Relationship between functional evaluation measures and self-assessment in nonacute low back pain.

STUDY DESIGN: The correlations between objective biomechanical indicators of function and self-assessment scores were examined retrospectively for 91 subjects with nonacute low back pain. OBJECTIVES: To examine the correlation between self-assessment, trunk range of motion (ROM), velocity, and complex mechanical coordination patterns of the spine in nonacute low back pain. SUMMARY OF BACKGROUND DATA: In low back pain, there is often little concordance between pain, physical impairment, and disability. Use of range of motion and velocity to enhance objectivity in impairment evaluations has been ineffectual. In this study, two hypotheses were examined: range of motion and velocity are controllable and inherently correlated with self-assessment; complex spinal coordination patterns such as range of lordosis cannot be controlled and are independent of self-assessment. METHODS: Self-assessment questionnaires were administered, and indexes of spinal motion and coordination were measured through skin marker kinematics. The correlation between self-assessments and biomechanical measures was determined. RESULTS: Self-assessments of function were significantly correlated with parameters prone to regulation: range of motion, velocity, and load lifted. In contrast, little correlation was found with measures of complex spinal coordination less susceptible to conscious or affective regulation, namely, range of lordosis and estimated segmental mobility. This effect was magnified with increased load. Self-assessment scores were significantly poorer among insurance referrals, regardless of functional status. CONCLUSIONS: Simple parameters of the functional examination, such as range of motion and velocity, are strongly correlated with cognitive state, and thus the information they supply is less than ideal. Complex spinal coordination is a better indicator of the degree of spinal dysfunction and enhances the process of differentiating between pain, disability, and functional impairment.

Improving the evaluation of benign low back pain.

STUDY DESIGN: A prospective, blind study was conducted to investigate the factors underlying the decisions of expert clinicians in diagnosis of acute, benign low back pain, compared with results obtained with an automated physical examination by machine. From the results, a strategy to significantly improve clinical diagnosis in cases of discordance was determined. OBJECTIVES: To identify factors in the clinical assessment of low back pain that indicate when independent diagnostic testing would be useful. SUMMARY OF BACKGROUND DATA: The clinical evaluation of low back pain is often dominated by subjective reports of pain. Published medical literature has underscored several inherent weaknesses of the clinical examination, and concerns have been raised about its effectiveness for assessing patients with low back pain. Thus, it has been proposed that objective measures to complement the clinician's examination would be beneficial in the formulation of dependable diagnoses. METHODS: Randomly designated subjects, who in describing their conditions were objective or role playing, were assessed by clinicians and a machine for diagnosis of low back pain assessment versus normal backs. Each subject's pain assessment was compared with a gold standard that was established by experts in low back pain. Components of the clinical examination were analyzed to assess which were the most informative in making a reliable diagnosis. The information content of the machine assessment was also analyzed and a strategy to complement the clinical diagnosis with the machine diagnosis determined. RESULTS: Discordance among the various components of the clinical examination was a strong indicator of when the efficacy of the clinical examination dropped below a random level of decision making. When there was discordance, incorporating the functional evaluation by machine into the clinical diagnosis improved the performance of the clinician. Notably, in nonobjective subjects, the accuracy of diagnosis was enhanced by as much as 69%. CONCLUSIONS: It is possible to improve the accuracy of clinical diagnosis by incorporating a functional evaluation by machine when there is discordance between physical examination findings and reported pain.

In vitro differentiation of peripheral blood T cells towards a type 2 phenotype is impaired in rheumatoid arthritis (RA).

We have examined the capacity of peripheral blood T cells from RA patients to be polarized in vitro towards a type 1 (T1) or a type 2 (T2) phenotype. Peripheral blood T cells from RA patients and from healthy donors were primed by 1 week of culture with soluble OKT3 in the presence of polarizing cytokines. The recovered T cells were restimulated and their cytokine secretion profile determined. Priming of T cells from RA patients in the presence of recombinant (r)IL-2 plus rIL-12 induced a shift towards a TI pattern, characterized by increased production of interferon-gamma, that was more pronounced than in the case of healthy donors. Conversely, priming of T cells from RA patients in the presence of IL-4 failed to induce a shift towards a T2 profile after 1 week, whereas it induced T cells from healthy donors to acquire such a profile characterized by heightened production of IL-4, IL-5 and IL-13. However, a T2 polarization profile emerged in T cells from RA patients that were primed in the presence of rIL-4 and subsequently maintained in culture in rIL-2 alone for 1 or 2 additional weeks. We conclude that in vitro differentiation of peripheral T cells towards a type 2 phenotype is impaired in RA. Nevertheless, conditions required to drive peripheral T cells towards a type 2 phenotype were established. Administration of autologous polyclonal T cells expressing a type 2 cytokine secretion profile is proposed as a therapeutic strategy in RA.

Evaluation of clinician and machine performance in the assessment of low back pain.

STUDY DESIGN: A prospective blind study to test and compare the performance of clinicians (evaluators) with that of an automated machine (the Spinoscope) in conducting an examination on randomly designated simulators/dissimulators and honest subjects to assess acute benign low back pain. OBJECTIVES: To test the impact of reported pain and history on the clinical examination and to compare the ability of clinicians and the machine to recognize normal findings in a controlled group of subjects with and without benign low back pain. BACKGROUND: The literature raises serious questions regarding the efficacy of the clinical examination for patients with low back pain. METHODS: A "gold standard" (clinical examination by experts in low back pain) was established against which the clinical examination by the evaluators and the machine assessment (incorporating weight-lifting ability) of honest subjects and simulators/dissimulators were compared using the receiver operating characteristic technique. The selection of subjects was performed according to strict inclusion and exclusion criteria. RESULTS: The evaluators were more accurate with the honest subjects, the machine more accurate with the simulators/dissimulators, and, for the entire population tested, the they were equivalent in accuracy (71% vs. 72% concordance). Results from the machine's expert system and from clinician readers of the machine data compared favorably. The machine's concordance with the gold standard increased with increasing loads lifted by the subject. CONCLUSION: By relying primarily on the subject's self-presentation, often to the exclusion of objective findings, the clinician may err in evaluating low back function when the patient does not report his or her true condition. The additional functional analysis provided by the machine offers the clinician objective, pertinent information to complement the findings from the clinical examination.

Stable polarization of peripheral blood T cells towards type 1 or type 2 phenotype after polyclonal activation.

Polarization of T lymphocytes towards type 1 (T1) or type 2 (T2) subsets producing a distinct array of cytokines plays a role in several diseases and could be used for therapeutic intervention. Bearing this purpose in mind, we have established suitable in vitro conditions to drive resting polyclonal human T cells towards stable T1 or T2 polarization profiles. Unselected peripheral lymphocytes from normal donors were primed with soluble anti-CD3 monoclonal antibody in the presence of selected sets of recombinant (r) human cytokines. Following this priming process the cytokine secretion profiles of the recovered T cells were assayed after restimulation, both at the population and single-cell levels. A marked shift towards T2 profile, characterized by heightened production of IL-4, IL-5 and IL-13, was obtained after priming in the presence of rIL-4 alone. Addition of rIL-2 partially antagonized this effect. In contrast, priming in the presence of rIL-2 and rIL-12 induced a shift towards a T1 pattern characterized by increased productions of IFN-gamma and IL-2. Strikingly, the T2 profile appeared more stable in culture than the T1 profile. We also observed that the CD4+ helper T cell subset was the major producer of T1 and T2 cytokines after restimulation. These results establish in vitro parameters to deliberately and reproducibly activate resting polyclonal T cells towards a defined and persistent cytokine secretion profile. Autologous T cells polarized under these conditions could be passively transferred as a therapeutic approach in diseases thought to result from imbalance between T1 and T2 responses.

The impact of inefficient clinical diagnosis on the cost of managing low back pain.

The clinical examination remains the pivotal factor in evaluating low back pain (LBP) for decisions concerning compensation and rehabilitation. Many practitioners believe it to be highly reliable, even though existing literature does not support this belief. Not only are there no data supporting the efficacy of clinical diagnosis for LBP, but also published data underscore its many inherent weaknesses. Healthcare risk managers need accurate clinical information to make decisions. If current clinical information is unreliable, then healthcare risk management strategies for LBP must be revised. This article reviews the work of many researchers in their attempts to unravel the problem of diagnosing LBP. The following conclusions were reached: The problem is significant and continues to increase. The problem is rooted in the clinician's strong dependency on reported pain, which may not always be a reliable source of objective information. Quantification of the impact of the objectivity of reported pain on clinical performance demonstrates the need for a independent source of functional data that can improve the diagnosis. Technology exists to complement the clinical examination, improve clinical performance, and thus reduce the cost associated with LBP management. The research results presented in this article unveil disturbing findings for healthcare risk managers. The strong bias clinicians reserve for reported pain may lead them to overrate pathology, treat patients inappropriately, prescribe unnecessary imaging tests, and generate unfounded medical opinions that are responsible for many disputes. Data are presented to demonstrate the financial benefits that result from the introduction of systematic objective controls via technology. These sound management principles allow the risk manager to determine the validity of claims and treatment proposals. Risk managers can then make informed decisions on contentious claims and regulate the large number of clinician-supported disability cases--decisions that represent significant savings.

The related cytokines interleukin-13 and interleukin-4 are distinguished by differential production and differential effects on T lymphocytes.

We have compared the production of the related cytokines IL-13 and IL-4 by T lymphocytes, and the effects of the two cytokines on these cells. IL-13 and IL-4 production differ in a number of respects. IL-13 is produced at higher levels than IL-4 by activated T lymphocytes, and its accumulation in the culture medium can be more prolonged, corresponding partly to differential mRNA accumulation and partly to a preferential depletion of IL-4 from the culture medium. Certain inducing combinations such as PMA and anti-CD28, stimulate high levels of IL-13 and IL-13 mRNA, but little or no IL-4 or IL-4 mRNA. The ratio of IL-13 to IL-4, both at protein and mRNA levels, is higher in CD8+ lymphocyte than in CD4+ lymphocyte populations. Although after in vitro polarization of peripheral blood lymphocytes leading to type 1 and type 2 populations, IL-13 is made principally by cells of a type 2 phenotype, as is IL-4; it can also be produced by type 1 CD4+ and CD8+ T lymphocyte clones making large amounts of IFN-gamma and very little IL-4. IL-13 and IL-4 exert different effects on T lymphocyte functions. IL-13 does not significantly inhibit the IL-2-induced T lymphocyte production of IFN-gamma, RANTES, MIP-1 alpha or MIP-1 beta, nor that of perforin mRNA, as does IL-4. We have also been unable to demonstrate STAT6 activation by IL-13 on T lymphocytes purified in a number of ways, despite strong activation of STAT6 by IL-4 in these cells. This is contrary to some previous reports, but is consistent with the notion that the majority of T lymphocytes lack functional IL-13 receptors. A higher and more prolonged T lymphocyte production of IL-13 than that of IL-4 may thus be permissible because IL-13 does not inhibit T-cell functions. Conversely, sustained IL-13 production may be partly due to the absence of receptor-mediated depletion of this cytokine.

[Action of cytokines IL-12 and IL-4 on T helper cells. Cellular immunity or humoral immunity?]. / L'action des cytokines IL-12 et IL-4 sur les lymphocytes T auxiliaires. Immunité cellulaire ou immunité humorale?

TWO SUBSETS OF T-HELPER CELLS: T-helpers are divided into two subpopulations called Th1 and Th2 depending on the pattern of cytokines they produce. These mutually antagonist subpopulations exert different functions: Th1 cells control cellular immunity whereas Th2 cells control humoral immunity. LYMPHOCYTE DIFFERENTIATION: Several factors are involved, but the presence of certain cytokines in the environment, where cellular interactions driving specific lymphocyte sensitization occur, is the main factor determining differentiation into Th1 or Th2. CRUCIAL ROLE OF IL-12 AND IL-4: IL-12 can polarize lymphocytes towards a Th1 phenotype and IL-4 can direct T lymphocytes towards a Th2 pattern. PRACTICAL IMPLICATIONS: The use of cytokines, or cytokine-inhibiting agents, offers a new strategic approach for intentional modulation of the immune response.

Molecular characterization of human stathmin expressed in Escherichia coli: site-directed mutagenesis of two phosphorylatable serines (Ser-25 and Ser-63).

Stathmin, a probable relay protein possibly integrating multiple intracellular regulatory signals [reviewed in Sobel (1991) Trends Biochem. Sci. 16, 301-305], was expressed in Escherichia coli at levels as high as 20% of total bacterial protein. Characterization of the purified recombinant protein revealed that it had biochemical properties very similar to those of the native protein. It is a good substrate for both cyclic AMP-dependent protein kinase (PKA) and p34cdc2, on the same four sites as the native eukaryotic protein. As shown by m.s., the difference in isoelectric points from the native protein is probably due to the absence of acetylation of the protein produced in bacteria. C.d. studies indicate that stathmin probably contains about 45% of its sequence in an alpha-helical conformation, as also predicted for the sequence between residues 47 and 124 by computer analysis. Replacement of Ser-63 by alanine by in vitro mutagenesis resulted in a ten times less efficient phosphorylation of stathmin by PKA which occurred solely on Ser-16, confirming that Ser-63 is the major target of this kinase. Replacement of Ser-25, the major site phosphorylated by mitogen-activated protein kinase in vitro and in vivo, by the charged amino acid glutamic acid reproduced, in conjunction with the phosphorylation of Ser-16 by PKA, the mobility shift on SDS/polyacrylamide gels induced by the phosphorylation of Ser-25. This result strongly suggests that glutamic acid in position 25 is able to mimic the putative interactions of phosphoserine-25 with phosphoserine-16, as well as the resulting conformational changes that are probably also related to the functional regulation of stathmin.

Students with learning disabilities in the university environment: a study of faculty and student perceptions.

This study examines faculty and student perceptions regarding university students with learning disabilities, sensitivity to such students' special needs, accommodations, and the perceived impact of a learning disability. Results reveal a general sensitivity to the special needs of students with learning disabilities; however, group differences suggest several areas warranting further attention.

Effects of variation of ion and methylation of carrier on the rate constants of macrotetralide-mediated ion transport in lipid bilayers.

The effects of methylation on the rate constants of carrier-mediated ion transport have been studied on monooleindecane bilayers with K+, Rb+, NH4+, and Tl+ ions, using the series of homologue carriers, nonactin, monactin, dinactin, trinactin, and tetranactin, each member of the series differing from the previous one by only one methyl group. Measurements of the amplitude and time constant of the current relaxation after a voltage jump over a large domain of voltage and permeant ion concentration, together with a computer curve-fitting procedure, have allowed us, without the help of steady-state current-voltage data, to deduce and compare the values of the various rate constants for ion transport: formation (kRi) and dissociation (kDi) of the ion-carrier complex at the interface, translocation across the membrane interior of the carrier (ks) and the complex (kis). With the additional information from steady-state low-voltage conductance measurements, we have obtained the value of the aqueous phase-membrane and torus-membrane partition coefficient of the carrier (gammas and gammas). From nonactin to tetranactin with the NH4+ ion, kis, and gammas are found to increase by factors of 5 and 3, respectively, kDi and gammas to decrease respectively by factors 8 and 2, while kRi and ks are practically invariant. Nearly identical results are found for K+, Rb+, and Tl+ ions. kRi, ks and kis are quite invariant from one ion to the other except for Tl+ were kRi is about five times larger. On the other hand, kDi depends strongly on the ion, indicating that dissociation is the determining step of the ionic selectivity of a given carrier. The systematic variations in the values of the rate constants with increasing methylation are interpreted in terms of modification of energy barriers induced by the carrier increasing size. Within this framework, we have been able to establish and verify a fundamental relationship between the variations of kis and kDi with methylation.