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Biomedical subjects

R M Bennett

Publications and source records attributed to R M Bennett.

At least 55 records · Page 3Linked to original sources
PubMed1993

Decision support models of leptospirosis in dairy herds.

Following the results of a survey which found that 61 per cent of dairy farmers felt that they needed more information about leptospirosis, and the strategies for its control and the costs and benefits involved, this paper describes the construction and preliminary results of two models of the disease intended to help explore the risks and financial implications of Leptospira interrogans serovar hardjo infection for dairy producers.

Animals↗
PubMed1993

Immunization of BALB/c mice with a monoclonal anti-DNA antibody induces an anti-idiotypic antibody reactive with a cell-surface DNA binding protein.

DNA binds to cell-surface proteins on human and murine leukocytes and induces secretion of the cytokine interleukin 6 (IL-6). Cell-surface DNA binding molecules have been shown to serve as target antigens for the production of autoantibodies in patients with systemic lupus erythematosus (SLE), and in lupus-prone mice. Recent studies have demonstrated that a subset of anti-anti-DNA antibodies, isolated from patients with SLE, are idiotypically related to antibodies reactive with a cell-surface DNA binding molecule. We now report that immunization of normal mice with a murine monoclonal anti-DNA antibody induces an anti-idiotypic response which has reactivity with a cell-surface DNA binding molecule. An anti-idiotypic anti-DNA monoclonal antibody (LB17) was isolated from the spleen of an immunized mouse. This monoclonal antibody blocked the binding of DNA to murine splenocytes and mimicked the functional effect of DNA by stimulating the secretion of IL-6. These experiments provide further evidence for an idiotypic connectivity between antibodies to cell-surface DNA binding proteins and anti-DNA antibodies. It is hypothesized that this idiotypic system is part of the network of natural autoantibodies and that its perturbation may give rise to pathogenic antibodies.

Animals↗
PubMed1993

Fibromyalgia and the facts. Sense or nonsense.

A recent flurry of important studies has provided critical new information that is relevant to the contemporary understanding of the fibromyalgia syndrome. The concept that these patients represent solely a form of masked depression or a distinctive syndrome of somatization is not supported by the current facts. Rather it would appear that a characteristic peripheral nociceptive component is modulated by an interplay of complex central factors. A disruption of the neuroendocrine axis controlling growth hormone production may be the link between disturbed sleep and muscle pain, as growth hormone is produced predominantly during stage four sleep. A paradigm to link some of these newer findings is presented.

Affect↗
PubMed1993

Fibromyalgia and quality of life: a comparative analysis.

The quality of life of women with fibromyalgia was explored and compared to the quality of life of women with rheumatoid arthritis, osteoarthritis, permanent ostomies, chronic obstructive pulmonary disease, insulin dependent diabetes, and healthy controls. The women with fibromyalgia consistently scored among the lowest in all domains measured. These results suggest that fibromyalgia may adversely affect quality of life to an extent not previously recognized.

Adult↗
PubMed1992

Low levels of somatomedin C in patients with the fibromyalgia syndrome. A possible link between sleep and muscle pain.

OBJECTIVE: Fibromyalgia is a common syndrome of musculoskeletal pain and fatigue. Lacking distinctive tissue or laboratory correlations, it has often been considered a form of "psychogenic rheumatism." In the present study, the notion that the stage-4 sleep anomaly typically seen in the fibromyalgia syndrome may disrupt growth hormone secretion was tested. Because growth hormone has a very short half-life, serum levels of somatomedin C were measured; somatomedin C is the major mediator of growth hormone's anabolic actions and is a prerequisite for normal muscle homeostasis. METHODS: Serum levels of somatomedin C were measured in 70 female fibromyalgia patients and 55 healthy controls, using a peptide-specific radioimmunoassay. RESULTS: Significantly lower levels of somatomedin C were observed in the fibromyalgia patients compared with controls (mean +/- SD 124.7 +/- 47 ng/ml versus 175.2 +/- 60 ng/ml; P = 0.000001). These results could not be explained by concomitant therapy or by weight, and in a subset of 21 patients in whom this was investigated, there was no correlation with various indices of disease activity. CONCLUSION: These findings indicate that there is a distinctive disruption of the growth hormone-somatomedin C neuroendocrine axis in a majority of fibromyalgia patients. It is hypothesized that this abnormality may explain the link between disturbed sleep and predisposition to muscle pain.

Adult↗
PubMed1992

A comparison of pain perceptions in women with fibromyalgia and rheumatoid arthritis: relationship to depression and pain extent.

Two studies were conducted to characterize the pain of fibromyalgia syndrome (FMS); to compare it to rheumatoid arthritis (RA) pain; and to examine the relationships between depression, pain extent, and pain description. Two methods of administering the McGill Pain Questionnaire (MPQ) were used. When the MPQ was administered in the standard manner, FMS pain could not be distinguished from RA pain. When participants were allowed to select as many words from an adapted MPQ as they wished, significant differences in word choice emerged. Depression and pain extent were major predictors of group differences in the evaluation of pain. However, depression scores contributed only 50% of the explanation for the differences in pain extent, with group membership contributing the other 50%. These findings suggest that the character and extent of pain in FMS are at least partially due to peripheral sensory components and not simply centrally controlled pain amplification secondary to depression.

Adult↗
PubMed1992

Nucleosomes and DNA bind to specific cell-surface molecules on murine cells and induce cytokine production.

The molecular basis for the cellular interaction of DNA and nucleosomes and the physiological consequences of this binding were examined. Both DNA and nucleosomes were demonstrated to bind specifically to the surface of human peripheral blood mononuclear cells and the murine T cell line S49. Western blots of S49 cell membranes, using probes of biotin-labeled DNA and nucleosomes, showed reactivity at 29 and 69 kDa. Functionally, the interaction of DNA and nucleosomes with murine spleen cells stimulated the release of significant amounts of IL-6 activity. There is evidence that nucleosomes, a product of apoptosis, are the major component of circulating DNA found in the plasma of patients with systemic lupus erythematosus (SLE). The interaction of nucleosomes with cell-surface DNA binding molecules may have physiological relevance to some of the immune aberrations observed in patients with SLE.

Animals↗
PubMed1992

Idiotypic mimicry of a cell surface DNA receptor: evidence for anti-DNA antibodies being a subset of anti-anti-DNA receptor antibodies.

Anti-idiotypic anti-DNA antibodies (anti-anti-DNA) have previously been described in both patients with systemic lupus erythematosus and healthy individuals. Jerne's hypothesis predicts that such antibodies would bear a paratope reactive with non-sequence specific DNA binding proteins. Here we have explored the notion of a molecular mimicry between anti-anti-DNA antibodies and antibodies to a previously described 28-29 kD cell surface DNA binding molecule. It was shown that affinity purified anti-anti-DNA antibodies inhibit the binding of DNA to cells and that MoAb to the 28-29 kD receptor react with anti-DNA antibodies. These findings indicate that a subset of anti-anti-DNA antibodies are idiotypically related to antibodies reactive with a cell surface DNA binding molecule. It is hypothesized that anti-DNA antibodies may arise when a convergence of genetic and environmental influences favours an unrestrained anti-idiotypic response to cell surface DNA binding molecule(s).

Antibodies, Anti-Idiotypic↗
PubMed1992

DNA binding to mouse cells is mediated by cell-surface molecules: the role of these DNA-binding molecules as target antigens in murine lupus.

Autoimmunity to a 28-29-kDa cell-surface DNA-binding molecule has previously been described in patients with systemic lupus erythematosus and related autoimmune diseases. This report describes experiments that implicate a similar antigen-antibody system in the evolution of autoimmunity in lupus-prone mice. DNA binding to murine spleen cells was found to be a saturable phenomenon that was inhibited by excess cold DNA and trypsinization. The role of autoimmunity to murine cell-surface DNA-binding molecules in lupus-prone mice (MRL lpr/lpr, MRL +/+, BXSB) was compared to normal mice (BALB/c, C3H.SW) by means of an assay that measured the inhibition of cell-surface DNA binding. Only sera from lupus strains had inhibitory activity and this component was shown to be an IgM autoantibody. Furthermore, we isolated a spontaneously occurring IgM monoclonal antibody from the spleen of an MRL/lpr mouse, which inhibited DNA binding to mouse cells. Time-course studies indicated that young female MRL/lpr mice lacked detectable activity against cell-surface DNA-binding molecules; however, by 8-10 weeks maximal inhibitory activity was observed. This response occurred prior to the development of significant antinuclear antibody activity. With the appearance of overt disease and anti-DNA antibodies, inhibition of DNA-binding activity became undetectable. These findings mirror previous studies on autoimmunity to a cell-surface DNA-binding molecule on human leucocytes, but have the added advantage of permitting the study of the temporal evolution of this inhibitory activity in relation to disease expression.

Animals↗
PubMed1992

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↗
PubMed1992

Individualizing the risk/benefit ratio of NSAIDs in older patients.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have provided safe, effective relief of pain and inflammation in millions of elderly patients. Their role in the therapy of rheumatic disease, particularly in helping patients to maintain an independent lifestyle, is indisputable. Despite this success, recent epidemiologic studies have confirmed an increased relative risk for a wide variety of significant toxicities. Advanced age has emerged as one of the most striking risk factors for all of the commonly associated side effects. However, considering the large proportion of the population using these drugs, the absolute risk is remarkably low. Recognizing those elderly individuals most likely to benefit and least likely to suffer from NSAID use is the key to their appropriate use.

Age Factors↗
PubMed1991

Symptoms of Raynaud's syndrome in patients with fibromyalgia. A study utilizing the Nielsen test, digital photoplethysmography, and measurements of platelet alpha 2-adrenergic receptors.

Twenty-nine female patients with fibromyalgia were questioned about symptoms of cold intolerance and Raynaud's syndrome; objective documentation of cold-induced vasospasm was obtained by a Nielsen test. Twelve patients (41%) had abnormal Nielsen test results, and 11 patients (38%) had elevated levels of platelet alpha 2-adrenergic receptors. There was a positive correlation between the percentage of change in finger systolic pressure on cooling (Nielsen test) and the number of alpha 2-adrenergic receptors. There was poor correlation between Raynaud's syndrome symptoms and an abnormal Nielsen test result. Digital photoplethysmography showed a normal waveform in 2 of 3 patients. We hypothesize that a subgroup of patients with fibromyalgia syndrome have an up-regulation of alpha 2-adrenergic receptors as a cause of their exaggerated reaction to cold.

Adult↗
PubMed1991

Autoimmunity to a 28-30 kD cell membrane DNA binding protein: occurrence in selected sera from patients with SLE and mixed connective tissue disease (MCTD).

Previous experiments have established the presence of a 30-kD DNA binding protein on the surface of human leukocytes. Herein we report that selected sera from patients with systemic lupus erythematosus (SLE) and MCTD are reactive with a 28-30 kD protein on immunoblots of peripheral blood mononuclear cells (PBMC) cell membrane preparations; the reactivity is abolished by prior incubation of the blot with DNA. Antibodies eluted from the 28-30 kD strip inhibited the binding of 3H. DNA to human PBMC. An immunomatrix of 28-30 kD reactive immunoglobulins was able to extract a 29-kD DNA binding protein from a PBMC cell membrane preparation. Flow cytometry experiments confirmed the cell surface IgG reactivity of sera with T lymphocytes. Additional experiments indicated that cell surface IgG binding was not due to antibodies binding to cell surface DNA, DNA anti-DNA immune complexes reacting with a DNA binding protein, anti-histone antibodies or anti-Sm antibodies. It is hypothesized that this autoimmune response could be one component of an idiotypic network involving anti-DNA antibodies.

Autoantibodies↗
PubMed1991

The fibromyalgia impact questionnaire: development and validation.

An instrument has been developed to assess the current health status of women with the fibromyalgia syndrome. The Fibromyalgia Impact Questionnaire (FIQ) is a brief 10-item, self-administered instrument that measures physical functioning, work status, depression, anxiety, sleep, pain, stiffness, fatigue, and well being. We describe its development and validation. This initial assessment indicates that the FIQ has sufficient evidence of reliability and validity to warrant further testing in both research and clinical situations.

Adult↗
PubMed1991

Fulminant thrombotic thrombocytopenic purpura in a patient with the limited form of scleroderma: successful outcome using plasma exchange.

A 35-year-old woman with a 20-year history of limited scleroderma presented with a 7-day history of low grade fever associated with a red colored urine, 2 days of jaundice and lower extremity petechiae. On admission she had a rapidly deteriorating neurological status associated with thrombocytopenia and microangiopathic anemia. A diagnosis of thrombotic thrombocytopenic purpura (TTP) was made and treatment begun with fresh frozen plasma, plasma exchange and pulse corticosteroids. After a stormy 28-day hospital course she was discharged without residual problems of TTP.

Adrenal Cortex Hormones↗