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Biomedical subjects

Robert M Bennett

Publications and source records attributed to Robert M Bennett.

15 recordsLinked to original sources
PubMed2007

Growth hormone perturbations in fibromyalgia: a review.

OBJECTIVE: Fibromyalgia (FM) is a syndrome characterized by chronic widespread pain, fatigue, disrupted sleep, depression, and physical deconditioning. In this article, we review the literature on the normal activity of the hypothalamic-pituitary-growth hormone-insulin-like growth factor-1 (HP-GH-IGF-1) axis and its perturbations in FM subjects. METHODS: Studies included in this review were accessed through an English language search of Cochrane Collaboration Reviews. Keyword MeSH terms included "fibromyalgia," "growth hormone" (GH), or "insulin-like growth factor-1" (IGF-1). RESULTS: Twenty-six studies enrolling 2006 subjects were reviewed. Overall, low levels of IGF-1 were found in a subgroup of subjects. Growth hormone stimulation tests often revealed a suboptimal response, which did not always correlate with IGF-1 levels. No consistent defects in pituitary function were found. Of the 3 randomized placebo controlled studies, only 9 months of daily injectable recombinant GH reduced FM symptoms and normalized IGF-1. CONCLUSIONS: These studies suggest that pituitary function is normal in FM and that reported changes in the HP-GH-IGF-1 axis are most likely hypothalamic in origin. The therapeutic efficacy of supplemental GH therapy in FM requires further study before any solid recommendations can be made.

Female↗
PubMed2005

Impact of fibromyalgia pain on health-related quality of life before and after treatment with tramadol/acetaminophen.

OBJECTIVE: To assess health-related quality of life (HRQOL) in patients with moderate-to-severe fibromyalgia pain compared with the general population, and to assess the relationship between pain severity and HRQOL before and after treatment with an analgesic. METHODS: Data were obtained from a randomized, double-blind study of patients with moderate-to-severe fibromyalgia pain. Patients received either tramadol/acetaminophen or placebo 4 times/day as needed for 91 days. HRQOL was measured with the Short Form 36 Health Survey (SF-36) and the Fibromyalgia Impact Questionnaire (FIQ). Baseline HRQOL scores were compared with a national sample of noninstitutionalized adults and a sample of patients with impaired HRQOL due to congestive heart failure. Patients with fibromyalgia were divided into tertiles by change in pain severity, and SF-36 scores were compared across the tertiles. Mean changes in SF-36 and FIQ scores were compared between treatment groups. RESULTS: Patients with fibromyalgia scored lower than the US norm on all SF-36 scales (P < 0.0001) and lower than patients with congestive heart failure on most scales. More severe pain was associated with greater impairment of HRQOL compared with less severe pain (P < 0.0001). Patients in the highest tertile for improved pain severity had greater improvement in HRQOL scores than patients in the lower tertiles. Compared with patients who received placebo (n = 157), patients treated with tramadol/acetaminophen (n = 156) showed greater improvement on SF-36 physical functioning, role physical, bodily pain, and physical summary scales, as well as FIQ scales for ability to do job, pain, and stiffness (P < 0.01). CONCLUSION: Moderate-to-severe fibromyalgia pain significantly impairs HRQOL, and effective pain relief in these patients significantly increases HRQOL.

Acetaminophen↗
PubMed2004

Activation of RAW264.7 macrophages by bacterial DNA and lipopolysaccharide increases cell surface DNA binding and internalization.

Bacterial DNA containing unmethylated CpG motifs is a pathogen-associated molecular pattern (PAMP) that interacts with host immune cells via a toll-like receptor (TLR) to induce immune responses. DNA binding and internalization into cells is independent of TLR expression, receptor-mediated, and required for cell activation. The objective of this study was to determine whether exposure of immune cells to bacterial DNA affects DNA binding and internalization. Treatment of RAW264.7 cells with CpG oligodeoxynucleotide (ODN) for both 18 and 42 h resulted in a significant increase in DNA binding, whereas non-CpG ODN had no effect on DNA binding. Enhanced DNA binding was non-sequence-specific, inhibited by unlabeled DNA, showed saturation, was consistent with increased cell surface DNA receptors, and resulted in enhanced internalization of DNA. Treatment with Escherichia coli DNA or lipopolysaccharide (LPS) also resulted in a significant increase in DNA binding, but treatment with interleukin-1alpha, tumor necrosis factor-alpha, or phorbol 12-myristate 13-acetate had no effect on DNA binding. Soluble factors produced in response to treatment with CpG ODN or LPS did not affect DNA binding. These studies demonstrate that one consequence of activating the host innate immune response by bacterial infection is enhanced binding and internalization of DNA. During this period of increased DNA internalization, RAW264.7 cells were hypo-responsive to continued stimulation by CpG ODN, as assessed by tumor necrosis factor-alpha activity. We speculate the biological significance of increasing DNA binding and internalization following interaction with bacterial PAMPs may provide a mechanism to limit an ongoing immune inflammatory response by enhancing clearance of bacterial DNA from the extracellular environment.

Animals↗
PubMed2003

Tramadol and acetaminophen combination tablets in the treatment of fibromyalgia pain: a double-blind, randomized, placebo-controlled study.

PURPOSE: To evaluate the efficacy and safety of a combination analgesic tablet (37.5 mg tramadol/325 mg acetaminophen) for the treatment of fibromyalgia pain. METHODS: This 91-day, multicenter, double-blind, randomized, placebo-controlled study compared tramadol/acetaminophen combination tablets with placebo. The primary outcome variable was cumulative time to discontinuation (Kaplan-Meier analysis). Secondary measures at the end of the study included pain, pain relief, total tender points, myalgia, health status, and Fibromyalgia Impact Questionnaire scores. RESULTS: Of the 315 subjects who were enrolled in the study, 313 (294 women [94%], mean [+/- SD] age, 50 +/- 10 years) completed at least one postrandomization efficacy assessment (tramadol/acetaminophen: n = 156; placebo: n = 157). Discontinuation of treatment for any reason was less common in those treated with tramadol/acetaminophen compared with placebo (48% vs. 62%, P = 0.004). Tramadol/acetaminophen-treated subjects also had significantly less pain at the end of the study (53 +/- 32 vs. 65 +/- 29 on a visual analog scale of 0 to 100, P <0.001), and better pain relief (1.7 +/- 1.4 vs. 0.8 +/- 1.3 on a scale of -1 to 4, P <0.001) and Fibromyalgia Impact Questionnaire scores (P = 0.008). Indexes of physical functioning, role-physical, body pain, health transition, and physical component summary all improved significantly in the tramadol/acetaminophen-treated subjects. Discontinuation due to adverse events occurred in 19% (n = 29) of tramadol/acetaminophen-treated subjects and 12% (n = 18) of placebo-treated subjects (P = 0.09). The mean dose of tramadol/acetaminophen was 4.0 +/- 1.8 tablets per day. CONCLUSION: A tramadol/acetaminophen combination tablet was effective for the treatment of fibromyalgia pain without any serious adverse effects.

Acetaminophen↗
PubMed2003

Pharmacological therapies in fibromyalgia.

The fibromyalgia syndrome (FMS) is a common, chronic, widespread pain disorder that mainly affects middle-aged women. In addition to pain complaints, fatigue and disturbed sleep are symptoms frequently reported by these patients. Many FMS patients also meet diagnostic criteria for mood disorders (e.g. depression) as well as other so-called 'functional somatic syndromes', including irritable bowel syndrome, temporomandibular joint disorder, and subsets of chronic low-back pain. A wide variety of medications are used to manage the eclectic symptomatology of FMS patients, although relatively few have been rigorously tested. This chapter provides a contemporary update of the state of FMS pharmacotherapy, with an emphasis on compounds that have been tested in double-blind, randomized, controlled trials. Particular attention is paid to the efficacy of these therapies on the associated symptoms and co-morbid syndromes commonly seen in FMS patients.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Towards epidemiological criteria for soft-tissue disorders of the arm.

BACKGROUND: The lack of universally agreed criteria has hampered population studies of the prevalence and causation of soft-tissue disorders of the upper limb. OBJECTIVES: To establish core variables for classification of the commonest disorders seen in population samples. METHODS: Consecutive new cases seen in clinical practice in five different centres were evaluated with respect to 30 variables shown to have discriminatory value in univariate analysis. Multivariate analysis using logistic regression modelling was carried out with these as the independent variables and with the clinical diagnosis as the dependent variable. RESULTS: A total of 1382 cases of soft-tissue disorder were recorded and only those diagnostic groups with 50 or more cases were included. In multivariate logistic regression, significant variables positively discriminating for each disorder were identified for carpal tunnel syndrome (n = 56), lateral epicondylitis (n = 87), tenosynovitis (n = 63), shoulder tendonitis (n = 157), non-specific upper limb disorder (n = 458), fibromyalgia (n = 124) and inflammatory arthritis (n = 100), which was used for comparison purposes. Significant discrimination for each model was demonstrated by the construction of receiver operating characteristic (ROC) curves and appropriate area under the curve statistics. CONCLUSIONS: This approach to classification criteria is based on multivariate modelling rather than on a consensus statement. This includes the effects of negative as well as positive associations. Further work is required on both the reproducibility of the clinical signs and the application of the criteria to other datasets.

Adolescent↗
PubMed2002

Adult growth hormone deficiency in patients with fibromyalgia.

Adult growth hormone (GH) deficiency is a well-described clinical syndrome with many features reminiscent of fibromyalgia. There is evidence that GH deficiency as defined in terms of a low insulin-like growth factor-1 (IGF-1) level occurs in approximately 30% of patients with fibromyalgia and is probably the cause of some morbidity. It seems most likely that impaired GH secretion in fibromyalgia is related to a physiologic dysregulation of the hypothalamic-pituitary-adrenal axis (HPA) with a resulting increase in hypothalamic somatostatin tone. It is postulated that impaired GH secretion is secondary to chronic physical and psychological stressors. It appears that impaired GH secretion is more common than clinically significant GH deficiency with low IGF-1 levels. The severe GH deficiency that occurs in a subset of patients with fibromyalgia is of clinical relevance because it is a treatable disorder with demonstrated benefits to patients.

Adult↗
PubMed2002

The rational management of fibromyalgia patients.

The exponential increase in pain research over the last 10 years has established fibromyalgia (FM) as a common chronic pain syndrome with similar neurophysiologic aberrations to other chronic pain states. As such, the pathogenesis is considered to involve an interaction of augmented sensory processing (central sensitization) and peripheral pain generators. The notion, that FM symptomatology results from an amplification of incoming sensory impulses, has revolutionized the contemporary understanding of this enigmatic problem and provided a more rational approach to treatment. To date, the management of FM has been mainly palliative, with the aims of reducing pain, improving sleep, maintaining function, treating psychologic distress and diminishing the impact of associated syndromes. The rapidly evolving neurophysiologic, psychophysiologic and molecular biologic basis for chronic pain states has already opened up new avenues for management which should be applicable to this difficult group of patients. Indeed, it is now possible to think about a "rational" approach to managing FM patients that was unthinkable just a few years ago.

Fibromyalgia↗
PubMed2002

Prescribing exercise for people with fibromyalgia.

Fibromyalgia (FM) is a costly and debilitating pain syndrome which is commonly encountered by advanced practice nurses working in acute care settings. Fibromyalgia affects nearly 6 million people in the United States, approximately 80% to 90% of whom are women. Symptoms of FM include widespread and localized pain, disrupted sleep, fatigue, visceral pain and other pain syndromes, neurological symptoms (eg, dizziness, numbness, tingling, impaired cognition), and exercise-induced pain. Difficulties remaining active with FM may lead to extreme deconditioning, inability to remain employed, and eventually even impaired ability in complete activities of daily living. Exercise that combats deconditioning without triggering pain is, therefore, a key component in treating FM. Clinicians who understand FM pain and associated symptoms can minimize the negative impact of deconditioning by prescribing disease-specific exercise for people with FM.

Cardiovascular Deconditioning↗
PubMed2002

A randomized controlled trial of muscle strengthening versus flexibility training in fibromyalgia.

OBJECTIVE: To determine the effectiveness of a muscle strengthening program compared to a stretching program in women with fibromyalgia (FM). METHODS: Sixty-eight women with FM were randomly assigned to a 12 week, twice weekly exercise program consisting of either muscle strengthening or stretching. Outcome measures included muscle strength (main outcome variable), flexibility, weight, body fat, tender point count, and disease and symptom severity scales. RESULTS: No statistically significant differences between groups were found on independent t tests. Paired t tests revealed twice the number of significant improvements in the strengthening group compared to the stretching group. Effect size scores indicated that the magnitude of change was generally greater in the strengthening group than the stretching group. CONCLUSION: Patients with FM can engage in a specially tailored muscle strengthening program and experience an improvement in overall disease activity, without a significant exercise induced flare in pain. Flexibility training alone also results in overall improvements, albeit of a lesser degree.

Adult↗