Hereditary deficiency of the seventh component of complement.

Deficiency of the seventh component of complement has been found in the serum of a 42-yr-old Caucasian woman who has Raynaud's phenomenon, sclerodactyly, and telangiectasia. Partial deficiency was found in the serum of the patient's parents and children, indicating a pattern of inheritance of autosomal codominance. Transfusion experiments indicated that exogenous C7 had a 91-h halk-life in the patient. There was no evidence for C7 synthesis after transfusion. No C7 inhibitors were detected in the patient's serum. The patient's serum was found to support the activation of complement by both the classical and properdin pathways to the C7 stage. The addition of C7 to the patient's serum permitted it to support hemolytic reactions initiated by either pathway. No defects could be detected in plasma or whole blood coagulation. The patient's serum was deficient in opsonizing unsensitized yeast particles in serum and in the generation of chemotactic factor by antigen-antibody complexes and endotoxin. Both deficiencies were corrected by the addition of C7. These observations suggest a key role for C7 for in vitro yeast phagocytosis and chemotaxis generation. However, the patient's lack of infections indicates a relatively minor role for C7 in human resistance to infection.

Hypersensitivity reaction to sulindac (Clinoril).

Sulindac (Clinoril), a nonsteroidal anti-inflammatory agent, has few reported neurologic toxic effects, all of which have been associated with systemic disease. To our knowledge, we describe the first reported case of isolated paresthesia and peripheral neuropathy, without systemic involvement, secondary to sulindac administration. A healthy, 30-year-old man, exposed to sulindac on two separate occasions, had an incapacitating isolated idential sensory neuropathy. The onset and duration of symptoms correlated directly to drug ingestion. This hypersensitivity response cannot be explained pathophysiologically by any mechanism. Repeated exposure and rechallenge of the subject to sulindac was deemed too dangerous, and precludes exact method to establish mechanisms to explain this transient, reproducible, idiosyncratic, adverse drug reaction.

Histological appearance of the synovium in early rheumatoid arthritis.

This report reviews and discusses studies on the synovial fluid and biopsy specimens of synovial membrane obtained during the first 6 weeks of synovitis that evolved into rheumatoid arthritis (RA). Five previously unreported cases are described. Early changes in the microvasculature and synovial lining seem to antedate the classical chronic inflammation of established RA. Further characterization in the joint tissues in very early RA offers opportunities for identification of exogenous triggers and may allow more appropriate targeting of early therapy to potentially reversible aspects of pathogenesis.

Zeta sedimentation ratio in rheumatic disease. Comparison of the zeta sedimentation ratio with the Wintrobe and Westergren sedimentation rates.

The zeta sedimentation ratios (ZSR) of 104 normal subjects and 106 rheumatology clinic patients were compared with their Westergren and Wintrobe erythrocyte sedimentation rates (ESR). The mean ZSR for normal subjects was 49.42 +/- 3.75%. The rheumatology clinic patients were separated into noninflammatory and inflammatory disease groups. The mean ZSR values for these groups were: noninflammatory, 51.60 +/- 5.33%; inflammatory, 59.43 +/- 7.32% (t = 5.5, p less than 0.001). The correlation between ZSR and ESR values was excellent. The ZSR determination has several advantages over the standard ESR in that it can be performed on blood anticoagulated with EDTA and need not be corrected for age, sex or packed cell volume. The ZSR is a rapid, reproducible test correlating well with rheumatic disease activity.

The zeta sedimentation ration (ZSR) as the routine monitor of disease activity in a general hospital.

Nine hundred eighty-one requests for sedimentation rates in a clinical laboratory were received and the zeta sedimentation ratio (ZSR) test was performed. The results were correlated with the patients' diagnoses and disease activity. This test was found to be a useful monitor of disease activity in a clinical setting. Substitution of the ZSR for the standard erythrocyte sedimentation rates (ESR) appears to be acceptable. The test is simple, rapidly performed, and reproducible.

Rheumatoid factor activity by rate nephelometry correlated with clinical activity in rheumatoid arthritis.

The purpose of this study was to evaluate, prospectively, the clinical usefulness of the rate nephelometric method for determining rheumatoid factor (RF) activity, measured in International Units (IU), in patients with rheumatoid arthritis. These results were compared with those of standard latex agglutination titration. The overall correlation between clinical activity and RF activity measured by rate nephelometry and serologic titration are similar, i.e., r = 0.47 (P less than 0.001) and r = 0.43 (p less than 0.001), respectively. However, on an individual patient basis, the nephelometric determination appears to correlate better with disease activity and response to therapy than do titers. The RF activity measured in IU would give the clinician a more sensitive and precise tool with which to follow RF activity in individual patients with active disease.

Pharmacokinetics of the R(-) and S(+) enantiomers of ibuprofen in the serum and synovial fluid of arthritis patients.

Eight patients with arthritis and knee effusions received 13 doses of a single 800-mg ibuprofen tablet every 8 hours. Serum and synovial fluid samples were obtained after the first and last doses and assayed for the R(-) and S(+) enantiomers of ibuprofen by a stereospecific assay. Since only S(+)-ibuprofen inhibits cyclo-oxygenase, a description of the time course of this isomer in synovial fluid is needed for the development of suitable pharmacodynamic models. The isomers were significantly different with respect to peak concentrations and areas under the concentration-time curves (AUC) in synovial fluid levels. No significant accumulation of either isomer was observed in serum or synovial fluid levels between the first and the last doses. The steady-state concentration of both isomers fluctuated less in synovial fluid than in plasma, and the synovial fluid concentrations of the S(+) isomer were about twice that of the R(-) isomer. The mean synovial albumin concentration was about 60% of the serum albumin concentration, and the steady-state isomer AUC values in synovial fluid were significantly correlated with the corresponding serum values after the differences between the two fluids with respect to albumin concentration were corrected. The authors conclude that binding of the isomers to albumin and the serum-synovial fluid albumin ratio controls the steady-state distribution of the ibuprofen isomers into synovial fluid. The ramifications of these findings in the development of satisfactory concentration-response relationships are discussed.

Ibuprofen kinetics in plasma and synovial fluid of arthritic patients.

After administration of a single dose and at steady state, ibuprofen concentrations were measured simultaneously in plasma and synovial fluid obtained from eight patients with rheumatoid arthritis. By seven hours after a dose at steady state, the mean synovial fluid: plasma ibuprofen concentration ratios were constant, and the synovial fluid levels were, on average, greater than those in plasma. The extent to which ibuprofen was bound to protein was somewhat greater in plasma than in synovial fluid. As a result, the mean synovial fluid:plasma free concentration ratio for seven-hour and later specimens was greater than that based on total concentrations. The degree of accumulation of ibuprofen in each fluid was minimal, consistent with its short half-life.

AI/Learn/Rheumatology. A computer-assisted educational system for teaching about rheumatic diseases.

Education of health professionals about the rheumatic diseases is in need of improvement. The computer is an instrument that can be used efficiently to educate large numbers of users. With specific educational principles in mind, we developed AI/Learn/Rheumatology, a computer-assisted interactive videodisc system for teaching the rheumatic diseases. While interacting with the user, it conveys knowledge using visual and problem-solving techniques. The system is efficient, enjoyable to use, and useful for small groups and independent study. It is applicable for teaching medical and allied health professional students, postgraduate trainees, and primary care physicians.

Spinal cord injury, spinal fracture, and spinal stenosis in ankylosing spondylitis.

The authors report a retrospective review of 105 patients with ankylosing spondylitis (AS) diagnosed over a 6-year period in Tucson, Arizona. In the series, there were 13 patients with spinal fractures and eight with severe spinal cord injury. Two patients with central cord contusion had no demonstrable cervical spine fracture. Injury was often trivial and dislocation at fractures sites was minimal, demonstrating the extreme fragility of these patients. Spinal stenosis, which has not previously been associated with AS, was documented in three cases. Pseudarthrosis, a destructive vertebral lesion that does not require surgical decompression or fusion, was found in four patients; this entity is believed to originate as a pathological or traumatic fracture. Atlanto-axial subluxation and basilar invagination associated with spinal ankylosis occurred in one patient. The study emphasizes the value of computerized tomography scanning of the spine for diagnosis, and halo-vest application as a nonoperative treatment for cervical immobilization. Early diagnosis and appropriate therapy to decompress, reduce, and immobilize unstable spinal lesions may result in reduction of the 29% mortality rate and 45% permanent neurological morbidity rate observed after spinal fracture in this series of AS patients. Because of the high operative complication rate observed, nonsurgical immobilization is the recommended treatment unless spinal dislocation or bone fragment displacement has occurred at the fracture site.

Lumbar spinal stenosis in a patient with diffuse idiopathic skeletal hypertrophy syndrome.

Lumbar spinal stenosis is associated with a variety of conditions, including dysplastic narrowing of the spine, lumbar spondylosis, Paget's disease, and achondroplastic dwarfism. No case of lumbar stenosis associated with diffuse idiopathic skeletal hyperostosis (DISH) previously has been described. It would appear that this case could represent either another manifestation of DISH characterized by involvement of the ligamentum flavum or coincidental association with lumbar spondylosis. In either case, physicians treating spinal and skeletal diseases should be aware of potential neurologic complications requiring surgical decompression due to narrowing of the spinal canal in this unusual disorder.

Introduction and classification of rheumatic diseases.

Rheumatic diseases affect a large segment of the world's population. The rheumatic diseases may be classified by type or by several clinical schema of signs and symptoms.

The use of drugs in rheumatic diseases.

Specific information concerning the use of nonsteroidal anti-inflammatory agents, salicylates, analgesics, remittive drugs, and other adjunctive treatments used for rheumatic diseases are addressed. Based on a good diagnosis, pharmacotherapy combined with other approaches can result in successful treatment of most cases of arthritis.

Osteoporosis, osteomalacia, rickets, and Paget's disease.

Although the common form of osteoporosis associated with aging can be treated, it is best to avoid the problem by not letting the disease develop. Osteomalacia is caused by inadequate or delayed mineralization of bone and is treated by correcting the abnormal intake, loss, or metabolism of vitamin D, phosphate, and calcium. Paget's disease is characterized by osteoclastic resorption of bone with new bone laid down in a disorganized fashion.

Hyperuricemia and gout. A modern approach to diagnosis and treatment.

Diagnosis of gout by crystal identification in synovial fluid is simple and definitive. To treat gout effectively, the physician must determine whether overproduction or underexcretion of uric acid is the underlying mechanism. The acute attack is treated initially with antiinflammatory agents. After the acute phase is controlled, lifelong definitive therapy for hyperuricemia is begun.

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.