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.     

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.

     

Multi-modular bone healing assessment in a randomized controlled clinical trial of root-end surgery with the use of leukocyte- and platelet-rich fibrin and an occlusive membrane

Clinical Oral Investigations - The aim of this study was to assess in a multi-modular manner the bone healing 1&nbsp;year post root-end surgery (RES) with leukocyte- and platelet-rich fibrin...