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Biomedical subjects

P Bacon

Publications and source records attributed to P Bacon.

At least 19 recordsLinked to original sources
PubMed2003

Course of Modic 1 six months after lumbar posterior osteosynthesis.

STUDY DESIGN: A prospective study was conducted to investigate the outcome of the Modic Type 1 inflammatory signal in magnetic resonance imaging (MRI) in 17 patients with chronic low back pain 6 months after instrumented posterior lumbar arthrodesis. OBJECTIVE: To assess the course of the inflammatory signal after stabilization of a painful intervertebral segment by posterior instrumentation alone visualized on MRI systematically performed 6 months after the operation. SUMMARY OF BACKGROUND DATA: In 1988, Modic and colleagues described three degenerative stages of vertebral endplates and subchondral bone. The inflammatory stage, or Stage 1, is correlated with substantial functional disability. According to these authors, Stage 1 lesions naturally transform into Stage 2, the fatty stage. In the literature, patients with Modic 1 signal tend to have good results after arthrodesis, better than those with Modic 2 lesions. METHODS: This study included 17 patients (average age, 46 years) who had experienced chronic low back pain more than 1 year and showed Modic 1 changes in MRI and disc narrowing on plain radiographs. Every patient underwent posterior screw-rod osteosynthesis and posterolateral arthrodesis. Disc disease had occurred subsequently to discectomy (n = 7), rapidly destructive disc disease (n = 5), or spondylolisthesis resulting from spondylolysis (n = 5). Clinical results were assessed according to a visual analog scale for pain, a functional disability score for the evaluation of patients with low back pain (Eiffel), and the validated French version of the self-administered Dallas quality-of-life test (DRAD). RESULTS: Systematic MRI at 6 months showed transformation from Modic 1 to Modic 0 (normal endplate signal) in 4 patients and transformation from Modic 1 to Modic 2 in the remaining 13 patients. Clinical evaluation was performed at 6 months (at the same time as the MRI) and at 1 year. In every patient, there was improvement in the visual analog score and the functional score, which remained stable at 1 year. CONCLUSIONS: According to the literature, most Modic 1 lesions change to become Stage 2 lesions in 18 to 24 months. In this study, 17 patients with Modic Type 1 signal had changes after 6 months. It appears that posterior osteosynthesis combined with posterolateral arthrodesis accelerates the course of Modic 1 lesions, probably by correcting mechanical instability.

Adult↗
PubMed2001

Role of NF-kappaB activity in apoptotic response of keratinocytes mediated by interferon-gamma, tumor necrosis factor-alpha, and tumor-necrosis-factor-related apoptosis-inducing ligand.

An important step in tumorigenesis involves loss of sensitivity to various apoptotic signals by malignant cells, imbuing them with an enhanced survival phenotype. NF-kappaB also regulates epidermal thickness, susceptibility to apoptosis, and tumor formation in skin. Keratinocytes were examined for their susceptibility to apoptosis using cytokines produced during an immunologic response to tumor antigens, i.e., interferon-gamma and/or tumor necrosis factor-alpha (TNF-alpha). The role for NF-kappaB in this response was examined using a retroviral vector containing a degradation-resistant form of IkappaBalpha. Whereas interferon-gamma and TNF-alpha either alone or in combination did not induce apoptosis in keratinocytes, after infection with the retrovirus to block NF-kappaB activation they became susceptible to TNF-alpha but not Fas-induced apoptosis. Moreover, when keratinocytes with repressed NF-kappaB activity were simultaneously treated with interferon-gamma, there was a synergistic induction of apoptosis by TNF-alpha that was dependent on FADD, tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL), and caspase activation. Molecular abnormalities accompanying repressed NF-kappaB activity included failure to induce TNF-RII receptor together with enhanced levels of TRAIL death receptor 4. The ability of interferon-gamma when combined with TNF-alpha to mediate keratinocyte apoptosis included induction of TRAIL coupled with diminished capacity of keratinocytes with repressed NF-kappaB activity to increase the TRAIL decoy receptor-1, as well as lower levels of several NF-kappaB-dependent antiapoptotic proteins accompanied by enhanced caspase 8 levels. These results indicate that interferon-gamma and TNF-alpha synergistically induce keratinocyte apoptosis when concomitant induction of NF-kappaB is blocked. Participants in the apoptotic response mediated by NF-kappaB, besides cell-survival proteins, include modulation of TRAIL and both death and decoy receptors. Thus, not only does NF-kappaB signaling influence the intrinsic survival pathway for keratinocytes in normal skin, but it may also play a role in determining the apoptotic response to cytokines generated during an immune response via TRAIL produced by the keratinocytes themselves.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Activity, damage and outcome in systemic vasculitis.

Current therapy has transformed the prognosis of the systemic vasculitides from diseases that had a high acute mortality rate to chronic relapsing diseases with high rates of morbidity. This improved survival has highlighted the need for better methods of monitoring disease activity and recording the accumulation of organ damage that occurs during the course of the disease. Several clinical indices have been developed that record disease activity, damage and the extent of disease. These validated indices allow a detailed assessment of the patient's response to therapy and provide an essential tool for insuring uniformity of patient monitoring in multi-centre trials. In addition, more data are now available supporting the use of these assessment tools as prognostic and outcome criteria for clinical studies. The development, properties, application and inter-relationships of the available clinical assessment tools for patients with systemic vasculitis are reviewed in this chapter.

Humans↗
PubMed2001

Is there an effect of acupuncture on the resting EEG?

OBJECTIVE: To investigate if acupuncture has a measurable effect on the resting electron EEG. SUBJECTS: 14 healthy volunteers with no neurological condition took part in the study. METHODS: Using a digital storage EEG recorder and quantitative frequency analysis techniques data were obtained before, during and after acupuncture stimulation. To minimize the effect of artefacts all data were collected with the subject alert, but with eyes closed. Manual stimulation of the LI 4 acupuncture site was undertaken for periods of 0.5, 1.0 and 2.0 min. Frequency analysis of the EEG data from each acupuncture event was compared to the baseline data to show any significant changes over the bandwidth 0.3 to 30 Hz. Only changes greater than 2 standard deviations were considered significant. RESULTS: In 10 subjects the frequency spectra remained unchanged during acupuncture, but in three significant increases were recorded in the amplitude of very low frequencies between 0.5 and 2 Hz and in one subject there was an increase in the amplitude of the alpha band during acupuncture. All spectra returned to their baseline values immediately after acupuncture. OUTCOME: The changes recorded in the delta band of individuals during acupuncture were large but highly variable. They arose at a frequency that is on the limit of the recording equipment and where recording and physiological artefacts are known to occur, although there was no evidence of artefactual contamination of the data. The one case in which there was an increase in the alpha band is attributed to suppression of the dominant rhythm initially brought about by anxiety concerning the procedure which subsequently disappeared during acupuncture as the subject relaxed. CONCLUSION: It is clear that there are no changes brought about by acupuncture in the resting EEG in the frequency range 2-30 Hz and no evidence to attribute changes below 2Hz to a direct affect of acupuncture.

Acupuncture Therapy↗
PubMed2001

Takayasu arteritis and atherosclerosis: illustrating the consequences of endothelial damage.

The excess of cardiovascular morbidity associated with chronic vasculitic disease has become a focus of considerable research, particularly regarding the link between endothelial damage and the development of atherosclerosis. We describe a case of Takayasu arteritis treated sub-optimally by today's standards, giving rise to an 11 year history of progressive, stepwise decline associated with cerebrovascular events and leading to early death. Postmortem findings presented a picture of chronic atherosclerotic disease but in a distribution consistent with lesions of Takayasu arteritis.

Aorta↗
PubMed2000

Id-1 delays senescence but does not immortalize keratinocytes.

Defining the molecular basis responsible for regulating the proliferative potential of keratinocytes has important implications for normal homeostasis and neoplasia of the skin. Under current culture conditions, neonatal foreskin-derived human keratinocytes possess a relatively short replicative lifespan. Recently it was reported that forced overexpression of the helix-loop-helix protein Id-1 was capable of immortalizing keratinocytes, secondary to activation of telomerase activity and suppression of p16/Rb-mediated growth arrest pathways. To investigate the relationship between Id-1, telomerase activity, telomere length, p16, Rb cell cycle regulators, and senescence, whole populations of keratinocytes were infected with a retrovirus to induce overexpression of Id-1. In these unselected cultures, enhanced Id-1 levels clearly extended the lifespan of keratinocytes, but Id-1 did not prevent the onset of replicative senescence. Under these experimental conditions, Id-1 expression did not trigger induction of telomerase activity, and there was progressive shortening of the telomeres that was accompanied by elevated p16 levels and prevalence of active Rb. The ability of Id-1 to postpone, but not prevent, senescence may be related to partial inhibition of p16 expression, as the Id-1-overexpressing cultures displayed a decreased capacity for 12-O-tetradecanoylphorbol-13-acetate-mediated p16 induction. Thus, while no immortalization was observed, Id-1 could delay the onset of replicative senescence in unselected human keratinocyte populations.

Apoptosis↗
PubMed2000

The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index for Systemic Lupus Erythematosus International Comparison.

OBJECTIVE: To compare patients with systemic lupus erythematosus (SLE) from different centers with respect to demographics and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) scores, and to assess whether the SLICC/ACR DI changed over time, and whether initial DI scores were related to outcome. METHODS: Members of SLICC completed DI scores and patient demographics on patients followed in their centers. Information was provided at 2, 5-10, and > 10 years of followup. Data were entered on computer and analyzed on SPSS/PC+ and SAS using descriptive statistics and analysis of variance. RESULTS: Information for 1297 patients within 2 years of first clinic visit was submitted from 8 centers. There were 1187 women and 110 men with a mean age at diagnosis of SLE of 32 years. Seven hundred sixty-two were Caucasian, 423 were black, and the remainder were of other races. There were more blacks in the American centers than in Canadian or European centers. Five centers provided information for the 3 time periods. The DI increased over time. Ninety-nine patients had died. Higher SLICC/ACR DI scores were documented in patients who went on to die. CONCLUSION: The SLICC/ACR DI is a valid measure for damage in SLE.

American Medical Association↗
PubMed1996

Nutritional care of the patient with HIV/AIDS.

Nutrition and diet plan an important role in regulating the immune system. People with HIV disease are prone to weight loss for a number of reasons, although this is not inevitable. The aim of nutritional therapy is to preserve body weight, particularly lean body mass.

Body Weight↗
PubMed1996

The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus.

OBJECTIVE: To develop and perform an initial validation of a damage index for systemic lupus erythematosus (SLE). METHODS: A list of items considered to reflect damage in SLE was generated through a nominal group process. A consensus as to which items to be included in an index was reached, together with rules for ascertainment. Each center submitted 2 assessments, 5 years apart, on 2 patients with active and 2 with inactive disease, of whom 1 had increased damage and the other had stable disease. Analysis of variance was used to test the factors physician, time, amount of damage, and activity status. RESULTS: Nineteen physicians completed the damage index on 42 case scenarios. The analysis revealed that the damage index could identify changes in damage seen in patients with both active and inactive disease. Patients who had active disease at both time points had a higher increase in damage. There was good agreement among the physicians on the assessment of damage in these patients. CONCLUSION: This damage index for SLE records damage occurring in patients with SLE regardless of its cause. The index was demonstrated to have content, face, criterion, and discriminant validity.

Health Status Indicators↗
PubMed1994

Clinical pharmacology and modification of autoimmunity and inflammation in rheumatoid disease.

The increased understanding of the mechanisms which underlie rheumatoid disease has been accompanied by a more appropriate use of the limited repertoire of therapeutic agents. Conventional second-line drugs still have a role in everyday practice. The efficacy of these agents in reducing the severity of clinical signs of joint inflammation, whilst at the same time causing significant reductions in the laboratory measures of the acute phase response is undoubtedly confirmed by meta-analysis of several therapeutic trials of these agents. Whether or not these agents can influence outcome, usually assessed in terms of radiological progression, is more contentious. Furthermore, their toxicity in long term use is not inconsiderable. However, newer agents may play a more important part in therapy in the future. Such therapy can be designed to specifically interfere with the abnormalities of the immune system which characterise rheumatoid arthritis. Many of the agents reviewed have been successfully applied to animal models of arthritis but we still await large randomised controlled studies in humans to determine their clinical efficacy and toxicity. In view of the complexity of the immunological abnormalities in rheumatoid arthritis, it may be necessary to consider using a number of such agents in any particular patient. This should result in more rational therapy in rheumatoid arthritis.

Animals↗
PubMed1994

Sensitivity to change of 3 Systemic Lupus Erythematosus Disease Activity Indices: international validation.

OBJECTIVE: Three indices, the SLE Disease Activity Index (SLEDAI), the Systemic Lupus Activity Measure (SLAM) and the British Isles Lupus Assessment Group (BILAG), have been found to be reliable and valid measures of disease activity in patients with systemic lupus erythematosus (SLE). Our aim was to investigate their use and comparative ability to assess change in disease activity over time. METHODS: Clinical and laboratory features of 8 patients with SLE on each of 3 consecutive visits were abstracted and sent in 3 separate packages to physicians from 8 centers. The order of the patient visit summaries was randomized, and the 3 indices rated in one of 6 specific sequences. RESULTS: The 3 indices were significantly (p < 0.01) correlated: SLEDAI/SLAM = 0.61, BILAG/SLAM = 0.55, SLEDAI/BILAG = 0.35. The sequence presented, the order of patients and order of index scoring did not contribute significantly (p > 0.05) to the variation of any of the 3 indices. All 3 indices detected differences among patients (p < 0.01). Differences between visits were detectable with SLEDAI (p = 0.04) but not with SLAM or BILAG: CONCLUSION: Our study confirms that the SLEDAI, SLAM and BILAG are comparable disease activity measures. SLEDAI appears to be sensitive to change in disease activity over time.

Computers↗
PubMed1993

Worldwide experience with etodolac (Lodine) 300 mg b.i.d. in the treatment of osteoarthritis.

Worldwide experience with the conventional formulation of etodolac (300 mg b.i.d.) was reviewed in 12 randomized, double-blind, parallel-group studies in patients with osteoarthritis (OA) of the hip or knee. The studies were conducted in 13 countries at 59 sites, and 1289 patients were enrolled. The results of 9 comparative and 3 placebo-controlled clinical studies were examined to compare the efficacy and safety of etodolac versus piroxicam, naproxen, indomethacin, indomethacin sustained-release (SR), and diclofenac SR. Efficacy assessments were made at pretreatment screening, baseline, and every 2 weeks thereafter during treatment until study completion up to 4, 6, or 8 weeks. The primary efficacy assessments were the patient's and physician's global evaluations, pain intensity and night pain, or joint tenderness and walking pain. Safety was assessed with reference to study events, reports of laboratory results, and vital signs measurements. Patients in all active treatment groups showed prompt response to therapy. According to the physicians' global evaluation, at least 64% of all etodolac-treated patients and 62% of all active-reference preparation-treated patients had improved by the end of the study. Similar results were seen in the patients' global evaluation. All of the study drugs were well tolerated. Eight (8%) percent of the etodolac-treated patients withdrew because of study events. The proportions of patients treated with active reference preparations and placebos who withdrew because of study events ranged from 3% to 18%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Responses to gram negative enteric bacterial antigens by synovial T cells from patients with juvenile chronic arthritis: recognition of heat shock protein HSP60.

OBJECTIVE: To investigate the antigenic specificity of synovial T cells in juvenile chronic arthritis (JCA). METHODS: Synovial fluid and peripheral blood mononuclear cells from 24 patients with JCA were tested for their proliferative responses to recall antigens, enteric organisms associated with reactive arthritis, influenza A and a recombinant preparation of a mycobacterial heat shock protein, HSP65. To investigate further recognition of this last antigen, synovial T cells from one B27+ patient with pauciarticular disease were cloned using HSP65. The specificity of the resultant clones was then examined. RESULTS: Marked synovial T cell responses to enteric organisms and to HSP65 were noted, particularly in HLA-B27+, pauciarticular patients; these were similar to those seen in a B27+ patient with reactive arthritis. Responses to enteric organisms and to HSP65 were significantly correlated, suggesting recognition of an epitope common to these antigen preparations. However, all of the T cell clones obtained using HSP65 proved to recognize E. coli derived antigens contaminating the recombinant HSP65 rather than the mycobacterial antigen; these contaminants included the 60 kDa E. coli HSP, GroEL. The GroEL specific T cells did not respond to heat shocked human cells; this suggests (but does not prove) that they do not crossreact with human HSP60. CONCLUSION: Synovial T cell recognition of antigens from enteric organisms associated with reactive arthritis is a common feature in pauciarticular JCA. Among the target antigens is the GroEL HSP, but T cells recognizing this antigen do not necessarily crossreact with the homologous human HSP60.

Antigens, Bacterial↗