A functional assay of protein C in human plasma

A functional assay for protein C in plasma is described in which barium eluates of plasma are incubated with bovine thrombin and rabbit thrombomodulin to activate protein C. The activated protein C solution is added to an activated partial thromboplastin time (APTT) system containing normal plasma and an APTT reagent (Dade ActinR). The prolongation of coagulation time after recalcification in this system is taken as a measure of the anticoagulant activity of protein C. When expressed as per cent of the value in pooled normal plasma, the results obtained by this method in 34 normal controls and in 3 untreated patients with protein C deficiency were very similar to those obtained by radioimmunoassay of protein C. In 2 patients with protein C deficiency and 23 patients without, all on dicoumarol or warfarin treatment, the anticoagulant activity of protein C was less than its antigen concentration. The day to day analytical coefficient of variation (SD/mean) was 12% at the 100% level (n = 12), and 10% at the 25% level (n = 12).     

Use of healthcare, patient satisfaction and burden of care in Guillain-Barre syndrome.

OBJECTIVE: The aim of this study was to investigate, in an unselected sample of patients with Guillain-Barré syndrome in Sweden, the utilization of healthcare resources, satisfaction with these resources, informal help and the burden of care on family caregivers during the first 2 years after onset. SUBJECTS: Forty-four patients were enrolled from 8 hospitals, and 42 of them were followed for 2 years. METHODS: Data on the utilization of hospital inpatient and outpatient care, primary care and community-based services were collected via computerized registry information, medical records and a specific protocol. Patient satisfaction and the burden on family caregivers were studied using questionnaires. RESULTS: Forty-one patients required inpatient hospitalization for a mean of 82 days. Patients with persistent dependency during activities of daily living had significantly longer hospital stays and more days of outpatient rehabilitation. The majority of patients were satisfied with their care, but dissatisfaction was found regarding information and finances. At 2 years after onset, 26% of patients still depended on informal help. The spouses expressed increased concern and responsibility for household and family. CONCLUSION: Patients with persistent disability due to Guillain-Barré syndrome were found to have long-term need for services from the healthcare system and informal help.     

Galactosylation of Serum IgA1 <Emphasis Type="Italic">O</Emphasis>-Glycans in Celiac Disease

In celiac disease, gluten ingestion provokes small-bowel mucosal injury and production of IgA autoantibodies against transglutaminase 2 (TG2). It has been suggested that in celiac patients IgA could mediate the transepithelial passage of gluten peptides in a mechanism involving the transferrin receptor. As IgA1 with galactose-deficient O-linked glycans has elevated affinity for the transferrin receptor, we assessed whether total serum IgA1 and IgA1 anti-TG2 autoantibodies in celiac patients are aberrantly glycosylated. We report that males with celiac disease have higher total serum levels of galactose-deficient IgA1 than non-celiac males. Furthermore, O-glycans of the disease-specific TG2 IgA1 autoantibodies in celiac patients exhibited elevated galactose deficiency. A gluten-free diet had no effect on the total serum levels of galactose-deficient IgA1, whereas the amount of galactose-deficient anti-TG2 IgA1 decreased. Thus, the undergalactosylated IgA1 molecules are not pathognomonic for celiac disease, but galactose deficiency in IgA1 could be an aggravating factor.     

Streptococcus pneumoniae Capsular Serotype 19F Is More Resistant to C3 Deposition and Less Sensitive to Opsonophagocytosis than Serotype 6B

The polysaccharide capsule is a major virulence mechanism of Streptococcus pneumoniae, shielding the bacterium from phagocytes. Capsule types may differ in their abilities to resist immune defense. Antibody-mediated complement activation and opsonophagocytosis are crucial in protection against pneumococcus. Conjugate vaccine trials suggest imperfect protection against 19F. We have previously shown that significantly more anti-19F than anti-6B antibody is needed for killing in the opsonophagocytic assay (OPA). In this study, we explored whether the amount of C3 deposited on serotype 6B and 19F pneumococcal strains reflects their sensitivity to opsonophagocytosis. We compared clinical 6B and 19F nasopharyngeal, middle ear, and blood isolates as well as reference OPA strains (n = 16) for their sensitivity to opsonophagocytosis and C3 deposition. Sixfold anticapsular antibody concentrations were required for 50% opsonophagocytic killing of 19F compared to that of 6B strains. Serotype 19F was more resistant to C3 deposition than 6B. Complement deposition and opsonophagocytosis were dependent on the concentration of anticapsular antibodies. Differences between pneumococcal serotypes in antibody-mediated protection may partly be explained by the abilities of the capsules to resist complement deposition. These findings support previous studies suggesting that higher antibody concentrations to the capsular polysaccharide are needed for protection against disease caused by serotype 19F than that caused by 6B.     

Different clinical severity of first episodes and recurrences of thrombotic thrombocytopenic purpura

The clinical course of thrombotic thrombocytopenic purpura (TTP) is characterized by recurrent disease episodes in up to 50% of cases. The clinical presentation and severity of different TTP episodes have not been systematically compared. Laboratory and clinical information from 51 patients with recurrent disease, derived from 136 patients with TTP included in the Milan TTP registry (URL: http://www.ttpdatabase.org), were used to compare mortality, symptoms and disease-related laboratory measurements in different disease episodes. The prevalence of severe neurological symptoms (coma, seizures, and focal neurological defects) was significantly lower in recurrences than in the first episode. Platelet counts and haemoglobin levels at presentation were higher in recurrences than in the first disease episode, and lactate dehydrogenase levels were lower. Also, mortality tended to be lower in the second and third disease episodes than in the first. Recurrences of TTP are generally milder than first episodes. These differences in severity should be taken into account in clinical research on TTP and in patient management.     

Longitudinal variations and predictors of increased perceived impact of multiple sclerosis, a two-year study

OBJECTIVE: To explore variations and the capacity of selected factors - contextual factors, disease-related characteristics, cognition, fatigue, mood and time - to predict an increase in the perceived physical and psychological impact of multiple sclerosis (MS) over a two-year period. METHODS: At an MS specialist clinic, 219 outpatients were included in the study and data were collected every 6 months. The Multiple Sclerosis Impact Scale was used for assessment of the perceived physical and psychological impact of MS. For statistical analysis of changes in impact during the study period, Friedman ANOVA was used and predictors of increased impact were explored with Generalized Estimating Equations employing proportional odds models. RESULTS: The majority had changes in perceived physical impact of established important magnitude and the psychological impact varied significantly. A period of more than 10 years since diagnosis, cognitive disability, fatigue and signs of depression were independent predictors of increase in physical impact. Weak or moderate sense of coherence, absence of immunomodulatory treatment, fatigue and signs of depression were independent predictors of increase in psychological impact. CONCLUSION: The fluctuation in perceived impact should be taken into account in clinical decision-making and when designing studies and interpreting the results. This study identifies the predictors of increased perceived physical and psychological impact that health-related services should pay special attention to, in order to provide interventions aimed at minimizing the perceived impact of MS.