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Biomedical subjects

G A McCain

Publications and source records attributed to G A McCain.

At least 19 recordsLinked to original sources

The fibromyalgia and myofascial pain syndromes: a preliminary study of tender points and trigger points in persons with fibromyalgia, myofascial pain syndrome and no disease.

Four experts on myofascial pain syndrome (MFP) performed trigger point examinations and 4 experts on fibromyalgia performed tender point examinations on 3 groups of subjects (7 patients with fibromyalgia, 8 with MFP, and 8 healthy persons) while blinded as to diagnosis. Local tenderness was common in both disease groups (65-82%), but was elicited in a greater proportion of MFP experts' examinations (82%). Active trigger points were found in about 18% of examinations of patients with fibromyalgia and MFP, but latent trigger points were rare in all groups. A more liberal definition of trigger point, however, resulted in a 38 and 23% positive rate among patients with fibromyalgia and MFP, respectively. Taut muscle bands and muscle twitches were common (50 and 30%, respectively) and noted equally in all 3 diagnostic groups. Problems with reliability were identified for taut bands, muscle twitch, and active trigger points. Our data are exploratory and tentative, but suggest that attention to definition and reliability are required to advance our knowledge of these common syndromes.

Fibromyalgia

Cognitive behavioral treatment of fibromyalgia syndrome: preliminary findings.

We used a simple quasiexperimental design to assess the efficacy of an inpatient cognitive-behavioral treatment program for persons with fibromyalgia syndrome (FS). Twenty-five participants were assessed on 3 occasions: (1) about 5 months before admission to the program, (2) on admission and (3) at discharge. In addition, the dependent variables (pain response measures) were divided into "target" (expected to change with treatment) and "nontarget" (not expected to change) to assess potential demand characteristics. Our results showed that, whereas no changes occurred in either target or nontarget variables between the initial assessment and admission, consistent changes were observed only in target variables between admission and discharge. Our data provide preliminary support for cognitive-behavioral treatment for FS.

Adolescent

Cytokine production and lymphocyte transformation during stress.

The production of interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN gamma) and blast transformation in peripheral blood mononuclear cells were assessed in medical students writing an academic examination. Blood samples were obtained on three occasions: (1) 1 month prior to the examination during a period of relatively low academic demand; (2) immediately after the examination; and (3) 10 days later. Results indicated that immune responses were significantly different immediately after the examination compared with the baseline and postexam measures. Lymphocyte responsiveness to both concanavalin A and pokeweed mitogen was decreased, as was the production of IFN gamma, supporting earlier reports of immunosuppression after relatively commonplace stressors. In contrast to predictions, IL-1 beta production was significantly elevated after the examination. Cortisol levels were also measured, but did not change across the three sample points. Our finding of an increase in IL-1 beta production suggests that stress may have different effects on different cell populations by enhancing the responses of monocytes and depressing those of lymphocytes.

Adult

Rheumatoid arthritis antirheumatic drug trials. I. Effects of standardization procedures on observer dependent outcome measures.

A study was designed to assess the effects of standardization procedures on reducing interobserver variability for outcome measures given in the current Food and Drug Administration and European League Against Rheumatism guidelines and others selected from the rheumatology literature. Over 2 days, 6 rheumatologists independently examined 6 patients with rheumatoid arthritis (RA) in predetermined order before and after standardizing their examination techniques. An important and beneficial effect of the standardization procedure was observed on the majority of outcome variables. Such reductions in observer variability have the potential to diminish sample size requirements for antirheumatic drug studies.

Adult

Rheumatoid arthritis antirheumatic drug trials. III. Setting the delta for clinical trials of antirheumatic drugs--results of a consensus development (Delphi) exercise.

Defining the minimum clinically important difference or delta to be detected in a clinical trial depends on a number of factors including the research hypothesis, patient characteristics, the nature of the intervention and the trial design. In 2 previous studies, we have developed standardized procedures for conducting outcome measurement based on current Food and Drug Administration and European League Against Rheumatism guidelines for RA clinical trials, and thereafter, determined the standard deviation for these outcome measures. In the final component of this series of studies, we employed a Delphi technique to establish estimates for delta and calculated the sample size requirements under different conditions of Type I and Type II error probabilities.

Arthritis, Rheumatoid

Rheumatoid arthritis antirheumatic drug trials. II. Tables for calculating sample size for clinical trials of antirheumatic drugs.

The calculation of sample size requires knowledge of the standard deviation (SD) of index variables. Unfortunately, there are no published lists of SD and it is exceedingly difficult to locate variance estimates based on relevant populations. We used standardized procedures to determine in 60 patients with rheumatoid arthritis (RA) the SD of key outcome measures recommended in current Food and Drug Administration and European League Against Rheumatism guidelines for RA clinical trials. We anticipate that these tables will be useful to clinical researchers in selecting outcome measures as well as for calculating sample size requirements for future clinical studies in RA.

Anti-Inflammatory Agents

In vitro effects of two gold compounds, and D-penicillamine on the production of interferon gamma.

There are contradictory reports on Interferon Gamma (IFN gamma) production by peripheral blood mononuclear cells (PBMC) in rheumatoid arthritis (RA). Since many patients previously studied were on Gold Sodium Thiomalate (GST), Auranofin (Auf), or D-Penicillamine (D-Pen) we have investigated the effects of these drugs on IFN gamma production using PBMC from normal controls (NC), and RA patients off GST, Auf, and D-Pen. Auf in low concentrations enhanced IFN gamma production by PBMC from NC but not RA; GST, and D-Pen had no effect. In other experiments PBMC were stimulated with concanavalin A (CONA A), or phytohemagglutinin (PHA). Auf, and GST inhibited IFN gamma production by CON A - stimulated NC and RA cells; D-Pen had no effect. Auf in low concentrations enhanced IFN gamma production by PHA - stimulated NC cells, but this effect was not seen with RA cells; GST inhibited both RA and NC cell production of IFN gamma, and D-Pen had no effect. Auf has a biphasic effect on IFN gamma production by NC cells with low concentrations being stimulatory or co-stimulatory, possibly by acting on T helper cells. Higher concentrations of Auf and GST, equivalent to those achieved in vivo in the course of therapy, inhibit IFN gamma production. These results suggest that gold therapy may affect IFN gamma production in RA, and could explain discrepancies noted in previous studies.

Adult

Regulation of autoimmunity in normal and rheumatoid individuals by bone marrow-derived natural suppressor cells and their suppressor factor: BDSF.

Natural suppressor activity is defined as the ability of unstimulated effector cells to suppress responses of lymphoid cells to antigenic and mitogenic stimuli in an MHC unrestricted manner. We have described natural suppressor cells in bone marrow exerting such a function through a suppressor factor termed BDSF. In this report we demonstrate the ability of BDSF to regulate the in vitro EBV- and PWM-induced production of both IgM and IgM rheumatoid factor antibodies of lymphoid cells obtained from normal individuals and those with rheumatoid arthritis. BDSF therefore may play a role in the normal BM microenvironment suppressing primary IgM antibody responses. Since autoantibody responses are similarly suppressed, functional alteration or lack of BDSF may be responsible for the emergence of autoantibody-producing cells in bone marrow during certain autoimmune states.

Arthritis, Rheumatoid

Clearance of inhaled particles in ankylosing spondylitis.

Patients with ankylosing spondylitis may uncommonly develop apical fibrobullous lung disease, the cause of which is unknown. It is postulated here that rigidity of the thoracic cage leads to reduced apical clearance of inhaled particles and may thereby predispose to chronic infection. Deposition and clearance of inhaled technetium-99m sulphur colloid particles were studied in eight male patients with ankylosing spondylitis who had chest wall rigidity (mean (SD) chest expansion 1.8 (1.07) cm) but normal chest radiographs. As a reference population eight healthy male volunteers were also studied. Particle deposition showed an increasing gradient from apex to base, with no significant difference between patients and controls. Clearance was assessed by comparing absolute counts, corrected for decay, at 24 hours with the baseline values. No delay in particle clearance in those with ankylosing spondylitis was apparent.

Adult

Improvements in pain responsiveness in patients with fibrositis after successful treatment with amitriptyline.

Thirty-six patients with fibrositis received low dose amitriptyline and placebo in a randomized double blind crossover study lasting 10 weeks. Amitriptyline was associated with significant changes on the outcome measures of pain, tender point sensitivity and patient assessment of well being. Clinically significant improvements for pain and tender point sensitivity and a statistically significant improvement in generalized pain responsiveness were found between patients who reported subjective improvement on amitriptyline and those who felt no change.

Adult

The problem of longterm disability payments and litigation in primary fibromyalgia: the Canadian perspective.

The determination of disability in fibromyalgia syndrome is problematic because of its perceived subjective nature and the absence of well defined criteria for diagnosis. This, together with an unclear idea of the natural history, creates problems in litigation and determination of rehabilitation costs. Lawyers and third party payers must cooperate with physicians to determine the "hidden costs" of fibromyalgia so that a fairer estimate of longterm disability is achieved.

Canada

Diurnal hormone variation in fibromyalgia syndrome: a comparison with rheumatoid arthritis.

Twenty patients with fibromyalgia syndrome and 20 patients with rheumatoid arthritis (RA) were assessed as outpatients over a 3 day period with respect to peak and trough levels of plasma cortisol, growth hormone, prolactin, ACTH and thyroid stimulating hormone. Patients with fibromyalgia syndrome had loss of diurnal variation in plasma cortisol (trough levels 347.3 +/- 254.7 vs 232.8 +/- 70.0 nmol/l, p less than 0.001) compared with RA patients. Thirty-five percent (7/20) of patients with fibromyalgia syndrome and only 5 percent (1/20) of those with RA exhibited abnormal dexamethasone suppression tests (p less than 0.001). No differences were noted in the diurnal variation of other hormones tested. Beck Depression Inventory scores were similar in both groups and no patient exhibited clinical evidence of depression. These data suggest alteration in the pituitary hypothalamic axis with respect to cortisol secretion in fibromyalgia syndrome, perhaps as a consequence of chronic pain.

Arthritis, Rheumatoid

Nonmedicinal treatments in primary fibromyalgia.

To date, few nonmedicinal treatments for primary fibromyalgia have been studied using acceptable scientific standards. This has led to rather arbitrary use of disparate treatment modalities, often in a haphazard sequence. Because primary fibromyalgia syndrome is a chronic painful condition, rationale for treatment should be based on present concepts of pain perception supported by studies in the basic sciences. Recent clinical studies in the treatment of primary fibromyalgia syndrome conforming to the scientific method have been discussed in light of what is presently known about pain transmission and perception.

Biofeedback, Psychology

A controlled study of the effects of a supervised cardiovascular fitness training program on the manifestations of primary fibromyalgia.

Forty-two patients with primary fibromyalgia were randomized into a 20-week program consisting of either cardiovascular fitness (CVR) training or simple flexibility exercises (FLEX) that did not lead to enhanced cardiovascular fitness. Patients were supervised by the same medical fitness instructors. Patients in neither group had contact with members of the other group, and were blinded as to the exercise taught to the alternative group. Groups met for 60 minutes 3 times each week. The compliance rate was 90%. Thirty-eight patients completed the study (18 with CVR training and 20 with FLEX). Blind assessments (standardized in preliminary trials to achieve acceptable inter-rater agreement) were performed by the same 2 examiners. After 20 weeks, patients receiving CVR training showed significantly improved cardiovascular fitness scores compared with those receiving FLEX training (t[35] = -4.22, P less than 0.003). Logistic regression analysis showed clinically and statistically significant improvements in pain threshold scores, which were measured directly over fibrositic tender points, in patients undergoing CVR (t[35] = 2.21, P less than 0.04). There was also a trend toward improvement in pain scores (visual analog scale) in the CVR group, but this did not reach statistical significance. There was no improvement in the percentage of body area affected by fibrositic symptoms or the number of nights per week or hours per night of disturbed sleep (self-report inventories). However, compared with the FLEX group, the CVR-trained patients improved significantly in both patient and physician global assessment scores.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Sodium aurothiomalate inhibits T cell responses to interleukin-2.

We studied the effects of the gold compound sodium aurothiomalate (SATM) on the responses of murine CTLL2 cells, and human T cells to Interleukin-2 (IL-2). SATM inhibited tritiated thymidine (3HTdR) incorporation by CTLL2 cells stimulated with human recombinant IL-2. Human T cells were cultured with phytohemagglutinin (PHA) in separate experiments and IL-2 receptor expression measured by using immunofluorescent anti-Tac serum; SATM inhibited IL-2 receptor expression. Furthermore, SATM when added concurrently with PHA, and IL-2 inhibited 3HTdR incorporation by human T cells in 5 day cultures. The kinetics of inhibition were further studied by adding PHA to T cells for 48 hours followed by the addition of SATM and IL-2; SATM inhibited 3HTdR incorporation even though receptor expression had occurred. These results suggest that SATM inhibits the stimulatory effects of IL-2 on T cells partly by interfering with IL-2 receptor expression, and partly by other mechanisms of action. These effects of SATM may explain some of the conflicting data in the literature on T cell responses to IL-2 in rheumatoid arthritis (RA), and suggest a possible mechanism of action for the drug in the treatment of RA.

Female

Effects of gold on the production of and response to human interleukin-1.

We studied the effects in vitro of sodium aurothiomalate (GSTM) on the production of, and response to, a monocyte supernatant with interleukin-1 (IL-1)-like activity. Monocyte supernatant was produced by human peripheral blood monocytes stimulated with lipoprotein polysaccharide, and its IL-1-like activity assayed by its effect on tritiated thymidine incorporation by C3H/HeJ mouse thymocytes. GSTM inhibited the thymocyte response to monocyte supernatant even when added to monocyte supernatant and thymocytes after 48 h of culture. GSTM also inhibited production of IL-1-like activity by monocytes, when added to culture within the first 22 h. Inhibition of both response to and production of monocyte supernatant was dose dependent. These effects of GSTM on Il-1-like activity may constitute one of the mechanisms of action of the drug in rheumatoid arthritis.

Adult

Pain perception and personality measures as discriminators in the classification of fibrositis.

Twenty patients with fibrositis were compared to age and sex matched groups of patients with rheumatoid arthritis (RA) and normal controls regarding personality variables measured by the Basic Personality Inventory (BPI) and responsiveness to experimentally induced pain. The group with fibrositis scored significantly higher than the normal group on 4 of the BPI scales and had lower pain threshold and tolerance than the normal group. The group with RA was found to be significantly different from the normal group on hypochondriasis and pain tolerance. Using only pain and personality measures, a statistical discriminant function that was developed resulted in a 72% classification accuracy for the 3 groups studied and 85% accuracy when only the 2 clinical groups were considered.

Adult

Role of physical fitness training in the fibrositis/fibromyalgia syndrome.

Cardiovascular fitness training has been suggested as a treatment for the fibrositis/fibromyalgia syndrome. Thirty-four patients with fibrositis/fibromyalgia who met Smythe's original criteria were randomly assigned to enter either a cardiovascular fitness training program or a program consisting only of flexibility exercises. Patients met in supervised groups three times weekly for a 20-week observation period. The cardiovascular fitness group underwent gradual heart rate-elevated training using a bicycle ergometer and achieved a 29.1 +/- 24.4 percent increase in peak work capacity at 170 beats per minute (PWC-170). Patients undergoing flexibility training had a net reduction in their PWC-170 scores of 4.3 +/- 9.4 percent. Patients in the cardiovascular fitness group had statistically significant improvements in the visual analogue pain scale of current pain intensity; total myalgic scores in which pain thresholds at five fibrositic tender points selected for acceptable intra-rater and inter-rater reliability were measured using a dolorimeter; percentage total body area affected as measured by self-administered pain diagrams; and patients' and physicians' global assessment scores. Psychologic profiles as measured by Symptom Checklist-90R also improved in the cardiovascular fitness group compared with the flexibility training group. It is concluded that cardiovascular fitness training is feasible in patients with fibrositis/fibromyalgia and that such training improves subjective measurements of pain-reporting behavior. A theoretic basis for improvements in pain measurement scales and psychologic profiles is discussed in light of recent literature.

Cardiovascular Physiological Phenomena