Biomedical subjects

P H Schur

Publications and source records attributed to P H Schur.

At least 19 recordsLinked to original sources

PubMed2005

Antibodies to C reactive protein.

BACKGROUND: C reactive protein (CRP) is a known indicator of inflammation. Serum CRP is often raised in patients with inflammatory conditions. OBJECTIVE: To determine whether individuals make antibodies to CRP and whether this might affect serum CRP concentrations. METHODS: An enzyme linked immunosorbent assay was developed for the detection of antibodies to CRP. Specificity of the reaction was determined by inhibition of the reaction. RESULTS: Sera from 413 patients were tested and 25 were found to be positive, particularly in patients with rheumatic diseases. Levels of anti-CRP did not correlate with serum CRP levels. CONCLUSIONS: The presence of low CRP levels may not reflect the presence of antibodies to CRP.

Arthritis, Rheumatoid↗

PubMed2005

Lateralized cognitive dysfunction in patients with systemic lupus erythematosus.

This study was designed to determine whether there is a lateralized pattern of cognitive dysfunction in patients with systemic lupus erythematosus (SLE). Fifty right-handed patients with SLE, but no history of cerebrovascular disease participated in the study. Thirty right-handed healthy subjects matched for age and education served as controls. SLE and healthy control subjects underwent a three-hour neuropsychological evaluation designed to measure attention, memory, visual spatial skills, verbal skills reasoning, psychomotor speed, and motor function. A cognitive disability index was created to identify cognitive impairment. Percentile tables based on the performance of all subjects were constructed for 20 component scores. Any subject with five or more component scores below the 25th percentile was designated impaired. Using this criterion, cognitive impairment was identified in 50% of patients with SLE and 20% of healthy controls. Patients with SLE were impaired on measures of psychomotor speed/fluency, verbal speed/fluency and verbal memory. This pattern of performance on neuropsycholgical testing was consistent with left hemisphere brain dysfunction. The observed deficits were not clearly attributable to vascular lesions and suggest immune-mediated effects on specific brain regions in a subgroup of patients with SLE.

Adult↗

PubMed2003

Clinical utility of the anti-CCP assay in patients with rheumatic diseases.

OBJECTIVES: To determine the frequency of antibodies to cyclic citrullinated peptides (CCP) in a group of patients with a diversity of rheumatic diseases. METHODS: 249 consecutive sera from an arthritis clinic sent for rheumatology testing were selected for testing with the anti-CCP2 assays and for the presence of rheumatoid factor (RF). Patient charts were reviewed for demographic information, clinical diagnosis, radiographic information, and other laboratory data. RESULTS: The sensitivity and specificity of anti-CCP reactivity for the diagnosis of rheumatoid arthritis (RA) were 66.0% and 90.4%, respectively. This compared with the sensitivity and specificity of RF for RA at 71.6% and 80.3%. Furthermore, 10/29 (34%) RF- patients with RA demonstrated reactivity to CCP. The presence of either anti-CCP or RF increased testing sensitivity for diagnosis of RA to 81.4%; the presence of both RF and anti-CCP demonstrated a testing specificity similar to that of anti-CCP reactivity alone for the diagnosis of RA (91.1%). CONCLUSIONS: The detection of anti-CCP is useful for the diagnosis of RA, in fact even more so than RF, because of its higher specificity.

Adolescent↗

PubMed2001

Monoclonal gammopathy of undetermined significance and exposure to breast implants.

BACKGROUND: Animal studies and uncontrolled case series in humans have suggested a possible association between breast implant exposure and monoclonal gammopathy. OBJECTIVE: To assess whether there is an increased risk of monoclonal gammopathy in women with silicone breast implants, we conducted a retrospective study of women exposed to breast implants and matched nonexposed women nested within a prospective cohort study (the Nurses' Health Study). METHODS: We used serum protein electrophoresis and immunoglobulin subtype by immunofixation to test 288 women exposed to breast implants and 288 age-matched, nonexposed women who previously had provided a blood sample (1989-1990) for monoclonal proteins. RESULTS: Among the women exposed to breast implants, 5 had monoclonal gammopathy of undetermined significance (MGUS) compared with 4 women among those not exposed (odds ratio, 1.25; 95% confidence interval, 0.27-6.39). The distribution of isotypes was similar across exposure groups. The exposed women with MGUS tended to be older than the nonexposed women (mean age, 60.4 years vs 52.5 years, respectively; P =.03). None of the 9 women with MGUS had reported multiple myeloma or other hematologic malignancies up through 1996. CONCLUSIONS: We find little evidence to support a substantial increased risk of MGUS in women exposed to breast implants. Larger studies are needed to determine if a more modest relationship exists.

Age Factors↗

PubMed2001

Prevalence of migraine in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the prevalence of migraine in patients with systemic lupus erythematosus (SLE), and to examine the relationships between headache type and other clinical, serologic, and treatment features of the disease. BACKGROUND: Headaches are common in SLE and are a significant source of patient disability. The exact prevalence of headaches in patients with SLE is unknown. The classification of headache syndromes in SLE is also unclear. Previous studies were based on small numbers of patients and the headache types and criteria to define headache types varied widely. METHODS: Four hundred fourteen patients meeting American College of Rheumatology criteria for the diagnosis of SLE were sent the University of California, San Diego Migraine Questionnaire. Patients who completed the questionnaire had their medical records reviewed for constitutional, respiratory, cardiac, vascular, skin, musculoskeletal, other neuropsychiatric, hematologic, renal, and immunologic manifestations of the disease. Recent corticosteroid, nonsteroidal anti-inflammatory drug, antimalarial, and immunosuppressive medications were also recorded. RESULTS: One hundred eighty-six patients completed the questionnaire. Sixty-two percent of patients reported headaches: 39% met diagnostic criteria for migraine and 23% met criteria for nonmigrainous headache. Of the patients with migraine, 56% met criteria for migraine without aura and 44% met criteria for migraine with aura. There were no significant associations between headache type and other clinical, serologic, or treatment features of the disease. CONCLUSIONS: There is a high prevalence of migraine in patients with SLE, and patients should be routinely evaluated for migraine symptoms.

Adolescent↗

PubMed2001

Abdominal thrombotic and ischemic manifestations of the antiphospholipid antibody syndrome: CT findings in 42 patients.

PURPOSE: To determine the abdominal computed tomographic (CT) findings in patients with antiphospholipid antibody syndrome (APS). MATERIALS AND METHODS: Retrospective review of medical records from two university medical centers from 1994 through 1997 revealed 215 patients who had a hypercoagulable state attributed to primary or secondary APS. Abdominal CT findings in these patients were reviewed for evidence of large-vessel occlusion or visceral ischemia. RESULTS: In 42 (19.5%) of 215 patients with APS (age range, 32-65 years; mean age, 42 years), abdominal thromboses or ischemic events were detected at CT. Twenty-two (52%) had major vascular thromboses, including those in the inferior vena cava (n = 10), portal and superior mesenteric veins (n = 7), splenic vein (n = 4), and aorta (n = 1). Thirty-six (86%) patients had abdominal visceral ischemia resulting in renal infarction (n = 22), bowel ischemia (n = 13), splenic infarction (n = 6), pancreatitis (n = 3), hepatic infarction (n = 1), and/or hepatic dysfunction with portal hypertension (n = 1). In some patients, more than one abdominal organ and/or vessel was involved. CONCLUSION: Patients who have circulating antiphospholipid antibodies are at risk for major abdominal vascular thromboses and organ infarction. Radiologists must be familiar with this syndrome; they may be the first physicians to suggest the diagnosis on the basis of findings of unusual or recurrent sites of thrombosis, especially in young patients.

Abdomen↗

PubMed2001

Lateralized EEG findings in patients with neuropsychiatric manifestations of systemic lupus erythematosus.

Routine and quantitative EEG were used to determine whether there is a lateralized pattern of electrophysiologic dysfunction in patients with diverse neuropsychiatric manifestations of SLE. Twenty consecutive patients with neuropsychiatric symptoms of SLE underwent 20-minute EEG recordings with an 18-channel polygraph. Ten 1-second intervals were randomly selected for each patient. Once selected, the intervals were analyzed for the presence of theta and delta slow activity. Mapping was done by four-point interpolation around the 18 acquired data points. On routine EEG, abnormalities were identified in 14/20 patients with SLE. In 12/14 patients, the abnormalities were localized to the left temporal region. Quantitative EEG analyses revealed theta and delta slow activity predominantly affecting the left hemisphere in 16/19 patients with SLE. Taken together, these findings suggest selective involvement of the left hemisphere in patients with diverse neuropsychiatric manifestations of SLE.

Adult↗

PubMed2000

Prospective analysis suggests susceptibility genes for deficiencies of IgA and several other immunoglobulins on the [HLA-B8, SC01, DR3] conserved extended haplotype.

The extended major histocompatibility complex (MHC) haplotype [HLA-B8, SC01, DR3] is increased in frequency among patients with immunoglobulin (Ig)A deficiency and common variable immunodeficiency. Because the genomic region from HLA-B to HLA-DR/DQ is virtually the same on all instances of the haplotype in the general population, we reasoned that all independent instances of [HLA-B8, SC01, DR3] carry MHC susceptibility genes for these disorders. To define immunoglobulin deficiencies determined by genes on this haplotype and their mode of expression and penetrance, serum immunoglobulin class and IgG subclass concentrations were determined prospectively in homozygotes and heterozygotes of this haplotype and in Caucasian controls. Prevalence of individual immunoglobulin deficiencies in persons with [HLA-B8, SC01, DR3] ranged from 13% to 37%, significantly higher than rates in non-carriers or general controls. We found significantly increased frequencies of IgA and IgG4 deficiency only in homozygotes (13.3% and 30%, respectively) compared with heterozygotes (1.7% and 3.4%) or non-carriers (1.6% each), suggesting recessive expression. In contrast, IgD and IgG3 deficiencies were significantly more common in both homozygotes (36.7% and 30%) and heterozygotes (20.3% and 17.5%) compared with controls (4.9% and 3.4%), suggesting dominant inheritance. These results indicate multiple distinct susceptibility genes, some recessive and others dominant, for deficiency of IgA, IgD, IgG3 or IgG4 (but not for IgE, IgG1, IgG2 or IgM) on [HLA-B8, SC01, DR3]. These observations may also help to explain the observed associations of [HLA-B8, SC01, DR3] with both IgA deficiency and common variable immunodeficiency and the common occurrence of IgG subclass deficiencies in some patients with IgA deficiency.

Common Variable Immunodeficiency↗

PubMed1999

Association of silicone breast implants with immunologic abnormalities: a prospective study.

PURPOSE: To study the possible association of silicone-breast-implant exposure and immunologic abnormalities within the Nurses' Health Study, an ongoing prospective cohort study of women. SUBJECTS AND METHODS: From this cohort, we randomly selected 200 women who had been exposed to silicone breast implants and who had never reported connective tissue diseases during 14 years of follow-up, and 500 age-matched, nonexposed women, including 100 with definite connective tissue diseases validated by medical record review, 100 with at least one symptom of a connective tissue disease, 100 with diabetes, and 200 healthy controls. Assays for antinuclear antibodies (ANA), including anti-dsDNA, anti-ssDNA, anti-Sm/RNP/Ro/La, and anti-Scl-70, rheumatoid factor, immunoglobulins, serum complement, and C-reactive protein level, and anticardiolipin, antithyroglobulin, antithyroid microsomal, and antisilicone antibodies were performed by standard techniques in blood samples collected in 1989 or 1990 before collection of silicone-breast-implant exposure data in 1992. RESULTS: ANA was positive (> or = 1:40) in 14% of women with silicone breast implants compared with 20% of healthy women (P = 0.11). Rheumatoid factor was positive (> or = 1:40) in 5% of women with silicone breast implants and 2% of healthy women (P = 0.16). Women with silicone breast implants had a significantly higher frequency of anti-ssDNA antibodies than healthy women (41% and 29%, P = 0.012). Duration of implant was associated with a higher frequency of anti-ssDNA antibodies (P = 0.03) but not with ANA or rheumatoid factor. No other significant differences in the frequencies of autoantibodies were observed in silicone breast implant-exposed women. Antisilicone antibodies were not found in any sample. CONCLUSION: We found no increased frequency of any immunologic abnormalities in women exposed to silicone breast implants, except for anti-ssDNA, which has unknown clinical relevance.

Adult↗

PubMed1999

CD4 TCRBV CDR3 analysis in prevalent SLE cases from two ethnic groups.

We examined CD4+ T cell TCRBV-CDR3 transcripts from 19 lupus patients and 16 controls to test the hypothesis that CD4+ TCRBV-CDR3 expression in SLE differs from normals. Within the disease group we also performed exploratory analyses to determine the association between risk of oligoclonality and HLA-DRB specificities and the duration of the CDR3 patterns. Oligoclonal patterns consistent with CDR3 restriction were three times more likely in SLE than in controls (OR = 3.7). TCRBV1, BV4, BV5.1, BV7, BV9, BV18 and BV22 gene segment CDR3 patterns of oligoclonality were seen exclusively among lupus patients. HLA-DRB3 increased the risk of oligoclonal expression in SLE. In four patients studied over time, the pattern of TCRBV-CDR3 expression was stable in a second sample obtained 6-14 months later. The increased frequency of CD4+ T cell TCRBV-CDR3 oligoclonal expression in SLE when compared to controls and the persistence of these patterns are consistent with an expanded pool of autoreactive CD4 T cells in SLE which recognize peptides derived from autoantigens. The association of HLA-DRB3 genes with increased risk of CDR3 oligoclonality among the SLE subjects is compatible with the hypothesis that molecules encoded by HLA-DRB3 may facilitate autoantigen recognition by CD4 T cells.

Adult↗

PubMed1999

A computer based intervention to reduce unnecessary serologic testing.

OBJECTIVE: Laboratory testing is important in the evaluation of patients with possible systemic rheumatic disease, but uncritical use of any test may result in misleading information and unnecessary costs. We attempted to reduce the number of unnecessary antinuclear antibody, rheumatoid factor, and complement level tests ordered by house officers at a large teaching hospital, where inpatient orders are written through a computer based order entry system. METHODS: We conducted a prospective cohort study of an interactive test ordering program. The intervention consisted of displaying post-test probability estimates during the usual physician order entry session. These estimates were based on pretest probabilities entered by the ordering physician and sensitivities and specificities derived from a literature review. Another group of test orders did not prompt the intervention and were considered controls. The outcome of interest was the percentage of tests canceled in the intervention group versus the control group. RESULTS: Eleven percent (11/99) of intervention orders were canceled, versus only one order among 236 controls (p = 0.001). However, there was no association between the physicians' pretest probability estimates and whether test orders were canceled (p = 0.59). Additionally, 43 of the 335 orders (13%) yielded positive tests, but only 4 patients (1%) were given new diagnoses of rheumatic disease. CONCLUSION: The computer based intervention significantly reduced orders for antinuclear antibody and rheumatoid factor levels by 10%. Further reductions without clinical harm are probably possible, since the yield of testing for new rheumatic diseases was low.

Adult↗

PubMed1998

EEG abnormalities in systemic lupus erythematosus.

The medical records of 478 SLE patients were reviewed. Ninety-five patients (19.9%) with a history of seizures were identified. EEG reports were available on 62. EEGs were interpreted as normal in 8 (12.9%) and abnormal in 54 (87.1%). Abnormal EEGs were reviewed for the presence of unilateral and bilateral abnormalities. Left hemisphere abnormalities were identified in 43 (79.6%), right hemisphere abnormalities in 4 (7.4%), and bilateral abnormalities in 7 (13.0%) patients with SLE. Abnormalities included theta and delta slowing and sharp wave activity. In 32 of the 43 (74.4%) patients with left hemisphere abnormalities, the abnormalities were localized to the left temporal leads. These findings suggest selective damage to the left temporolimbic region in patients with SLE.

Adult↗

PubMed1997

Proteins phosphorylated during stress-induced apoptosis are common targets for autoantibody production in patients with systemic lupus erythematosus.

Proteins cleaved by interleukin-1 beta converting enzyme family proteases during apoptosis are common targets for autoantibody production in patients with systemic lupus erythematosus (SLE). We have tested the possibility that proteins phosphorylated in cells undergoing apoptosis are also targets for autoantibody production in patients with autoimmune disease. Sera from 9/12 patients containing antinuclear antibodies (10/12 meeting diagnostic criteria for SLE or a lupus overlap syndrome), precipitated new phosphoproteins from lysates derived from Jurkat T cells treated with apoptotic stimuli (i.e., Fas-ligation, gamma irradiation, ultraviolet irradiation), but not with an activation (i.e., CD3-ligation) stimulus. Sera derived from individual patients precipitated different combinations of seven distinct serine-phosphorylated proteins. None of these phosphoproteins were included in precipitates prepared using sera from patients with diseases that are not associated with autoantibody production or using serum from rheumatoid arthritis patients. Protein phosphorylation precedes, or is coincident with, the induction of DNA fragmentation, and is not observed when apoptosis is inhibited by overexpression of bcl-2. Serum from four patients precipitated a serine/threonine kinase from apoptotic cell lysates that phosphorylates proteins of 23-, 34-, and 46-kD in in vitro kinase assays. Our results suggest that proteins phosphorylated during apoptosis may be preferred targets for autoantibody production in patients with SLE.

Apoptosis↗

PubMed1997

Molecular analysis of major histocompatibility complex allelic associations with systemic lupus erythematosus in Taiwan.

OBJECTIVE: To investigate the association of HLA class II alleles/haplotypes, type I C2 deficiency gene, and tumor necrosis factor a gene promoter allele (TNF2) with systemic lupus erythematosus (SLE) in the Chinese population in Taiwan. METHODS: The HLA-DRB1 and DQB1 alleles were studied in 105 SLE patients and 115 controls by the polymerase chain reaction (PCR)/sequence-specific oligonucleotide probe method, the subtyping of DRB1*15/16 and DRB5 by PCR with sequence-specific primers, type I C2 deficiency gene by PCR, and TNF2 by PCR-Nco I restriction fragment length polymorphism. RESULTS: The frequencies of the HLA class II alleles DRB1*02, DRB1*1502, DRB5*0102, DQB1*0501, and DQB1*0602 and DR2-associated haplotypes DRB1* 1501,DRB5*0101,DQB1*0602 and DRB1*1502,DRB5* 0102,DQB1*0501 were higher among SLE patients than among controls; however, only DQB1*0501 was statistically significantly associated with SLE. No specific allele/haplotype was significantly associated with lupus nephritis. No subject had type I C2 deficiency. SLE patients had a marginally higher percentage of TNF2, which was in linkage disequilibrium with DR3. Since DR3 was not associated with SLE in this Taiwanese Chinese population, TNF2 might play a role in the immunopathogenesis of SLE. CONCLUSION: Although no HLA-DRB1 allele was found to be significantly associated with SLE, the associations with DQB1*0501 and TNF2 suggest that DQB1 and tumor necrosis factor a may be important genetic factors in SLE susceptibility in the Chinese population in Taiwan.

Adult↗

PubMed1997

Elevation of bioactive transforming growth factor-beta in serum from patients with chronic fatigue syndrome.

The level of bioactive transforming growth factor-beta (TGF-beta) was measured in serum from patients with chronic fatigue syndrome (CFS), healthy control subjects, and patients with major depression, systemic lupus erythematosis (SLE), and multiple sclerosis (MS) of both the relapsing/remitting (R/R) and the chronic progressive (CP) types. Patients with CFS had significantly higher levels of bioactive TGF-beta levels compared to the healthy control major depression, SLE, R/R MS, and CP MS groups (P < 0.01). Additionally, no significant differences were found between the healthy control subjects and any of the disease comparison groups. The current finding that TGF-beta is significantly elevated among patients with CFS supports the findings of two previous studies examining smaller numbers of CFS patients. In conclusion, TGF-beta levels were significantly higher in CFS patients compared to patients with various diseases known to be associated with immunologic abnormalities and/or pathologic fatigue. These findings raise interesting questions about the possible role of TGF-beta in the pathogenesis of CFS.

Depression↗

PubMed1997

It is lupus?

It has been said that the essence of medicine is the reduction of uncertainty for patients and physicians (Ludo Baghius). Confronting patients who have some symptoms suggesting lupus but who do not meet criteria for classic SLE is challenging. Evaluating and caring for these patients, when not making a diagnosis of SLE, demands clinical acumen, confidence, and effective communication skills.

Adult↗

PubMed1996

Fas ligand mutation in a patient with systemic lupus erythematosus and lymphoproliferative disease.

The pathogenesis of systemic lupus erythematosus (SLE) is multifactorial and multigenetic. The apoptosis genes, fas and fas ligand (fasL), are candidate contributory genes in human SLE, as mutations of these genes result in autoimmunity in several murine models of this disease. In humans, fas mutations result in a familial autoimmune lymphoproliferative syndrome, but defects in FasL have not yet been identified. In this study, DNA from 75 patients with SLE was screened by single-stranded conformational polymorphism analysis for potential mutations of the extracellular domain of FasL. A heterozygous single-stranded conformational polymorphism for FasL, was identified in one SLE patient, who exhibited lymphadenopathy. Molecular cloning and sequencing indicated that the genomic DNA of this patient contained an 84-bp deletion within exon 4 of the fasL gene, resulting in a predicted 28 amino acid in-frame deletion. Analysis of PBMC from this patient revealed decreased FasL activity, decreased activation-induced cell death, and increased T cell proliferation after activation. This is the first report of defective FasL-mediated apoptosis related to a mutation of the human Fasl, gene in a patient with SLE and suggests that fasL mutations are an uncommon cause of the disease.

Amino Acid Sequence↗

PubMed1996

Utility of anti-Sm, anti-RNP, anti-Ro/SS-A, and anti-La/SS-B (extractable nuclear antigens) detected by enzyme-linked immunosorbent assay for the diagnosis of systemic lupus erythematosus.

OBJECTIVE: To determine the utility of anti-extractable nuclear antigen (anti-ENA) antibodies detected by enzyme-linked immunosorbent assay as a predictor for the diagnosis of systemic lupus erythematosus (SLE). METHODS: Among 2,185 serum samples sent for testing for antinuclear antibodies (ANA) by indirect immunofluorescence, 259 consecutive patients with positive ANA were identified. Medical charts of these patients were reviewed to assess the clinical diagnosis, with the reviewer having no knowledge of the anti-ENA result. Clinical data were abstracted for all patients, and diagnoses established using American College of Rheumatology criteria. The utility of ENA antibodies in the diagnosis of SLE was determined by univariate and multivariate analysis among all patients who were positive for ANA, patients who were positive for ANA and for anti-double-stranded DNA (anti-dsDNA), and patients who were positive for ANA and negative for anti-dsDNA. Clinical differences between SLE patients with and those without anti-ENA antibodies were assessed. RESULTS: Anti-ENA antibodies, especially anti-Ro/SS-A, showed strong predictive diagnostic value among ANA+/anti-dsDNA- patients, but were of no utility among ANA+/anti-dsDNA+ patients. The only clinical manifestations that were more common among anti-ENA+ SLE patients were pleuritis and the use of hydroxychloroquine. CONCLUSION: The presence of anti-ENA antibodies, especially anti-Ro/SS-A, is a useful predictor for the diagnosis of SLE, primarily among patients attending a referral rheumatology center who are positive for ANA and negative for anti-dsDNA. No major clinical differences were noted among ANA+ SLE patients with versus those without ENA.

Antibodies, Antinuclear↗