's (1975) result regarding natural kind terms applies to all general terms whatever, and hence shows that all such terms have wide meanings.1 But I wish to show here, first, that neither Burge's (...) initial thought experiment nor a second type of example that Burge describes supports either of these conclusions. Second, I will identify the proper conclusion to draw from Burge's discussion and show that this conclusion does not really pose a serious problem for individualism about the mental. And finally, I will argue that Burge's discussion does not in fact provide a conclusive reason for believing its proper conclusion. (shrink)

BackgroundAwareness of aging brings to light one’s own perceived behavioral, physical, and cognitive changes associated with getting older. Personality and physical illness are each related to two components of awareness of aging: attitudes toward own aging, and awareness of age-related changes. Here, we move beyond main effects to examine how personality and arthritis interact with respect to awareness of aging.Materials and Methods296 participants completed online self-report questionnaires of personality, arthritis, ATOA, and AARC gains and losses.ResultsWe ran three hierarchical (...) multiple regression models to test how personality traits and arthritis interacted to predict ATOA, AARC gains, and AARC losses, respectively. Higher extraversion was related to positive ATOA, and higher openness was related to positive ATOA and more AARC gains. Higher neuroticism was related to negative ATOA, more AARC losses, and less AARC gains. We found a main effect for arthritis, where those with arthritis reported more AARC losses. Lastly, we found a significant interaction between arthritis and agreeableness when predicting AARC gains. Among those with low agreeableness, people with arthritis reported significantly more AARC gains compared to those without arthritis.ConclusionPersonality and arthritis are each important for awareness of aging. Overall, our study suggests that for those with arthritis, it is especially important to consider behavioral and cognitive factors related to agreeableness, as they may be important means of promoting positive views on aging. (shrink)

Background Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants. In pediatrics, data on equipoise are lacking. We hypothesize that 1) lack of equipoise at enrolment among parents may reduce recruitment; 2) lack of equipoise during participation may reduce retention in patients assigned to a less favoured treatment-strategy. Methods We compared preferences of (...) parents/patients at enrolment, documented by a questionnaire, with preferences developed during follow-up by an interview-study to investigate equipoise of child-participants and parents in the BeSt-for-Kids-study. This trial in new-onset Juvenile Idiopathic Arthritis-patients consists of three strategies. One strategy comprises initial treatment with a biological disease-modifying-antirheumatic-drug, currently not standard-of-care. Semi-structured interviews were conducted with 23 parents and 7 patients, median 11 months after enrolment. Results Initially most parents and children were not in equipoise. Parents/patients who refused participation, regularly declined due to specific preferences. Many participating families preferred the biological-first-strategy. They participated to have a chance for this initial treatment, and would even consider stopping trial-participation when not randomized for it. Their conviction of superiority of the biological-first strategy was based on knowledge from internet and close relations. According to four parents, the physician-investigator preferred the biological-first-strategy, but the majority stated that she had no preferred strategy. In phase 2, preferences tended to change to the treatment actually received. Conclusions Lack of equipoise during enrolment did not reduce study recruitment, mainly due to the fact that preferred treatment was only available within the study. Still, when developing a trial it is important to evaluate whether the physicians’ research question is in line with preferences of the patient-group. By exploring so-called ‘informed patient-group’-equipoise, successful recruitment may be enhanced and bias avoided. In our study, lack of equipoise during trial-participation did not reduce retention in those assigned to a less favoured option. We observed a change for preference towards treatment actually received, possibly explained by comparable outcomes in all three arms. (shrink)

Objectives: To elicit the perceptions and preferences of patients with rheumatoid arthritis regarding information and participation in treatment decision-making. To analyse the patients’ narratives on the background of the ethical discourse on various approaches to treatment decision-making. Design: In-depth interviews with themes identified using principles of grounded theory. Participants: 22 patients with long-standing rheumatoid arthritis. Main outcome measures: Qualitative data on patients’ perceptions and preferences regarding information and participation in decision-making about treatment. Results: Decision-making about treatment has been (...) described by the patients as a process consisting of different stages with shifting loci of control and responsibility. Patients initially received one treatment recommendation and were not aware of alternative treatment options. Those participants in this study who wanted information about negative effects of a treatment cited “interest in one’s own health” and the potential “use of information” as reasons for their preference. The physicians’ expert knowledge and clinical experience regarding the effects of medication were cited as arguments by patients for a treatment recommendation. Conclusions: The patients’ accounts of decision-making about treatment differ from models of physician–patient relationship that have been put forward in ethical discourse. These differences may be relevant with respect to the starting point of an ethical analysis of treatment decision-making. Patients’ accounts with respect to a lack of information on treatment alternatives point to ethically relevant challenges regarding treatment decision-making in clinical practice. (shrink)

ObjectiveLeveraging an integrative multimodal MRI paradigm to elaborate on the hippocampus-derived structural and functional changes in children and adolescents with juvenile idiopathic arthritis and to explore potential correlations within the “joint-inflammation-brain” axis during the period of central neural system development.MethodsTwenty-one patients with JIA all completed the multimodal MRI scanning, laboratory tests, and neuropsychological assessments; meanwhile, 23 matched controls were recruited. We then harnessed the spherical harmonics with a point distribution model and the ROI-to-voxel functional connectivity to measure the hippocampal (...) shape and hippocampo-cortical FC patterns. Correlation analysis was performed to explore the potential links in neuroimaging features with disease-related indices.ResultsCompared to controls, JIA patients only presented an atrophic tendency in the posterior part of the bilateral hippocampus. The hippocampo-cortical FC revealed the between-group divergences mainly located at the pain matrix, striatum, and temporal lobe. Remarkably, the enhanced FC between the right hippocampus and postcentral cortex is positively correlated with the disability index, while the weakened FC of right anterior hippocampus with right insula and that of left posterior hippocampus with left superior temporal gyrus was inversely related to the erythrocyte sedimentation rate and anxiety status, separately.ConclusionAs with macroscopic damages, the altered functional-connectome patterns of the hippocampus in JIA patients might be more sensitive to detect the early neuropathological changes. Moreover, the functional disturbances were demonstrated associated with the physical disability, inflammation, and emotional status. These findings may enlighten us on the underlying neuropathological mechanism of CNS comorbidities in JIA. (shrink)

Rheumatoid arthritis is a progressive systemic autoimmune disease characterized by inflammation of the joints and surrounding tissues, which seriously affects the life of patients. The Sharp/van der Heijde method has been widely used in clinical evaluation for the RA disease. However, this manual method is time-consuming and laborious. Even if two radiologists evaluate a specific location, their subjective evaluation may lead to low inter-rater reliability. Here, we developed an efficient model powered by deep convolutional neural networks to solve these (...) problems and automated the overall scoring on hand X-rays. The depthwise separable convolution technique is used based on ResNet-50 due to the high resolution of hand X-rays. An inverted residual block is introduced to devise a ResNet-Dwise50 model to enhance the efficiency of the model. The model was trained and tested using bilateral posteroanterior images of 3818 patients. The experiment results show the ResNet-Dwise50 model achieved an MAE of 14.90 and RMSE of 22.01 while ensuring high efficiency. There was no statistical difference between the average scores given by two experienced radiologists and predicted scores from our model. (shrink)

Cortisone, initially known as ‘compound E’ was the medical sensation of the late 1940s and early 1950s. As early as April 1949, only a week after Philip Hench and colleagues first described the potential of ‘compound E’ at a Mayo Clinic seminar, the New York Times reported the drug’s promise as a ‘modern miracle’ in the treatment of rheumatoid arthritis. Given its high profile, it is unsurprising that historians of medicine have been attracted to study the innovation of cortisone. (...) It arrived at the end of a decade of ‘therapeutic revolutions’, kicked off by penicillin transforming the treatment of bacterial infections and ending with hopes of a revolution in the treatment of non-infectious, chronic inflammatory diseases. Despite these studies of cortisone’s introduction, few historians have taken the story forward and considered how cortisone was adopted and adapted into clinical practice. This article tells the longer of how the drug and its derivatives were taken from research laboratories and integrated into clinical practice; what has in recent decades become known as translational medicine. In exploring cortisone’s first decade in Britain, we focus specifically on its role in the treatment of RA. Our approach is always to consider cortisone’s use in the context of other treatments available to clinicians, and at local and national institutional settings. We do not discuss the many other therapeutic uses of cortisone, which ranged for topical applications for skin diseases to the management of cancers, especially childhood leukaemia, nor do we discuss its close analogue ACTH—AdenoCorticoTropic Hormone. We think there are lessons in our study for TM policies today. (shrink)

The above-mentioned article has been published online on 7 November 2019 as part of topical collection ‘_Before Translational Medicine: Laboratory Clinic Relations_’.

In the past decade, the availability of genetically modified animals has enabled the discovery of interesting roles for phosphatidylinositol 3‐kinase‐γ (PI3Kγ) and ‐δ (PI3Kδ) in different cell types orchestrating innate and adaptive immune responses. Therefore, these PI3K isoforms appear to be attractive drug targets for the treatment of diseases caused by unrestrained immune reactions. Currently, pharmacological targeting of PI3Kγ and/or PI3Kδ represents one of the most promising challenges for companies interested in the development of novel safe treatments for inflammatory diseases. (...) In this review we provide a general outline of PI3Kγ‐ and PI3Kδ‐specific functions in distinct subsets of inflammatory cells. We also discuss the therapeutic impact of novel compounds targeting PI3Kγ, PI3Kδ or both, in mouse models of autoimmune disorders (systemic lupus erythematosus (SLE) and rheumatoid arthritis), respiratory diseases (allergic asthma and chronic obstructive pulmonary disease) and cardiovascular dysfunctions (atherosclerosis and myocardial infarction). (shrink)

Philosophers of language have tended to focus on examples that are not politically significant in any way. We spend a lot of time analyzing natural kind terms: We think hard about “water” and “pain” and “arthritis.” But we don’t think much about the far more politically significant kind terms (natural or social—it's a matter for dispute) like “race,” “sex,” “gender,” “woman,” “man,” “gay,” and “straight.” In this essay, I will try to show, using the example of “woman,” that it's (...) worth thinking about terms like these, for at least three reasons: (1) There are some interesting puzzles. (2) Politically significant terms matter to people's lives— and it's worth spending at least some of our energy thinking about things that matter in this way. (3) Most importantly, interesting methodological issues emerge at the intersection of philosophy of language and politics. (shrink)

Tyler Burge has argued that an incorrect understanding of a word can be sufficient for possessing the concept the word literally expresses. His well-known 'arthritis' case involves a patient who understands 'arthritis' incorrectly, but who nevertheless, according to Burge, possesses the concept arthritis. Critics of Burge have objected that there is an alternative concept that best matches the patient's understanding and that this, therefore, is the patient's concept. The paper first argues that Burge's response to this objection (...) is unconvincing. A better response is then developed. It is argued that there is no alternative concept that matches the incorrect understanding, since the patient thinks he has a partial understanding. This, together with points about ordinary psychological explanation and modes of presentations of concepts, establish that it is impossible to undermine Burge's social externalism by appealing to the idea that an alternative concept matches the incorrect understanding. (shrink)

Ageing causes progressive decline in metabolic, behavioural, and physiological functions, leading to a reduced health span. The extracellular matrix (ECM) is the three‐dimensional network of macromolecules that provides our tissues with structure and biomechanical resilience. Imbalance between damage and repair/regeneration causes the ECM to undergo structural deterioration with age, contributing to age‐associated pathology. The ECM ‘Ageing Across the Life Course’ interdisciplinary research network (ECMage) was established to bring together researchers in the United Kingdom, and internationally, working on the emerging field (...) of ECM ageing. Here we report on a consultation at a joint meeting of ECMage and the Medical Research Council / Versus Arthritis Centre for Integrated Research into Musculoskeletal Ageing, held in January 2023, in which delegates analysed the key questions and research opportunities in the field of ECM ageing. We examine fundamental biological questions, enabling technologies, systems of study and emerging in vitro and in silico models, alongside consideration of the broader challenges facing the field. (shrink)

Starting dialysis at an advanced age is a clinical challenge and an ethical dilemma. The advantages of starting dialysis at “extreme” ages are questionable as high dialysis-related morbidity induces a reflection on the cost- benefit ratio of this demanding and expensive treatment in a person that has a short life expectancy. Where clinical advantages are doubtful, ethical analysis can help us reach decisions and find adapted solutions. Mr. H is a ninety-year-old patient with end-stage kidney disease that is no longer (...) manageable with conservative care, in spite of optimal nutritional management, good blood pressure control and strict clinical and metabolic evaluations; dialysis is the next step, but its morbidity is challenging. The case is analysed according to principlism (beneficence, non-maleficence, justice and respect for autonomy). In the setting of care, dialysis is available without restriction; therefore the principle of justice only partially applied, in the absence of restraints on health-care expenditure. The final decision on whether or not to start dialysis rested with Mr. H (respect for autonomy). However, his choice depended on the balance between beneficence and non-maleficence. The advantages of dialysis in restoring metabolic equilibrium were clear, and the expected negative effects of dialysis were therefore decisive. Mr. H has a contraindication to peritoneal dialysis (severe arthritis impairing self-performance) and felt performing it with nursing help would be intrusive. Post dialysis fatigue, poor tolerance, hypotension and intrusiveness in daily life of haemodialysis patients are closely linked to the classic thrice-weekly, four-hour schedule. A personalized incremental dialysis approach, starting with one session per week, adapting the timing to the patient’s daily life, can limit side effects and “dialysis shock”. An individualized approach to complex decisions such as dialysis start can alter the delicate benefit/side-effect balance, ultimately affecting the patient’s choice, and points to a narrative, tailor-made approach as an alternative to therapeutic nihilism, in very old and fragile patients. (shrink)

This paper charts the concepts of grip and the bodily auxiliary in Maurice Merleau-Ponty to consider how they find expression in disability narratives. Arguing against the notion of “maximal grip” that some commentators have used to explicate intentionality in Merleau-Ponty, I argue that grip in his texts functions instead as a compensatory effort to stave off uncertainty, lack of mastery, and ambiguity. Nearly without exception in Phenomenology of Perception, the mobilization of “grip” is a signal of impending loss, and is (...) offered as a strategy for managing failure rather than as an example of sure-footed mastery. I read Merleau-Ponty alongside Mary Felstiner's Out of Joint: A Public and Private Story of Arthritis to explore these other, attenuated dimensions of grip. Finally, the paper turns to Harriet McBryde Johnson's memoir Too Late to Die Young as an example of a way of thinking disabled embodiment otherwise. (shrink)

Semantic externalism is the view that the meanings of referring terms, and the contents of beliefs that are expressed by those terms, are not fully determined by factors internal to the speaker but are instead bound up with the environment. The debate about semantic externalism is one of the most important but difficult topics in philosophy of mind and language, and has consequences for our understanding of the role of social institutions and the physical environment in constituting language and the (...) mind. In this long-needed book, Jesper Kallestrup provides an invaluable map of the problem. Beginning with a thorough introduction to the theories of descriptivism and referentialism and the work of Frege and Kripke, Kallestrup moves on to analyse Putnam’s Twin Earth argument, Burge’s arthritis argument and Davidson’s Swampman argument. He also discusses how semantic externalism is at the heart of important topics such as indexical thoughts, epistemological skepticism, self-knowledge, and mental causation. Including chapter summaries, a glossary of terms, and an annotated guide to further reading, _Semantic Externalism_ an ideal guide for students studying philosophy of language and philosophy of mind. (shrink)

Philosophy and science employ abstract hypothetical scenarios- thought experiments - to illustrate, defend, and dispute theoretical claims. Since thought experiments furnish no new empirical observations, the method prompts two epistemological questions: whether anything may be learnt from the merely hypothetical, and, if so, how. Various sceptical arguments against the use of thought experiments in philosophy are discussed and criticized. The thesis that thought experiments in science provide a priori knowledge through non-sensory grasping of abstract entities is discussed and rejected. The (...) thesis that thought experimentation consists in manipulations of mental models is examined and found to be of limited epistemological relevance. It is argued that thought experiments are associated with characteristic arguments in a manner similar to ordinary experiments. It is further argued that thought experiments function in the same way as experiments in general: by providing premises for their associated arguments. Like other experiments, a thought experiment is successful when the premises it provides are true. This holds both for philosophical and scientific thought experiments. An argument schema is proposed and shown to be a formal analogue to that associated with ordinary experiments; similar in being subject to epistemological holism; but differing in being modal: in employing statements about possibility and necessity. The evaluation of thought experiments thus depends on how modal statements may be justified. Intuition and conceivability are discussed as sources of modal justification and found problematic. Instead it is suggested that evaluation proceed by accommodation of the statements describing the experiment's hypothetical scenario. The method of accommodation is developed and applied to five influential thought experiments in philosophy: the brain in a vat; Putnam's Twin Earth; Burge's arthritis example; Searle's Chinese Room; and Newcomb's problem. Its application shows some of these to be failed, others to be successful only relative to controversial philosophical doctrines. (shrink)

The provider–patient relationship is typically regarded as an expert-to-novice relationship, and with good reason. Providers have extensive education and experience that have developed in them the competence to treat conditions better and with fewer harms than anyone else. However, some researchers argue that many patients with long-term conditions (LTCs), such as arthritis and chronic pain, have become “experts” at managing their LTC. Unfortunately, there is no generally agreed-upon conception of “patient expertise” or what it implies for the provider–patient relationship. (...) I review three prominent accounts of patient expertise and argue that all face serious objections. I contend, however, that a plausible account of patient expertise is available and that it provides a framework both for further empirical studies and for enhancing the provider–patient relationship. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:My Patient, TeacherMarissa BlumI remember meeting Beatriz about 12 years ago when security was called to her office visit room by the fellow doctor-in-training who was seeing her. She was yelling loudly about her pain medications, causing a terrific commotion. I stepped in to relieve the fellow and tried to calm her down and move the visit along without anyone getting hurt or further upset. And from then on, (...) Beatriz was moved to my schedule from the fellow's for her monthly visits for her knee pain and refills of fentanyl and oxycodone. She had terrible knees and walked with a cane, almost always accompanied by her son. At one point, she came to our clinic asking to be seen but couldn't, and then fell onto her knees and rolled onto her back in the wait-room, clutching and waiving her cane, expelling expletives and railing at anyone who wanted to help but denying them that privilege. It was as though she relished exposing her pain and a lifetime of hardship for all to confront. I came down from my office to talk with her and when I couldn't convince her to get up on her own, we called EMS to assist and they took her away in an ambulance.For the first few years, I recoiled seeing her name on my schedule each month. I knew I would have to endure a barrage of labile emotions and complaints not just about her constant pain and feelings of inadequacy of her pain medications, but also about her other doctors and how they don't respond to her, or about how the rest of her family shows no care for her. Initially, these visits were hard because they were unpredictable and Beatriz also had bipolar disorder and maybe borderline personality too. I never knew which type of Beatriz I would walk in to see: Angry, tearful, lamentful, and all of those faces were difficult for me. But we met every month for years. During those visits, which almost always were attended by her son, who quietly sat by to either gently rebuff or passively agree with her, I learned so much about her and her very hard life. She was left to raise two children alone, unskilled and ill with hepatitis C, which led to liver cancer, followed later by breast cancer. She chose not to pursue additional therapy for breast cancer, expressing a fatalistic view of her life and intimating she in some way deserved the ailments that she developed. She saw me for disabling knee and hip arthritis that took away her independence and ability to scale the outdoor steps to her second-floor apartment and required the assistance of her son to dress, bathe and care for her. Beatriz never knew this, and I didn't share [End Page 18] it with her, but on one of my early morning drives into North Philadelphia, I saw her on a sun-baked unfriendly street, struggling to move around with her walker. She had many reasons to be angry, and the 30 minutes I spent with her every month became a catharsis for her to unload all that she felt.During my medical training, I encountered hundreds of patients—mostly all in the hospital setting—who might be characterized as difficult and understandably; no one who is relegated to the hospital setting, acutely or chronically ill and requiring inpatient care, could possibly be in the best mood of their lives. Somehow, it was easier for me to care for patients in these snapshot encounters that I controlled. I dictated my time in the room and didn't necessarily have to encounter the same challenging patient longitudinally, which made certain encounters much easier to bear. I realize now I wasn't fully processing the burdens carried by these patients in a way that enabled me to be a compassionate and fully present physician to them. It was an adaptation to the fast-paced life of residency, where one just has to get the job done and move on to the next task without time to process or reflect on difficult patient interactions. This is a... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:“We Need to Cut the Neck!”Confronting Psychological and Moral Distress during Emergency Cricothyrotomy1Stephanie CooperEnoughYou didn’t die in the ER, but rather, began your inexorable demise. The last, first, and only words I ever heard you utter was the weak mewl “tight, tight” as the blood pressure cuff constricted your left arm. You were 98–years–old, bed–bound, at the end. Your world was already partitioning itself from us, your brain tunneling (...) down the uneven corridors of consciousness. A concretion of otoliths muffled your hearing, and fatigue burdened your ancient heart.Your name–band encircled your skinny ankle like a bird. Deformed by arthritis, you were caged within yourself, imprisoned by senescence. You could not declare yourself to us. Words disintegrated into moans and your grimace became animal.When you came back from x–ray—hypotensive with multiple neck fractures confirmed—you could speak no more. Your pulse slowed, your blood pressure plummeted. I jammed a gloved finger against your femoral pulse, faint and tired. [End Page E5]“What’s her DNR status?” I gravely asked your nurse.The DNR paperwork for once had arrived with the patient. “No CPR” she said with relief. But then the paperwork went on, forcing me—the waitress of tragedy—to serve up the hash of an impossible menu.As health care providers, we are all often tasked with performing contradictory actions: the pain of IV insertion followed by the morphine push, drilling deeper into broken bone in order to plate it, the inadvertent cracking of ribs during chest compressions. We sometimes must perform violent action in the hope of sustaining and resurrecting life. We are asked to perform the impossible, the contradictory, the painful. And sometimes the actions we must take catalyze an inexorable chain reaction of actions, which can end in death–prolonging and painful interventions that we did not intend.Although our culture may imagine that one can choose one’s meal at the end–of–life fast–food franchise of death, such is not the case. You can’t suddenly decide you’re a vegetarian. You can’t order the cheeseburger without the cheese—and we all are getting the burger, in the end. Ordering the heart–squeezing drugs without the CPR to circulate them, or the antibiotics without the fluid to counter dehydration, is like ordering the burger without the bun. Sometimes the possible choices are not necessarily realistic choices. You get served what you get served, and perhaps we should question the assumption that we have the ability to choose at all.Your DNR form proclaimed no CPR but then said that antibiotics and intubation were okay—the cheeseburger without the cheese. An unfortunate choice for you, me, and the rest of us, as your death menu led to a very unhappy meal.You were comatose. I stuck a tongue blade deep into your desiccated throat. You did not gag. This means I should have intubated you, but morally, I couldn’t. To what end? You were 98 years old, broken, moribund. If you hadn’t suffered multiple neck fractures, or if you were a vibrant elder who had just walked off Mt. Rainier, maybe the story would have been different. But you? I doubted that you truly had a chance of ever feeling joy again. You were somebody’s wife, somebody’s mother. I knew this step would lead to the domino of unstoppable steps. I refused to flog your corpse.I called your daughter Kay on her cell phone, told her that you were in critical condition and that she should come to the ER immediately. But how to begin to tell a daughter her mother is dying, let alone over a cell phone? Gentle but surreal and impersonal, my voice tried to tell your daughter that the interventions you needed would likely kill you. I have seen enough human suffering to know. To me, the choices were clear: death by nature’s irrefutable course, versus a more painful, protracted, and violent death by what we’d do to you.Kay arrived in a wheelchair and scooted up to your bedside. Like all daughters, she wasn’t ready for you... (shrink)

“There's a new whistleblower in Washington,” according to CNN News. He is Food and Drug Administration scientist David Graham, who claims that the FDA failed to warn the public about certain drugs' dangerous side effects and pressured him to change his research's conclusion that the arthritis drug Vioxx caused heart attacks. Another Washington whistleblower, Dr. Jonathan Fishbein of the National Institutes of Health, alleged that he was fired because “he had raised concerns about sloppy practices that might endanger patient (...) safety” in a study of the AIDS drug nevirapine.Graham and Fishbein thus joined the ranks of whistleblowers who have gained some prominence in recent years for their reporting of corporate or institutional misconduct. The best-known whistleblowers—the FBI's Coleen Rowley, Enron's Sherron Watkins, and WorldCom's Cynthia Cooper, who together received Time magazine's Whistleblower Person of the Year Award in 20024 - focused public attention on the reform of corporate accounting and legal practices. (shrink)

This paper draws on findings from interviews with people donating blood for a large epidemiological study of psoriatic arthritis concerned with identifying the genetic component in the aetiology of this disease. The 27 qualitative research interviews addressed peoples' reasons for agreeing to be involved in the biomedical research project, their hopes and expectations in relation to the study, and their views about the donation of a blood sample for the genetic element of the research. The involvement of these research (...) subjects can be characterized in terms of an investment in the future health of an imagined community, in which the NHS featured prominently. (shrink)

In December 1998, two groups of scientists announced that they had successfully isolated and cultured human pluripotent stem cells. This news was greeted with both tremendous enthusiasm and concern. Because these cells can develop into most types of cells or tissues in the human body, they hold great promise for scientific research and medical advances. For example, stem cells can potentially be used to:Generate cells and tissues for transplantation and therapy for conditions such as Parkinson’s disease, spinal cord injury, stroke, (...) burns, heart disease, diabetes, and arthritis;Improve scientists’ understanding of the complex events that occur during normal human development, as well as the abnormal events which cause conditions such as birth defects and cancer; andSubstantially change the development and testing of drugs. New medications could be tested initially on stem cells, and only drugs which were safe and effective on the cells would be tested further on laboratory animals and humans. (shrink)

This study appeared in full in the last issue of Research Ethics Review (2007; 3 (2): 53). John Harris is investigating the effectiveness of a new regime for the treatment rheumatoid arthritis. His role involves asking patients to fill out a questionnaire that normally takes about 35 minutes to complete. The case study outlines three events: a patient whose eyesight is poor, another who cannot read and a receptionist who is discovered reading some of the completed questionnaires.

Autoimmune diseases such as rheumatoid arthritis and gastrointestinal disorders such as stomach ulcers are often treated with drugs. NSAIDs, a common treatment in rheumatoid arthritis, may cause stomach ulcers which call for additional medications, notably antacids in the sense of drugs that suppress acid secretion by the stomach. Infection with Helicobacter pylori also plays a role in the ulcers. The infection is typically treated with antibiotics added to antacids. Considering NSAIDs and antacids, we suspect that overmedication is common (...) to the extent that particular diets are a better option. Current research and current treatments with these drugs are also problematic since circadian rhythms are mostly disregarded. All the processes involved in the disorders treated show marked variations in the course of the day. Hence experiments conforming to the guidelines of evidence-based medicine, and treatments in line with them, have outcomes strongly depending on the time factor. This calls for reforms in medicine with fresh inputs from biology. (shrink)

Autoimmune diseases such as rheumatoid arthritis and gastrointestinal disorders such as stomach ulcers are often treated with drugs. NSAIDs, a common treatment in rheumatoid arthritis, may cause stomach ulcers which call for additional medications, notably antacids in the sense of drugs that suppress acid secretion by the stomach. Infection with Helicobacter pylori also plays a role in the ulcers. The infection is typically treated with antibiotics added to antacids. Considering NSAIDs and antacids, we suspect that overmedication is common (...) to the extent that particular diets are a better option. Current research and current treatments with these drugs are also problematic since circadian rhythms are mostly disregarded. All the processes involved in the disorders treated show marked variations in the course of the day. Hence experiments conforming to the guidelines of evidence-based medicine, and treatments in line with them, have outcomes strongly depending on the time factor. This calls for reforms in medicine with fresh inputs from biology. (shrink)

We are living through a demographic transition from a world in which there were lots of young people and very few older adults to one in which the numbers in these age groups are becoming more evenly balanced. One reason for this is that more of us are living into our seventies, eighties, nineties, and beyond. That is the good news. Unfortunately, the chance of developing chronic illnesses (including diabetes, arthritis, and dementia) is typically higher for people in these (...) older age groups than for those who are younger. Because we do not know how to cure these illnesses, many of us will spend at least some of this extra time with one or more chronic illness. While we are more likely than in the past to live into older age, we are likely to be living with illness when we get there. That raises a challenge: how should we respond to this change? (shrink)

Surgical clinical trials have seldom used a "sham" or placebo surgical procedure as a control, owing to ethical concerns. Recently, several ethical commentators have argued that sham surgery is either inherently or presumptively unethical. In this article I contend that these arguments are mistaken and that there are no sound ethical reasons for an absolute prohibition of sham surgery in clinical trials. Reflecting on three cases of sham surgery, especially on the recently reported results of a sham-controlled trial of arthroscopic (...) surgery for arthritis of the knee, I present an ethical analysis that focuses on the methodological rationale for use of sham surgery, risk-benefit assessment, and informed consent. (shrink)

Philosophy traditionally deals with such lexicalized concepts as WISDOM, VIRTUE, REASON, WORLD VIEW, INFINITE UNIVERSE, and PHILOSOPHY. They trigger interest in philosophy, particularly because they are difficult to understand and explain. It is all the more surprising that many contemporary philosophers focus on such concepts as DOG, CHAIR, and FLIGHT to build their theories and provide examples. The article argues that to preserve topical equilibrium and avoid methodological problems, both classes of concepts should be involved in philosophical theorization and exemplification. (...) The first part critically discusses attempts at identifying these classes as ordinary vs. big (Gauker), empirical vs. pure (Kant), and concrete vs. abstract (contemporary psycholinguistics). It introduces the opposite pair simple empirical vs. complex demanding concepts as an alternative heuristic tool to evaluate concepts. The second part elaborates on the concept of concept and structural similarities between the two classes of concepts in semantic and ‘onomantic’ perspectives. The third part shows that despite structural similarities, such factors as the availability of empirical data, identification of the referent, historical and theoretical loadedness, complexity, and demandingness indicate that simple empirical and complex demanding concepts should be addressed in different ways. The final part elaborates on the notion of topical equilibrium as a philosophical method and norm and discusses two further examples (COW and ARTHRITIS) from contemporary debates in conceptual engineering. (shrink)

This book covers lymphoproliferative disorders in patients with congenital or acquired immunodeficiencies. Acquired immunodeficiencies are caused by infections with the human immunodeficiency virus or arise following immunosuppressive therapy administered after organ transplantation or to treat connective tissue diseases such as rheumatoid arthritis. It was recently discovered that various diseases or therapeutic modalities that induce a state of immunosuppression may cause virally driven lymphoproliferations. This book summarizes for the first time this group of immunodeficiency-associated lymphoproliferations.

Introduction: Globally, vitamin D deficiency is one of the most common deficiencies, affecting nearly half the world's population. The objective of this survey was to assess and compare the knowledge about vitamin D and the perceived state of health in Emirati and international tourist female students in Dubai, UAE. Methods: This is a cross-sectional study that took place in universities in Dubai, UAE. This survey consisted of 17 multiple choice questions. The first part of the survey assessed levels of supplementation, (...) diet and UV exposure. Another section evaluated the participants’ self-assessed state of health regarding vitamin D testing, symptoms related to vitamin D deficiency and general welbeing. The collected data were statistically analyzed using SPSS statistics for windows version 26.0 (SPSS Inc., Chicago, IL). Statistical significance was set at P<0.05. Results: 105 respondents were Emiratis and 65 were international students. The average age was 21, with an average BMI 23.3. Almost one-third of each group reported using Vitamin D supplements once weekly. The majority of both groups reported rarely getting tanned. Almost all participants reported regular consumption of Vitamin-D rich foods. In both groups, more than half reported consuming milk and cheese regularly and up to one-third reported consuming fish in a regular manner. Although more than half of the students rated their health as good; more than two-thirds reported experiencing muscle pain; only half reported having their blood Vitamin D levels measured once; half reported experiencing problems with concentration and more than three-quarters reported experiencing bad mood in the past month. The prevalence of these symptoms was almost similar across different categories of vitamin D supplementation, tanning habits, dietary intake, or nationality. No statistically significant differences were noted between the 2 groups. Conclusion: more Emirati students were aware of the association between vitamin D and osteoporosis than International tourist students (40% vs. 21.9%, respectively; p<0.05). On the other hand, both groups had lower knowledge about the relationship between vitamin D deficiency and depression, Rheumatoid Arthritis and Hypertension, and the optimal vitamin D level; however, no statistically significant differences were noted regarding this knowledge of Emiratis and international students. (shrink)

Two types of interleukin 1 (IL‐1α and IL‐1β) have been defined by purifying the molecules from activated human peripheral blood cells, followed by cloning and expressing the molecules in Escherichia coli. Both types of IL‐1 stimulate proliferation and differentiation of T‐ and B‐lymphocytes and induce cartilage proteoglycan degradation but differ in other properties. For example, demineralization and appears to be a major mediator in the pathogenesis of joint erosion in rheumatoid arthritis. Synthetic adjuvants elicit the production of IL‐1 separate (...) from endogenous pyrogen, and this property is required for the new generation of vaccines based on antigens produced by recombinant DNA technology. (shrink)

Dr. M is a fifty-nine-year-old internist with a successful practice in a major Eastern United States city. He has lived in this city his whole life and is a highly esteemed citizen. Because of his broader social concerns and energetic support of activities to improve access to health care and quality of care for the underserved, Dr. M became involved in a number of local and regional medical organizations and quickly rose to prominence as as a director of a board (...) of a major national organization. In this position, he was an effective, articulate spokesperson, highly respected for his integrity and thoughtfulness.Before one of the meetings of thithis s board, Dr. M personally contacted the organization's other directors, including me, to warn us that we might be hearing some scandalous news about him. He wanted us first to hear it from him personally. This was the scandalous news.Dr. M had assumed the care of a patient of a recently retired colleague. The patient was an older woman with multiple musculoskeletal complaints related to lumbar stenosis and advanced degenerative arthritis of the spine, which left her in immense pain. (shrink)

In 2006, Bill Crain was a psychology professor and his wife, Ellen, a pediatrician. They purchased a run-down farm in upstate New York, and two years later opened Safe Haven Farm Sanctuary. It is now home to over 170 animals rescued from slaughter. In Animal Stories, Bill writes about how he and Ellen decided to start the sanctuary and tells the stories of 25 animals and their many surprising behaviors. Read about Katie, a hen who cared for a little partridge; (...) Cesar, a little goat who constantly gets into trouble; Reggie, a rooster who instilled fear in all the staff; Milo, a goat who suddenly charged the dominant Duncan to defend his mother; four rambunctious young turkeys who quietly listened to a reverent Girl Scout ceremony; Ducky, a turkey who, despite severe arthritis, walked from her barn to greet a Buddhist monk; Ethel, an elderly cow who assumes the responsibility of a matriarch; and many others. In addition to enjoying the stories, readers will learn a great deal about nonhuman animals. (shrink)

Human B cell stimulatory factor 2 (originally designated BSF2) was initially characterized and isolated as a T cell‐derived factor that caused the terminal maturation of activated B cells to immunoglobulin producing cells. Molecular cloning of the cDNA has revealed that BSF2 is identical with 26 kD protein, interferon β2, plasmacytoma growth factor and hepatocyte stimulating factor and the designation “IL‐6” has been proposed for this molecule. It is now known that BSF2/IL‐6 has a wide variety of biological functions and that (...) abnormal regulation of BSF2/IL‐6 expression may be related to the pathogenesis of certain autoimmune diseases such as rheumatoid arthritis and multiple myeloma. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:I Am Not Sure?Paul E. LevinIt was a beautiful Friday morning, a few weeks into the summer. My schedule appeared lighter than usual and I even envisioned leaving work a bit early. Maybe a challenging bike ride before dinner. I was sitting in the chairman’s office having our weekly meeting. One of our junior faculty members called... he needed help. He was on call and a 32–year–old pregnant woman (...) with a displaced femoral neck fracture had just been transferred to our emergency department (ED). Ms. B tripped in her kitchen last evening. She was unable to stand and was brought to the local ED by ambulance.My colleague was concerned that he wouldn’t be able to successfully reduce the fracture. The long–term prognosis of the hip joint depended on a successful reduction of the femoral neck fracture. In addition, there was an ongoing debate in the orthopaedic literature related to the urgency of operative care to prevent osteonecrosis of the femoral head. I reviewed the x–rays, didn’t anticipate a problem and let him know that I would come to the operating room (OR) to assist. “No”, he responded, “I am not comfortable caring for this patient”. I immediately left the office, went to the hospital and assumed care of the patient. Clearly, my plans for a bike ride were gone, but I had the opportunity to help a woman in need of expert orthopaedic care.Ms. B had been admitted to the obstetrical service. She was a 32–year–old woman of Haitian descent who had recently immigrated to the United States. She had very limited English comprehension and her primary spoken languages were French and Creole. She was alone, in a hospital in a foreign country. She was 24 weeks pregnant with her first child and had no other co–morbidities. Her pregnancy had ben progressing uneventfully.When I first met Ms. B she was lying on a stretcher in an observation unit on the obstetrical floor. She appeared frightened. Two orthopaedic residents were present and obtaining consent for surgical repair of the hip. In their minds there was nothing to discuss, the patient had a displaced femoral neck fracture and needed to have surgery immediately. In their minds, no other options were available and obtaining consent would be straightforward. I introduced myself, sat down on a lab stool by the bed and began a conversation. I needed to meet the patient, understand who she was and discuss treatment. I am not sure that obtaining an informed consent is ever “straightforward” when [End Page 14] a doctor is explaining to a patient that they require emergency surgery. This discussion surely would not be easy or straightforward.We utilized a telephone interpretation service. Every question and response required the transfer of the handset between the patient and physician. Ms. B was in pain and frightened. She immediately expressed concern about her pregnancy and her baby. I arranged for her to meet all of the physicians who would possibly be involved in her care and the care of her baby. Each consultant could explain their area of expertise and potential involvement in the care of Ms. B and her child. She met and had an opportunity to talk with the obstetrician on call, a maternal fetal medicine (MFM) fellow and a neonatologist. I supplied the orthopaedic information. I explained the severity of the injury, the risks of osteonecrosis either with or without surgery as well as concerns over non–union and traumatic arthritis of the hip. Undoubtedly, in a healthy 32–year–old woman who wasn’t pregnant, early surgical intervention would be the most appropriate management in hopes of preserving a normal hip joint. We also discussed the possibility of treating her without surgery. She would be administered pain medication, which were known to be safe during pregnancy, and allowed to begin to ambulate with a walker or crutches. I explained potential problems without surgery and what options would be available to treat any problems that developed with her hip after the child was born. Of course, hip fractures in pregnant woman are very rare, and as a result treating a... (shrink)