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Biomedical subjects

L A Bradley

Publications and source records attributed to L A Bradley.

At least 19 recordsLinked to original sources
PubMed2004

Increased DNA fragmentation and ultrastructural changes in fibromyalgic muscle fibres.

OBJECTIVE: To determine whether there is evidence of increased DNA fragmentation and ultrastructural changes in muscle tissue of patients with fibromyalgia (FM) compared with healthy controls. METHODS: Muscle tissues from 10 community residents with FM and 10 age and sex matched healthy controls were examined "blindly" for the presence of DNA fragmentation by two different methods: terminal deoxynucleotidyl transferase (TdT) staining (TUNEL) and the FragEL-Klenow DNA fragmentation detection kit. Ultrastructural analysis of tissue was performed by electron microscopy. RESULTS: DNA fragmentation was detected by both methods in 55.4 (SEM 2.5)% of the nuclei in muscle tissue of patients with FM compared with 16.1 (4.1)% (p<0.001) of the nuclei in healthy controls. Contrary to expectation, no typical features of apoptosis could be detected by electron microscopy. The myofibres and actin filaments were disorganised and lipofuscin bodies were seen; glycogen and lipid accumulation were also found. The number of mitochondria was significantly lower in patients with FM than in controls and seemed to be morphologically altered. CONCLUSION: The ultrastructural changes described suggest that patients with FM are characterised by abnormalities in muscle tissue that include increased DNA fragmentation and changes in the number and size of mitochondria. These cellular changes are not signs of apoptosis. Persistent focal contractions in muscle may contribute to ultrastructural tissue abnormalities as well as to the induction and/or chronicity of nociceptive transmission from muscle to the central nervous system.

Adult↗
PubMed2002

Assigning risk for Smith-Lemli-Opitz syndrome as part of 2nd trimester screening for Down's syndrome.

OBJECTIVES: To design a reliable model in the context of prenatal screening for assigning the risk in an individual pregnancy of Smith-Lemli-Opitz syndrome (SLOS) and assess its performance. SETTING: A 2nd trimester screening programme for Down's syndrome that measures unconjugated estriol (uE3) along with other serum markers. METHODS: Development of individual risk estimates with a trivariate model incorporating measurements of maternal serum uE3, alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) in both SLOS and unaffected pregnancies. RESULTS: Population parameters were computed for the three analytes, as were pairwise correlation coefficients and truncation limits, based on an unbiased collection of 29 affected pregnancies. Published parameters were used for unaffected pregnancies. With a cut off level of risk of 1:50, 62% of SLOS pregnancies can be detected by initially identifying 0.34% of unaffected pregnancies as screen positive. About 1 in 90 screen positive pregnancies will be affected. CONCLUSIONS: It is possible to screen for SLOS as an add on to existing 2nd trimester maternal serum screening, if uE3 is already being measured. A large, prospective trial is necessary to determine whether diagnostic testing can be performed in maternal urine or serum rather than amniotic fluid.

Biomarkers↗
PubMed2001

Psychosocial and health status variables independently predict health care seeking in fibromyalgia.

OBJECTIVE: To determine whether variables derived from the self-regulatory model of health and illness behavior accurately predict status as a patient or nonpatient with fibromyalgia (FM). METHODS: Subjects were 79 patients who met American College of Rheumatology (ACR) criteria for FM and 39 community residents who met ACR criteria for FM but had not sought medical care for their symptoms (nonpatients). Subjects were administered 14 measures that produced 6 domains of variables: background demographics and pain duration; psychiatric morbidity; and personality, environmental, cognitive, and health status factors. These domains were entered in 4 different hierarchical logistic regression analyses to predict status as patient or nonpatient. RESULTS: The full regression model was statistically significant (P < 0.0001) and correctly identified 90.7% of the subjects with a sensitivity of 92.4% and a specificity of 87.2%. The best individual predictors of group status were self-reports of self-efficacy, negative affect, recent stressful events, and perceived pain. Relative to nonpatients, patients reported higher levels of negative affect and perceived pain and a greater number of recent stressful experiences, as well as lower levels of self-efficacy. CONCLUSION: Consistent with the self-regulatory model of health and illness behavior, psychosocial and health status variables predict health care-seeking behavior in persons with FM independently of background demographics and psychiatric morbidity. These variables may influence the severity of symptoms experienced by persons with this disorder as well as their health care-seeking behavior, but they are not necessary to produce abnormal pain sensitivity in FM.

Activities of Daily Living↗
PubMed2001

Theoretical perspectives on the relation between catastrophizing and pain.

The tendency to "catastrophize" during painful stimulation contributes to more intense pain experience and increased emotional distress. Catastrophizing has been broadly conceived as an exaggerated negative "mental set" brought to bear during painful experiences. Although findings have been consistent in showing a relation between catastrophizing and pain, research in this area has proceeded in the relative absence of a guiding theoretical framework. This article reviews the literature on the relation between catastrophizing and pain and examines the relative strengths and limitations of different theoretical models that could be advanced to account for the pattern of available findings. The article evaluates the explanatory power of a schema activation model, an appraisal model, an attention model, and a communal coping model of pain perception. It is suggested that catastrophizing might best be viewed from the perspective of hierarchical levels of analysis, where social factors and social goals may play a role in the development and maintenance of catastrophizing, whereas appraisal-related processes may point to the mechanisms that link catastrophizing to pain experience. Directions for future research are suggested.

Adaptation, Psychological↗
PubMed2000

Pain complaints in patients with fibromyalgia versus chronic fatigue syndrome.

Individuals with fibromyalgia (FM) and/or chronic fatigue syndrome (CFS) report arthralgias and myalgias. However, only persons with FM alone exhibit abnormal pain responses to mild levels of stimulation, or allodynia. We identify the abnormalities in the neuroendocrine axes that are common to FM and CFS as well as the abnormalities in central neuropeptide levels and functional brain activity that differentiate these disorders. These two sets of factors, respectively, may account for the similarities and differences in the pain experiences of persons with FM and CFS.

Brain↗
PubMed2000

Use of neuroimaging to understand abnormal pain sensitivity in fibromyalgia.

This paper examines the use of neuroimaging to measure change in regional cerebral blood flow (rCBF) produced by pain in patients with fibromyalgia and in healthy individuals. Fibromyalgia patients differ from healthy persons in rCBF distribution in several brain structures involved in pain processing and pain modulation both at rest and during experimental pain induction. These abnormalities may contribute to abnormal pain sensitivity as well as the maladaptive pain behaviors that characterize many patients with fibromyalgia. We anticipate that future neuroimaging studies will enhance our understanding of abnormal pain sensitivity and of pain management interventions aimed at altering central nervous system function in patients with fibromyalgia.

Blood Flow Velocity↗
PubMed2000

Expression of the precursor of secretoneurin, secretogranin II, in the synovium of patients with rheumatoid arthritis and osteoarthritis.

OBJECTIVE: Secretoneurin (SN) is a neuropeptide that is chemotactic for mononuclear cells and it has been suggested to be involved in the mediation of pain; there is also evidence that SN is involved in the inflammation process. As secretogranin II (SGII) is the precursor of SN, we investigated expression of SGII mRNA and SN protein in the synovium of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Snap frozen synovial tissue specimens from 12 patients with RA and 11 patients with OA were examined. RNA was isolated and cDNA copied by reverse transcription. The expression of SGII was determined by polymerase chain reaction and in situ hybridization (ISH). SGII expressing cells were compared with CD68 positive cells stained by immunohistochemistry. SN protein was also detected by immunohistochemistry. RESULTS: A 524 bp SGII-specific fragment could be amplified by PCR from the cDNA of all specimens. ISH showed scattered expression of SGII in both RA and OA synovial tissue; its expression pattern was characterized by positive staining for SGII in both the lining and the sublining layer. Immunohistochemical double labeling with anti-CD68 antibodies revealed expression of SGII in CD68 negative, fibroblast-like cells, whereas CD68 positive macrophages did not. In RA and OA, the SGII staining by ISH was positive with a diffuse staining throughout the entire synovial tissue. SN protein expression was scattered in RA but more intense in OA synovium. CONCLUSION: The expression of SGII mRNA in RA and OA synovial fibroblasts clearly supports the hypothesis that SN is involved in the synovial tissue inflammation in both diseases. The significant lower SN expression in RA could be due to an inhibitory mechanism with respect to the SN levels in synovial fluid. SN might be involved in the modulation of afferent nerve transmission and therefore might play a role in the sensation of pain, especially in patients with OA.

Antigens, CD↗
PubMed1999

Psychological and behavioral approaches to pain management for patients with rheumatic disease.

This article reviews the efficacy of the psychological and behavioral pain management interventions that have been evaluated among adult patients with rheumatoid arthritis (RA), osteoarthritis (OA), and fibromyalgia (FM). Using published criteria for empirically validated interventions, it is concluded that cognitive-behavioral therapies and the Arthritis Self-Management Program represent well-established treatments for pain among patients with RA and OA. These interventions involve education, training in relaxation and other coping skills, and rehearsal of these skills in patients' home and work environments. There currently are no psychological or behavioral interventions for pain among FM patients that can be considered as well-established treatments. Future intervention research should use clinically meaningful change measures in addition to conventional tests of statistical significance, attend to the pain management needs of children, and assess whether outcomes produced in university-based treatment centers generalize to those in local treatment settings.

Behavior Therapy↗
PubMed1999

Screening for hereditary hemochromatosis: are DNA-based tests the answer?

Universal screening for hereditary hemochromatosis (HH) has been proposed by many experts, with understandable enthusiasm: HH can cause fatal complications, which are preventable with early treatment. The disorder involves excess iron accumulation that can result in tissue iron overload, with secondary cirrhosis, diabetes, heart failure, impotence and arthritis. These complications are preceded by years of iron accumulation, and most are believed to be preventable by removal of excess iron by phlebotomy. Thus, early identification and treatment - the quintessential functions of health screening - seem to make sense for HH. However, the available screening tests are imperfect. While they can identify many persons at increased risk from HH, the proportion that will develop serious clinical manifestations related to iron overload is not known with certainty. DNA-based tests do not provide a simple resolution to these questions.

Genetic Testing↗
PubMed1999

Issues in implementing prenatal screening for cystic fibrosis: results of a working conference.

OBJECTIVE: To summarise a conference convened to examine how cystic fibrosis screening might appropriately be introduced into routine prenatal practice. METHODS: Participants included experts from various relevant disciplines. Systematic reviews and data from individual trials were presented; issues were identified and discussed. RESULTS: Judged by published criteria, prenatal cystic fibrosis screening is suitable for introduction. Screening can be performed cost effectively by identifying racial/ethnic groups at sufficient risk and then using either of two models for delivering laboratory services. Validated educational materials exist. Ethical issues are not unique. CONCLUSIONS: Once adequate facilities for patient and provider education, testing, counselling, quality control, and monitoring are in place, individual programmes can begin prenatal screening for cystic fibrosis.

Clinical Trials as Topic↗
PubMed1998

Immunohistochemical and molecular studies of serotonin, substance P, galanin, pituitary adenylyl cyclase-activating polypeptide, and secretoneurin in fibromyalgic muscle tissue.

OBJECTIVE: Because former investigations have reported abnormal changes in the expression of serotonin (5-hydroxytryptamine [5-HT]) and substance P (SP) in serum and cerebrospinal fluid, this study sought to determine whether 5-HT and pain-modulating neuropeptides (SP, galanin [GA], pituitary adenylyl cyclase-activating polypeptide, and secretoneurin) were expressed abnormally in the muscle tissue of patients with fibromyalgia (FM). METHODS: Snap-frozen muscle tissue specimens (deltoid muscles) from 10 patients with FM (mean disease duration 15 years) and from 10 healthy control subjects were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) of RNA preparations from muscle cells, and by immunohistochemistry methods (alkaline phosphatase-anti-alkaline phosphatase and immunogold-silver) using specific primers as well as antibodies. When specific messenger RNA (mRNA) was detected by RT-PCR, in situ RT-PCR was performed for mRNA localization. RESULTS: Specific mRNA for the examined substances was absent in 9 of 10 FM patients and in 10 of 10 controls. No differences between the FM patients and controls could be detected in the muscle tissue by immunohistochemistry. In 1 FM patient, mRNA for the GA receptor could be shown. CONCLUSION: This study showed that 5-HT and neuropeptides are not produced in the muscle of patients with FM, and therefore do not appear to be involved in the peripheral induction of pain in this chronic, painful disorder.

Adult↗
PubMed1998

Sexual and physical abuse in women with fibromyalgia: association with outpatient health care utilization and pain medication usage.

OBJECTIVE: To evaluate the relationship between sexual and/or physical abuse and health care usage in patients with fibromyalgia (FM) and identify variables that may influence this relationship. METHODS: We assessed history of sexual/physical abuse, health care utilization, and medication usage, as well as related variables in 75 women with FM using standardized questionnaires, structured interviews, and laboratory pain perception tasks. RESULTS: Fifty-seven percent of FM patients reported a history of sexual/physical abuse. Compared to non-abused patients, abused patients reported significantly greater utilization of outpatient health care services for problems other than FM and greater use of medications for pain (P < or = 0.025). Consistent with our expectations, abused patients also were characterized by significantly greater pain, fatigue, functional disability, and stress, as well as by a tendency to label dolorimeter stimuli as painful regardless of their intensities (P < or = 0.05). Additional analyses suggested that the high frequency of sexual/physical abuse in our patients was associated primarily with seeking health care for chronic pain rather than the FM syndrome itself or genetic factors. CONCLUSION: There is an association in FM patients between sexual/physical abuse and increased use of outpatient health care services and medications for pain. This association may be influenced by clinical symptoms, functional disability, psychiatric disorders, stress, and abnormal pain perception. The relationships among these variables should be further tested in prospective, population-based studies.

Adolescent↗
PubMed1998

A multiplex ARMS test for 10 cystic fibrosis (CF) mutations: evaluation in a prenatal CF screening program.

In Maine, prenatal screening for cystic fibrosis (CF) is offered through primary care providers. Cheekbrush (buccal) samples are routinely tested for eight mutations by multiplex PCR amplification of five exons, followed by dot-blot hybridization with pooled allele-specific oligonucleotides (ASO). The ASO methodology is widely used and effective, but somewhat time and labor intensive when applied to CF carrier testing or couple-based prenatal screening in the general pregnant population. Amplification Refractory Mutation System (ARMS) is an improvement of the PCR that allows rapid detection of mutations involving single base changes or small deletions/insertions. In this study, two multiplex ARMS reactions are used to test for 10 common CF mutations. Clinical evaluation of the ARMS test includes a retrospective study of 140 banked samples (54 cell line, proficiency testing, and buccal controls; 86 clinical buccal samples) with known CF genotype (57 with CF mutations, 83 no mutation), followed by a prospective trial in which 309 buccal samples are analyzed con-currently using both methods. The success rate of the ARMS test in buccal lysates is comparable to the ASO method; all CF mutations are successfully identified. For testing nonsterile buccal lysates with low DNA concentrations, optimized performance in the ARMS method is obtained using Amplitaq Gold polymerase. The ARMS method developed is easy, rapid (1 day), and avoids the need for ASO probe labeling, dot-blotting and autoradiography. This study provides further evidence that ARMS methodology is suitable for clinical CF mutation analysis.

Cheek↗
PubMed1998

Detecting sincerity of effort: a summary of methods and approaches.

Despite the widespread use of methods that are supposed to detect the sincerity of patients' efforts in clinical assessment, little has been written summarizing the literature that addresses the reliability and validity of measurements obtained with these methods. The purpose of this article is to review the literature on the reliability and validity of scores for Waddell's nonorganic signs, descriptions of pain behavior and symptom magnification, coefficients of variation, correlations between musculoskeletal evaluation and function, grip measurements, and the relationship between heart rate and pain intensity. The authors of the articles reviewed conclude that none of these methods have been examined adequately. Some of these methods, such as Waddell's nonorganic signs, were not developed for the purpose of detecting sincerity of effort. Clinicians are encouraged to critically read the literature addressing these methods. With further research, some of the discussed methods may prove useful. Until such research is reported in the peer-reviewed literature, however, clinicians should avoid basing evaluation of sincerity of effort on these tests. Therapists are encouraged, instead, to use a biobehavioral approach to better understand and address the complex factors underlying delayed recovery.

Disability Evaluation↗