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J G Hanly

Publications and source records attributed to J G Hanly.

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

Brain synaptosomal antibodies in systemic lupus erythematosus.

Nervous system involvement in systemic lupus erythematosus (SLE) has been linked to the production of autoantibodies that may bind to surface antigens on neuronal cells and cause cellular dysfunction. At present, little is known of the target antigens recognized by these antibodies. The aim of the present study was to examine reactivity to rat brain synaptosomes (RBS) in sera from patients with SLE. Sera from 73 unselected SLE patients and controls were studied. Crude RBS were prepared by differential centrifugation and enriched fractions of synaptosomes (SY-E), myelin (MY-E) and mitochondria (MI-E) were obtained by sucrose density centrifugation. Rat liver (RL) was used for control antigens. Wheat-germ lectin affinity chromatography yielded membrane-enriched fractions of RBS, RL and whole rat brain (WRB). Antibody binding was examined by Western blotting. IgM reactivity was detected in 12/73 sera (16%) and was directed to proteins of 62K, 48K 37K molecular weight. IgG reactivity was present in 5/73 sera (7%) to proteins of 52K, 48K, 37K and 29K molecular weight. Except for binding to the 52K and 37K proteins these autoantibodies were not detected in control sera. Reactivity was usually absent, or present in reduced amounts, in WRB and RL. Additional experiments revealed that binding of IgM to 62K was found predominantly in SY-E and MY-E fractions, 48K in SY-E and MI-E fractions and 37K in the SY-E fraction. Binding of IgG to 48K and 29K was detected in the SY-E and MI-E, but reactivity to 52K and 37K was restricted to the SY-E fraction. Thus, sera from SLE patients contain antibodies to synaptosomal antigens that may contribute to the neuropsychiatric manifestations of the disease.

Animals↗
PubMed1993

Single photon emission computed tomography in the diagnosis of inflammatory spondyloarthropathies.

OBJECTIVE: The role of bone scintigraphy in the evaluation of patients with inflammatory spondyloarthropathy is controversial and previous studies have reported a lack of sensitivity and specificity. The aim of our study was to determine whether single photon emission computed tomography (SPECT) scanning would enhance the clinical utility of bone scintigraphy in the detection of inflammatory axial disease, in particular sacroiliitis. METHODS: Twenty patients with definite sacroiliitis (New York criteria > 1) on plain film radiographs and 20 age matched controls were studied. Bone scintigraphy and SPECT scanning were carried out 2 h after an intravenous injection of 99mTc imidodiphosphonate (IDP). A quantitative and qualitative assessment of radiopharmaceutical uptake in the sacroiliac (SI) joints was derived from planar films and a qualitative analysis of uptake in the SI joints was derived from SPECT scans. All films were read without knowledge of patient identification. RESULTS: Quantitative analysis of planar films did not identify any difference between study and control groups (p > 0.05). Qualitative assessment of planar films identified features of sacroiliitis more frequently in patients than in controls (p < 0.05) with a sensitivity of 25% and a specificity of 95%. SPECT scanning also revealed enhanced radiopharmaceutical uptake in the SI joints more frequently in patients than in controls (p < 0.001) with a sensitivity of 85% and a specificity of 90%. Increased uptake in the lumbar facet joints and costovertebral joints was identified in 3 patients. Similar abnormalities were not detected in the control group. CONCLUSION: Our results indicate that SPECT scanning is both sensitive and specific for the detection of established sacroiliitis and may also identify inflammatory disease at other sites in the spine.

Adult↗
PubMed1993

Cognitive deficits in systemic lupus erythematosus.

Several independent studies have now demonstrated the presence of significant cognitive impairment in SLE patients. Such impairment, whether it precedes or follows overt NP events, suggests compromise of the neural substrate, irrespective of overt clinical NP symptomatology. The association between cognitive impairment and brain cross-reactive autoantibodies suggests one mechanism for CNS involvement in SLE that warrants further study; the data relating specific cognitive deficits to the presence of specific antibodies raise the intriguing possibility of system- or structure-specific immune-mediated involvement in the CNS. Whatever the mechanism, cognitive impairment in SLE may have significant implications for daily functioning of some lupus patients and requires the selection of appropriate psychosocial and somatic treatment strategies.

Central Nervous System Diseases↗
PubMed1992

Characteristics of immunocompetent cells in synovial membranes from multiple sites in patients with rheumatoid arthritis.

The phenotypic characterization of enzymatically dissociated mononuclear cells in synovial membrane samples from multiple sites in two patients with rheumatoid arthritis (RA) were examined by fluorescence activated flow cytometry. In synovial membrane samples from each patient there was a consistent increase in the proportion of CD8+ cells (suppressor/cytotoxic), CD14+ cells (monocytes/macrophages), and HLA-DR+ cells compared with paired peripheral blood mononuclear cells. The proportion of CD4+ cells (helper/inducer) in synovial membrane was variable. Studies of in vitro production of IgM and IgM rheumatoid factor in one patient showed strikingly similar values for synovial membrane rheumatoid factor production at the two sites, which was enhanced compared with production in peripheral blood. These results suggest that in individual patients with RA the intra-articular immune response is comparable at multiple anatomical sites and that it is distinct from that in peripheral blood.

Antigens, CD↗
PubMed1992

Magnetic resonance imaging in the detection of sacroiliitis.

The value of magnetic resonance imaging (MRI) in establishing the diagnosis of sacroiliitis was studied in 20 patients with established or suspected disease on conventional radiographs and in 10 healthy subjects. Coronal T1 weighted, axial T2 weighted and proton density MRI images of the sacroiliac joints in addition to plain film radiographs were obtained. All films were graded from 0 to 4 according to the modified New York criteria and independently for changes in joint width, erosions, sclerosis and ankylosis. Using the modified New York criteria, more abnormalities were detected by MRI than by conventional radiography (p = 0.04). This was due to the detection of definite abnormalities (grades 2-4) by MRI in joints that were graded normal or suspicious (grades 0-1) on plain films (p = 0.01). MRI tended to be superior to plain films in visualizing erosions. Only MRI detected abnormalities of articular cartilage (19 patients) and in subchondral bone marrow (7 patients). The latter 2 types represented fatty infiltration and inflammatory change. Intraobserver and interobserver variation were similar for the interpretation of MRI scans and plain film radiographs. These results suggest that MRI detects changes of established sacroilitis. Due to its ability to directly image articular cartilage it may be particularly useful in patients with early disease.

Adult↗
PubMed1992

Cognitive impairment in patients with systemic lupus erythematosus.

Seventy unselected patients with systemic lupus erythematosus (SLE) were studied to determine the prevalence of cognitive impairment and the association with other clinical variables. Twenty-five patients with rheumatoid arthritis (RA) and 23 healthy subjects were used as controls. All patients were evaluated with a battery of standardized neuropsychological tests to determine ability in 8 areas of cognitive function. Clinically overt neuropsychiatric (NP) SLE, cumulative disease manifestations and concurrent medications were documented. In patients with SLE, generalized disease activity was expressed using the SLE disease activity index. Cognitive impairment was identified in 15/70 (21%) patients with SLE, 1/25 (4%) patients with RA and in 1/23 (4%) healthy subjects (p = 0.042). The prevalence was higher in patients with active NP-SLE at the time of assessment (2/5, 40%) compared to patients with inactive NP-SLE (2/10, 20%) but was also increased in those patients who had never had known clinical NP-SLE (11/55, 20%). A history of serositis (p = 0.015), active SLE (p = 0.064) and corticosteroid use (p = 0.027) at the time of assessment were more common in patients with cognitive impairment. The results suggest that cognitive impairment is increased in patients with SLE. It may occur independently of clinically overt NP-SLE and is more common in patients with active disease who are receiving corticosteroids.

Adult↗
PubMed1992

Brain pathology in systemic lupus erythematosus.

Brain pathology was documented in 10 patients with systemic lupus erythematosus (SLE), 7 of whom had clinical neuropsychiatric SLE prior to death. This was manifested by seizures (5 patients), organic brain syndrome (3 patients) and psychosis (2 patients). Multifocal cerebral cortical microinfarcts, associated with microvascular injury, were documented in 4 patients and in our study constituted the predominant histopathologic abnormality attributable to SLE. Changes of a healed vasculitis in medium sized leptomeningeal vessels were seen in 1 case. Agreement between the clinical and pathologic classification of neuropsychiatric SLE was observed in 7/10 (70%) cases and the strongest association was between the presence of cerebral microinfarcts and seizures (4/5 patients, p less than 0.05). No correlation was observed with anticardiolipin, anti-P, lymphocytotoxic and antineuronal antibodies.

Adolescent↗
PubMed1991

Strength and function in the normal and rheumatoid hand.

We have reevaluated the Martin vigorimeter to measure grip strength in healthy subjects, and patients with rheumatoid arthritis (RA), and investigated the correlation of grip strength and hand function using the Jebsen hand function tests and Purdue pegboard test before and after treatment. The vigorimeter showed good test-retest reliability (r greater than 0.911) and interrater reliability (r greater than 0.915). Test-retest reliability was greater than 0.97 for the Jebsen test, and greater than 0.94 for the Purdue test in healthy individuals. Seventeen patients with RA were studied at intervals of 1 to 16 weeks. Active joint count and grip strength both improved significantly. Improvement in grip strength correlated with improvement in active joint count. Hand function tests were significantly impaired in the patients with RA.

Adolescent↗
PubMed1990

Phenotypic characteristics of dissociated mononuclear cells from rheumatoid synovial membrane.

The phenotypic characteristics of enzymatically dissociated synovial membrane mononuclear cells from 8 patients (14 samples) with rheumatoid arthritis (RA) were assessed by fluorescence activated flow cytometry and compared to peripheral blood (PB) mononuclear cells from 18 patients with RA and 14 normal controls. There was no significant difference between the percentage of CD4+ and CD8+ lymphocytes in synovial membrane compared to RA and normal PB. Double labelling experiments revealed similar percentages of CD4+ CDw29+ (helper-inducer) and CD4+ CD45R+ (suppressor-inducer) cells in RA and normal PB. In contrast, SM CD4+ CDw29+ cells were present in significantly higher proportions than in RA and normal PB (p less than 0.001). Conversely, synovial membrane CD4+ CD45R+ cells were present in significantly lower proportions than in RA and normal PB (p less than 0.001). A similar pattern of CDw29 and CD45R antigen expression was noted on CD8+ lymphocytes reflecting increased killer-effector (p less than 0.001) and decreased suppressor-effector (p less than 0.001) cells, respectively. Other experiments revealed a significant increase in the percentage of synovial membrane CD20+ cells (B lymphocytes) and HLA-DR+ cells compared to RA PB (p less than 0.02 and p less than 0.001) and normal PB (p less than 0.01 and p less than 0.005), and similar proportions of CD14+ cells (monocytes/macrophages). Our results suggest that RA synovial membrane contains populations of T and B lymphocytes that differ quantitatively and qualitatively from those in PB. These may account for some of the abnormalities in intraarticular humoral and cellular immune responses in patients with RA.

Antigens, CD↗
PubMed1989

Lymphoid irradiation in intractable rheumatoid arthritis. Long-term followup of patients treated with 750 rads or 2,000 rads.

Twenty patients with intractable rheumatoid arthritis were randomized to receive 750 or 2,000 rads of lymphoid irradiation (LI) in a double-blind comparative study, and were followed for a maximum of 48 months (mean 40 months) after treatment. During followup, sustained immunomodulation (including lymphopenia, particularly of the T helper cell subset; reduced ratio of helper cells to suppressor cells; and impaired in vitro lymphocyte proliferation in response to phytohemagglutinin and pokeweed mitogen) was observed. Significant improvements in early morning stiffness, Ritchie articular index, pain score, grip strength, and 15-meter walk time were observed in both treatment groups, but these were not sustained through the followup period. Progressive joint damage was observed radiologically in both groups during followup. Thus, LI induced sustained immunosuppression, but resulted in only short-lived clinical improvement and was associated with progressive joint erosion in these patients.

Arthritis, Rheumatoid↗
PubMed1989

The association between sequential changes in serum antineuronal antibodies and neuropsychiatric systemic lupus erythematosus.

To determine the significance of changes in serum antineuronal antibody levels in systemic lupus erythematosus, 9 patients who had a rise and 11 patients who had a fall in neuronal antibody titre over a mean duration of 2.1 years (range 0.25-5.2) were identified. These changes were examined in the light of concurrent changes in other serological variables, overall disease activity, neuropsychiatric disease and neuropsychological tests. Changes in antineuronal antibodies were frequently associated with concurrent changes in anti-DNA antibodies and overall disease activity. When neuropsychiatric disease or cognitive dysfunction were present, their course showed a close correlation with changes in antineuronal antibody levels. The results support the association between antineuronal antibodies and neuropsychiatric-systemic lupus erythematosus, but suggest that their measurement will provide useful information of disease status in only a subpopulation of patients.

Antibodies↗
PubMed1989

Liver lymphoma in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) has been associated with an increased incidence of lymphoma. We describe the occurrence of hepatic lymphoma, which was likely primary in origin, in a patient with SLE and discuss the etiologic and diagnostic implications.

Aged↗
PubMed1988

Lupus pregnancy. A prospective study of placental changes.

Eleven patients with systemic lupus erythematosus (SLE) were monitored prospectively during pregnancy. Clinical and serologic features of disease activity were recorded, and after delivery, a careful search for pathologic changes in the placenta was carried out. Seven patients delivered live infants, and 4 patients had unsuccessful pregnancies, with fetal loss occurring between 12 and 27 weeks of gestation. One of these 4 patients had active SLE at delivery, and all had circulating lupus anticoagulant and thrombocytopenia. Other serologic abnormalities, including anticardiolipin and anti-Ro antibodies, were not associated with fetal loss. The overall placental size was reduced in SLE patients compared with that in healthy controls and in diabetic controls. A variety of pathologic changes were noted, including placental infarction, intraplacental hematoma, deposition of immunoglobulin and complement, and thickening of the trophoblast basement membrane. The reduction in placental size appeared to enhance the clinical significance of these pathologic changes.

Antibodies↗
PubMed1988

A novel neuronal antigen identified by sera from patients with systemic lupus erythematosus.

Using human neuroblastoma cell lines (IMR-6, NMB-7, SK-N-Mc, SK-N-SH) as sources, we characterized surface neuronal antigens as an initial step in determining the pathogenic role and clinical significance of neuronal antibodies in systemic lupus erythematosus (SLE) patients. SLE sera were screened for the presence of surface neuronal antibodies using a mixed hemadsorption assay. Thirty SLE sera were further tested by Western blotting and immunoprecipitation of lysed IMR-6 cells. Western blotting revealed binding to predominantly intracellular antigens, none of which was restricted to neuroblastoma cells. In contrast, immunoprecipitation experiments demonstrated binding to a 97K antigen, which appeared to be of surface origin, by 3 SLE sera. This was not present on non-neuronal cells and was not precipitated by sera from healthy or disease controls. This 97K antigen was also precipitated from the neuroblastoma cell line NMB-7, but was not present on SK-N-Mc or SK-N-SH cells. Precipitation was depleted by preabsorption with viable IMR-6 and NMB-7 cells, but not with non-neuronal cells. Thus, some SLE sera recognize a 97K neuronal antigen on select neuroblastoma cells.

Antibodies↗
PubMed1988

Psoriatic spondyloarthropathy: a long term prospective study.

Fifty two patients with psoriatic spondyloarthropathy were monitored prospectively over a mean of 57 months (range 30-107). A comprehensive protocol was used to assess clinical and radiological features of disease activity and severity. Serial radiographs showed a significant increase in the number of patients with syndesmophyte formation and sacroiliitis. In contrast, there was no significant increase in the number of patients with inflammatory neck pain or stiffness, back pain or stiffness, cervical spine limitation, or sacroiliac tenderness. Similarly, there were no significant changes in any of the direct or indirect measurements of thoracolumbar spine mobility. The presence of HLA-B27 did not appear to influence disease progression. These results suggest that although patients with psoriatic spondyloarthropathy have radiological progression of their disease, this remains clinically silent and does not compromise spinal mobility.

Adult↗
PubMed1986

Lymphoid irradiation in intractable rheumatoid arthritis. A double-blind, randomized study comparing 750-rad treatment with 2,000-rad treatment.

Twenty patients with intractable rheumatoid arthritis were treated with 750-rad or 2,000-rad lymphoid irradiation in a randomized double-blind comparative study. Over a 12-month followup period, there was a significant improvement in 4 of 7 and 6 of 7 standard parameters of disease activity following treatment with 750 rads and 2,000 rads, respectively. Transient, short-term toxicity was less frequent with the lower dose. In both groups, there was a sustained peripheral blood lymphopenia, a selective depletion of T helper (Leu-3a+) lymphocytes, and reduced in vitro mitogen responses. These changes did not occur, however, in synovial fluid. These results suggest that 750-rad lymphoid irradiation is as effective as, but less toxic than, that with 2,000 rads in the management of patients with intractable rheumatoid arthritis.

Adult↗