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Biomedical subjects

R G Cooper

Publications and source records attributed to R G Cooper.

At least 19 recordsLinked to original sources

Electro and acoustic myography for noninvasive assessment of lumbar paraspinal muscle function.

In 31 normal subjects (17 male), aged 19-48 years, and 8 patients with chronic low back pain (4 male), aged 37-55 years, the repeatability of surface recordings of acoustic myography (AMG) and electromyography (EMG) were examined in the lumbar paraspinal muscles. Five isometric test positions were examined. In 21 of the normal subjects, four positions tested were: quiet standing, half extension from prone lying, full extension from prone with and without resistance. In 10 of the normal subjects and the 8 back pain patients, a standardised, unsupported horizontal position with the upper body over the end of a couch was tested. The AMG and EMG signals were full-wave rectified and integrated (iAMG and iEMG). The variability of recordings during repeated 5-s isometric contractions was assessed by analysis of variance (ANOVA) and the coefficient of variation (CV) was calculated from the ANOVA. Both recording techniques produced the most repeatable results during the unsupported, horizontal hold position. In the normal subjects, CV were, iAMG 5.6%, iEMG 4.9%; and in the patients, iAMG 4.4%, iEMG 2.6%. The CV for the other four isometric test positions ranged from 15.3% to 29.4% for iAMG, and 8% to 15.7% for iEMG. These results demonstrated that a controlled test manoeuvre for examining AMG and EMG of the paraspinal muscles was vital for repeatable recordings. The CV for the standardised, horizontal position were lower than for previously published results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Cytokine inter-relationships and their association with disease activity in arthritis.

In order to investigate the relationships between cytokine production and arthritic disease we have determined the concentrations of immunoreactive interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, tumour necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha), IFN-gamma, and soluble IL-2-receptor (sIL-2R), as well as bioactive IL-1 and IL-6, in synovial fluids (SF) and plasma of patients with a variety of arthritides. Careful assay revealed only minimal concentrations of IL-1, particularly its biologically active form, in SF. No IL-1 was detectable in the plasma of patients that had IL-1 in their SF. Concentrations of both immunoreactive IL-1 beta and TNF-alpha in SF of rheumatoid arthritis (RA) patients were significantly higher than those in SF from patients with other inflammatory arthritides or osteoarthritis (OA). IL-6 and sIL-2R concentrations in both SF and plasma were higher in RA patients than in OA patients, and were significantly correlated. Approximately half of the SF from patients with all arthropathies contained detectable IFN-alpha, whilst IFN-Y was present in less than 10%. There were significant associations between IL-6, sIL-2R, IL-1 beta, TNF-alpha and IFN-alpha. The concentration of these cytokines, where detectable, was also related to leukocyte counts in the SF, as well as to parameters assessing local and systemic disease activity. Although IL-6 was the cytokine most clearly related to other cytokines, and to parameters assessing disease activity, the relationship between general articular disease activity and IL-6 was only evident in patients with arthropathies other than rheumatoid arthritis.

Arthritis

Radiographic demonstration of paraspinal muscle wasting in patients with chronic low back pain.

This study investigated whether paraspinal muscle wasting occurs in association with chronic low back pain (LBP). Cross-sectional areas (CSA) of spinal and paraspinal structures were measured radiographically, at the level of L4, in 43 patients with recent and 44 with chronic LBP. Crude anthropometry demonstrated no differences between the groups with regard to L4 and paraspinal and psoas muscle CSAs, but inter-individual differences were large. Since body weight correlated significantly with L4 CSA this dimension was used as an 'internal standard' and further inter-individual comparisons were made using paraspinal: L4 and psoas: L4 (i.e. muscle to bone) CSA ratios. Muscle assessments made in this 'relative' fashion revealed significant reductions in paraspinal and psoas dimensions in patients with chronic compared to recent onset LBP. These changes could cause paraspinal and psoas muscle weakness and thereby predispose to spinal instability and progressive dysfunction.

Adult

Abnormal temperature control suggesting sympathetic dysfunction in the shoulder skin of patients with frozen shoulder.

In view of the possibility that sympathetically mediated pain could be responsible for frozen shoulder symptoms we compared shoulder skin vasomotor control in 11 patients with frozen shoulder and 17 similarly aged normal subjects without shoulder pain. Using computer-assisted thermography the shoulder skin temperature was assessed before and following a 'cold challenge' which consisted of a 15 degrees C cold pack being held against the skin for 60 sec. Both prior to and immediately following the cold challenge shoulder skin temperatures tended to be lower in the patients. During a 10-min rewarming phase, however, the between-group temperature difference increased and became significant at the 0.05 level. These abnormalities of temperature control in patients clearly suggest sympathetic dysfunction in the dermatome subserving pain sensation from the affected shoulder. Whether these abnormalities are primary or secondary remains unresolved.

Adult

Differential metabolism of 25-hydroxyvitamin D3 by cultured synovial fluid macrophages and fibroblast-like cells from patients with arthritis.

Differential metabolism of 25-hydroxyvitamin D3 (25(OH)D3) has been shown for macrophages and fibroblast-like cells (possibly synoviocytes) cultured for two to 50 days after isolation from the synovial fluid of 12 patients with various forms of inflammatory arthritis. Macrophages synthesised the active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the synthesis of which was increased by bacterial lipopolysaccharide, a known macrophage activating factor. In contrast, fibroblast-like cells formed 24, 25-dihydroxyvitamin D3 (24,25(OH)2D3), synthesis of which was stimulated by 1,25(OH)2D3 and inhibited by lipopolysaccharide. The synthesis of 1,25(OH)2D3 and 24,25(OH)2D3 by macrophages and fibroblast-like cells respectively was inhibited by ketoconazole, indicating that both hydroxylases are dependent on cytochrome P-450. Mean (SEM) synovial fluid and serum 25(OH)D3 concentrations were 16.7 (1.7) and 22.2 (2.6) ng/ml and those of 1,25(OH)2D3 were 29.4 (4.8) and 43.3 (4.0) pg/ml respectively. In most cases concentrations were lower in synovial fluid than in paired serum samples, but in two patients 1,25(OH)2D3 concentrations were greater in synovial fluid than in serum, suggesting local synthesis within the affected joints.

24,25-Dihydroxyvitamin D 3

Bone abnormalities and severe arthritis in pachydermoperiostosis.

Two patients with pachydermoperiostosis were studied in whom the predominant features at presentation were severe and disabling knee and ankle joint pain in association with distal long bone pain. Analysis of synovial fluid from the knee joints showed non-inflammatory changes. In one patient a bicortical iliac crest bone biopsy specimen, taken after labelling with demeclocycline, showed appositional rates which were increased in cortical bone but reduced in trabecular bone. This mismatching resulted in trabecular osteoporosis, which occurred in association with increased numbers of osteoclasts, findings which suggest differential functional changes affecting the two bony envelopes.

Adolescent

Inhibition by prostaglandin E1 and E2 of 1,25-dihydroxyvitamin D3 synthesis by synovial fluid macrophages from arthritic joints.

Previous work has shown that renal metabolism of 25-dihydroxyvitamin D3 (25(OH)D3) to the active metabolite, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is stimulated by prostaglandin E2 and inhibited by acetylsalicylate (aspirin). As prostaglandins are primary inflammatory mediators and synovial fluid macrophages are known to synthesise 1,25(OH)2D3 in vitro, the effects of prostaglandin E1, prostaglandin E2, and aspirin on the metabolism of 25(OH)D3 by cells cultured from synovial fluid of patients with inflammatory arthritis were investigated. Most cultures contained non-proliferating macrophages which formed 1,25(OH)2D3; however, two of 13 cultures contained colonies of rapidly proliferating fibroblast-like cells which formed 24,25(OH)2D3 (24,25(OH)2D3). Prostaglandin E1 and prostaglandin E2 (0.01-10 mumol/l) induced marked inhibition of 1,25(OH)2D3 synthesis (up to 94%) in a dose dependent manner after preincubations of 24 hours but not over straightforward six hour incubations. Exposure of macrophages to aspirin (1 mumol/l-1 mmol/l) for 24 hours did not affect 1,25(OH)2D3 synthesis unless the cells had been pretreated with lipopolysaccharides, in which instance 1 mM aspirin increased 1,25(OH)2D3 synthesis. Lipopolysaccharide is a macrophage activating factor which stimulates macrophages to form 1,25(OH)2D3, and it also induces prostaglandin synthesis which would be inhibited by aspirin. Taken together these results suggest that prostaglandin E1 and prostaglandin E2 synthesised by macrophages may act in an autocrine manner to attenuate the ability of macrophage activating factors, such as lipopolysaccharide, to stimulate 1,25(OH)2D3 synthesis. Prostaglandins synthesised by other inflammatory cells may also inhibit 1,25(OH)2D3 synthesis in a paracrine manner. In contrast, prostaglandin E2 and aspirin had limited effects on fibroblast 24,25(OH)2D3 synthesis. This study shows that the effects of prostaglandin E1, prostaglandin E2, and aspirin in macrophages contrast with those previously reported for the renal 25(OH)D3-1alpha-hydroxylase, where prostaglandin E2 stimulated and aspirin inhibited enzyme activity. These results further emphasise that synthesis of 1,25(OH)2D3 in non-renal sites is independently regulated, which is consistent with it having an immunological role at a local level rather than playing a part in systemic calcium homeostasis.

Alprostadil

Muscle sounds during voluntary and stimulated contractions of the human adductor pollicis muscle.

The relationships between force, electromyography (EMG), and muscle sounds recorded by acoustic myography (AMG) were investigated for both voluntary and stimulated isometric contractions in the adductor pollicis muscle. Voluntary activity was performed at 10, 25, 50, 75, 85, and 100% of maximal voluntary contraction (MVC) force. Stimulated contractions were produced by supramaximal electrical stimulation of the ulnar nerve at the wrist at frequencies of 10, 20, 30, 50, 70, and 100 Hz. Contractions lasted for 4 s each, and were performed in random order with a 3-min rest between each. The voluntary and stimulation studies were performed in random order between subjects. Simultaneous recordings were obtained for force, force oscillation (from the differentiated force signal), and raw and integrated AMG (IAMG) and EMG (IEMG). During voluntary contractions, IAMG increased with force up to MVC (r2 = 0.99, P less than 0.001) in a curvilinear fashion and a similar relationship was seen between force and IEMG (r2 = 0.99, P less than 0.001). Conversely, during stimulated contractions as stimulation frequency increased, IAMG decreased in a fashion mirroring the frequency-force curve. The frequency of the AMG signal matched stimulation frequency and declines in total IAMG were due to reductions in amplitude of the AMG signal. The stimulation frequency-oscillation of force relationship was identical to that seen for stimulation frequency and IAMG. Integrated EMG increased linearly with stimulation frequency (r = 0.99). The stimulation results suggest that muscle sounds reflect oscillation of muscle fibers and that AMG signal characteristics are determined by motor control mechanisms rather than intrinsic contractile processes.

Acoustics

Elevated endothelial-cell-stimulating angiogenic factor activity in rodent glycolytic skeletal muscles.

1. Capillary density is greater in skeletal muscles comprised of predominantly oxidative (type I) fibres than in those comprised of mainly glycolytic (type II) fibres. In order to investigate further the angiogenic mechanisms involved in muscle capillarization, endothelial-cell-stimulating angiogenic factor activities in various rodent skeletal muscles were compared. 2. Eleven untrained adult male Wistar rats were killed and the predominantly oxidative (type I) muscle,s soleus and heart, the predominantly glycolytic (type II) muscle, extensor digitorum longus, and the mixed-fibre muscle, gastrocnemius, were removed. Each sample was separately homogenized and centrifuged and the supernatants were diafiltered to isolate the low-molecular-mass fraction containing endothelial-cell-stimulating angiogenic activity. This was assayed for its ability to activate latent collagenase and was expressed as units, where 1 unit represents the percentage activation of the enzyme h-1 (mg of protein in the supernatant)-1. 3. The results (medians and ranges) demonstrated significantly greater endothelial-cell-stimulating angiogenic factor activity in extensor digitorum longus muscle (2.14 units, 0.62-2.87 units, n = 13) than in soleus (0.82 units, 0.59-1.79 units, n = 15), gastrocnemius (0.34 units, 0.28-0.40 units, n = 4) or heart (0.43 units, 0.16-0.52 units, n = 11) (P less than 0.01 for each) muscle. 4. These findings suggest that endothelial-cell-stimulating angiogenic activity in muscle is either inversely or not related to the local capillary density, which may be at or near a maximum in physiologically contracting, predominantly oxidative muscles.

Angiogenesis Inducing Agents

The role of epidural fibrosis and defective fibrinolysis in the persistence of postlaminectomy back pain.

Clinical features, contrast-enhanced lumbar tomographic findings, and biochemical plasma fibrinolytic parameters were critically assessed in 70 patients suffering severe, chronic postsurgical low-back and radicular pain to determine the cause of their persisting symptoms. Patients exhibited gross functional disability and significant impairment of plasma fibrinolytic activity, compared with 84 normal control subjects. This fibrinolytic defect appeared attributable to disproportionate increases in circulating plasminogen activator inhibitor-1 levels. Clinical features were slightly worse in patients with radiologic epidural fibrosis, whereas the frequency of radiologic abnormalities, including epidural fibrosis, was higher in patients with fibrinolytic abnormalities. The results, however, demonstrated no significant associations between patients' symptoms and signs and their biochemical and radiologic abnormalities.

Arachnoiditis

Relationships between local inflammation, interleukin-6 concentration and the acute phase protein response in arthritis patients.

Interleukin-6 (IL-6) concentrations in knee joint synovial fluids and paired plasma samples of arthritis patients were examined with respect to each other and parameters of the inflammatory response. Synovial fluid and plasma IL-6 concentrations were significantly higher in patients with inflammatory arthritis than those detected in patients with osteoarthritis (P less than 0.001). The IL-6 concentrations in synovial fluids were considerably higher than, but significantly correlated with (r = 0.65; P less than 0.001), those of plasma. Furthermore, synovial fluid IL-6 concentrations in bilaterally inflamed knees were significantly correlated (r = 0.79; P less than 0.001) and there was a significant correlation with the extent of inflammatory cell infiltrate (r = 0.75; P less than 0.001). In unselected rheumatoid arthritis patients there was only a weak correlation between IL-6 and plasma C-reactive protein (CRP) concentration, and no correlation between IL-6 and erythrocyte sedimentation rate (ESR). However, both ESR and CRP concentration were highly correlated with plasma IL-6 concentration in patients with other inflammatory arthritides, particularly psoriatic and HLA B27 positive spondyloarthritis (r = 0.72-0.94; P less than 0.005). These relationships suggest that IL-6 production in inflammed knee joints can be a significant determinant of acute phase protein responses in arthritis patients, although the situation in patients with rheumatoid arthritis is more complex and may be influenced by other disease-related factors.

Acute-Phase Reaction

Paraspinal muscle fibrosis: a specific pathological component in ankylosing spondylitis.

The histological appearance of percutaneous superficial paraspinal muscle biopsy specimens from eight patients with ankylosing spondylitis was compared with that of biopsy specimens from 13 control patients with similar degrees of disability and spinal immobility due to severe, chronic mechanical back pain. In both groups marked type II muscle fibre atrophy was shown. Additionally, in patients with ankylosing spondylitis there were obvious increases in perifibre connective tissue in association with central migration of cell nuclei but without evidence of inflammation. Qualitative electromyography failed to show denervation changes in either group. Paraspinal muscle fibrosis, occurring over and above atrophic changes due to disuse, seems to be a specific pathological component of ankylosing spondylitis which may be of particular importance in early disease as it may contribute towards back stiffness and weakness.

Adult

Fibrinolytic enhancement with stanozolol fails to improve symptoms and signs in patients with post-surgical back pain.

An open trial with the fibrinolytic enchancing agent stanozolol was completed by eighteen patients (14 male) with severe back and radicular pain, despite previous lumbar surgery for prolapsed intervertebral disc. Assessments of their pain, disability and plasma fibrinolytic activity were undertaken before and after 12 or 24 months of therapy. Prior to treatment patients exhibited significant fibrinolytic abnormalities when compared with 84 normal controls; euglobulin clot lysis time (ELT) 442 vs 157 mins and fibrin plate lysis area (FPLA) 61 vs 113 mm2 respectively (p less than 0.01 for both). Stanozolol therapy normalised patients' fibrinolytic activity within three months. Disappointingly there were no concomitant clinical improvements in spinal pain or mobility despite 12 or 24 months of treatment. These results may indicate that perineural fibrosis, once formed, is not amenable to such therapy.

Adult

An investigation of managed health care case managers.

Managed care case management is a relatively new concept within health and rehabilitation. As such, it lacks both definition and profiles of those providing services. This paper constructs a definition of managed care case management and presents the detailed results of a survey that identified the characteristics of case managers in the Midwest. The survey was mailed to 250 subjects. The respondents of the survey (N = 56) were relatively young (the largest number of respondents were 30 to 39 years of age), relatively new to their jobs (means = 2.2 years), and were typically employed full-time. They primarily served mental health (n = 43) and physically impaired (n = 30) clients. The highest number of their service referrals were made to vocational rehabilitation specialists, social workers, occupational therapists, nurses, and physical therapists.

Administrative Personnel

Effect of low frequency fatigue on human muscle strength and fatigability during subsequent stimulated activity.

Fatiguing contractions of the adductor pollicis muscle were produced by intermittent supramaximal stimulation of the ulnar nerve in a set frequency pattern, in six normal subjects. At the end of an initial fatiguing contraction series, low frequency fatigue (LFF) had been induced and persisted at 15 min of recovery. Stimulated fatiguing activity was then repeated in an identical fashion to the initial series. At high frequencies, declines in force were similar for both series. At low frequencies, declines in force were greater during the second series despite similar changes in compound muscle action potential amplitude. This confirmation that LFF persists during subsequent stimulated activity, and reduces low but not high frequency fatigue resistance, suggests that the impaired endurance of fatigued muscle during voluntary activity primarily results from peripheral changes at low frequency. These findings also have implications for therapeutic electrical stimulation of muscle.

Action Potentials

Myofibrillar activation failure in McArdle's disease.

Contractile properties of the adductor pollicis muscle were examined in 9 normal volunteers and 7 patients with histochemically proven myophosphorylase deficiency (McArdle's disease). Fatiguing contractions were produced by supramaximal stimulation of the ulnar nerve, delivered over a range of frequencies, to allow further examination of the mechanisms responsible for the premature fatigue in patients. The excessive reductions in force, demonstrated in patients at all frequencies, were not associated at high frequencies (50 and 100 Hz) with excessive declines in excitation (measured as compound muscle action potential). These results demonstrate that, in patients, myofibrillar activation failure occurs over and above that due to excitation failure. Abnormal slowing of relaxation mechanisms was also confirmed. These findings appear consistent with the hypothesis of inhibition of various ATPases by metabolic products. The observed, clear differences between normal subjects and myophosphorylase-deficient patients constitute the basis of an objective screening procedure for this and other glycolytic disorders.

Adolescent

The development of structural complexity in the child's concept of family: the effect of cognitive stage, sex, and intactness of family.

Twenty-eight boys and 28 girls at each of the Piagetian preoperational, concrete operational, and formal operational cognitive stages were given an interview focusing on their concepts of family. Half of each group were from intact families, and half were from divorced families. Interviews were scored for two structural aspects of the concept of family: conceptual level, and use of dimensions that structure the concept. The complexity of children's concepts was strongly related to cognitive stage and, to a lesser degree, to sex. Frequency of use of concept dimensions was strongly affected by general developmental level, though not specifically cognitive stage, and by intactness of family, but to a lesser degree by sex. Specific information is provided on the effect of these factors on perceptions of family composition, parental roles, and breadth of family activities.

Adolescent