Diagnostic performance of aPS/PT antibodies in neuropsychiatric lupus and cardiovascular complications of systemic lupus erythematosus

Abstract

Background: Systemic lupus erythematosus (SLE) is associated with a constellation of complications affecting multiple organs, including neuropsychiatric manifestations (NPSLE) and ischaemic events, leading to increased long-term morbidity. Antiphospholipid antibodies (aPL) are a major determinant of vascular inflammation and thromboembolic risk. The diagnostic role of anti-phosphatidylserine/prothrombin (aPS/PT) antibodies in this setting is incompletely defined.

Aim: To verify whether aPS/PT add to diagnostics and disease stratification in patients with SLE with or without other aPL.

Methods: 131 consecutive patients were studied, including 20 patients with SLE and secondary antiphospholipid syndrome (APS). aPS/PT IgG and IgM were assessed through ELISA and patients were stratified based on the presence of other aPL, on their clinical and laboratory features at time of blood sampling and on their clinical history. Synthetic indices of disease activity, chronic damage and cardiovascular risk were calculated at time of venipuncture.

Results: Fifty-one (38.9%) patients with SLE had aPS/PT and 15 (11.5%) patients had aPS/PT as the only aPL (aPS/PT-only). aPS/PT-only patients had a significantly higher prevalence of NPSLE than quadruple aPL-negative patients (p?=?.007). Patients with aPS/PT were more likely to have a history of ischaemia, thrombocytopenia and Libman–Sacks’ endocarditis. The presence of aPS/PT also associated with previous accrual of at least one damage item (p?=?.043), but had limited predictive values for damage progression in the short term.

Conclusion: aPS/PT antibodies provide non-redundant information that could contribute to risk assessment and stratification of patients with SLE.     

Reproductive planning after genetic counselling: a perspective from the last decade

Studies from the last decade on factors influencing reproductive planning after genetic counselling were reviewed. Increased possibilities of DNA-analysis and prenatal diagnosis might have brought about a shift in the paramountcy of factors influencing reproductive planning after genetic counselling. In contrast to the literature in the seventies, the magnitude of the genetic risk was no longer found to be one of the decisive factors in postcounselling reproductive planning. Instead, the interpretation of the risk as high or low and the desire to have children appeared to be paramount. The impact of new developments in DNA-analysis in prenatal diagnosis and presymptomatic testing will be an important subject for future studies on factors influencing reproductive planning.     

Family cancer histories predictive of a high risk of hereditary non-polyposis colorectal cancer associate significantly with a genomic rearrangement in hMSH2 or hMLH1

Hereditary non-polyposis colorectal cancer (HNPCC) results from inactivating germline mutations in a set of DNA-mismatch-repair genes, of which the most clinically relevant are hMSH2 and hMLH1. Computer-assisted pedigree risk assessment tools are available to assist in the calculation of an individual's likelihood of bearing such a deleterious mutation. One such tool, cancergene version 3.4 (http://www3.utsouthwestern.edu/cancergene) was used to assess the risk of a deleterious mutation in the genes hMSH2 and/or hMLH1 in a series of probands selected from a panel of 67 South-western Ontario kindred previously identified as likely candidates for HNPCC by established clinical criteria. A DNA sample isolated from peripheral blood leukocytes obtained from each of these probands was examined for genomic rearrangement using the multiplex ligation-dependent probe amplification (MLPA) method. Of the individuals calculated to have a risk of >50% of a hMSH2 or hMLH1 gene mutation by the CancerGene risk assessment tool, 69% (9/13) were shown to have a genomic rearrangement resulting in the deletion of one or more exons of one of these two genes. Family cancer histories predictive of a high risk of HNPCC significantly associate with a genomic rearrangement in hMSH2 or hMLH1.     

Relative contribution of vertical,within-farm and between-farm transmission of Mycoplasma synoviae in layer pullet flocks

ABSTRACT

In this study, the relative contribution of vertical transmission, within-farm transmission and between-farm transmission of Mycoplasma synoviae in layer pullet flocks was quantified using logistic regression analysis. Data from 311 Dutch pullet flocks, of which 172 (55%) were positive for M. synoviae, were included in the study. Also the M. synoviae status of the parent stock of these flocks was included. The M. synoviae status was determined with the M. synoviae rapid plate agglutination test. Data analysis showed that vertical transmission was the most important transmission route for M. synoviae in layers as is demonstrated by an odds ratio of 5.8 (P?=?0.000). A positive association with M. synoviae infections was found for layer pullet flocks on a multi-house farm where at least one other flock was M. synoviae-positive compared to single-house farms (odds ratio 3.1, P?=?0.022), while a negative association was found when no other M. synoviae-positive flocks were present (odds ratio?=?0.2, P?=?0.003). No association was found between M. synoviae status of pullet flocks and poultry farm density. Odds ratios were 0.54 (P?=?0.288) and 0.34 (P?=?0.073), respectively, for medium and highest poultry farm density compared to lowest poultry farm density. This is the first time that the relative contribution of horizontal and vertical transmission of M. synoviae has been quantified. These results can be extrapolated to M. synoviae control in general, and emphasize the importance of M. synoviae control in parent stock and practical channelling.     

Pathway to biomarker discovery in psoriatic arthritis

ABSTRACT

Introduction

Biomarkers may help influence long-term outcomes of psoriatic disease by improving the objective assessment of the presence and severity of psoriatic arthritis (PsA) and by guiding treatment selection. However, there are no validated biomarkers for PsA.     

Solid tumor screening recommendations in trisomy 18

The purpose of this study was to determine whether trisomy 18 patients are at an increased risk of tumor development and require formal tumor screening recommendations. A literature search of trisomy 18 patients with reports of tumors or malignancies, and compilation of all previously reported as well as new unreported cases was performed. 67 patients with trisomy 18 were found to have documented malignancies. 44 patients had hepatoblastomas, 21 patients had Wilms tumors, one patient had a functional neurogenic neoplasia, and one patient had Hodgkins lymphoma. The increasing numbers of reported malignancies in patients with trisomy 18 supports the indication for an early screening process. Specific screening recommendations are outlined consisting of imaging exams and laboratory values performed at specific intervals.     

Oral contraceptive use in relation to age at menopause in the DOM cohort

BACKGROUND: We investigated the hypothesis that long-term use of oral contraceptives (OCs), in particular high-dose OCs, could postpone age at menopause. METHODS: Data was used from 8701 women who participated in a breast cancer screening programme in Utrecht (DOM-3 cohort), and who did not use hormone replacement therapy (HRT) or OCs in the 4 years prior to their last menses. Data on OC-use, menopausal status, age at menopause, year of birth, parity, smoking behaviour, socio-economic status, body mass index and age at menarche was available. Use of high-dose OCs has been defined in this study as OC-use before 1972. The data was analysed by means of linear regression and Cox's proportional hazards analysis. Women still menstruating, women with surgical menopause and women lost to follow-up were censored at their last known date of menstruation. Endpoint was the natural menopause (n = 4589). RESULTS: The use of high-dose OCs advanced the onset of menopause by approximately 1.2 months for every year of OC-use compared with no OC-use. High-dose OC-use for > or = 3 years, adjusted for confounding variables, increased the risk of earlier menopause compared with no OC-use (adjusted hazard ratio 1.12; 95% CI 1.03--1.21). The use of lower dose OCs did not increase the risk of earlier menopause (adjusted hazard ratio 1.00; 95% CI 0.91--1.09). CONCLUSIONS: These results are inconsistent with the hypothesis that long-term use of OCs could postpone the onset of menopause by inhibiting follicle depletion. Possible explanations are discussed.     

Analysis of sensitization to carboxymethylcellulose: Identification of high risk group using ELISA and histamine release experiment

Objective and Design: Carboxymethylcellulose (CMC) has been considered to be inert and is commonly used as an additive in medicines, foods and cosmetics. However, we experienced a patient who developed an anaphylactic reaction to CMC after an upper gastrointestinal examination using a barium meal containing CMC. Therefore, we examined the incidence of sensitization by CMC in healthy subjects, and categorized the high risk group prone to developing anaphylactic response to CMC.Methods: An ELISA for detecting CMC-specific IgE antibody was developed using serum from the patient as a positive control. In the ten subjects exhibiting high anti-CMC IgE among 387 normal populations, histamine release from isolated leukocytes was performed.Results: Five of ten subjects with a high IgE titer showed a significant CMC-induced histamine release from leukocyte preparations in vitro as observed in the patient, and were classified as high risk group. There was a correlation between sensitization by CMC and that by Japanese cedar pollen. The incidence of sensitization in females was 2.4 fold higher than that in males.Conclusions: The combination of ELISA and histamine release experiment made it possible to identify the high risk group for developing anaphylactic response. The administration of high dose CMC as a suspending agent in barium sulfate or injectable corticosteroids to this group should be avoided to prevent anaphylactic reactions in the clinic.Received 18 August 2003; returned for revision 29 September 2003; accepted by M. J. Parnham 10 December 2003     

Angiographic findings and the Type A pattern assessed by means of the Bortner Scale

In 117 male subjects, biological variables as well as the Bortner Scale, a paper-and-pencil technique used to assess the type A pattern, were compared with angiographic findings. A summation score of coronary lesions correlated significantly with serum cholesterol and a coronary risk profile but not with the type A pattern. The number of stenoted arteries correlated significantly with age and serum cholesterol but, again, not with the Bortner score. The reasons for the results are discussed.