Intra-articular corticosteroids. An updated assessment

Local corticosteroid injections are a relatively safe and effective adjunct in managing rheumatoid arthritis, other connective tissue arthropathies, and soft tissue rheumatism. Rheumatoid synovitis may be suppressed for three months or longer using relatively insoluble microcrystalline preparations. No convincing evidence exists, however, that joint erosive changes are retarded, and steroid injections should be considered ancillary to rest, physical therapy, nonsteroidal anti-inflammatory agents, and disease modifying antirheumatic drugs. The few controlled studies in hip and knee osteoarthritis have demonstrated only modest, fleeting beneficial effects. Nonetheless, clinical experience suggests that intra-articular steroids often ameliorate acute exacerbations of knee osteoarthritis associated with significant effusions, symptomatic involvement of interphalangeal and other nonweight-bearing articulations, synovial cysts, and lumbar facet arthropathy. Judicious use of intrasynovial injections seldom produces significant adverse effects. Iatrogenic infectious arthritis follows one in 14,000-50,000 injections. Rapid acceleration of cartilage attrition is observed rarely. The concept of "corticosteroid arthropathy" is based largely on subprimate animal studies and several anecdotal case reports; limited investigation of primate (monkey) models has shown no significant long-term deleterious effect on cartilage.     

The clinical algorithm nosology: a method for comparing algorithmic guidelines.

Concern regarding the cost and quality of medical care has led to a proliferation of competing clinical practice guidelines. No technique has been described for determining objectively the degree of similarity between alternative guidelines for the same clinical problem. The authors describe the development of the Clinical Algorithm Nosology (CAN), a new method to compare one form of guideline: the clinical algorithm. The CAN measures overall design complexity independent of algorithm content, qualitatively describes the clinical differences between two alternative algorithms, and then scores the degree of similarity between them. CAN algorithm design-complexity scores correlated highly with clinicians' estimates of complexity on an ordinal scale (r = 0.86). Five pairs of clinical algorithms addressing three topics (gallstone lithotripsy, thyroid nodule, and sinusitis) were selected for interrater reliability testing of the CAN clinical-similarity scoring system. Raters categorized the similarity of algorithm pathways in alternative algorithms as "identical," "similar," or "different." Interrater agreement was achieved on 85/109 scores (80%), weighted kappa statistic, k = 0.73. It is concluded that the CAN is a valid method for determining the structural complexity of clinical algorithms, and a reliable method for describing differences and scoring the similarity between algorithms for the same clinical problem. In the future, the CAN may serve to evaluate the reliability of algorithm development programs, and to support providers and purchasers in choosing among alternative clinical guidelines.     

Virtual trajectories of single-joint movements performed under two basic strategies.

The framework of the equilibrium point hypothesis has been used to analyse motor control processes for single-joint movements. Virtual trajectories and joint stiffness were reconstructed for different movement speeds and distances when subjects were instructed either to move "as fast as possible" or to intentionally vary movement speed. These instructions are assumed to be associated with similar or different rates of change of hypothetical central control variables (corresponding to the speed-sensitive and speed-insensitive strategies). The subjects were trained to perform relatively slow, moderately fast and very fast (nominal movement times 800, 400 and 250 ms) single-joint elbow flexion movements against a constant extending torque bias. They were instructed to reproduce the motor command for a series of movements while ignoring possible changes in the external torque which could slowly and unpredictably increase, decrease, or remain constant. The total muscle torque was calculated as a sum of external and inertial components. Fast movements over different distances were made with the speed-insensitive strategy. They were characterized by an increase in joint stiffness near the midpoint of the movements which was relatively independent of movement amplitude. Their virtual trajectories had a non-monotonic N-shape. All three arms of the N-shape scaled with movement amplitude. Movements over one distance at different speeds were made with a speed-sensitive strategy. They demonstrated different patterns of virtual trajectories and joint stiffness that depended on movement speed. The N-shape became less apparent for moderately fast movements and virtually disappeared for the slow movements. Slow movements showed no visible increase in joint stiffness.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modulation of concanavalin A-induced, antigen-nonspecific regulatory cell activity by leu-enkephalin and related peptides.

We have developed a system in which human peripheral blood mononuclear cells (PBMC) stimulated with concanavalin A (Con A) can be examined for regulatory cell activity upon coculture with responder cells undergoing mitogenic proliferation. Low concentrations of Con A resulted in the induction of helper function, while higher concentrations of Con A induced suppressor activity in the PBMC population. However, for each individual donor a particular concentration of Con A can be found at which point no regulatory cell activity is observed. This "balance point" provides a set of conditions under which the ability of an immunomodulator to up-regulate or down-regulate the system can be studied. The ability of leu-enkephalin to positively or negatively regulate an immune response was examined under these circumstances. The addition of leu-enkephalin to cultures stimulated by Con A at this balance point enhanced both suppressor cell (Ts) and helper cell (Th) activity in a concentration-dependent manner. The induction of Ts activity displayed a bimodal response at concentrations between 10(-12) to 10(-13) M and 10(-9) to 10(-10) M, while the induction of Th activity was consistently observed at 10(-11) M. Similar effects were seen with either of the peptides Tyr-Gly and Tyr-Gly-Gly, corresponding to the first two and three amino acids of the N-terminal ends of the enkephalins. Th activity was consistently enhanced at 10(-13) M Tyr-Gly-Gly and 10(-14) M Tyr-Gly. This suggests that leu-enkephalin may either positively or negatively regulate immune responses and that the intact leu-enkephalin molecule is not required for these effects.     

Nutrition in Acute Pulmonary Disease

Acutely stressed patients with chronic pulmonary disease have a particular need for accurate nutritional assessment and appropriate nutritional therapy. Loss of skeletal muscle, often extensive, can be paralleled by dramatic alterations in cellular function; inadvertent provision of excessive calories or of individual substrates may produce more harm than benefit. In the absence of a single "gold standard" for nutritional assessment and monitoring, no single value should take precedence over the entire clinical picture, which should be thoughtfully assessed and reassessed, with both the patient's nutritional needs and the consequences of their provision kept in mind. In the future, assessments of the impact of nutritional intervention will probably rely more heavily on functional tests of specific organs and of the immune system. Intervention will be based not only on provision of calories, individual substrates, vitamins, and minerals, but also on control of the inflammatory response in order that the nutrients may be properly utilized.     

Passive listening and task related P300 measurement for the evaluation of dementia and pseudodementia

The late evoked potential P300 was tested in three groups of subjects. These consisted of 25 patients suffering from dementia (Group I), 14 patients suffering from pseudodementia due to severe depressive disease (Group II), and 24 age-matched normal controls (Group III). Since patients suffering from dementia frequently have difficulties in counting targets in the "oddball" paradigm, we evaluated the usefulness of a Passive Listening condition. With the classical "oddball" paradigm, 78% of the subjects were correctly related to one of the three groups examined. The "P300-like" wave form produced in the Passive Listening condition was not found to be sensitive enough to allow such a distinction.     

Immunological similarity between a cyanobacterial enzyme and a nuclear DNA-encoded plastid-specific isozyme from spinach

The immunochemical properties of the plastid and cytosolic isozymes of phosphoglucose isomerase (glucosephosphate isomerase; D-glucose-6-phosphate ketol-isomerase, EC 5.3.1.9) in spinach (Spinacia oleracea) and the single phosphoglucose isomerase enzyme from the cyanobacterium Synechococcus sp. were compared by an application of the enzyme-linked immunosorbent assay. Utilizing antibodies made in rabbits against subunits of purified plastid and cytosolic phosphoglucose isomerase isozymes from spinach, we demonstrate that the plastid isozyme is immunochemically more similar to the cyanobacterial enzyme than to the spinach cytosolic counterpart. The antiserum to plastid phosphoglucose isomerase crossreacted strongly with plastid phosphoglucose isomerases from other flowering plants. The antiserum to cytosolic phosphoglucose isomerase crossreacted with other plant cytosolic phosphoglucose isomerase isozymes. The results are consistent with the hypothesis [Weeden, N. F. (1981) J. Mol. Evol. 17, 133-139] that the nuclear gene specifying plastid phosphoglucose isomerase was derived from a prokaryote after the incorporation of a plastid-like symbiont into the ancestral plant cell.     

Pharmacokinetics and metabolism of β-2′-deoxythioguanosine and 6-thioguanine in man

Summary Resistance to the antileukemic agent 6-thioguanine (TG) inevitably develops in animal tumors. However, a new agent, -2-deoxythioguanosine (-TGdR) can overcome TG resistance in animal tumor models and is therefore of potential clinical use. The pharmacokinetics of radiolabeled TG were compared with those of -TGdR in patients with cancer after intravenous administration. [³⁵S]--TGdR (5.4 mg/kg, 200 mg/m², 200 Ci total) was administered to five patients; the radiolabel in the plasma declined with an initial half-life (t_1/2) of 14 min and a terminal t_1/2 of 19.3 h. Within 24 h, 65% of the radiolabel was excreted in the urine. In contrast, after administration of [³⁵S]-6-TG (3.4 mg/kg, 125 mg/m², 200 Ci total) the average initial t_1/2 was 40 min while the terminal phase t_1/2 was 28.9 h. Urinary excretion of the radiolabel was 75% of the dose 24 h after administration. Both thiopurines were rapidly and extensively degraded and excreted as 6-thioxanthine, inorganic sulfate, S-methyl-6 thioxanthine, and 6-thiouric acid in addition to other products. Small amounts of unchanged drug were also excreted. These studies suggest that -TGdR is merely a latent form of TG.Deceased, to whose memory this paper is dedicated     

Frostbite of the upper extremity

Human capacity for physiologic adaptation to cold is minimal; we survive by insulating ourselves with protective clothing. In addition to the irreversible direct injury caused by ice crystallization, the authors have outlined four possible mechanisms by which indirect injury may damage tissue. Other than rapid rewarming, there is no uniformly accepted protocol for the treatment of frostbite injury. Attempting to sort out the world's literature on frostbite in an effort to present a comprehensive treatment protocol is a daunting task. In addition to the probably irreversible direct injury caused by ice crystallization, the authors have outlined at least four possible mechanisms by which indirect injury may damage tissue. The literature is full of various treatment protocols that allegedly are beneficial despite addressing different mechanisms. Mills described 10 different categories of medications, each addressing one of four possible mechanisms, used in the clinical treatment of frostbite injury over a 30-year period. Analyzing this information is even more confusing when one realizes that there is little uniformity in animal models employed to generate these data. This is further complicated by the lack of clinical correlation with the most common experimental model--liquid nitrogen rapid freezing. The risk of frostbite is highest when psychiatric disturbance, intoxication, or unplanned circumstances lead to cold exposure without adequate protective clothing. As tissue freezes, both direct and indirect factors cause injury. Most therapies have been aimed at limiting indirect injury, in an attempt to limit progressive tissue loss. Rapid rewarming is universally accepted, but the benefits of other modalities are still controversial. Traditionally, observation and delayed amputation have been employed to manage frostbite. More recently, triple-phase bone scans have been used to distinguish between tissue that is irreversibly destined for necrosis and tissue that is at-risk for necrosis, but potentially salvageable. Early operation can be used to provide at-risk tissue with a new blood supply and preserve both function and length in the upper extremity.