Natural human antibodies to synthetic peptide autoantigens: correlations with age and autoimmune disease.

Clinically healthy humans as well as patients suffering from various autoimmune diseases produce natural antibodies against a variety of self-components. Such antibodies have been proposed to carry out a physiologic role in maintaining the integrity of self, as well as potentially destructive roles in the generation of autoimmune diseases. Because human autoantigens, particularly membrane proteins, are usually present in extremely small amounts, it is generally impossible to obtain enough to carry out a detailed characterization of the antibodies or the antigenic determinants recognized. To circumvent this difficulty, we developed synthetic autoantigens predicted from the gene sequence of two functionally critical membrane proteins; the band 3 anion transport protein which is found on all cells, and the T-cell receptor (beta chain) which is the antigen-specific receptor on thymus-derived lymphocytes. We have investigated the natural human IgM and IgG antibody responses to peptides selected on the basis of predicted molecular surface exposure and previously known antigenicity, and correlate levels of binding with changes in age and by comparison with autoimmune diseases. We report that the IgM response to synthetic autoantigens tends to be higher than that of IgG molecules, but significant IgG binding occurs to some peptides. This situation is particularly noticeable in comparison of rheumatoid arthritis patients with normal individuals. Distinct peptide portions of individual molecules are recognized differently by the autochthonous immune system as manifested by age dependence of the response and differential levels of IgM and IgG activity. The synthetic autoantigens that tend to generate the highest amounts of natural antibody are those that are either exposed on the surface of the cell (band 3 peptides) or are exposed in the predicted 3-dimensional folding of the molecule (T-cell receptor beta peptides). Rheumatoid arthritis patients tend to give higher IgM reactivities to both band 3 and Tcr beta peptides than do normals, with this effect being less pronounced in the distinct autoimmune disease systemic lupus erythematosus. Studies of normal humans ranging in age from 20 to 90 years suggest two major patterns for the IgM natural antibody response to synthetic peptides giving high response. The first is that the level of IgM reactivity is high early in life and remains high throughout. The second pattern is one in which the reaction is high in younger individuals, but diminishes substantially in the latter decades of life.(ABSTRACT TRUNCATED AT 400 WORDS)

Arthritis and aging.

Thirty-seven million Americans suffer from some form of arthritis and the prevalence of arthritis among the elderly is particularly high. Therefore it is not surprising that there is a large new literature directed toward the epidemiology and health services for the older individual with arthritis. Many studies in osteoarthritis have refined the minutia or confirmed earlier work. Osteoarthritis increases with age and accounts for 46 million patient visits each year, with knee arthritis accounting for the most common complaint initiating such visits. Late stage rheumatoid arthritis has again been strongly associated with shortened life span, and factors predicting early death have been identified. Meanwhile, the "pyramid model" of rheumatoid arthritis treatment has been challenged. Of interest is the identification of obesity as a major risk factor for disability in elderly patients with arthritis and the fact that the incidence of hip fracture in the elderly, already known to be high, may be increasing. A provocative report suggests that mass screening for osteoporosis followed by selective treatment may be more cost effective than empirical treatment of all postmenopausal women.

The incidence of attempted CPR in nursing homes.

We studied the frequency with which cardiopulmonary resuscitation (CPR) is attempted on residents of American nursing homes. Each author (all members of the Clinical Practice Committee of the American Geriatrics Society) completed a questionnaire in 1989 about policy and practice regarding CPR during 1988 in each of three to seven nursing homes, by questioning the medical or nursing director or the administrator. Because of the vagaries of nursing home record-keeping, data from some homes were allowed when they were "accurate to within 10%." Data from 58 nursing homes, totalling 10,836 bed-years were available. In 33 of these homes, accounting for 5,425 bed-years, CPR was never attempted. CPR was more likely to be foregone in nursing homes with religious affiliation than in nursing homes without (13 of 17 vs 18 of 38; chi 2 = 4.0; P less than 0.05). Religious affiliation was unknown for three nursing homes. Academic affiliation (10 of 16 vs 20 of 37 in non-affiliated nursing homes) and non-profit status (14 of 19 vs 16 of 23 in for-profit nursing homes) did not significantly affect the likelihood that CPR would never be used. In 31 of 54 nursing homes with explicit do not resuscitate (DNR) policies, CPR was never performed, compared to 2 of 4 homes without such policies. For nursing homes with complete data, there were 1,196 deaths in 32 facilities where CPR was never attempted compared to 1,294 deaths for 24 nursing homes with CPR. For 22 nursing homes without CPR, there were 2,172 emergency room transfers compared to 1,363 emergency room transfers in 18 nursing homes where CPR was attempted.(ABSTRACT TRUNCATED AT 250 WORDS)

Decline of height with age in adults in a general population sample: estimating maximum height and distinguishing birth cohort effects from actual loss of stature with aging.

The decline in stature with age among adults is well documented. Although part of this represents a birth cohort effect, actual height declines among older individuals are known to contribute to the effect. In this study we used longitudinal changes in the heights of adults in a general population sample to determine the rate of decline in height over time in individuals of different ages. This allowed an estimation of the age at which decline in height begins, a value close to age 40 in both sexes. It also allowed derivation of equations from which the maximum height of subjects can be estimated on the basis of their sex, current height, and age. These equations should prove useful when examining the effect of aging per se on physiological measurements that are height dependent. The data also allow one to compare the magnitude of the effect of year of birth with that of the actual decline in height seen among the elderly. We estimate that approximately 60% of the smaller stature of older male subjects and 45% of the smaller stature of older female subjects is a birth cohort effect deriving from the secular trend toward greater stature; the remainder is a result of an actual decrement in height after the age of 40.

Family practice and internal medicine clinical judgment in a university setting.

There were no significant differences between family practice and internal medicine residents in the proportion of total diagnoses that were reasonable (72 percent and 77 percent, respectively) and unreasonable (14 percent and 15 percent, respectively) or average number of consultations requested per examination (.15 and .16, respectively). There was a significant difference between the two types of physicians in the average number of laboratory tests requested per examination (1.42 per family practice and 1.88 per internal medicine) and average number of x-ray examinations requested per examination (0.35 for family practice and 1.02 for internal medicine). The average length of examination for internal medicine tended to be longer than for family practice. Although generalizability of this study is limited, the results suggest that there may be important differences in the practice patterns of family practice and internal medicine with implications for training programs.

Assessing clinical judgment with standardized patients.

Family physicians and general practitioners see the majority of patients with uncomplicated rheumatic disease, yet information on database collection and clinical judgment in such practices is limited. Trained patients with uncomplicated rheumatic disease (standardized patients) were used to evaluate these abilities in 26 family physicians at the University of Arizona College of Medicine in blinded, but previously consented to, brief new encounters. Ability to formulate an assessment and to plan was evaluated as well as ability to collect diagnostic information. Few physicians explored the psychosocial impact of the illness (4 percent) or the role of depression (0 percent). In the brief encounter with a localized complaint, little inquiry was directed to systemic disease (46 percent). Physicians more uniformly asked about the chief complaint (96 percent) and time of onset (88 percent). Physical examination items most commonly omitted were evaluation of systemic joint involvement (69 percent) and muscle wasting in the involved area (59 percent). Referral occurred on 15 percent of encounters and patient education occurred in 62 percent. Three quarters of physicians developed an adequate assessment and virtually all developed an adequate patient care plan.

Non-articular rheumatism.

Non-articular rheumatism is one of the most common afflictions of humankind that arises anywhere in the musculoskeletal system (except the joints). Carefully differentiating non-articular rheumatism from arthritis or the generalized pain syndromes promotes effective management of some of the most common disorders of patients in a physician's practice.

The use of trained patient instructors for teaching and assessing rheumatologic care.

The training of professionals in rheumatologic care requires review and study. To improve teaching methods, 6 patients with stable rheumatic disease were trained to evaluate and teach medical students by using themselves as models for musculoskeletal examinations. Checklists for scoring performance and content were developed. Criteria established to give evidence of the validity of the checklists and of the reliability of the patient instructors in their scoring were met or exceeded. The patient instructors are now an integral part of the Preparation for Clinical Medicine curriculum at our institution and serve as resources for evaluation and teaching in the continuing education of practicing professionals.

Once-daily treatment of rheumatoid arthritis with choline magnesium trisalicylate.

A pilot study evaluated once-daily treatment of rheumatoid arthritis with choline magnesium trisalicylate (CMT) in patients diagnosed as having classical or definite rheumatoid arthritis, with morning stiffness as a major complaint. Twenty patients were selected who, in an earlier phase of the study, had found twice-daily treatment with CMT effective and tolerable. Efficacy was evaluated in 15 of these patients and safety was evaluated in all 20. Comparisons were made with the twice-daily regimen and with previous nonsteroidal anti-inflammatory drug (NSAID) therapy. Changes in clinical indicators (numbers of painful and swollen joints and the duration of morning stiffness) showed that once-daily treatment with CMT was as effective as twice-daily treatment with CMT or as treatment with other prior NSAIDs in controlling signs and symptoms of rheumatoid arthritis. Side effects in both the twice-daily and the once-daily treatment regimens were similar in incidence and nature.

Arthritis: preferred learning methods among Arizona therapists.

Arizona occupational and physical therapists were surveyed about their needs for education in arthritis. Responses to statements regarding attitudes, knowledge, willingness to learn, and preferred methods of learning were subjected to chi-square analysis. The results showed that a significant number of both occupational and physical therapists are deficient in knowledge about the disease and maintain negative attitudes about patients with rheumatoid arthritis. Both groups indicated a high interest in continuing education about arthritis. The preferred method of learning was self-study guides.

Impact of intensive education and interaction with health professionals on patient instructors.

The use of patients as instructors in teaching medical students and physicians the musculoskeletal examination has proven to be an effective method of learning. However, the effect on the patient instructors (PIs) of their intensive training and the numerous physical examinations made of them has been unknown. In this study, eight patients with stable rheumatoid arthritis were given the Taylor-Johnson Temperament Assessment (TJTA) when they were recruited as PIs and every six months thereafter for two years. Individual interviews focusing on the changes taking place in the patient instructors' lives were also conducted. Three PIs left the program early in their training. Observed changes in TJTA scores were frequently positive for the five who remained in the study. Interview results indicate positive changes in terms of confidence, competence, and emotional stability. All five PIs have continued in their role as PIs and have also expanded into other responsibilities. It is concluded that the patient instructor program was certainly not harmful to the individual PIs and, in fact, was mostly beneficial to them as well as to physicians and medical students.

Amyloidosis presenting as priapism.

A sixty-five-year-old white man presented with sudden onset of painful, priapism. Review of pathologic specimens at the time of surgical decompression revealed massive amyloid infiltration. Purpura, organ enlargement, gastrointestinal bleeding, and congestive heart failure developed subsequently. Postmortem examination revealed widespread amyloidosis. To our knowledge this is the first report of amyloidosis presenting with priapism.

Autosensitization to DNA: evidence for an immunologic basis.

A 59-year-old female with spontaneous painful ecchymoses developed ecchymoses after intracutaneous injection of washed autologous whole blood cells and calf thymus DNA. Immunofluorescent studies of the spontaneous lesions revealed granular deposits of IgM, C3, factor B and properdin at the dermal-epidermal junction but no deposits in her normal skin. T cells were decreased in number but responded normally to polyclonal mitogens and did not transform in response to DNA containing antigens. Repair of UV-damaged DNA by her lymphocytes appeared to be depressed. The findings presented here are the first immunologic abnormalities uncovered in this disorder and may help in understanding the pathogenesis of the inflammatory lesions seen in autosensitization to DNA.