Characterisation of chronic lateral epicondylalgia using the McGill pain questionnaire, visual analog scales, and quantitative sensory tests

Aims: To characterise chronic lateral epicondylalgia using the McGill Pain Questionnaire, Visual Analog Scales for pain and function, and Quantitative Sensory Tests; and to examine the relationship between these tests in a population with chronic lateral epicondylalgia. Method: Fifty-six patients (29 female, 27 male) diagnosed with unilateral lateral epicondylalgia of 18.7 months (mean) duration (range 1-300), with a mean age of 50.7 years (range 27-73) participated in this study. Each participant underwent assessment with the McGill Pain Questionnaire (MPQ), Visual Analog Scales (VAS) for pain and function. and Quantitative Sensory Tests (QST) including thermal and pressure pain thresholds, pain free grip strength, and neuromeningeal tissue testing via the upper limb tension test 2b (ULTT 2b). Results: Moderate correlation (r = .338-.514, p = .000-.013) was found between all indices of the MPQ and VAS for pain experienced in the previous 24 hours and week. Thermal pain threshold was found to be significantly higher in males. A significant poor to moderate correlation was found between the Pain Rating Index (PRI) in the sensory category of the MPQ and ULTT2b scores (r = .353, p = .038). There was no other significant correlation between MPQ and QST data. Pain free grip strength was poorly yet significantly correlated with duration of pathology (r = 318, p = .038). Conclusion: The findings of this study are in agreement with others (Melzack and Katz, 1994) regarding the multidimensional nature of pain, in a condition conventionally conceived as a musculoskeletal pain state. The findings also suggest that utilisation of only one pain measurement tool is unlikely to provide a thorough clinical picture of pain experienced with chronic lateral epicondylalgia.

A study of five cervicocephalic relocation tests in three different subject groups

Objective: To compare head relocation accuracy in traumatic ( whiplash), insidious onset neck pain patients and asymptomatic subjects when targeting a natural head posture (NHP) and complex predetermined positions. Design: A case-control study. Setting: University-based musculoskeletal research clinic. Participants: Sixty-three volunteers divided into three groups of similar gender and age: Group 1 (n=21) an asymptomatic group; group 2 (n=20) insidious onset neck pain; group 3 (n=22) a history of whiplash injury. Intervention: Five randomly ordered tests designed to detect relocation accuracy of the head. Outcome measures: A 3-Space Fastrak system measured the mean absolute relocation error of three trials of each relocation test. Results: A significant difference was found between groups in one of the tests targeting the NHP (p=0.001). Post-hoc pairwise comparisons revealed a significant difference (pless than or equal to0.05) between the asymptomatic group and each symptomatic group. The difference between the symptomatic groups just failed to reach significance (p=0.07). None of the other four tests revealed significant differences. Conclusion: The test of targeting the NHP indicates that relocation inaccuracy exists in patients with neck pain with a trend to suggest that the deficit may be greater in whiplash patients. Tests employing unfamiliar postures or more complex movement were not successful in differentiating subject groups.

Polymerase chain reaction tests for the identification of Ross River, Kunjin and Murray Valley encephalitis virus infections in horses

Objective To develop and validate specific, sensitive and rapid diagnostic tests using RT-PCR for the detection of Ross River virus (RRV), Kunjin virus (KV) and Murray Valley encephalitis virus (MVEV) infections in horses. Methods Primer sets based on nucleotide sequence encoding the envelope glycoprotein E2 of RRV and on the nonstructural protein 5 (NS5) of KV and MVEV were designed and used in single round PCRs to test for the respective viruses in infected cell cultures and, in the case of RRV, in samples of horse blood and synovial fluid. Results The primer pairs designed for each of the three viruses amplified a product of expected size from prototype viruses that were grown in cell culture. The identity of each of the products was confirmed by nucleotide sequencing indicating that in the context used the RT-PCRs were specific. RRV was detected in serums from 8 horses for which there were clinical signs consistent with RRV infection such that an acute-phase serum sample was taken and submitted for RRV serology testing. The RRV RT-PCR was analytically sensitive in that it was estimated to detect as little as 50 TCID50 of RRV per mL of serum and was specific in that the primer pairs did not amplify other products from the 8 serum samples. The RRV primers also detected virus in three independent mosquito pools known to contain RRV by virus isolation in cell culture. Samples from horses suspected to be infected with KV and MVEV were not available. Conclusion Despite much anecdotal and serological evidence for infection of horses with RRV actual infection and associated clinical disease are infrequently confirmed. The availability of a specific and analytically sensitive RT-PCR for the detection of RRV provides additional opportunities to confirm the presence of this virus in clinical samples. The RTPCR primers for the diagnosis of KV and MVEV infections were shown to be specific for cell culture grown viruses but the further validation of these tests requires the availability of appropriate clinical samples from infected horses.

Provision of 4-1BB ligand enhances effector and memory CTL responses generated by immunization with dendritic cells expressing a human tumor-associated antigen

Up-regulation of receptor-ligand pairs during interaction of an MHC-presented epitope on dendritic cells (DCs) with cognate TCR may amplify, sustain, and drive diversity in the ensuing T cell immune response. Members of the TNF ligand superfamily and the TNFR superfamily contribute to this costimulatory molecule signaling. In this study, we used replication deficient adenoviruses to introduce a model tumor-associated Ag (the E7 oncoprotein of human papillomavirus 16) and the T cell costimulatory molecule 4-IBBL into murine DCs, and monitored the ability of these recombinant DO to elicit E7-directed T cell responses following immunization. Splenocytes from mice immunized with DCs expressing E7 alone elicited E7-directed effector and memory CTL responses. Coexpression of 4-1BBL in these E7-expressing DO increased effector and memory CTL responses when they were used for immunization. 4-1BBL expression up-regulated CD80 and CD86 second signaling molecules in DO. We also report an additive effect of 4-IBBL and receptor activator of NF-kappaB/receptor activator of NF-kappaB ligand coexpression in E7-transduced DC inummogens on E7-directed effector and memory CTL responses and on MHC class II and CD80/86 expression in DCs. Additionally, expression of 4-1BBL in E7-transduced DCs reduced nonspecific T cell activation characteristic of adenovirus vector-associated immunization. The results have generic implications for improved or tumor Ag-expressing DC vaccines by incorporation of exogenous 4-1BBL. There are also specific implications for an improved DC-based vaccine for human papillomavirus 16-associated cervical carcinoma.

Reciprocal changes in forebrain contents of glycogen and of glutamate/glutamine during early memory consolidation in the day-old chick

Passive avoidance learning is with advantage studied in day-old chicks trained to distinguish between beads of two different colors, of which one at training was associated with aversive taste. During the first 30-min post-training, two periods of glutamate release occur in the forebrain. One period is immediately after the aversive experience, when glutamate release is confined to the left hemisphere. A second release, 30 min later, may be bilateral, perhaps with preponderance of the right hemisphere. The present study showed increased pool sizes of glutamate and glutamine, specifically in the left hemisphere, at the time when the first glutamate release occurs, indicating de novo synthesis of glutamate/glutamine from glucose or glycogen, which are the only possible substrates. Behavioral evidence that memory is extinguished by intracranial administration at this time of iodoacetate, an inhibitor of glycolysis and glycogenolysis, and that the extinction of memory is counteracted by injection of glutamine, supports this concept. A decrease in forebrain glycogen of similar magnitude and coinciding with the increase in glutamate and glutamine suggests that glycogen rather than glucose is the main source of newly synthesized glutamate/glutamine. The second activation of glutamatergic activity 30 min after training, when memory is consolidated into stable, long-term memory, is associated with a bilateral increase in pool size of glutamate/glutamine. No glycogenolysis was observed at this time, but again there is a temporal correlation with sensitivity to inhibition by iodoacetate and rescue by glutamine, indicating the importance of de novo synthesis of glutamate/glutamine from glucose or glycogen. (C) 2003 Elsevier B.V All rights reserved.

Enhanced effector and memory CTL responses generated by incorporation of receptor activator of NF-kappa B(RANK)/RANK ligand costimulatory molecules into dendritic cell immunogens expressing a human tumor-specific antigen

The outcome of dendritic cell (DC) presentation of Ag to T cells via the TCR/MHC synapse is determined by second signaling through CD80/86 and, importantly, by ligation of costimulatory ligands and receptors located at the DC and T cell surfaces. Downstream signaling triggered by costimulatory molecule ligation results in reciprocal DC and T cell activation and survival, which predisposes to enhanced T cell-mediated immune responses. In this study, we used adenoviral vectors to express a model tumor Ag (the E7 oncoprotein of human papillomavirus 16) with or without coexpression of receptor activator of NF-kappaB (RANK)/RANK ligand (RANKL) or CD40/CD40L costimulatory molecules, and used these transgenic DCs to immunize mice for the generation of E7-directed CD8(+) T cell responses. We show that coexpression of RANK/RANKL, but not CD40/CD40L, in E7-expressing DCs augmented E7-specific IFN-gamma-secreting effector and memory T cells and E7-specific CTLs. These responses were also augmented by coexpression of T cell costimulatory molecules (RANKL and CD40L) or DC costimulatory molecules (RANK and CD40) in the E7-expressing DC immunogens. Augmentation of CTL responses correlated with up-regulation of CD80 and CD86 expression in DCs transduced with costimulatory molecules, suggesting a mechanism for enhanced T cell activation/survival. These results have generic implications for improved tumor Ag-expressing DC vaccines, and specific implications for a DC-based vaccine approach for human papillomavirus 16-associated cervical carcinoma.