Clarithromycin and prednisolone inhibit cytokine production in chronic rhinosinusitis

Objectives. Long-term, low-dose macrolide therapy is effective in the treatment of chronic rhinosinusitis. The mechanism of its anti-inflammatory effect and how this differs from corticosteroids remains unclear. The effect of clarithromycin and prednisolone on interleukin-5, interleukin-8, and granulocyte-macrophage colony-stimulating factor production by cultured chronic sinusitis nasal mucosa was examined in the study. Study Design and Methods. Nasal mucosa was obtained from 11 patients with chronic sinusitis. This tissue was cultured for 24 hours in the presence of clarithromycin or prednisolone at a variety of concentrations. Cytokine levels were determined by enzyme-linked immunoassay. Results. Clarithromycin and prednisolone each produced significant reductions in interleukin-5, interleukin-8, and granulocyte-macrophage colony-stimulating factor production. There was no significant difference between the effects of clarithromycin and prednisolone. Conclusion: Macrolide antibiotics are capable of inhibiting pro-inflammatory cytokine production in vitro and are as potent as prednisolone. This mechanism is likely to be at least partly responsible for the clinical efficacy of macrolide antibiotics in chronic rhinosinusitis. Key Words. Macrolide, prednisolone, sinusitis, enzyme-linked immunosorbent assay, cytokine.

Donor-derived b2a2-specific T cells for immunotherapy of patients with chronic myeloid leukemia

The BCR-ABL fusion proteins, b2a2 and b3a2, are potential targets for a beneficial graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation for chronic myeloid leukemia (CML). This study demonstrates that CD4(+) T cells specific to the b2a2 peptide can be generated from a normal allogeneic stem cell transplant donor after stimulation with monocyte-derived dendritic cells (Mo-DC) using culture conditions applicable to clinical use. Stimulation of donor T-cell enriched mononuclear cells (MNC) with b2a2-pulsed Mo-DC produced approximately 3 x 10(9) b2a2-specific CD4(+) T cells. The CD4(+) T cells were HLA-DR7 restricted. These results confirm that the generation of donor derived b2a2-specific T cells for clinical use is feasible and warrants clinical testing after stem cell transplantation.

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.

Cost comparison of hospital- and home-based treatment models for acute chronic obstructive pulmonary disease

This trial compared the cost of an integrated home-based care model with traditional inpatient care for acute chronic obstructive pulmonary disease (COPD). 25 patients with acute COPD were randomised to either home or hospital management following request for hospital admission. The acute care at home group costs per separation ($745, CI95% $595-$895, n = 13) were significantly lower (p < 0.01) than the hospital group ($2543, CI95% $1766-$3321, n = 12). There was an improvement in lung function in the hospital-managed group at the Outpatient Department review, decreased anxiety in the Emergency Department in the home-managed group and equal patient satisfaction with care delivery. Acute care at home schemes can substitute for usual hospital care for some patients without adverse effects, and potentially release resources. A funding model that allows adequate resource delivery to the community will be needed if there is a move to devolve acute care to community providers.

Crohn's disease with oral presenting signs masquerading as chronic osteomyelitis

Background: A case of Crohn's disease (CD) was diagnosed following recognition of oral and systemic signs and symptoms in a 19-year-old male patient. Methods: Clinical investigation utilized included blood tests (full blood count, electrolytes, urea, creatinine, liver function tests), computed tomogrphy scans, magnetic resonance imaging scans, oral biopsies, colonoscopy and biopsies of the terminal ileum and colon. Results: A diagnosis of CD was made which then allowed appropriate medical treatment to be initiated. Conclusion: The importance of a thorough medical history and full physical examination with appropriate investigations as dictated by clinical findings is demonstrated.

Myoelectric manifestations of sternocleidomastoid and anterior scalene muscle fatigue in chronic neck pain patients

Objective: This study compares myoelectric manifestations of fatigue of the sternocleidomastoid (SCM) and anterior scalene (AS) muscles between 10 chronic neck pain subjects and 10 normal matched controls. Methods: Surface electromyography (sEMG) signals were recorded from the sternal bead of SCM and AS muscles bilaterally during submaximal isometric cervical flexion contractions at 25 and 50% of the maximum voluntary contraction (MVC). The mean frequency, average rectified value and conduction velocity of the sEMG signal were calculated to quantify myoelectric manifestations of muscle fatigue. Results: For both the SCM and AS muscles, the Mann-Whitney U test indicated that the initial value and slope of the mean frequency in neck pain patients were greater than in healthy subjects (P < 0.05). This was significant both at 25 and 50% of MVC. Conclusions: These results suggest: (a) a predominance of type-II fibres in the neck pain patients and/or (b) greater fatigability of the superficial cervical flexors in neck pain patients. These results are in agreement with previous muscle biopsy studies in subjects with neck pain, which identified transformation of slow-twitch type-I fibres to fast-twitch type-IIB fibres, as well as the clinical observation of reduced endurance in the cervical flexors in neck pain patients. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

Core outcome domains for chronic pain clinical trials: IMMPACT recommendations

Objective. To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of data, encourage more complete reporting of outcomes, simplify the preparation and review of research proposals and manuscripts, and allow clinicians to make informed decisions regarding the risks and benefits of treatment. Methods. Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 27 specialists from academia. governmental agencies, and the pharmaceutical industry participated in a consensus meeting and identified core outcome domains that should be considered in clinical trials of treatments for chronic pain. Conclusions. There was a consensus that chronic pain clinical trials should assess outcomes representing six core domains: (1) pain, (2) physical functioning, (3) emotional functioning, (4) participant ratings of improvement and satisfaction with treatment, (5) symptoms and adverse events, (6) participant disposition (e.g. adherence to the treatment regimen and reasons for premature withdrawal from the trial). Although consideration should be given to the assessment of each of these domains, there may be exceptions to the general recommendation to include all of these domains in chronic pain trials. When this occurs, the rationale for not including domains should be provided. It is not the intention of these recommendations that assessment of the core domains should be considered a requirement for approval of product applications by regulatory agencies or that a treatment must demonstrate statistically significant effects for all of the relevant core domains to establish evidence of its efficacy. (C) 2003 International Association for the Study of Pain.

Effects of glucose-insulin-potassium infusion on chronic ischaemic left ventricular dysfunction

Background: Glucose-insulin-potassium (GIK) infusion improves cardiac function and outcome during acute ischaemia. Objective: To determine whether GIK infusion benefits patients with chronic ischaemic left ventricular dysfunction, and if so whether this is related to the presence and nature of viable myocardium. Methods: 30 patients with chronic ischaemic left ventricular dysfunction had dobutamine echocardiography and were given a four hour infusion of GIK. Segmental responses were quantified by improvement in wall motion score index (WMSI) and peak systolic velocity using tissue Doppler. Global responses were assessed by left ventricular volume and ejection fraction, measured using a three dimensional reconstruction. Myocardial perfusion was determined in 15 patients using contrast echocardiography. Results: WMSI (mean (SD)) improved with dobutamine (from 1.8 (0.4) to 1.6 (0.4), p < 0.001) and with GIK (from 1.8 (0.4) to 1.7 (0.4) p < 0.001); there was a similar increment for both. Improvement in wall motion score with GIK was observed in 55% of the 62 segments classed as viable by dobutamine echocardiography, and in 5% of 162 classed as non-viable. There was an increment in peak systolic velocity after both doputamine echocardiography (from 2.5 (1.8) to 3.2 (2.2) cm/s, p < 0.01) and GIK (from 3.0 (1.6) to 3.5 (17) cm/s, p < 0.001). The GlK effects were not mediated by changes in pulse, mean arterial pressure, lactate, or catecholamines, nor did they correlate with myocardial perfusion. End systolic volume improved after GlK (p = 0.03), but only in 25 patients who had viable myocardium on dobutom ne echocardiography. Conclusions: In patients with viable myocardium and chronic left ventricular dysfunction, GlK improves wall motion score, myocardial velocity, and end systolic volume, independent of effects on haemodynamics or catecholamines. The response to GlK is observed in areas of normal and abnormal perfusion assessed by contrast echocardiography.

In overweight patients with chronic hepatitis C, circulating insulin is associated with hepatic fibrosis: implications for therapy

Background/Aims: Host factors such as increased body mass index (BMI) and genotype-specific viral factors contribute to the development of steatosis in patients with chronic hepatitis C (HCV). We hypothesized that host metabolic factors associated with increased BMI may play a role in disease progression. Methods: Fasting serum was collected from 160 patients with chronic HCV at the time of liver biopsy and 45 age, gender and BMI matched controls, and assessed for levels of insulin, c-peptide and leptin. Results: Patients with viral genotype 3 had more severe steatosis (P = 0.0001) and developed stages 1 and 2 fibrosis at a younger age (P < 0.05) than patients with genotype 1. For both genotypes, overweight patients had significantly more steatosis and increased insulin and leptin levels. In contrast to lean patients, there was a statistically significant increase in circulating insulin levels with increasing fibrosis in overweight patients with chronic HCV (P = 0.03). Following multivariate analysis, insulin was independently associated with fibrosis (P = 0.046) but not inflammation (P = 0.83). There was no association between serum leptin levels and stage of fibrosis. Conclusions: Increasing circulating insulin levels may be a factor responsible for the association between BMI and fibrosis in patients with HCV, irrespective of viral genotype. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Unraveling the barriers to reconceptualization of the problem in chronic pain: The actual and perceived ability of patients and health professionals to understand the neurophysiology

To identify why reconceptualization of the problem is difficult in chronic pain, this study aimed to evaluate whether (1) health professionals and patients can understand currently accurate information about the neurophysiology of pain and (2) health professionals accurately estimate the ability of patients to understand the neurophysiology of pain. Knowledge tests were completed by 276 patients with chronic pain and 288 professionals either before (untrained) or after (trained) education about the neurophysiology of pain. Professionals estimated typical patient performance on the test. Untrained participants performed poorly (mean +/- standard deviation, 55% +/- 19% and 29% +/- 12% for professionals and patients, respectively), compared to their trained counterparts (78% +/- 21% and 61% +/- 19%, respectively). The estimated patient score (46% +/- 18%) was less than the actual patient score (P < .005). The results suggest that professionals and patients can understand the neurophysiology of pain but professionals underestimate patients' ability to understand. The implications are that (1) a poor knowledge of currently accurate information about pain and (2) the underestimation of patients' ability to understand currently accurate information about pain represent barriers to reconceptualization of the problem in chronic pain within the clinical and lay arenas. (C) 2003 by the American Pain Society.

3: Rehabilitation principles for treating chronic musculoskeletal injuries

Evaluation of patients for rehabilitation after musculoskeletal injury involves identifying, grading and assessing the injury and its impact on the patient's normal activities. Management is guided by a multidisciplinary team, comprising the patient, doctor and physical therapist, with other health professionals recruited as required. Parallel interventions involving the various team members are specified in a customised management plan. The key component of the plan is active mobilisation utilising strengthening, flexibility and endurance exercise programs. Passive physical treatments (heat, ice, and manual therapy), as well as drug therapy and psychological interventions, are used as adjunctive therapy. Biomechanical devices or techniques (eg, orthotic devices) may also be helpful. Coexisting conditions such as depression and drug dependence are treated at the same time as the injury. Effective team communication, simulated environmental testing and, for those employed, contact with the employer facilitate a staged return to normal living, sports and occupational activities.