Evaluation of the VIDAS Listeria (LIS) immunoassay for the detection of Listeria in foods using demi-Fraser and Fraser enrichment broths, as modification of AOAC Official Method 999.06 (AOAC Official Method 2004.06).

A multilaboratory study was conducted to compare the VIDAS LIS immunoassay with the standard cultural methods for the detection of Listeria in foods using an enrichment modification of AOAC Official Method 999.06. The modified enrichment protocol was implemented to harmonize the VIDAS LIS assay with the VIDAS LMO2 assay. Five food types--brie cheese, vanilla ice cream, frozen green beans, frozen raw tilapia fish, and cooked roast beef--at 3 inoculation levels, were analyzed by each method. A total of 15 laboratories representing government and industry participated. In this study, 1206 test portions were tested, of which 1170 were used in the statistical analysis. There were 433 positive by the VIDAS LIS assay and 396 positive by the standard culture methods. A Chi-square analysis of each of the 5 food types, at the 3 inoculation levels tested, was performed. The resulting average Chi square analysis, 0.42, indicated that, overall, there are no statistical differences between the VIDAS LIS assay and the standard methods at the 5% level of significance.

Filter function and immune complex trapping in splenic ellipsoids.

The role of splenic ellipsoids in the trapping of particulate material and immune complexes was investigated in mink (Mustela vison). The ellipsoids were prominent, with typical features such as a permeable endothelium and a discontinuous basement membrane surrounded by a sheath of macrophages and reticular cells. Ellipsoidal trapping of circulating particles was demonstrated 10 min after intracardiac injection of colloidal carbon and fluorescent microspheres. Preformed peroxidase-antiperoxidase immune complexes were detected in ellipsoids 10 min and also 1 h after intracardiac injection. Erythrocytes were frequently observed in the ellipsoidal sheath, and many phagocytized fragments of erythrocytes were found in the ellipsoidal macrophages. It was concluded that mink ellipsoids are effective blood filters with a role in retention of circulating particulate material, and that mammalian splenic ellipsoids also have the ability to trap immune complexes.

Kinetics of glycosaminoglycan deposition in splenic AA amyloidosis induced in mink.

The kinetics of splenic glycosaminoglycan (GAG) expression in mink has been investigated during the course of AA amyloid induction, i.e. at 3 to 6 weeks of lipopolysaccharide (LPS) treatment. Splenic amyloid was demonstrated by means of Congo red staining in five of 19 LPS-treated mink. Chondroitin/dermatan sulfate (CS/DS), as well as heparan sulfate proteoglycans (HSPG), was extracted from amyloid and control spleens. Independently of the presence of amyloid, the total amount of splenic GAGs increased with the duration of LPS treatment, and an HSPG population was found confined to the LPS-treated spleens. The differential expression of various PG and GAG epitopes in mink spleen was investigated with the help of immunohistochemistry. The amyloid deposits were shown to contain GAG chains of CS and HS, and the core proteins of DSPG decorin and the HSPGs perlecan and agrin. Decorin and perlecan were shown in normal spleens localized to the splenic ellipsoids, an early target for AA amyloid deposition. The constitutive expression of PGs at predilection sites for amyloid deposition and their increased expression in the tissues developing amyloidosis at these early stages show that PGs are available for the formation and deposition of AA amyloid.

Neuropsychological function in systemic lupus erythematosus: a five-year longitudinal study.

OBJECTIVE: To evaluate potential changes in cognitive functions over a 5-yr period in patients with systemic lupus erythematosus (SLE). METHODS: Twenty-eight patients with SLE were examined at baseline and after a mean follow-up of 60.7+/-5.0 months using standardized neuropsychological tests. Group changes in performance over time were measured and the effects of baseline values for subsequent changes in individual variables after 5 yr were evaluated. RESULTS: When all SLE patients were considered as a group, seven out of nine (78%) neuropsychological variables remained unchanged and two (22%) improved significantly during the observation period, possibly due to methodological bias. Analysis of the importance of the level of initial cognitive performance for subsequent changes during the observation period, demonstrated that cognitive changes were not significantly influenced by baseline levels, except for a trend in three of nine variables. Neither demographic nor disease-associated quantitative factors were associated with cognitive changes over time. CONCLUSION: Cognitive dysfunction seems to be a relatively stable feature of central nervous system involvement in SLE. A decrease in performance over time was not demonstrated consistently in the majority of domains.

Transesophageal and transthoracic echocardiography and Doppler-examinations in systemic lupus erythematosus.

OBJECTIVE: To search for cardiac abnormalities in systemic lupus erythematosus (SLE). METHODS: 35 patients examined by 2-D transthoracal Doppler and transesophageal echocardiography. RESULTS: Mitral and aortic valve abnormalities were seen in 12 patients (34%) respectively, and occurred altogether in 16 patients (46%). They were in general significantly associated with longer disease duration, but not with anticardiolipin antibodies (aCL), disease activity, or any other variable, except for time on corticosteroids. which was significantly longer in patients with aortic valve calcifications. CONCLUSION: Valve masses and valve thickening--often in combination--are the most frequent structural findings in SLE, occurring more often on the aortic than on the mitral valves. Factors other than antiphospholipid antibodies, medication, hypertension, or coronary heart disease seem to be responsible for this phenomenon. Drugs that modulate inflammation in endo- and pericardial tissue may, at least in part, be responsible for the observed mitral valve calcifications and pericardial fibrosis.

Sicca symptoms and secondary Sjögren's syndrome in systemic lupus erythematosus: comparison with rheumatoid arthritis and correlation with disease variables.

OBJECTIVE: Firstly, to study the prevalence of ocular and oral sicca symptoms, reduced tear and saliva production, and the minimum frequency of secondary Sjögren's syndrome (sSS) in systemic lupus erythematosus (SLE). Secondly, to compare sicca symptoms and findings with those of matched patients with rheumatoid arthritis (RA), and sicca symptoms with those in healthy controls. Finally, to study possible associations of clinical variables with sicca symptoms and sSS in SLE. METHODS: Self reported sicca symptoms were recorded in 81 patients with SLE aged < or =70, 81 matched patients with RA, and 81 matched healthy controls. Other study variables included Schirmer-I test (S1T), unstimulated whole saliva, health status measures (in SLE and RA), disease activity, accumulated organ damage, and serological markers (in SLE). RESULTS: A significantly higher proportion of patients with SLE reported sicca symptoms than healthy controls. Further, a significantly higher proportion reported ocular sicca symptoms (43 and 21%, respectively) and had pathologically reduced S1T compared with RA (46 and 21%, respectively). No difference was seen in oral sicca symptoms and saliva production. In SLE, sicca symptoms were associated with fatigue, and sSS with anti-SSB or anti-SSA antibodies, or both. CONCLUSIONS: An increased prevalence of sicca symptoms was found in patients with SLE compared with controls, and a higher prevalence of ocular sicca symptoms and reduced tear production in SLE compared with RA. Sicca problems should be considered in the care of patients with SLE, especially those with anti-SSB and/or anti-SSA antibodies who have sicca symptoms and fatigue.

Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow.

Cognitive dysfunction is found in a considerable proportion of patients with systemic lupus erythematosus (SLE). SPECT provides an estimate of regional cerebral blood flow (rCBF) which has been claimed to be sensitive to detect brain involvement in SLE. It is, however, uncertain if these perfusion defects are related to cognitive dysfunction. In the present study we investigated whether cerebral dysfunction assessed by neuropsychological measures was associated with changes in rCBE Fifty-two SLE patients were examined with a battery of neuropsychological tests and MRI of the brain. For each patient 99mTC-HMPAO-SPECT was performed with the visual cortex as reference, and a reduction in rCBF of > 15% was considered abnormal. Regional CBF was performed with an automated computer program quantitatively estimating blood perfusion in 16 symmetrical sectors of the brain. Several sectors of the brain showed varying areas of reduced rCBF with the temporal lobes most frequently involved. There were generally no associations between cognitive level of functioning and reduced rCBF. MRI demonstrated cerebral infarcts in 9 (17%) patients. In general rCBF was reduced in all sectors of the brain in patients with infarcts, although statistical significant difference in rCBF between patients with and without infarcts was only seen in the parietal lobe. Several neuropsychological functions were influenced by the presence of cerebral infarcts. There was no significant association between immunological measures and SPECT findings or neuropsychological measures. Neuropsychological dysfunction in SLE was associated with the presence of cerebral infarcts detected by MRI, but not by changes in rCBF. SPECT seems to add little if any information to that obtained by clinical examination, neuropsychological testing, and MRI. Since anticoagulation may prevent cerebral infarcts, such prophylactic intervention may be of importance in preventing cognitive deterioration.

Folate supplementation during methotrexate treatment of patients with rheumatoid arthritis. An update and proposals for guidelines.

The efficacy of weekly low-dose methotrexate treatment of rheumatoid arthritis is well documented. Efficacy and adverse effects are both dose dependent. and adverse effects rather than lack of efficacy are the main reason for discontinuing therapy. Several adverse effects are related to folate deficiencies, largely due to the antifolate properties of methotrexate. In order to reduce adverse effects without compromising drug efficacy, numerous clinical investigations have been performed using supplementation with folic or folinic acid during methotrexate therapy of patients with rheumatoid arthritis, addressing both the timing of folate supplementation and the weekly folate-to-methotrexate ratio. Based on these studies, an individually adjusted supply of folic acid rather than folinic acid is proposed. For many patients, however, a properly balanced diet is sufficient to avoid folate deficiency.

Peripheral neuropathy in systemic lupus erythematosus--a longitudinal study.

OBJECTIVE: Peripheral neuropathy (PN) is reported to occur in 5-27% of patients with systemic lupus erythematosus (SLE) mostly as a length-dependent sensorimotor axonopathy. Studies over time have not been performed. Design - Longitudinal study. SUBJECTS AND METHODS: Thirty-three Caucasian SLE patients consented to participate in the study and were subjected to clinical examination, laboratory tests, and nerve conduction velocity (NCV) studies. At the follow-up 7 years later, 7 patients (21%) were dead, 4 refused to participate, and 2 did not want to perform NCV studies. Twenty patients were thus available for longitudinal study. RESULTS: When all SLE patients were considered on a group basis at follow-up, 8 (33%) out of 24 NCV parameters showed significant deterioration despite correction for time, while 16 (67%) were unchanged. Analysis of change from baseline showed that, except for F-responses, several NCV changes were highly dependent (negative regression coefficients) on baseline levels at start of study. No demographic, laboratory, or disease associated quantitative factor was associated with these changes in NCV parameters over time. Nor was a consistent effect on NCV parameters from any qualitative demographic or disease associated factor confirmed by Repeated Measures ANOVA analyses. CONCLUSIONS: A modest progressive neuropathic process exists in patients with SLE. Important is also the finding that, over time, the abnormalities of NCV parameters fluctuate in the individual patients, and the impairments are not necessarily irreversible. This study also shows no association to medication, demographic-, or other disease associated factors.

Somatic and psychological features of headache in systemic lupus erythematosus.

OBJECTIVE: Headaches--especially of migrainous type--have been considered part of the disease spectrum of systemic lupus erythematosus (SLE). We wished to characterize prevalence and types of headaches in SLE and find out if headache is associated with disease, personality traits, or other psychological factors. METHODS: Fifty-eight consecutive Caucasian patients with SLE were given a clinical examination. We recorded SLE disease activity according to the SLE Disease Activity Index, types of headache according to International Headache Society criteria, and personality traits and emotional status according to Minnesota Multiphasic Personality Inventory-2 and Beck Depression Inventory (BDI). RESULTS: Thirty-eight SLE patients (66%) were headache sufferers; of these, 22 patients (38%) had migraine and 21 (36%) had tension-type headache. Headaches were not associated with disease activity or any other disease associated variable, including tests for antiphospholipid antibodies. Migraine was associated only with a tendency to social isolation and anxiety, while tension-type headache was associated with psychological distress, such as anxiety, somatic complaints, reduced energy, mental tension, social discomfort and withdrawal, and depressive mood according to the BDI. CONCLUSION; Migraine and tension-type headaches occur frequently in patients with SLE. Migraine shows the same clinical presentation as in a non-SLE population, and may not be part of a neuropsychiatric disease spectrum. This also applies to tension-type headache, which in contrast to migraine shows some associations with emotional and personality traits, and could represent components of a chronic pain syndrome.

Disease course in systemic lupus erythematosus: changes in health status, disease activity, and organ damage after 2 years.

OBJECTIVE: To examine changes in health status, disease activity, and organ damage after 2 years and to study possible disease variables predicting change in health status, disease activity, and organ damage at followup in systemic lupus erythematosus (SLE). Second, to compare changes in health status in patients with SLE to that of matched patients with rheumatoid arthritis (RA) and matched healthy controls. METHODS: A 2 year longitudinal observational study, measuring health status (Short-Form 36. visual analog scale for pain and fatigue, modified Health Assessment Questionnaire, patient global assessment of disease activity), disease activity, and organ damage in 87 patients with SLE. Health status measures in SLE were compared to 65 matched RA patients selected from the Oslo RA register and to 77 matched healthy controls from the population register. RESULTS: On a group level the SLE patients showed stable health status measures and disease activity scores 2 years after baseline, but organ damage scores increased significantly. Increase in organ damage was significantly and independently predicted by baseline scores of disease activity and organ damage, health status, and disease activity by the respective baseline scores. Changes in health status measures over 2 years were similar in SLE, RA, and healthy controls. CONCLUSION: Our 2 year longitudinal observational SLE study showed a stable course of health status and disease activity, whereas organ damage increased. Disease activity and organ damage at baseline predicted the latter. Our results indicate the value of careful monitoring of disease activity over time in SLE and individually tailored treatment guided by the predictors of course and outcome.

Characterization of proteoglycans and glycosaminoglycans in splenic AA amyloid induced in mink.

Amyloidosis of the protein AA type is readily induced in mink using repeated injections of bacterial lipopolysaccharide (LPS). We have characterized splenic proteoglycans/glycosaminoglycans (PGs/GAGs) in mink during amyloidogenesis. Moderate to rich amounts of amyloid exhibiting green birefringence was demonstrated by polarization microscopy of the splenic section stained with Congo red in seven out of eight minks after 10 weeks of LPS-treatment, and a significant increase in the total amount of PGs and GAGs in AA amyloid spleens was observed (two to eight times that in unstimulated animals). Intact PGs as well as free GAGs were extracted, and heparan sulfate (HS) was the most abundant GAG in the amyloid as well as in the control spleens. The GAGs showing the most pronounced increase in the amyloid spleens was of the chondroitin sulfate/dermatan sulfate (CS/DS) type and these were extracted in the form of free GAG chains. We conclude that there is a selective enrichment of PGs/GAGs in extracted splenic amyloid in the mink, which confirms to previous observations in human amyloid as well as in other animal species, supporting their pathogenic significance in the formation of AA amyloid.

Glycosylation of immunoglobulin light chains associated with amyloidosis.

AL amyloidosis is a fatal disease caused by deposition of immunoglobulin light chains in a fibrillarforin (AL) in various organs. By searching the Kabat database of immunoglobulin sequences using the KabatMan software, we have shown that there is a preponderance of the consensus glycosylation sequon (AsnXxxSer/Thr) in the framework regions of amyloid light chains. We have characterised by computer graphics simulations, NMR spectroscopy and carbohydrate biochemistry the structure and conformation of the oligosaccharide from amyloid protein AL MS (lamba1) and from the amyloid associated Bence Jones protein of patient MH (kappa1). These proteins have glycosylation in the hypervariable complementarity-determining region versus framework region, respectively. Both contained a 2-6 sialylated core fucosylated biantennary chain mostly with bisecting GIcNAc. Together our results suggest that light chain glycosylation may be one of several modifications which may render the protein more prone to amyloid formation.

The amino acid sequence of a monoclonal gamma 3-heavy chain from a patient with articular gamma-heavy chain deposition disease.

Abnormal deposition of proteins, including monoclonal immunoglobulin gamma-heavy chains, may cause tissue damage and organ dysfunction. We here report the amino acid sequence of the free gamma-heavy chains present in serum and urine of the first reported case (patient G. L.) of synovial heavy chain deposition disease. The protein was heavily deleted and consisted of the hinge, in addition to the CH2 and CH3 domains, in a dimeric form, thus lacking its variable domain as well as the CH1 domain. The sequence was consistent with the gamma 3 subclass (gamma 3GL). Gm typing revealed the gamma 3 allotypes G3m(b0) and G3m(b1) in accordance with the residues Pro123, Phe128, Thr171 and Phe268 in gamma 3GL. Furthermore, the gamma 3GL molecule was glycosylated at Asn in position 129. Finally, the gamma 3GL protein was shown to contain a typical binding site for the first complement component, C1q, namely the residues Glu150, Lys152 and Lys154, with the potential of binding and activating complement, causing tissue damage following deposition.

Bone mineral density in systemic lupus erythematosus: comparison with rheumatoid arthritis and healthy controls.

OBJECTIVES: To examine bone mineral density (BMD) frequency of osteoporosis and reduced bone mass in systemic lupus erythematosus (SLE), and compare the data of the SLE patients with matched rheumatoid arthritis (RA) patients and healthy controls. Secondly, to study possible correlations between BMD, demographic and disease variables in the SLE patients. METHODS: Measures of BMD assessed by dual energy x ray absorptiometry were obtained from 75 SLE patients aged

Is there a pathogenic link between gamma heavy chain disease and chronic arthritis?

In 1991, gamma heavy chain disease was diagnosed in a 43-year-old female, who 3 years earlier had contracted an erosive seronegative chronic arthropathy. In 1996, her lymphoproliferative disorder required treatment with melphalan and prednisolone. Laboratory studies revealed a gamma3 heavy chain monoclonal component in serum and urine. Massive localization of plasma cells and blasts with cytoplasmic or cell membrane staining for gamma3 chains, but no staining for light chains, was observed by immunohistochemical studies of bone marrow as well as affected synovial tissue. Large amounts of extracellular gamma3-chains were also deposited in the synovial membrane. This is the first documentation of gamma heavy chain deposition disease directly affecting articular structures. Whether it represents the primary pathogenic event followed by reactive inflammatory changes in the joints, or another example of gamma heavy chain disease preceded by chronic arthritis, remains elusive. Regardless, several common cellular and molecular mechanisms discussed here suggest a pathogenic link between the two disease processes.

Myopathy and neuropathy in rheumatoid arthritis. A quantitative controlled electromyographic study.

OBJECTIVE: To test the hypothesis that patients with rheumatoid arthritis (RA) have clinical or subclinical evidence of peripheral neuropathy or myopathy. METHODS: We studied 40 seropositive women with RA, mean age 46.6 years (SD 6.4), and 56 healthy controls, mean age 43.0 years (SD 9.1). Patients had a mean disease duration of 13.0 years (SD 7.8). We performed electromyographic examination of 4 muscles [extensor digitorum communis (EDC), biceps brachii (BB), vastus lateralis (VL), and tibialis anterior (TA)] on the right side in both groups. Quantitative data included percentage of polyphasic potentials, motor unit potential amplitude, area, duration, turns, and number of polyphasic potentials. RESULTS: There were statistically significantly higher proportions of polyphasic potentials in 3 muscles in patients compared with controls. Mean number of phases in EDC was 4.6 (SD 0.4) in the patients and 4.1 (0.5) in controls (p = 0.0001). The values for the VL were 4.1 (SD 0.4) in patients compared with 3.6 (0.4) in controls (p = 0.0001), and in the TA 4.5 (SD 0.5) versus 4.0 (0.4) (p = 0.0001). We also found significantly increased duration of motor unit potentials in the VL and TA of patients. The amplitudes of motor unit action potentials were not significantly different in the 2 groups. CONCLUSION: The study reveals an increased prevalence of neurogenic but not myogenic changes in patients with RA compared with controls.

Prognostic factors for the development of fibromyalgia in women with self-reported musculoskeletal pain. A prospective study.

OBJECTIVE: To estimate the risk of developing fibromyalgia (FM) in women with self-reported pain and to estimate the relative risk of a series of variables. METHODS: As part of a population study, 214 women with self-reported pain were interviewed and examined in 1990 and 1995. In 1990, 39 of these women fulfilled the American College of Rheumatology criteria for FM. The other 175 women represented a continuum of pain extent from nonchronic pain to chronic widespread pain, and were assessed as individuals at risk for developing FM. Potential risk factors for FM were registered in 1990 and analyzed by bivariate and multiple statistical methods in the total sample and also in a subgroup of 115 women with limited pain. RESULTS: Forty-three (25%) women developed FM. Having > or = 4 associated symptoms, pain of > or = 6 years' duration, back pain, alternately hard/loose stools, and self-assessed depression were found to be predictors. Pain in the lower arm and a feeling of swelling were more weakly associated. In women with limited pain, pain > or = 6 years' duration, > or = 4 associated symptoms, not feeling refreshed in the morning, and paresthesia were found to be predictors. A weaker association was found with self-assessed depression and a lack of formal education. CONCLUSION: A high cumulative incidence of FM was found and a diversity of predictors for FM were identified in the total sample and also in women with limited pain. Of the variables that were part of the FM syndrome, back pain predicted FM, while tender points and pain in the neck did not. Moreover, > or = 4 associated symptoms, self-assessed depression, and longlasting pain were shown to be important predictors.