Course and characteristics of anaemia in patients with rheumatoid arthritis of recent onset.

OBJECTIVE: To describe the incidence, cause, and course of anaemia in rheumatoid arthritis (RA). METHODS: Medical records of 225 patients who received a diagnosis of RA between 1990 and 1992 were reviewed longitudinally for mention of anaemia. Anaemia was classified as anaemia of chronic disease if ferritin concentrations reflected adequate body iron stores. Among iron depleted anaemic patients, iron deficiency anaemia was identified using the response to iron supplementation. RESULTS: Anaemia developed in 64% of the patients, mostly within 18 months of follow up, but disappeared again in 54% of those patients. The prevalence of anaemia varied from 39% to 53% throughout follow up. Iron depletion was found in 38% of anaemic patients; 40% of them did not recover from their anaemia after iron supplementation and were classified as having anaemia of chronic disease. Anaemia of chronic disease thus caused 77% and iron deficiency anaemia 23% of observed anaemia. Recovery from anaemia occurred in 42% of the patients with anaemia of chronic disease and in 72% of iron depleted patients after iron supplementation. Anaemic patients, particularly those with anaemia of chronic disease, had a significantly greater number of the American College of Rheumatism criteria for RA, significantly more erosive joint damage, and significantly increased concentrations of serum rheumatoid factor than patients without anaemia. CONCLUSION: Anaemia appeared as a frequent and dynamic manifestation. Recovery and recurrence of anaemia was observed throughout follow up, leading to a longstanding and relatively high prevalence of the condition. Iron deficiency was diagnosed frequently and follow up revealed a considerable overlap with anaemia of chronic disease, making this the most important cause of anaemia in RA. Recovery from anaemia occurred more frequently in iron depleted anaemic patients than in those with anaemia of chronic disease. Anaemic patients, particularly those with anaemia of chronic disease, seemed to have a more serious course of their RA compared with non-anaemic patients.     

A randomized controlled trial of artemotil (beta-arteether) in Zambian children with cerebral malaria

The efficacy and safety of intramuscular artemotil (ARTECEF) was compared to intravenous quinine in African children with cerebral malaria. This prospective block randomized open-label study was conducted at two centers in Zambia. Subjects were children aged 0 to 10 years of age with cerebral malaria and a Blantyre Coma Score of 2 or less. Ninety two children were studied; 48 received artemotil and 44 quinine. No significant differences in survival, coma resolution time, neurologic sequelae, parasite clearance time, and fever resolution time were seen between the two regimens. Rates for negative malaria smears one month after therapy were similar in both groups. Artemotil was a well-tolerated drug in the 48 patients in this study. It appears to be at least therapeutically equivalent to quinine for the treatment of pediatric cerebral malaria. It has the advantage of being able to be given intramuscularly once daily for only five days.     

Genetic characterization of the nef gene from human immunodeficiency virus type 1 group M strains representing genetic subtypes A, B, C, E, F, G, and H

Most efforts to characterize sequence variation of HIV isolates has been directed toward the structural envelope gene. Few studies have evaluated the sequence variability of auxiliary genes such as nef. In this study 41 new HIV-1 strains, representing the majority of the described envelope subtypes of HIV-1 (A to H), were genetically characterized in the nef region. Phylogenetic analysis showed that 34 strains could be classified in the same subtype in nef and env, and 7 (19%) of the 41 new viruses were recombinants. For two of the seven strains, recombination occurred upstream of the nef gene, whereas for five of the seven strains recombination occurred within the nef gene with a crossover close to the 5' end of the LTR (long terminal repeat). The low intersubtype distance between subtype B and D in the nef gene confirms previous observations in the pol, env, and gag genes, which suggest a common ancestor for these subtypes. The majority of all the previously described functional domains in the nef gene were relatively conserved among the different subtypes, with only minor differences being observed. The myristoylation signal among the different subtypes, with only minor differences being observed. The myristoylation signal was less conserved for subtype C, with one or more amino acid changes being observed at positions 3, 4, and 5. The highly conserved acidic region (positions 62 to 65), critical for the enhancement of viral synthesis with an increased virus growth rate, was less conserved among the subtype G strains from our study. At least three epitopic regions of the nef gene have been defined and each can be recognized by CTLs under a variety of HLA restrictions; all were also relatively well conserved between the different genetic subtypes. Despite the relatively important genetic variation in nef sequences obtained among the different genetic subtypes, functional domains and CTL epitopes were relatively well conserved. In vitro and/or in vivo studies are necessary to study the relevance of the observed differences.     

Noninvasive assessment and monitoring of the pulmonary circulation.

In pulmonary vascular disease, changes in the pulmonary vascular bed will lead to altered pulmonary haemodynamics. This review describes the application of several physiological principles to measure these changes noninvasively by means of novel techniques. Flow characteristics of blood through the pulmonary vascular bed alter in pulmonary vascular disease. Recent developments in magnetic resonance imaging and computed tomography make it possible to visualise and quantify these abnormal flow patterns. Information regarding pulmonary perfusion can also be obtained by measuring the electrical impedance changes in the lung by electrical impedance tomography. A more indirect approach to measure the pulmonary blood flow is the measurement of the absorption of acetylene, a perfusion limited gas. Information on the pulmonary vascular bed can also be obtained by the measurement of exhaled products of the pulmonary vascular endothelium, such as nitric oxide. Although all the techniques described offer new ways to diagnose or monitor pulmonary vascular disease, clinical data on these techniques are limited. Further improvement and evaluation of the clinical value of these techniques are therefore obligatory before they can be used in clinical practice.     

Percutaneous transradial coronary palmaz-schatz stent implantation,guided by intravascular ultrasound

Intravascular ultrasound (IVUS) allows accurate assessment of stent deployment, its use being confined to the use of 8 French (F) guiding catheters. We evaluated the feasibility of combining transradial artery Palmaz-Schatz stent implantation through 6F guiding catheters with IVUS for assessment of stent diameter after delivery at moderate inflation pressures (10-12 atmospheres [atm]) with compliant balloons and after high pressure dilatations with balloons of intermediate compliance. In 8 consecutive patients, 12 stents were delivered with Scimed® Express^TM balloon catheters at 10-12 atm followed by IVUS (EndoSonics® CathScanner; Visions® FX 3.5F 20 MHz transducer). An ultrasound study was repeated after high pressure dilatations (16-20 atm) with Schneider® Magical Speedy^TM balloon catheters. The balloon diameters were derived from manufacturer provided specifications. In all patients the transducer could easily be advanced through the guiding catheters. Reference diameter of the stented segment was 3.7 ± 0.5 mm (2.7-4.5) and the diameter of Scimed® Express^TM balloons during inflation was 4.0 ± 0.3 mm (3.6-4.7). Stent diameter was 3.0 ± 0.1 mm (2.8-3.2) (P < 0.001 compared to the reference and the balloon diameter). The diameter of the Schneide® Magical Speedy^TM balloons at secondary dilatations with 16 ± 3 atm (14-20) was 4.1 ± 0.4 mm (3.3-4.5) (P = 0.50 compared to the initial balloon diameter). Final stent diameter was 3.3 ± 0.4 mm (2.9-4.1) (P = 0.02 compared to the initial stent diameter). All stents were symmetrically deployed and well apposed. No damage to vessel or stents was detected after passage of the transducer. Thus ultrasound guided stenting via 6F guiding catheters is feasible, and high pressure dilatations with balloons of intermediate compliance results in better stent expansion than after 10-12 atm inflations with compliant balloon catheters.     

Mixed functional characteristics correlating with TCR‐ligand koff‐rate of MHC‐tetramer reactive T cells within the naive T‐cell repertoire

The low frequency of antigen‐specific naïve T cells has challenged numerous laboratories to develop various techniques to study the naïve T‐cell repertoire. Here, we combine the generation of naïve repertoire‐derived antigen‐specific T‐cell lines based on MHC‐tetramer staining and magnetic‐bead enrichment with in‐depth functional assessment of the isolated T cells. Cytomegalovirus (CMV) specific T‐cell lines were generated from seronegative individuals. Generated T‐cell lines consisted of a variety of immunodominant CMV‐epitope‐specific oligoclonal T‐cell populations restricted to various HLA‐molecules (HLA‐A1, A2, B7, B8, and B40), and the functional and structural avidity of the CMV‐specific T cells was studied. Although all CMV‐specific T cells were isolated based on their reactivity toward a specific peptide‐MHC complex, we observed a large variation in the functional avidity of the MHC‐tetramer positive T‐cell populations, which correlated with the structural avidity measured by the recently developed Streptamer k_off‐rate assay. Our data demonstrate that MHC‐tetramer staining is not always predictive for specific T‐cell reactivity, and challenge the sole use of MHC‐tetramers as an indication of the peripheral T‐cell repertoire, independent of the analysis of functional activity or structural avidity parameters.     

Activation profile of dorsal root ganglia Iba-1 (+) macrophages varies with the type of lesion in rats

The interactions between neurons, immune and immune-like glial cells can initiate the abnormal processes that underlie neuropathic pain. In the peripheral nervous system the resident macrophages may play an important role. In this study we investigated in experimental adult Sprague-Dawley rats how Iba-1 (ionized calcium binding adaptor molecule 1) (+) resident macrophages in the dorsal root ganglion (DRG) are activated after a spinal nerve ligation (SNL) or streptozotocin (STZ)-induced diabetes. The activation profile was defined by comparing the responses of resident macrophages against microglia in the spinal cord as they share a common origin. After SNL, the Iba-1 (+) macrophages in L5 DRG reached their activation peak 5 days later, clustered as satellite cells around large A-neurons, expressed the MHC-II marker, but did not show p-p38 and p-ERK1/2 activation and did not secrete IL-18. After STZ-induced diabetes, the Iba-1 (+) macrophages reached their activation peak 1 week later in L4 and L5 DRG, remained scattered between neurons, expressed the MHC-II marker only in L5 DRG, did not show p-p38 and p-ERK1/2 activation and did not secrete any of the investigated cytokines/chemokines. These responses suggest that depending on the type of lesion DRG Iba-1 (+) resident macrophages have different activation mechanisms, which are dissimilar to those in microglia.     

8p21.3 deletions are rare causes of non-syndromic autism spectrum disorder

neurogenetics - A de novo 0.95 Mb 8p21.3 deletion had been identified in an individual with non-syndromic autism spectrum disorder (ASD) through high-resolution copy number variant analysis....     

Determinants and Reference Ranges of Serum Immunoglobulins in Middle-Aged and Elderly Individuals: a Population-Based Study

Purpose

In clinical practice, currently one reference range for serum immunoglobulin (Ig) A, G, and M is applied to all adults, although various factors may influence Ig serum levels. Population-based data on determinants of IgA, IgG, and IgM and recommendations for subgroup specific reference ranges are lacking. We aimed to provide an overview of determinants of IgA, IgG, and IgM in community-dwelling middle-aged and elderly individuals and explore determinants that influence Ig reference ranges.

Methods

Within the Rotterdam Study, we performed linear regression analyses for the association of demographic, lifestyle, and cardiovascular factors with serum IgA, IgG, and IgM. We furthermore calculated Ig reference ranges (based on percentiles), both overall and within relevant subgroups.

Results

We included 8768 participants (median age 62 years). IgA and IgG increased non-linearly with higher age (P?<?.0001 for both). Women had lower IgA (beta:???0.24; 95% confidence interval [95% CI]:???0.29;???0.20) and IgG (beta:???0.33; 95% CI:???0.44;???0.23), but higher IgM levels (beta: 0.08; 95% CI: 0.04;0.13) than men. Former and particularly current smoking were associated with lower IgA and IgG (betas between???0.07 and???1.03). Higher alcohol consumption was associated with lower IgG (beta for heavy drinking:???0.70; 95% CI:???0.91;???0.48). Corticosteroid use was associated with lower IgG (beta:???1.12; 95% CI:???1.58;???0.66). Associations with cardiovascular factors were heterogeneous and differed between sexes.

Conclusion

Age, sex, smoking, alcohol consumption, corticosteroid use, and cardiovascular factors are determinants that should be considered when interpreting serum Ig levels in middle-aged and elderly individuals and may require adjusted reference ranges.