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Biomedical subjects

J G Hanly

Publications and source records attributed to J G Hanly.

At least 37 records · Page 2Linked to original sources
PubMed1998

Evaluation of patients with CNS involvement in SLE.

Patients with systemic lupus erythematosus (SLE) may present with a wide array of neuropsychiatric (NP) clinical features. This may either be a primary manifestation of SLE, the result of a complication of the disease or its therapy, or a concurrent disease process. As there is no single diagnostic gold standard for NP-SLE, the assessment of individual patients is heavily dependent upon clinical evaluation in addition to information from studies of autoantibodies, brain structure and function. Despite their lack of diagnostic sensitivity and specificity, these tests frequently provide information that can be used to support or refute the clinical impression. They may also provide a basis for the prospective evaluation of the efficacy of therapeutic interventions in individual patients with NP-SLE.

Brain Diseases↗
PubMed1997

The reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in patients with systemic lupus erythematosus.

OBJECTIVE: To test the reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in the assessment of patients with SLE. METHODS: Ten patients with SLE, representing a spectrum of damage and activity, were included. Each patient was examined by 6 of 10 physicians from 5 countries, representing 10 lupus clinics. The SLICC/ACR Damage Index was used to assess accumulated damage, and the SLEDAI was used to assess disease activity. The order of the patients and physicians was randomized according to a Youden square design. RESULTS: The SLICC/ACR Damage Index detected differences among patients (P < 0.001). There was no detectable observer difference (P = 0.933), and there was no order effect (P = 0.261). Similar results were obtained with the SLEDAI. There was concordance in the SLICC/ACR Damage Index among observers, despite a wide spectrum of disease activity detected by the SLEDAI. CONCLUSION: Physicians from different centers are able to assess patients with SLE in a reproducible way, using the SLEDAI to assess disease activity and the SLICC/ACR Damage Index to assess accumulated damage.

Adult↗
PubMed1997

Disease activity, cumulative damage and quality of life in systematic lupus erythematosus: results of a cross-sectional study.

The relationship between disease activity, cumulative damage and self-reported quality of life was examined in 96 patients with Systematic Lupus Erythematosus (SLE). Disease activity was measured by the SLE Disease Activity Index (SLEDAI) and cumulative damage by the Systematic Lupus International Cooperating Clinics/ACR damage index (DI). Quality of life was assessed by the Medical Outcomes Survey Short Form 20 (SF-20) self-report questionnaire which consists of six subscales. The study population was predominantly Caucasian (91%) and female (90%). The mean (+/- s.d.) age was 42.0 +/- 11.0 years and disease duration was 7.5 +/- 5.5 years. SLEDAI scores varied from 0-28, with a mean (+/- s.d.) of 4.8 +/- 5.2. The mean (+/- s.d.) DI score was 0.74 +/- 1.06, with a range of 0-5. Subscales of the SF-20 varied from 0-100 and the range of mean (+/- s.d.) scores varied from 35.0 +/- 42.2 to 70.5 +/- 28.7. There was no correlation between SLEDAI and DI scores or between SLEDAI scores and any of the six subscales of the SF-20. Likewise there was no correlation between DI scores and SF-20 subscales with the exception of Health perception (r = 0.34, P = 0.02). These results indicate that there are at least three independent dimensions of health status in SLE, namely disease activity, cumulative damage and quality of life. Furthermore, the extent of inflammatory disease activity and irreversible target organ damage are not the sole determinants for quality of life in SLE patients.

Adolescent↗
PubMed1997

Adrenal failure in systemic lupus erythematosus.

We describe a 39-year-old woman who developed Addison's disease 2 years after diagnosis of systemic lupus erythematosus (SLE). Examining her initial presentation, there is evidence to suggest that adrenal dysfunction may have commenced at the time of diagnosis of SLE. We suggest the need for considering adrenal dysfunction in patients with SLE with systemic complaints.

Addison Disease↗
PubMed1996

Self-assessment of disease activity by patients with rheumatoid arthritis.

OBJECTIVE: To determine the reliability of self-assessment of disease by patients with rheumatoid arthritis (RA), with a particular emphasis on the assessment of articular swelling. METHODS: A questionnaire was developed using components from validated instruments. Information was obtained on global function, global joint tenderness/swelling, and joint pain (10 cm visual analog scales), duration of musculoskeletal morning stiffness (grade 1-6), ACR functional score (grade 1-4), tender joint count (0-20), tender joint score (0-60), swollen joint count (0-20), and swollen joint score (0-60). Data were collected prospectively on 61 patients with RA in a teaching clinic or office practice by 4 staff rheumatologists. Patient questionnaires were completed within 24 h before physician assessments. Followup assessments were carried out on 27 patients after a mean interval of 3 months (range 0.5-6). RESULTS: At the initial assessment there was a significant correlation between patient and physician assessments for global function (r = 0.83; p = 0.01) [intraclass correlation coefficient (ICC) = 0.83; p < 0.01], global joint tenderness/swelling (r = 0.83; p < 0.01) (ICC = 0.83; p < 0.01), global joint pain (r = 0.83; p < 0.01) (ICC = 0.81; p < 0.01), duration of morning stiffness (r = 0.83; p < 0.01) (ICC = 0.85; p < 0.01), ACR functional score (r = 0.61; p < 0.01) (ICC = 0.62; p < 0.01), tender joint count (r = 0.57; p < 0.01) (ICC = 0.31; p < 0.01), and tender joint score (r = 0.60; p < 0.01) (ICC = 0.35; p < 0.01). However, there was poor correlation between patient and physician assessments for both swollen joint count (r = 0.16; p > 0.05) (ICC = -0.02; p > 0.05) and swollen joint score (r = 0.24; p > 0.05) (ICC = 0.12; p > 0.05). Longitudinal analysis indicated significant correlation between changes in patient and physician assessments in all variables except swollen joint count and score. CONCLUSION: Although there was good correlation between most variables for patient and physician assessments of disease activity in RA, there were substantial differences in the assessment of joint swelling. This objective determinant of disease activity cannot be ascertained in self-report measures of health status.

Adult↗
PubMed1996

Beta 2-glycoprotein I and anticardiolipin antibody binding to resting and activated cultured human endothelial cells.

OBJECTIVE: To examine beta 2-glycoprotein I (beta 2-GPI) binding and its ability to augment IgG anticardiolipin (aCL) antibody binding to resting and cytokine activated endothelial cells in vitro. To evaluate the ability of IgG aCL antibody positive sera to induce endothelial cell activation in vitro. METHODS: IgG with aCL activity was isolated by affinity purification from 6 patients with systemic lupus erythematosus (SLE) and 3 patients with primary antiphospholipid antibody syndrome (APS). Human umbilical vein endothelial cells (HUVEC) were cultured in serum-free conditions and examined in a resting state or after activation with tumor necrosis factor alpha (TNF-alpha). HUVEC were exposed to beta 2-GPI alone, IgG alone or IgG plus beta 2-GPI. Finally, we examined the ability of sera from the same patients with SLE and primary APS to activate HUVEC in culture. RESULTS: Neither beta 2-GPI, IgG aCL, nor IgG aCL plus beta 2-GPI bound to resting or cytokine activated endothelial cells. In addition, sera from the same patients did not induce in vitro activation of endothelial cells as assessed by enhanced surface expression of intercellular adhesion molecule, vascular cell adhesion molecule, and E-selectin. CONCLUSION: Results suggest that beta 2-GPI deposition on either resting or activated endothelial cells and modulation of its proposed in vivo anticoagulant activity through subsequent aCL antibody binding does not account for the thrombotic manifestations of APS.

Antibodies, Anticardiolipin↗
PubMed1995

Immunomodulating effects of synchronised plasmapheresis and intravenous bolus cyclophosphamide in systemic lupus erythematosus.

Recent studies have suggested that synchronised plasmapheresis and intravenous pulse cyclophosphamide therapy reduce disease activity in SLE patients. The aim of the present study was to examine the immunomodulating effects of this therapy and compare it with changes seen with cyclophosphamide alone. Four patients with active SLE were studied. Two were treated with synchronised therapy and two received cyclophosphamide only for up to 26 weeks. Disease activity was measured by the SLE disease activity index (SLEDAI). Immunological studies were performed immediately prior to each treatment. Patients in both treatment groups improved as reflected by a fall in mean SLEDAI scores: synchronised therapy 33.5 to 11; cyclophosphamide only 13.5 to 4.5. Following synchonised therapy only there was a prompt and sustained increase in the mean percentage of CD8+ cells (20.8 to 54.8) which resulted in a fall in the CD4:CD8 ratio (1.95 to 0.62). With both treatment modalities there was a fall in the proportion of CD20+ cells (B lymphocytes) (synchronised therapy 10.5 to 3.2; cyclophosphamide only 5.6 to 2.2). However, only synchronised therapy resulted in a fall in the in vitro production of immunoglobulins which was unchanged or increased following cyclophosphamide alone. These results suggest that although both treatment modalities are efficacious in the treatment of active SLE they produce different immunomodulatory effects. Thus, both therapies reduce the number of circulating B lymphocytes whereas synchronised therapy also modifies cellular immunity by promoting the emergence of a phenotypic suppressor T lymphocyte population.

Adjuvants, Immunologic↗
PubMed1995

Requirement of beta 2 glycoprotein I as cofactor in the binding for IgM and IgA anticardiolipin antibodies.

OBJECTIVE: To determine if IgM and IgA anticardiolipin (aCL) antibodies require beta 2 glycoprotein I (beta 2-GPI) as a cofactor for antibody binding. METHODS: Sera were selected from 7 patients with systemic lupus erythematosus (SLE), 6 of whom had high IgM and 6 high IgA aCL antibody binding. Control sera were obtained from 2 healthy individuals with no aCL antibodies. Serum proteins were initially separated by sepharose CL6B get filtration chromatography, and IgM was further purified by affinity chromatography with mannan binding protein. IgA was isolated from CL6B filtrate by jacalin lectin affinity chromatography. Levels of beta 2-GPI in the immunoglobulin preparations were determined by antigen capture ELISA: Anticardiolipin antibody binding IgM and IgA was examined by ELISA with and without the addition of beta 2-GPI (10 micrograms/ml) or 4% normal human serum and expressed in optical density units (OD). RESULTS: beta 2-GPI was required as a cofactor for IgM aCL antibody binding in 4 to 6 patients with SLE. In these, antibody binding to cardiolipin increased from (mean +/- SEM) 0.10 +/- 0.01 TO 1.06 +/- 0.22 (p = 0.005) with the addition of beta 2-GPI. For IgA, 5 of 6 patients with SLE demonstrated a requirement of beta 2-GPI as a cofactor. Antibody binding increased from 0.27 +/- 0.05 to 1.77 +/- 0.35 (p = 0.003) with the addition of beta 2-GPI. CONCLUSION: beta 2-GPI is required as a cofactor for IgM and IgA aCL antibody binding.

Antibodies, Anticardiolipin↗
PubMed1994

Brain reactive autoantibodies and cognitive impairment in systemic lupus erythematosus.

Nervous system involvement in SLE encompasses a wide array of clinical manifestations which may reflect multiple etiologic factors including autoantibodies to nervous tissue antigens. The aim of the present study was to examine the association between autoantibodies to a wide range of brain antigens and cognitive abnormalities in an unselected population of 70 SLE patients. Using a battery of standardized neuropsychological tests, cognitive impairment was identified in 15/70 (21%) SLE patients compared with 1/25 (4%) patients with rheumatoid arthritis and 1/23 (4%) healthy subjects (P = 0.04). Integral membrane proteins were isolated from dissociated brain cells by temperature-induced phase separation with Triton X-114. Synaptosomes were isolated by differential centrifugation and membrane enriched fractions were prepared by lectin affinity chromatography. Western blotting identified IgG reactivity to a wide range of proteins (MW 22-52 K) in SLE patients. The proteins identified were distinct from well-characterized intracellular antigens including ribosomal P proteins. There was no significant difference in the prevalence of anti-brain antibodies between SLE patients who were cognitively impaired and those who were not impaired. Furthermore, there was no association between the presence of autoantibodies and subsets of cognitive dysfunction. These results suggest that circulating autoantibodies to brain antigens are not responsible for the abnormalities in cognitive function in SLE patients.

Adolescent↗
PubMed1994

Clinical course of cognitive dysfunction in systemic lupus erythematosus.

OBJECTIVE: To prospectively evaluate changes in cognitive function in a cohort of unselected patients with systemic lupus erythematosus (SLE) and controls over a 12 month period. METHODS: Seventy female patients with SLE, 25 patients with rheumatoid arthritis (RA) and 23 healthy subjects (age and sex matched) were evaluated using the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the Wechsler Memory Scale-Revised (WMS-R), the California Verbal Learning Test (CVLT) and the National Adult Reading Test-Revised to identify impairment in 8 areas of cognitive function. Cumulative disease manifestations and current medications were documented, and disease activity was expressed using the SLE disease activity index (SLEDAI). Decision rules were determined for overall cognitive impairment. RESULTS: At baseline, 21% (15/70) of patients with SLE were impaired compared to 4% (1/25) of patients with RA and 4% (1/23) of healthy subjects (p = 0.042). After a mean interval of 12.8 months (range: 11-17) 84% (59/70) of patients with SLE, 44% (11/25) of patients with RA and 80% (17/23) of healthy subjects were reassessed. This included all subjects who were impaired at the initial assessment. Using the same decision rules as at baseline, 12% (7/59) of patients with SLE were impaired at followup compared to none of the patients with RA and healthy subjects. Over the period of study cognitive impairment persisted in 3 patients with SLE, resolved in 12 and evolved in 4 others. There was no apparent association between changes in cognitive function and concurrent changes in generalized disease activity, overt neuropsychiatric disease or corticosteroid medication. CONCLUSION: Our results suggest that cognitive dysfunction in patients with SLE is evanescent, does not necessarily lead to irreversible neurologic compromise and changes independently of other clinical variables.

Adult↗
PubMed1994

Early recognition of sacroiliitis by magnetic resonance imaging and single photon emission computed tomography.

OBJECTIVE: To evaluate the role of magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) in the detection of sacroiliitis in patients with clinical features of inflammatory back disease but without conventional radiographic changes. METHODS: Twenty-four patients with inflammatory low back pain (ILBP) and normal or suspicious changes of sacroiliitis (New York criteria: 0-1) on conventional radiography, in addition to 12 control subjects were studied. MRI, bone and SPECT scans of the sacroiliac (SI) joints were obtained and interpreted without knowledge of patient identification. MRI scans were scored according to the modified New York criteria and examined for the presence of joint fluid, abnormalities in articular cartilage and in the underlying marrow signal. A quantitative and qualitative assessment of radiopharmaceutical uptake in the SI joints was derived from planar bone scan films and SPECT scans. RESULTS: MRI detected features of scaroiliitis in 54% of patients with ILBP and in 17% of controls (p = 0.07). Quantitative and qualitative analysis of planar bone scan films did not reveal any differences between the 2 patient groups. In contrast, SPECT scanning identified sacroiliitis in 38% of patients with ILBP compared to none in controls (p = 0.05). When MRI and SPECT scanning were combined there was evidence of sacroiliitis in 63% of patients with ILBP and in 17% of controls (p = 0.025). CONCLUSION: MRI and SPECT bone scanning provide objective and complementary evidence of sacroiliitis in patients with clinical features of inflammatory spinal disease in the absence of conventional radiographic changes.

Adult↗
PubMed1993

Antibodies to brain integral membrane proteins in systemic lupus erythematosus.

Wheat germ lectin affinity chromatography and temperature-induced phase separation with Triton X-114 were evaluated for the isolation of surface neuronal antigens from rat and human brain and from human neuroblastoma cell lines IMR-6 and SK-N-SH. Both techniques yielded surface proteins which were free of contamination by intracellular proteins but temperature-induced phase separation was technically less demanding and less expensive, required a shorter assay time and resulted in a superior quantity and quality of isolated proteins. Rat brain surface proteins were used for characterization of antineuronal antibody reactivity in sera from patients with systemic lupus erythematosus (SLE). Western blotting identified reactivity in 15 of 75 (20%) SLE sera compared to five of 95 (5%) normal controls (P 0.006). In rat brain the molecular weight of the individual proteins identified ranged from 59 kDa to 22 kDa. Six of these were also present in human brain and two were present in neuroblastoma cell lines. Absorption studies indicated that some of the antigenic proteins were either restricted to brain tissue or shared with other non-neuronal tissues. These techniques should facilitate the characterization of antineuronal antibody reactivities and lead to a clearer understanding of their role in the pathogenesis of autoimmune neurologic disease.

Adult↗
PubMed1993

Cognitive impairment and autoantibodies in systemic lupus erythematosus.

Nervous system involvement in systemic lupus erythematosus (SLE) includes a wide array of manifestations some of which have been associated with specific autoantibodies. These include reactivity to surface neuronal and lymphocyte antigens, ribosomal P and cardiolipin. The aim of the present study was to examine the association between cognitive abnormalities and these autoantibodies in an unselected female population of SLE patients. Using a battery of standardized neuropsychological tests, cognitive impairment was identified in 15/70 (21%) SLE patients compared to 1/25 (4%) patients with rheumatoid arthritis and 1/23 (4%) healthy subjects (P = 0.04). Circulating antineuronal antibodies were measured by indirect immunofluorescence using human neuroblastoma cell lines IMR-6 and SK-N-SH. Lymphocytotoxic antibodies were measured by microcytotoxicity. Antibodies to ribosomal P and cardiolipin were measured by ELISA. Antineuronal antibodies were detected in 34%, lymphocytotoxic antibodies in 47%, anti-P antibodies in 17% and anticardiolipin antibodies in 24% of patients. In the cognitively impaired and unimpaired SLE patients there was no significant difference in the prevalence of antineuronal antibodies (33 vs 35%), lymphocytotoxic antibodies (40 vs 50%), anti-P antibodies (20 vs 17%) or anticardiolipin antibodies (7 vs 29%). The titre and isotype of autoantibodies were also similar in both groups. These results suggest that autoantibodies which have previously been associated with nervous system manifestations of SLE are not likely to be directly involved in the pathogenesis of cognitive dysfunction.

Antibodies, Anticardiolipin↗
PubMed1993

Patterns of cognitive impairment in patients with systemic lupus erythematosus.

This study examined neuropsychological test performance in a representative sample of 70 female patients with SLE. The influence of current or past clinically overt central nervous system involvement, use of corticosteroid medications and overall disease activity were evaluated. The results suggest two distinct patterns of cognitive dysfunction. Impaired delayed recognition memory was associated with past or current nervous system involvement, suggesting the presence of a residual neurologic deficit. Increased disease activity was associated with impaired immediate memory and concentration which may represent transient and diffuse central nervous system effects. Although corticosteroid use was associated with poor word list recall, group differences were not statistically significant when disease activity was considered as a covariate in the analysis. Follow-up studies are required to determine if these abnormalities persist or fluctuate with changes in disease activity and concurrent medications.

Adrenal Cortex Hormones↗
PubMed1993

Cutaneous sarcoidosis and foreign bodies.

A histopathological diagnosis of sarcoidosis is, by convention, one of exclusion and is reached only when other potential causes of granulomatous disease, such as foreign bodies, are eliminated. We report herein three cases of systemic sarcoidosis with cutaneous manifestations of the disease, in which polarizable foreign particles were associated with the granulomata in the skin. We submit (a) that a granulomatous foreign body reaction and sarcoidosis are not mutually exclusive, (b) that particulate foreign matter may actually serve as a nidus for granuloma formation in sarcoidosis, and (c) that the occasional presence of extraneous material within the granulomata of sarcoidosis requires greater recognition by pathologists.

Adult↗