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Background The What Matters Most (WMM) study was initiated to evaluate symptoms, AD-related impacts, treatment-related needs, preferences, and priorities among individuals with or at risk for Alzheimer’s disease (AD) and their care partners. The objective of this qualitative study phase was to identify a comprehensive set of concepts of interest that are meaningful to individuals across the AD continuum. Methods Interviews were conducted with 60 clinically referred individuals and care partners across 5 AD stages (n = 12 each): group 1 (non-clinically impaired individuals with AD pathology), group 2 (individuals with mild cognitive impairment and AD pathology), group 3 (individuals with mild AD), group 4 (individuals with moderate AD and their care partners), and group 5 (care partners of individuals with severe AD). Interviews were conducted by experienced interviewers, audio-recorded, and transcribed. Dominant trends were identified in each interview and compared across subsequent interviews to generate themes or patterns in descriptions of AD symptoms, impacts, and desired treatment outcomes. Results All participants endorsed current issues related to memory; nearly all participants (n = 55; 92%) across the five groups endorsed symptoms related to communication and language. Groups 1–3 reported an impact on mood/emotions (n = 23; 64%) and a decrease in social activities or outgoingness (n = 17; 47%). Current and future concerns reported by the overall sample included memory (n = 48; 80%), dependence (n = 40; 67%), and “other” concerns (n = 33; 55.0%) (e.g., uncertainty about the future, burdening others). The most desired AD treatment outcomes were improvement or restoration of memory (n = 40; 67%) and stopping AD progression (n = 35; 58.3%). Group-level differences were observed in the symptoms, impacts, and desired treatment outcomes among patients and care partners across the AD continuum. Conclusions Cognitive functioning issues—particularly in memory and communication—are present even in preclinical and early-stage AD, including among those without a formal AD diagnosis. While the impacts of AD vary across the disease-severity spectrum, improved memory and disease modification were treatment outcomes considered most important to participants across all 5 AD stages. Neuropsychological assessments traditionally used in AD clinical trials may not evaluate the often-subtle concepts that are important to patients and care partners. Results from this study will inform the second phase of the WMM project—a quantitative study to elicit the relative importance of these concepts of interest to people at risk for and living with AD and their care partners.

Objective.To develop a fibromyalgia (FM) survey questionnaire for epidemiologic and clinical studies using a modification of the 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia (ACR 2010). We also created a new FM symptom scale to further characterize FM severity.Methods.The ACR 2010 consists of 2 scales, the Widespread Pain Index (WPI) and the Symptom Severity (SS) scale. We modified these ACR 2010 criteria by eliminating the physician’s estimate of the extent of somatic symptoms and substituting the sum of 3 specific self-reported symptoms. We also created a 0–31 FM Symptom scale (FS) by adding the WPI to the modified SS scale. We administered the questionnaire to 729 patients previously diagnosed with FM, 845 with osteoarthritis (OA) or with other noninflammatory rheumatic conditions, 439 with systemic lupus erythematosus (SLE), and 5210 with rheumatoid arthritis (RA).Results.The modified ACR 2010 criteria were satisfied by 60% with a prior diagnosis of FM, 21.1% with RA, 16.8% with OA, and 36.7% with SLE. The criteria properly identified diagnostic groups based on FM severity variables. An FS score ≥ 13 best separated criteria+ and criteria− patients, classifying 93.0% correctly, with a sensitivity of 96.6% and a specificity of 91.8% in the study population.Conclusion.A modification to the ACR 2010 criteria will allow their use in epidemiologic and clinical studies without the requirement for an examiner. The criteria are simple to use and administer, but they are not to be used for self-diagnosis. The FS may have wide utility beyond the bounds of FM, including substitution for widespread pain in epidemiological studies.

Objective To assess the performance of a generic health-related quality of life (HRQOL) measure in a rheumatology clinic population. Methods Participants (n = 619) with fibromyalgia, rheumatoid arthritis, or osteoarthritis receiving care from rheumatologists completed mailed questionnaires that included the Behavioral Risk Factor Surveillance System (BRFSS) HRQOL measure and condition-specific measures assessing disability, pain, fatigue, and helplessness. The BRFSS assesses global health and number of days in the past 30 of poor physical or mental health or activity limitation. The overall sample was described, followed by comparison of adjusted scores on all HRQOL measures by diagnosis. Results Participants reported mild difficulty with activities of daily living, marked pain and fatigue, and moderate helplessness. Participants reported a mean of 8 or more days out of 30 of poor physical and mental health and activity limitations; more than 40% reported poor or fair health. Participants with fibromyalgia reported more ill health on condition-specific measures and the BRFSS HRQOL measures than did participants with osteoarthritis or rheumatoid arthritis. Conclusion The BRFSS HRQOL measure is a brief, easily administered, generic health indicator that shows differences among rheumatic disease diagnoses.

Fibromyalgia and other chronic pain and fatigue syndromes constitute an increasingly greater societal burden that currently is not being approached effectively by traditional Western medicine. Although the hallmarks of fibromyalgia--chronic widespread pain, fatigue, and multiple other somatic symptoms--have neurophysiologic and endocrinologic underpinnings, these biological aspects derive primarily from psychological variables. Female gender, adverse experiences during childhood, psychological vulnerability to stress, and a stressful, often frightening environment and culture are important antecedents of fibromyalgia. To understand fibromyalgia and related syndromes and to provide optimum care requires a biopsychosocial, not a biomedical, viewpoint.

Objective. To determine the specificity of anti-CD45 autoantibodies in systemic lupus erythematosus (SLE) for native CD45 and for CD45 expressed by T cells and B cells, and at different stages of cellular activation. Methods. CD45 purified from different types of lymphocytes was examined by immunoblotting with sera from patients with SLE. Indirect immunofluorescence experiments were performed with purified anti-CD45 autoantibodies. Results. IgM anti-CD45 autoantibodies in SLE recognize native CD45 expressed on the surface membrane of viable lymphocytes and CD45 purified from activated peripheral T cells and certain T cell lines, but not CD45 purified from B cells or resting peripheral T cells. The presence or absence of reactivity is independent of the individual isoforms expressed. Conclusion. Recognition of CD45 by IgM antilymphocyte autoantibodies in SLE varies with the lineage and state of activation of the lymphocyte target. This pattern of reactivity is consistent with autoantibody specificities involving CD45 glycoforms, rather than CD45 isoforms.

Objective To develop simple, practical criteria for clinical diagnosis of fibromyalgia that are suitable for use in primary and specialty care and that do not require a tender point examination, and to provide a severity scale for characteristic fibromyalgia symptoms. Methods We performed a multicenter study of 829 previously diagnosed fibromyalgia patients and controls using physician physical and interview examinations, including a widespread pain index (WPI), a measure of the number of painful body regions. Random forest and recursive partitioning analyses were used to guide the development of a case definition of fibromyalgia, to develop criteria, and to construct a symptom severity (SS) scale. Results Approximately 25% of fibromyalgia patients did not satisfy the American College of Rheumatology (ACR) 1990 classification criteria at the time of the study. The most important diagnostic variables were WPI and categorical scales for cognitive symptoms, unrefreshed sleep, fatigue, and number of somatic symptoms. The categorical scales were summed to create an SS scale. We combined the SS scale and the WPI to recommend a new case definition of fibromyalgia: (WPI > or =7 AND SS > or =5) OR (WPI 3-6 AND SS > or =9). Conclusion This simple clinical case definition of fibromyalgia correctly classifies 88.1% of cases classified by the ACR classification criteria, and does not require a physical or tender point examination. The SS scale enables assessment of fibromyalgia symptom severity in persons with current or previous fibromyalgia, and in those to whom the criteria have not been applied. It will be especially useful in the longitudinal evaluation of patients with marked symptom variability.

The fibromyalgia syndrome with its associated chronic pain and multiple painful tender points occurs in more than 25% of patients with systemic lupus erythematosus (SLE). Variables that contribute to pain sensitivity and other symptomatology in fibromyalgia include female gender, poor sleep, deconditioning, a variety of psychological elements, negative beliefs and attributions, and loss of control. Adverse childhood experiences, especially sexual abuse, contribute to vulnerability to chronic, unrelieved stress and psychological distress as adults. Psychological stress in turn leads to dysregulation of the hypothalamic-pituitaryadrenocortical (HPA) axis, the autonomic nervous system, and central nociceptive processing. Proinflammatory cytokines are important mediators, both centrally and peripherally, of fatigue, poor sleep, musculoskeletal pain, and “sickness” in fibromyalgia and SLE. Although the psychological stress and distress that accompanies comorbid fibromyalgia in SLE negatively influences functional impairment and quality of life, and contributes importantly to fatigue and cognitive impairment, the available evidence does not support a role in flares of SLE disease activity or in major organ system injury over time. Optimum clinical assessment and therapy of SLE requires recognition of the contribution of fibromyalgia to overall morbidity in SLE. © 2003, Elsevier Science (USA).

Just as our caveman forebears were frail in the face of predatory animals, we are frail in today's society of childhood neglect or abuse, bumper-to-bumper traffic, frustration at work, and multiple daily hassles. The same neuroendocrine systems and pain regulatory mechanisms that protected early man during acute stress are still encoded in our genome, but may be maladaptive in psychologically and physiologically vulnerable people faced with chronic stress. Many patients with fibromyalgia become vulnerable because of the long-lasting psychological and neurophysiological effects of negative experiences in childhood. Ill-equipped with positive cognitive, emotional, and behavioral skills as adults, they display maladaptive coping strategies, low self-efficacy, and negative mood when confronted with the inevitable stressors of life. Psychological distress ensues, which reduces thresholds for pain perception and tolerance (already relatively low in women) even further. Converging lines of psychological and neurobiological evidence strongly suggest that chronic stress-related blunting of the HPA, sympathetic, and other axes of the stress response together with associated alterations in pain regulatory mechanisms may finally explain the pain and fatigue of fibromyalgia. Vulnerable people who can be classified by the ACR criteria as having fibromyalgia do not have a discrete disease. They are simply the most ill in a continuum of distress, chronic pain, and painful tender points in the general population.

Autoantibodies to surface antigens on lymphocytes and other cells of the immune system may contribute to the development of immunoregulatory and other cellular immune abnormalities in patients with active systemic lupus erythematosus. Of special interest in this respect are autoantibodies to CD45 (leukocyte-common antigen, T200), a plasma membrane protein tyrosine phosphatase implicated in the regulation of lymphocyte functional activity, including cytotoxicity, proliferation, and differentiation.

Unselected sera from patients with various rheumatic, inflammatory bowel, and autoimmune skin diseases (n = 268) were examined against human cell lysate by immunoblotting procedures, to determine the prevalence of autoantibodies to stress proteins (heat-shock proteins) hsp60 (homolog of Escherichia coli groEL and mycobacterial 65K antigens), hsp73, and hsp90. Using standard, sensitive and specific assay conditions, IgG and IgM autoantibodies to these stress proteins were not demonstrable, or were detected infrequently, in sera from control subjects (n = 36) and from patients with rheumatoid arthritis, Sjögren's syndrome, ankylosing spondylitis, Reiter's syndrome, systemic lupus erythematosus, and systemic sclerosis. Autoantibodies to hsp60 were relatively more common (greater than or equal to 20% of sera) in patients with mixed connective tissue disease, polymyositis/dermatomyositis, psoriatic arthritis, inflammatory bowel disease, epidermolysis bullosa acquisita, and bullous pemphigoid. Anti-hsp73 autoantibodies were detected in 20% or more of the sera from patients with Lyme disease and ulcerative colitis. Taken together, these data extend the spectrum of autoimmune and inflammatory diseases in which humoral anti-stress protein autoreactivity develops. However, the paucity of humoral autoreactivity to stress proteins in patients with systemic lupus erythematosus and rheumatoid arthritis argues against a direct role of anti-stress protein autoantibodies in the pathogenesis of these disorders.

The clinical and serologic characteristics of 17 patients with onset of systemic lupus erythematosus (SLE) after age 50 were compared with those of 49 younger patients. All patients were followed prospectively for a mean duration of 47 months. A clinical and serological data base was established for each patient, and information collected at each visit to a lupus clinic was analyzed by computer. The clinical featured distinguishing old-age SLE were a low incidence of significant renal disease and prominent pleuropericarditis and arthritis throughout the period of followup. Serologic abnormalities were milder in older patients. Thus, hypocomplementemia, anti-DNA antibodies, and C1q precipitins occurred less frequently, and rheumatoid factor was more often present than in younger patients with SLE. Regression analysis suggested linear change in disease expression with age rather than distinct age-related subgroups.

Circulating T cells bearing receptors for the Fc portion of IgG (T gamma) were identified by sensitive immunofluorescent techniques with rabbit IgG b4 allotype/anti-b4 complexes. A twofold decrease in both proportion and absolute number of T gamma cells was found in patients with active systemic lupus erythematosus (SLE) relative to values obtained during disease remission. The reduction in T gamma cells was most evident in patients with severe hypocomplementemia. A deficit of T gamma cells in active patients was not demonstrated. The percentage of total T cells rosetting with sheep erythrocytes was reduced in peripheral blood of most patients regardless of disease activity status, but particularly during SLE exacerbation. Cells lacking intrinsic surface immunoglobulin, IgG Fc receptors, and receptors for sheep erythrocytes were increased. These cells, operationally termed null, exhibited an inverse linear relationship with T cells that was not apparent in regression analyses performed against other lymphocyte subpopulations. Such differences were not found for B cells and IgG receptor-bearing non-B/non-T cells which were present in normal proportions in virtually all patients. The origin and functional significance of these unusual lymphocyte subpopulation abnormalities are discussed.

SummaryIn systemic lupus erythematosus (SLE) three populations of blood mononuclear cells from patients with systemic lupus erythematosus (SLE) and from normal controls were examined for their responses to graded concentrations of phytohemagglutinin (PHA). In normal controls, H3 thymidine uptake of unfractionated cells (FH) was greater than that of T cells (Fab Col). In contrast, SLE Fab Col cells responded better than FH cells in 44% of patients tested. SLE mononuclear cells devoid of adherent monocytes (NRIg) also responded better than FH cells.The results indicate that hyporesponsiveness to PHA seen in some SLE patients is moderated by an adherent cell which may be functioning as a suppressor cell.

Members of the American Rheumatism Association (ARA) were surveyed to determine their views on the content and quality of their annual meeting. Responses were received from 1,208 members. ARA members were generally positive about the major components of the annual meeting program, but there were significant differences in opinion between practitioners and academicians. Practitioners favored a reduction in basic science material and an increase in didactic clinical sessions. Academicians were more likely to feel that recent annual meetings have adequately addressed their educational needs. These findings have implications for the planning of future annual meetings of the ARA.

In a prospective study 26 of 29 patients with systemic lupus erythematosus had cold-reactive antilymphocyte antibodies cytotoxic for autologous lymphocytes and lymphocytes from normal subjects. The level of antilymphocyte antibodies was highly correlated, by linear regression analysis, with lymphopenia in these patients. The data suggested that both the avidity and the concentration of these antibodies were important determinants in this relationship. A clear association between increased antilymphocyte antibody activity and exacerbation of SLE was demonstrated. Apart from lymphopenia, however, neither type of clinical manifestation nor any particular serologic abnormality appeared to be related to the presence of antilymphocyte antibodies.

Using indirect immunofluorescence and flow cytometry, we determined the proportion and number of T3+, T4+, and T8+ cells in the peripheral blood of patients with systemic lupus erythematosus whose sera were positive for cold-reactive antilymphocyte antibodies versus values in patients whose sera were negative for these antibodies. There was a disproportionate reduction in T4+ peripheral lymphocytes when cold-reactive antilymphocyte antibodies preferentially cytotoxic for this subpopulation were present in autologous serum. The decrease in this subset was responsible for a reduction in the T4:T8 ratio; variation in the number and proportion of T8+ cells was insignificant. A similar, but autoantibody-independent, alteration in the T4+ subpopulation was found in patients who were receiving prednisone therapy. A relationship between T cell population abnormalities and systemic lupus erythematosus disease activity, per se, was not observed.

The influence of genetic and nongenetic factors on abnormalities of the immune response in systemic lupus erythematosus (SLE) was studied in 9 sets of twins in which one or both twins had SLE. Particular emphasis was placed on contrasting the results between the sibs of 3 monozygotic pairs discordant for clinical SLE. Depression of cell-mediated immunity, determined by lymphocyte blastogenic response to mitogens, was associated with the clinical expression of illness. In contrast, autoreactive antilymphocyte antibodies and lymphocyte tubuloreticular structures were found in both clinically affected and unaffected subjects and were more prominently associated with the presence of other serologic abnormalities. No evidence of antigens or cell surfaces determinants unique to affected sibs was encountered.

Antilymphocyte antibodies in serum from patients with systemic lupus erythematosus (SLE), as detected by microcytotoxicity and indirect immunofluorescence, were predominantly cold reactive and of the IgM class. These IgM antibodies were most active at 4 degrees C. IgG antibodies were infrequent, and were only minimally lymphocytotoxic. Most sera were cytotoxic for autologous lymphocytes and were equally reactive with normal and SLE lymphocytes, as well as with B- and T-cell preparations. Separate T- and B-cell specificities, which appeared not to be related to HL-A determinants, were identified by differential absorption experiments. The functional significance of these antilymphocyte antibodies is discussed.

Stress proteins have been highly conserved during evolution not only because of their fundamental importance in the response of the cell to stressful assaults, but also because they have critical roles in cellular activation and cell growth, regulation of protein function, protein transport, and protein assembly. Research focusing on the basic cell biology of stress proteins is intense at present, and will surely continue to be for some time to come. Of particular interest to immunologists and rheumatologists is the convergence of data in several fields that suggest that stress proteins in microorganisms that commonly infect humans may be triggers of humoral and cellular autoimmune responses and consequent overt autoimmune disease expression. Thus, stress proteins of M tuberculosis and other bacteria are close homologs of stress proteins in mammals, and may be involved in the pathogenesis of adjuvant-induced arthritis in rats and, possibly, of RA and reactive arthritis in humans. A great deal of work remains to be done in this area, including (a) generation and propagation of specifically reactive T cell clones, (b) molecular delineation of the immune recognition elements and critical epitopes shared by microbial stress proteins and host proteins, (c) definition of the relative contribution of alpha beta and gamma delta TCRs to T cell reactivity to stress proteins, and (d) clarification of the circumstances that enable persistent T cell autoreactivity to stress proteins. The data at hand are sufficiently compelling, however, to suggest that vaccination against T cells that recognize stress proteins may eventually become part of our therapeutic armamentarium to prevent or cure some forms of arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)

SUMMARY Patients with systemic lupus erythematosus frequently develop antilymphocyte antibodies as measured by complement-dependent cytotoxicity and immunofluorescence assays. Highest titres of both of the major IgM and IgG classes occur during phases of active disease, and their presence is associated with essentially the entire spectrum of immune system functional abnormalities in this disorder. While the full range of antibody specificities requires further clarification, antibodies to many discrete lymphocyte populations have been described, including B cells, T cells, and T cell subsets. Antibodies to T cell subsets are of special interest because of their relationship with subset depletion in vivo, and their capacity to reproduce, through effects on normal cells in vitro, the same types of immunoregulatory abnormalities characteristic of lymphocytes isolated from patients with SLE. Suppressor/inducer and suppressor/effector T cells appear to be the main targets in this regard. Antibodies specific for activated T lymphocytes exist as well, and this type has the unusual property of interfering with events operant in production of/response to interleukin-2, a critical step controlling the expansion of specifically-reactive T cells and the induction of other lymphokines. In addition to complement-mediated lysis and antibody-dependent cell-mediated cytotoxicity, anti-lymphocyte antibodies have the potential to influence immune system function by several non-cytotoxic mechanisms, including surface antigen modulation and ligand/receptor triggering. Despite the large amount of data which has been accumulated concerning the cell type specificity and functional effects of anti-lymphocyte antibodies in SLE, little is known about the nature of the surface membrane molecules with which they react. Application of cell cloning and molecular biology technology should rectify this deficiency in the near future. Although it is likely that antilymphocyte antibodies are of relevance to immune system pathophysiology in SLE, it remains to be determined whether these interesting antibodies reflect secondary events, or have some more fundamental significance.

Using the direct migration inhibition test, response to measles antigen in patients with systemic lupus erythematosus (SLE) was found to be decreased when compared with that of normal subjects. No alteration was observed in similar experiments using parainfluenza type 1 and rubella antigens. The specific decrease in measles antigen effect showed no obvious correlation with activity of SLE or with the presence of lymphocytotoxic antibodies. Whether the specificity of the decrease in reactivity is due to some particular relationship between the measles virus or antigen and SLE, or to the possibility that measles reactivity is a more sensitive indicator of a generalized defect of cell-mediated immunity, remains unclear.

For nearly a quarter-century, glomerulonephritis in systemic lupus erythematosus (SLE) has been the prototype of immune complex-mediated renal injury in man. Through investigation in many laboratories, most notably that of Dr. Henry Kunkel at The Rockefeller University, steady progress in our understanding has ensued. Certain important issues remain to be clarified. As a sign of sustained interest and vigor in this area, new observations continue to force changes in thinking about the mechanisms operant in this type of tissue injury. Therefore, it is appropriate to review briefly the lines of evidence which are important in the evolution of current concepts, and which may be relevant to interpretation of the experimental data obtained by immunochemical analysis of cryoprecipitates.

An autoimmune response to certain nuclear antigens frequently develops in patients receiving prolonged therapy with procainamide. In order to define events involved in the initiation of this immune response, patients with myocardial infarction were studied early after starting procainamide and at later times. Polynucleotide antibodies and circulating polynucleotide antigens were sought by sensitive assay techniques in the sera of these patients. Very high titers of antiribonucleoprotein developed selectively in the majority of these patients after short-term therapy with procainamide. Such antibodies were infrequent in the long-term therapy group, most of whose members exhibited anti-single-strand DNA and were symptomatic with overt procainamide-induced lupus. Patients with acute myocardial infarction who did not receive procainamide did not develop anti-polynucleotide antibodies, but rather had high levels of free ribonucleoprotein antigen in their serum. Various interpretations of these data are discussed.

Paired serum and cerebrospinal fluid specimens from 19 patients with SLE and central nervous system dysfunction were studied with respect to cerebrospinal fluid IgG index (a measure of intrathecal IgG synthesis), isoelectric focusing using immunoperoxidase staining techniques to detect oligoclonal IgG, and determination of the cerebrospinal fluid/serum albumin quotient (Q albumin) as a measure of blood-brain barrier integrity. Twenty-five patients without neurologic disease and 70 patients with a variety of non-SLE neurologic disorders were also studied for comparison. Of most interest was the observation that 42 percent of the patients with SLE had cerebrospinal fluid oligoclonal IgG, usually in association with elevation of the cerebrospinal fluid IgG index. In addition, two of the cerebrospinal fluid specimens that exhibited oligoclonal IgG also had increased titers of alpha-interferon. Q albumin was normal (under 9.0) in 12 of 13 patients with SLE, who had seizure, psychosis, or cranial neuropathy as principal central nervous system manifestations (mean +/- SD = 5.3 +/- 2.4), but was significantly elevated (mean +/- SD = 27.4 +/- 18.8, p less than 0.001) in five of six patients with diffuse, major central nervous system injury, for example, encephalopathy with coma, transverse myelopathy, paraparesis. Blood-brain barrier impairment was not correlated either with presence of circulating immune complexes or with other clinical or serologic evidence for extra-central nervous system disease activity. Taken together, the data suggest that, within the limitations of the techniques used, impairment of the blood-brain barrier in SLE may be secondary to the central nervous system lesion, rather than a result of systemic immune complex injury. In addition, substantial evidence is provided for an ongoing humoral immune response within the central nervous system in this disorder, which, in certain patients, may be associated with the production of intrathecal alpha-interferon.

Serologic studies were performed on 25 patients with systemic lupus erythematosus (SLE) during 29 acute episodes of central nervous system (CNS) disease. Increased anti-DNA antibody and decreased total serum hemolytic complement activity were observed only in those patients with associated extra-CNS disease manifestations. Patients with isolated CNS disease were otherwise in apparent clinical and serological remission regarding these two indices. No special association of cold-reactive IgM antilymphocyte antibodies was demonstrable in patients with ongoing CNS injury. Of special interest was an increased incidence of anti-Sm antibodies in the patients with CNS dysfunction relative to that in a large group of patients without neuropsychiatric disease. The incidence of anti-RNP was not increased. The data do not support direct involvement in SLE brain injury of either DNA/anti-DNA complexes or of lymphocytotoxic antibodies cross-reactive with brain cells, but do suggest an association of anti-Sm with CNS disease in this disorder.

Sera from 20 patients with systemic lupus erythematosus (SLE) and active central nervous system (CNS) dysfunction were examined by indirect immunofluorescence for antibodies to neuronal membrane determinants. Warm-reactive IgG antibodies were demonstrable in 82% (9/11) of patients with clinical evidence for seizures or diffuse CNS disease, but these antibodies generally were absent in non-CNS SLE sera or when focal neurologic deficit or psychosis was the primary CNS manifestation. Cold-reactive antibodies of the IgM class were equally prevalent in patients with or without CNS disease and appeared to be more directly correlated with extra-CNS systemic illness. Absorption experiments with lymphocytes, brain homogenate, and various other tissues suggested a predominant brain-specificity for IgG antibodies and partial lymphocyte cross-reactivity for IgM antibodies. Interpretations of this special association between IgG anti-brain antibodies and diffuse CNS dysfunction in SLE are discussed.

Neonatal rats born of and nursed by mothers immunized with Torpedo acetylcholine receptor protein developed a defect of neuromuscular transmission as indicated by reduced miniature endplate potential amplitudes. It is likely that antibodies to the Torpedo receptor protein were passively transferred to the neonates in the milk. With the exception of the route of transfer, this neonatal form of experimental autoimmune myasthenia gravis appears to be similar to its human counterpart, and thus can serve as an experimental model.

The Medical Research Education Subcommittee of the American Rheumatism Association surveyed a random selection of large and small programs in internal medicine and family practice residency programs in order to evaluate their rheumatology training. Formal rheumatology training is offered in 90% of these residency programs, but many available positions are not being filled. A full-time staff rheumatologist was present at 69% of large internal medicine programs, 32% of small internal medicine programs, and 11% of family practice programs. The methods of rheumatology training are similar in most programs, although small internal medicine programs and family practice programs more often utilize physicians' offices or outside medical centers for the rheumatology elective training. A majority of the directors of these residency programs thought that many basic skills and techniques were not taught adequately and that the training of their rheumatology residents was not equal to that of residents in cardiology or gastroenterology.

Six years ago, pentazocine (Talwin) was introduced as a potent, "nonaddicting" analgesic. With its increasing popularity clear evidence has emerged that pentazocine is in fact potentially addicting. 1 Swanson et al 2 recently described 30 hospitalized pentazocine abusers. As a group, these patients were medically sophisticated and had abused other addicting drugs before taking pentazocine, which usually was obtained by prescription and was self-administered parenterally. Nearly one half of the patients reported by Swanson et al 2 exhibited a peculiar, expansive, woody sclerosis of the skin and subcutaneous tissues around injection sites. These changes, originally described by Parks et al, 3 may become very extensive, with development of large, poorly healing ulcers extending to muscle. Additional features, which may allow the diagnosis to be suspected even before a history of pentazocine abuse is obtained, are a "halo of hyperpigmentation" around the ulcers and the lack of concern by the patient

A young woman ingested approximately 13 gm of an over-the-counter acetaminophen preparation and died seven days later in profound coma. Postmortem findings included massive centrilobular hepatic necrosis and renal tubular necrosis. Although hepatotoxicity secondary to acetaminophen overdose is well recognized in Britain, this entity has received little emphasis in the United States. Recognition of the potentially severe consequences is important because early treatment with sulfhydryl compounds may prevent serious liver injury. ( JAMA 236:1874-1875, 1976)

Large demonstrations, mass rallies of varying degrees of peacefulness ranging from quiet gatherings to violent confrontations, riots, and such "happenings" as rock music festivals must be recognized as common events in the United States today. Physicians must be prepared to care for these large numbers of people under conditions considerably more primitive than at conventional gatherings. Two kinds of medical problems arise from crowds of this magnitude—those routine medical problems that are statistically to be expected and those unique to the event, such as trauma, exposure, fatigue, poor sanitation, hunger, drug reactions, tear gas exposure, and psychiatric problems. A protocol for the delivery of medical care during civil disorders has been previously presented. 1 This paper describes the program of medical care organized by the Washington, DC, Chapter of the Medical Committee for Human Rights (MCHR) for the mass antiwar demonstrations of Nov 13, 14, and 15, 1969, in Washington