Antiphospholipid antibodies: Paradigm in transition

Objectives

This is a critical review of anti-phospholipid antibodies (aPL). Most prior reviews focus on the aPL syndrome (APS), a thrombotic condition often marked by neurological disturbance. We bring to attention recent evidence that aPL may be equally relevant to non-thrombotic autoimmune conditions, notably, multiple sclerosis and ITP.

Organization

After a brief history, the recent proliferation of aPL target antigens is reviewed. The implication is that many more exist. Theories of aPL in thrombosis are then reviewed, concluding that all have merit but that aPL may have more diverse pathological consequences than now recognized. Next, conflicting results are explained by methodological differences. The lupus anticoagulant (LA) is then discussed. LA is the best predictor of thrombosis, but why this is true is not settled. Finally, aPL in non-thrombotic disorders is reviewed.

Conclusion

The current paradigm of aPL holds that they are important in thrombosis, but they may have much wider clinical significance, possibly of special interest in neurology.     

Penetrance of the C28Y/C282Y genotype of the HFE gene

OBJECTIVE: Hereditary hemochromatosis is a common genetic disease caused by accumulation of iron in the body. Most cases are homozygous for the C282Y mutation in the HFE gene, but only a minority of homozygotes will ever suffer from clinical hemochromatosis. Estimates of the penetrance of the C282Y/C282Y genotype vary greatly. The purpose of this study was to estimate the penetrance using a stringent definition, i.e. liver cirrhosis. MATERIAL AND METHODS: The results from previous phenotypic population screening for hereditary hemochromatosis were combined with findings in hospital databases in order to estimate the number of C282Y homozygotes with and without liver cirrhosis in a Norwegian county. The penetrance of the C282Y/C282Y genotype was estimated as the fraction of C282Y homozygotes with liver cirrhosis. We also calculated the expected number of male C282Y homozygotes with liver cirrhosis using figures for age-specific accumulated risk. RESULTS: The prevalence of liver cirrhosis in male homozygotes is between 3.4% and 5.0%. This figure is compatible with an accumulated risk of liver cirrhosis that increases from 0.2% at 35 years to about 10% at 65 years of age. In female homozygotes, the prevalence of liver cirrhosis is 0.3%. CONCLUSIONS: A small but significant number of Norwegian male C282Y homozygotes will contract liver cirrhosis if their hemochromatosis is not diagnosed and treated in time. The penetrance is much lower in women than in men.     

Assessment of everyday functioning in young children with disabilities: an ICF-based analysis of concepts and content of the Pediatric Evaluation of Disability Inventory (PEDI)

BACKGROUND: Assessment of everyday functioning in children may depend to a considerable extent on the framework used to conceptualise functioning and disability. The Pediatric Evaluation of Disability Inventory (PEDI) has incorporated the mediating role of the environment on disability, using different measurement scales. The construction of the Functional Skills scales, which measure capability, and the Caregiver Assistance scales, which measure performance, was based on the Nagi disablement scheme. The International Classification of Functioning, Disability and Health (ICF) represents a new framework of functioning and disability that could be used to compare the measurement constructs and the content of different outcome measurements. PURPOSE: To examine the conceptual basis and the content of the PEDI using the ICF. METHOD: Phrases that describe the conceptual basis of the PEDI scales and of the ICF classifications were systematically collected and compared. Two researchers classified the item content of the Functional Skills scales independently before consensus was reached. RESULTS: The analyses indicate that the conceptual basis of the PEDI scales to a large extent match the ICF concepts of activity, participation and environmental factors. Both the PEDI and the ICF use the constructs of capacity and performance, but differ in how to operationalise these constructs. The classification of the Functional Skills scales shows that the PEDI primarily is a measure of activities and participation. The frequently use of environmental codes to classify the context of the requested functions demonstrates that the PEDI has incorporated the environment into the assessment. CONCLUSIONS: Our analyses indicate that the ICF could serve as a conceptual framework to clarify the measurement construct of the PEDI scales, and as taxonomy to describe and clarify the item content of the Functional Skills scales. Both as framework and taxonomy the ICF showed limitations in covering functioning in early childhood.     

Antiphospholipid antibodies (APLA) in immune thrombocytopenic purpura (ITP) and antiphospholipid syndrome (APS)

Antiphospholipid antibodies (APLA) are associated with anti-phospholipid syndrome (APS), a thrombotic disorder, but they are also frequently detected in immune thrombocytopenic purpura (ITP), a bleeding disorder. To investigate possible differences of APLA between these two disorders, we assayed IgG and IgM APLA by ELISA in 21 patients with ITP and 33 with APS. The APLA reacting against two protein target antigens, beta(2)-glycoprotein 1 (beta2GP1) and FVII/VIIa, and four phospholipids [cardiolipin (CL), phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylethanolamine (PE)] as well as lupus anticoagulant (LA) were analyzed. We made the following observations: (i) IgG and IgM antibodies to beta2GP1 and IgM antibodies to FVII/VIIa were more common in APS than ITP, P < 0.05, while IgG antibodies against the phospholipids (aCL, aPC, aPS, aPE) were more common in ITP than APS, P < 0.05; (ii) multiple APLA > or =3 antigens) were more frequent in APS than ITP, P < 0.05; (iii) LA was frequently associated with APS but was absent in ITP; (iv) APLA is quite common in ITP: two-thirds were positive for at least one APLA. In summary, APLA are prevalent in ITP but their profile differs from APS. In APS, antibodies were predominantly against beta2GP1 and 80% had positive LA, while in ITP the APLA reacted most often with the phospholipids without LA. The difference in APLA may result in opposite clinical manifestations in two disorders.     

Cardiorespiratory fitness in relation to self-reported physical function in cancer patients after chemotherapy

AIM: The aim of this study was to estimate the association between objective cardiorespiratory fitness (CRF) and subjective self-reported physical function, taking into account the influence of mental distress. We hypothesized an association between these parameters, since they might be thought to measure parts of the same phenomenon. METHODS: Approximately 1 month after discontinuation of all primary treatment, 90 cancer patients aged 18-50 years treated with chemotherapy were surveyed. CRF was determined by the Astrand-Ryhming indirect cycle ergometer test, which indicate peak VO2 in mL x kg(-1) x min(-1) (predicted VO2max). Self-reported physical function was assessed by The European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). The relation between VO2max and self-reported physical function was estimated by multiple linear regression. Mental distress (assessed by The Hospital Anxiety and Depression scale), age, gender, body mass index (BMI), time from treatment to physical test and diagnoses were included as potential confounders. RESULTS: There was no association between predicted VO2max and self-reported physical function. Mental distress was negatively associated with self-reported physical function (P<0.001), but is not associated with predicted VO2max. CONCLUSIONS: The results suggest that predicted VO2max does not reflect self-reported physical function and vice versa in cancer patients after chemotherapy. If information about cardiac and/or pulmonary status is required, direct or indirect measures of VO2max should be used.     

Association between level of physical activity and lung function among Norwegian men and women: the HUNT study.

OBJECTIVE: To estimate the association between level of physical activity in 1984-1986 and 1995-1997 and lung function in 1995-1997 among Norwegian men and women aged 28-80 years. DESIGN: In 1984-1986 and 1995-1997, all residents of Nord-Tr?ndelag County, Norway, aged > or =20 years were invited to participate in the Nord-Tr?ndelag Health Studies. These analyses included a sample that took part in both studies and underwent spirometry (n = 8047). We used linear regression models adjusting for potential confounders stratified by sex and age groups (28-49 years, 50-69 years and > or =70 years) to estimate the association between forced expiratory volume in 1 second (FEV1) and physical activity. RESULTS: Men and women who were physically active in 1985 and 1995 had the highest lung function in both sexes and in all age groups. The reduction in FEV1 ranged from 20 ml to 170 ml, similar to 1-7% of predicted values dependent on physical activity level. Lung function was also associated with body mass index (BMI), height, smoking and subjective health. CONCLUSIONS: The findings show that a high level of physical activity corresponds to about 3-5 years of normal decline in FEV1 (30 ml/year), and may therefore overcome the disadvantages of a decline in FEV1 from increasing age.     

Cytotoxic effect of different camptothecin formulations on human colon carcinoma in vitro

Two innovative 20-S-camptothecin (CPT) formulations, previously found suitable to achieve therapeutically relevant CPT concentrations, were assessed for their in vitro cytotoxic potential as compared to an aqueous CPT solution, using the MTT assay. The formulations, cationic CPT-containing liposomes (CPT-Lip), hydroxypropyl-beta-cyclodextrin (HP-beta-CD) complexed CPT (CPT-CD) and a saturated aqueous CPT solution (CPT-Sol), were diluted in culture medium to appropriate CPT concentrations (4.7-300 ng/ml), and incubated with HT-29 and SW-480 human colon carcinoma cell lines. IC50 values were calculated after 48 and 72 h incubation for the HT-29 and SW-480 cell lines, respectively, and were found to be of the same magnitude for all formulations, with only a slight difference (CPT-Sol相似文献