Adaptive short-term plasticity in the typical reading network.

The left temporo-parietal cortex (TPC) is crucial for phonological decoding, i.e., for learning and retaining sound-letter mappings, and appears hypoactive in dyslexia. Here, we tested the causal contribution of this area for reading in typical readers with transcranial magnetic stimulation (TMS) and explored the reading network's response with fMRI. By investigating the underlying neural correlates of stimulation-induced modulations of the reading network, we can help improve targeted interventions for individuals with dyslexia. 28 typical adult readers overtly read simple and complex words and pseudowords during fMRI after effective and sham TMS over the left TPC. To explore differences in functional activation and effective connectivity within the reading network, we performed univariate and multivariate analyses, as well as dynamic causal modeling. While TMS-induced effects on reading performance and brain activation showed large individual variability, multivariate analyses revealed a shift in activation in the left inferior frontal cortex for pseudoword reading after effective TMS. Furthermore, TMS increased effective connectivity from the left ventral occipito-temporal cortex to the left TPC. In the absence of effects on reading performance, the observed changes in task-related activity and the increase in functional coupling between the two core reading nodes suggest successful short-term compensatory reorganization in the reading network following TMS-induced disruption. This study is the first to explore neurophysiological changes induced by TMS to a core reading node in typical readers while performing an overt reading task. We provide evidence for remote stimulation effects and emphasize the relevance of functional interactions in the reading network.

Assessment of clinical competence of medical students by using standardized patients with musculoskeletal problems.

OBJECTIVE: To assess medical students' clinical competence in addressing musculoskeletal problems. METHODS: Nineteen junior medical students completed 2 standardized patient-based tests structured to capture their clinical decisions from undiagnosed chief complaint to management. RESULTS: No student approached the highest possible score on either test, and the students as a group received less than half the possible points on 5 important aspects of diagnostic reasoning. CONCLUSION: Standardized patient-based tests can be structured to provide enlightening information about medical students' clinical competence with regard to musculoskeletal problems.

A comparison of medical drainage (needle aspiration) and surgical drainage (arthrotomy or arthroscopy) in the initial treatment of infected joints.

Acute infectious arthritis remains a clinical emergency where early diagnosis and appropriate therapy are essential to a successful outcome. The therapeutic requirements for a successful outcome include early diagnosis, appropriate antibiotics, joint mobilization and adequate drainage. The method of drainage can be medical with needle aspiration or surgical with arthroscopic or open surgical debridement. The literature review presented in this chapter supports the value of the initial use of medical therapy in the management of the acutely infected joint, with surgical drainage reserved for failure of medical management or for initial drainage of hip infections where needle aspiration is difficult.

Routine drug treatment of septic arthritis.

Drug treatment of septic arthritis must be initiated promptly and rationally. An accurate diagnosis of the infecting micro-organism must be made as quickly as possible. Antibiotic treatment should be started even before this is achieved using clues from the clinical evaluation and from the stained smear of synovial fluid as guides. Later, the choice and dose of the drug can be adjusted based upon the results of the culture and the bacterial sensitivity to the drug. Anti-inflammatory drugs make a real contribution to control of the postinfectious synovitis that frequently occurs, but they should not be used until control of the infection has become evident. Early diagnosis and treatment make it possible to restore joint function to normal in the majority of patients.

Infectious arthritis and osteomyelitis.

Awareness of the possibility of sepsis constitutes the single most important step needed to effectively diagnose and treat a bone or joint infection. Once suspected, the diagnosis can usually be confirmed by identification of the causative microorganism. Treatment can be curative but requires prompt use of appropriate antibiotics and adequate drainage to achieve optimal results, that is, the restoration of the preinfectious level of musculoskeletal function.

Assay, purification and further characterization of 7S C1q-precipitins (C1q-p) in hypocomplementemic vasculitis urticaria syndrome and systemic lupus erythematosus.

C1q-precipitins (C1q-p) are comprised of 7S IgG with C1q-binding activity found in sera of patients with hypocomplementemic vasculitis urticaria syndrome ( HVUS ) and systemic lupus erythematosis (SLE). We have utilized C1q-coated polystyrene beads to selectively isolate C1q-p and to establish a sensitive and quantitative assay of C1q-p and immune complex activity. Purified C1q-p was comprised of polyclonal IgG which retained 7S sedimentation and solid phase C1q-binding activity at physiological ionic strength both in the presence and absence of normal human sera. No precipitation interaction was observed between C1q-p and fluid-phase C1q or C1 under the conditions tested. Purified C1q-p had no activity in the Raji cell immune complex activity. C1q-p activity also was observed in and purified from SLE serum; this activity was distinguishable from 7S immune complex activity detected by Raji cells which was also present in SLE serum. These studies indicate that C1q-p is a 7S IgG molecule found in HVUS as well as some SLE sera and has activity in C1q-binding but not in Raji cell-binding immune complex assays. These data also suggest that C1q-p is a monomeric, polyclonal IgG with preferential affinity for bound C1q. In addition to its potential role in immune complex disease, C1q-p may also provide an important tool for studying the interaction of immunoglobulin and C1q, and should contribute important information to understanding the pathobiology of immune complex disease.

Four-way, multicenter, crossover trial of ibuprofen, fenoprofen calcium, naproxen, and tolmetin sodium in osteoarthritis: comparative clinical profiles.

One hundred forty-one subjects with osteoarthritis completed this double-blind, multicenter, crossover trial comparing four nonsteroidal anti-inflammatory (NSAI) agents after single-blind aspirin stabilization. Preferences of both patients and physicians showed the following rank order from most to least preferable: tolmetin sodium, naproxen, ibuprofen, fenoprofen calcium. By all but three of more than 20 measures of efficacy, tolmetin sodium and naproxen were the more effective pair and fenoprofen calcium and ibuprofen the less effective pair of the four. Eight of nine measures of tolerability suggested the following rank order from best to worst tolerated: ibuprofen, naproxen, tolmetin sodium, fenoprofen calcium, aspirin. Few differences among the newer NSAI agents compared in this study achieved statistical significance. Nevertheless, the tolerability-efficacy relationships that emerge from studies of this type can help to define rational approaches to the use of these drugs in rheumatic diseases.

Effects of diflunisal on platelet function and fecal blood loss.

The effects of diflunisal, a nonacetylated difluorinated salicylate, on platelet function were compared with those of aspirin and placebo. In a randomized, double-blind trial, normal subjects were given diflunisal, 250, 500, or 1,000 mg twice daily; aspirin, 650 or 1,300 mg twice daily; or placebo for 8-day periods. Diflunisal, 250 mg, had no effect on platelet function, whereas 500 mg induced minimal inhibition of collagen-induced release of platelet serotonin, and 1,000 mg inhibited platelet malondialdehyde-production, moderately prolonged template bleeding times (p = NS), and increased fecal blood loss (p less than 0.05). In contrast, aspirin, 650 mg, markedly inhibited collagen-induced platelet aggregation and serotonin release, and 1,300 mg prolonged bleeding time (p less than 0.01) and increased focal blood loss (p less than 0.01). The effects of aspirin lasted for up to 5 days, whereas changes induced by diflunisal had returned to baseline 24 hours after the drug was discontinued. We conclude that in doses in the same range as those of aspirin diflunisal inhibits platelet function less.

Fibronectin in rheumatoid and non-rheumatoid arthritic synovial fluids and in synovial fluid cryoproteins.

Concentrations of fibronectin, immunoglobulins G, M, and A, and C3 and C4 components of complement, and other plasma proteins were determined in synovial fluids from patients with rheumatoid arthritis (RA) and other diseases (non-RA). Fibronectin concentrations were two to three times greater in all synovial fluids than in plasma, and RA synovial fluids had a significantly higher mean concentration than non-RA fluids (883 microgram per ml vs. 588 microgram per ml, respectively, p less than 0.01). The mean concentrations of other synovial fluid constituents were less than their mean plasma concentrations. These results suggest that unlike other plasma constituents, either plasma fibronectin is concentrated in synovial fluids or that a substantial portion of synovial fluid fibronectin may be derived from synovial tissue cells. Both the C3 and C4 complement components were present in lower concentrations in RA than in non-RA synovial fluids. The C3 contents showed a statistically significant negative correlation with the fibronectin contents. Fibronectin was also found in all synovial fluid cryoprotein fractions tested, although its content varied greatly as a percent of the total cryoprotein protein (0.01 to 43 percent). The data show that fibronectin is a consistent constituent of synovial fluid cryoproteins in agreement with our previously reported finding that fibronectin is found in all serum cryoglobulin fraction tested.

Effects of diflunisal on platelet function and fecal blood loss.

The effects of diflunisal, a nonacetylated difluorinated salicylate, on platelet function were compared with those of aspirin and placebo. In a randomized, double-blind trial, normal subjects were given diflunisal, 250, 500, or 1,000 mg twice daily; aspirin, 650 or 1,300 mg twice daily; or placebo for 8-day periods. Difunisal, 250 mg, had no effect on platelet function, whereas 500 mg induced minimal inhibition of colagen-induced release of platelet serotonin, and 1,000 mg inhibited platelet malondialdehyde production, moderately prolonged template bleeding times (P = NS), and increased fecal blood loss (P less than 0.05). In contrast, aspirin, 650 mg, markedly inhibited collagen-induced platelet aggregation and serotonin release, and 1,300 mg prolonged bleeding time (P less than 0.01) and increased fecal blood loss (P less than 0.01). The effects of aspirin lasted for up to 5 days, whereas changes induced by diflunisal had returned to baseline 24 hr after the drug was discontinued. We conclude that in doses in the same range as those of aspirin diflunisal inhibits platelet function less.

Plasma fibronectin is a component of cryoglobulins from patients with connective tissue and other diseases.

Twenty-four washed cryoglobulin precipitates were examined for the presence of plasma fibronectin, immunoglobulins, complement components Clq and C3, and fibrinogen. Plasma fibronectin was detected in all preparations by immunodiffusion with antifibronectin serum, whereas the other components were found in some but not all of the cryoglobulins.

Binding of fibronectin to Clq; inhibition of binding by aggregated IgG.

Fibronectin was shown to bind to C1q using alkaline phosphatase conjugated fibronectin and C1q coated polystyrene tubes. The binding of the alkaline phosphatase conjugated fibronectin to C1q was dose dependent and inhibited by fibronectin and by the sulfated polymers heparin and chondroitin sulfate. The fibronectin interaction was inhibited only slightly by gelatin indicating that the fibronectin-gelatin interaction was different from that with C1q. Heat aggregated IgG blocked the binding of fibronectin to C1q and fibronectin inhibited the binding of aggregated IgG to C1q. These results suggest that fibronectin may be a factor affecting the determination of immune complexes in serum specimens by C1q binding assays.

Fibronectin associated with Clq in a Clq isolation procedure.

The complement component Clq, prepared by euglobulin precipitation of serum to which EDTA or EGTA had been added, contained fibronectin (FN) as detected by radioimmunoassay and immunodiffusion methods. The FN contents of the Clq preparations varied between 3 and 29% by weight of the Clq contents. Adsorptions of sera with polymerized IgG (an absorbent for Clq) in the presence or absence of EDTA removed all detectable Clq and between 12 and 95% of the FN. In a similar manner, adsorptions of sera and Clq preparations with insolubilized gelatin (to which FN will bind) reduced greatly or removed completely the FN component but also strikingly reduced the Clq contents. High salt concentration or the addition of EDTA did not alter the gelatin absorption results indicating that the association was not sensitive to high ionic condition and that Clq was equally bound as Clq or as the Cl complex. The results suggest that FN and Clq bind individually to both gelatin and IgG or that FN and Clq co-associate, accounting for removal of one component when the other is bound to its expected adsorbent.

A hypocomplementemic vasculitic urticarial syndrome. Report of four new cases and definition of the disease.

We describe four new patients with a unique syndrome of persistent urticaria, with leukoclastic angiitis, severe angioedema, occasional life-threatening laryngeal edema, arthritis, arthralgia, neurologic abnormalities and pronounced persistent hypocomplementemia. The complement abnormalities involved markedly reduced levels of the Clq subunit of the first component of complement (Cl) in the presence of near normal levels of Clr and Cls subunits of Cl; modest to marked depletion of the fourth component of complement (C4), the second component of complement (C2) and the third component of complement (C3); and normal levels of the fifth through ninth components of complement (C5 through C9) and properdin factors B and D. A striking serologic abnormality found in all patients was the presence of low molecular weight (7S) proteins which precipitated with Clq in agarose gels; these previously were shown to be comprised at least in part of immunoglobulin G. The present experience is offered to help to define the clinical, histopathologic and serologic characteristics of this entity, designated hypocomplementemic vasculitic urticarial syndrome, and to emphasize its distinctiveness and prevalence.

Efficacy of compression gloves in rheumatoid arthritis.

Twenty-three patients with rheumatoid arthritis whose disease had become stabilized while receiving non-steroidal, anti-inflammatory drugs and/or gold salt injections entered an 8 week crossover study in which the effect of a compression glove worn during sleep was compared to a loosely fitting glove made of the same material. Improvement in hand symptoms was greater with the compression glove than with the control glove as regards morning stiffness, pain, night time throbbing, numbness or heaviness and a subjective assessment of swelling (p = 0.01). In addition, swelling of the proximal interphalangeal joints was slightly reduced (p = 0.05). These data suggest that the night time use of compression gloves in patients with rheumatoid arthritis can improve hand symptoms and exert a mild, transiently beneficial effect upon the degree of hand swelling.