Clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus patients

The aim of this study was to investigate the clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus (SLE) patients. IgG antinucleosome antibodies were detected by a qualitative enzyme immunoassay (immunodot) in the sera of SLE patients at onset of disease. The patients were divided into two groups according to the result of the antinucleosome antibodies test: positive (group A) and negative (group B). The two groups were also evaluated for clinical and biological parameters. Of 84 patients with SLE, 66 (78.6%) had antinucleosome antibodies. Among 21 patients negative for anti-double-stranded DNA (anti-dsDNA), 5 (23.8%) were antinucleosome positive. The most common initial features were haematological disorders (80.1%) and arthritis or arthralgias (79.8%). Renal disorders, observed in 59.5% of SLE patients, were more common in group A compared to group B (65 vs 38%) (p=0.04). The European Consensus Lupus Activity Measurement (ECLAM) mean score was higher in group A (6.42) than in group B (4.44) (p=0.002). Antinucleosome antibodies were positive in nearly one-fourth of SLE patients negative for anti-dsDNA. We found a correlation between antinucleosome antibodies, nephritis and SLE disease activity. Therefore, the determination of circulating antinucleosome antibodies could be a useful parameter for early diagnosis and follow-up of SLE patients.     

Benzylthiouracil induced ANCA-positive vasculitis: study of three cases and review of the literature

Introduction

Vasculitis with antineutrophilic cytoplasmic antibodies (ANCA) have been reported in patients treated with anti-thyroid drugs, especially propylthiouracil. Benzylthiouracil, which exhibits similar structural likeness with propylthiouracil, has been recently observed to be associated with Anca-positive vasculitis.

Cases report

We present a study of three women with Grave's disease aged 21, 37 and 40 years, who were treated with benzylthiouracil. These patients developed vasculitis characterized by constitutional symptoms (two patients), joint pain (two patients), renal involvement (two patients), pulmonary hemorrhage (one patient) and multiple neuropathy (one patient). All patients presented p-ANCA with anti-MPO pattern. Discontinuation of benzylthiouracil and treatment with corticosteroids improved systemic involvement in all patients.

Conclusion

Much like other anti-thyroid drugs, benzylthiouracil can be associated with ANCA-positive vasculitis. Because of the gravity of this complication, clinical monitoring is recommended in patients taking benzylthiouracil. If vasculitis develops, the anti-thyroid drug should be discontinued and corticosteroid treatment, with immunosuppressors in some cases, is initiated.     

Gastrointestinal manifestations in severe scorpion envenomation

OBJECTIVES: To evaluate the type and incidence of gastrointestinal manifestations secondary to scorpion envenomation and their prognostic significance. PATIENTS AND METHODS: All patients admitted to our ICU for scorpion envenomation were included in this retrospective chart review of a 13-year period (1990 - 2002). RESULTS: During the study period, 951 patients were admitted for scorpion envenomation and 72 (7.6%) died. Ages ranged from 0.5 to 90 years with a mean of 14.7 +/- 17.4 years. Gastrointestinal symptoms were present in 700 patients (73.6%): nausea in 24 (2.5%), vomiting in 687 (72.2%) and diarrhea in 41 patients (4.3%). At univariate analysis, the presence of diarrhea was associated with a fatal outcome (P < 0.05). Diarrhea was also correlated with other indicators of severe envenomation and poor prognosis: respiratory failure (P = 0.01), neurological failure (P < 0.0001), liver failure (P < 0.0001) and low blood pressure requiring catecholamine support (P = 0.02). The multivariate analysis showed that young age (age less than 5 years), fever > 38.5 degrees C, neurological failure and pulmonary edema were independent factors of severity. Digestive disorders were more frequent in children and in this subgroup diarrhea appeared to be associated with poor outcome. In a subset of patients for whom data were available, fatal cases demonstrated significantly higher liver enzymes levels on admission. CONCLUSION: In Tunisia, gastrointestinal symptoms are often observed in severe scorpion envenomations, especially in young patients. In children, diarrhea and elevated liver enzymes are associated with poor prognosis.     

Combination of venoarterial PCO2 difference with arteriovenous O2 content difference to detect anaerobic metabolism in patients

OBJECTIVE: Under conditions of tissue hypoxia total CO2 production (VCO2) should be less reduced than O2 consumption (VO2) since an anaerobic CO2 production should occur. Thus the VCO(2)/VO(2) ratio, and hence the venoarterial CO2 tension difference/arteriovenous O2 content difference ratio (DeltaPCO2/C(a-v)O2), should increase. We tested the value of the DeltaPCO2/C(a-v)O2 ratio in detecting the presence of global anaerobic metabolism as defined by an increase in arterial lactate level above 2 mmol/l (Lac+). DESIGN AND SETTING: Retrospective study over a 17-month period in medical intensive care unit of a university hospital. PATIENTS: We obtained 148 sets of measurements in 89 critically ill patients monitored by a pulmonary artery catheter. RESULTS: The DeltaPCO2/C(a-v)O2 ratio was higher in those with increased ( n=73) than in the normolactatemic group (2.0+/-0.9 vs. 1.1+/-0.6, p<0.0001). Among all the O2- and CO2-derived parameters the DeltaPCO2/C(a-v)O2 ratio had the highest correlation with the arterial lactate level ( r=0.57). Moreover, for a threshold value of 1.4 the DeltaPCO2/C(a-v)O2 ratio predicted significantly better than the other parameters (receiver operating characteristic curves) the presence of hyperlactatemia (positive and negative predictive values of 86% and 80%, respectively). The overall survival estimate at 1 month was greater when the DeltaPCO2/C(a-v)O2 ratio was less than 1.4 on the first set of measurements (38+/-10% vs. 20+/-8%, p<0.01). CONCLUSION: The DeltaPCO2/C(a-v)O2 ratio seems a reliable marker of global anaerobic metabolism. Its calculation would be helpful for a better interpretation of pulmonary artery catheter data.     

Association study of human leukocyte antigen-DRB1 alleles with rheumatoid arthritis in south Tunisian patients

The aim of this study is to explore relationship between HLA-DRB1 alleles and the susceptibility and clinical features of rheumatoid arthritis (RA) in the south Tunisian population. We studied 142 RA patients and 123 controls matched for age, sex, and ethnicity. HLA-DRB1 genotyping and HLA-DRB1*04 subtypes were performed using polymerase chain reaction/sequence-specific primers. Association was assessed based on the χ (2) test and odds ratio with 95% confidence interval. For multiple comparisons, p value was corrected (p (c)) with Bonferroni test. Two alleles, HLA-DRB1*04 (p=0.045, p(c)=NS) and HLA-DRB1*10 (p=0.021, p(c)=NS), were found to have increased frequencies in RA patients compared to controls. In contrast HLA-DRB1*08 allele was found to have a decreased frequency in patients compared to controls (p=0.044, p(c)=NS). Molecular subtyping of the most prevalent allele (DRB1*04) revealed increased frequencies of HLA-DRB1*04:05 in patients compared to controls (p=0.013, p(c)=NS) whereas HLA-DRB1*04:02 showed a protective effect (p=0.005, p(c)=0.04). Moreover, stratified analyses indicated statistically significant associations between HLA-DRB1*04 allele and anti-cyclic peptides antibodies positivity (ACPA(+)) and rheumatoid factor positivity (RF(+); p(c)=0.03, for both subgroups), HLA-DRBI*10 and ACPA(+) and the presence of another autoimmune disease (p(c)=0.05 and p(c)=0.007, respectively), and HLA-DRB1*04:05 and RF(+) and erosion (p(c)=0.005 and p(c)=0.049; respectively). A significant decrease in the frequency of the DRB1*04:02 allele was observed in patients with ACPA(+) and RF(+) subgroups (p(c)=0.04 and p(c)=0.02, respectively). Our results showed that there was a trend of positive association of HLA-DRB1*04 and HLA-DRB1*10 with RA as such and significant associations with the disease severity in the south Tunisian population.     

Characterizing left ventricular mechanical and electrical activation in patients with normal and impaired systolic function using a non-fluoroscopic cardiovascular navigation system

Purpose

Cardiac disease frequently has a degenerative effect on cardiac pump function and regional myocardial contraction. Therefore, an accurate assessment of regional wall motion is a measure of the extent and severity of the disease. We sought to further validate an intra-operative, sensor-based technology for measuring wall motion and strain by characterizing left ventricular (LV) mechanical and electrical activation patterns in patients with normal (NSF) and impaired systolic function (ISF).

Methods

NSF (n?=?10; ejection fraction?=?62.9?±?6.1%) and ISF (n?=?18; ejection fraction?=?35.1?±?13.6%) patients underwent simultaneous electrical and motion mapping of the LV endocardium using electroanatomical mapping and navigational systems (EnSite? NavX? and MediGuide?, Abbott). Motion trajectories, strain profiles, and activation times were calculated over the six standard LV walls.

Results

NSF patients had significantly greater motion and systolic strains across all LV walls than ISF patients. LV walls with low-voltage areas showed less motion and systolic strain than walls with normal voltage. LV electrical dyssynchrony was significantly smaller in NSF and ISF patients with narrow-QRS complexes than ISF patients with wide-QRS complexes, but mechanical dyssynchrony was larger in all ISF patients than NSF patients. The latest mechanical activation was most often the lateral/posterior walls in NSF and wide-QRS ISF patients but varied in narrow-QRS ISF patients.

Conclusions

This intra-operative technique can be used to characterize LV wall motion and strain in patients with impaired systolic function. This technique may be utilized clinically to provide individually tailored LV lead positioning at the region of latest mechanical activation for patients undergoing cardiac resynchronization therapy.

Clinical trial registration

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01629160.

     

The unique insert in myosin VI is a structural calcium-calmodulin binding site

Myosin VI contains an inserted sequence that is unique among myosin superfamily members and has been suggested to be a determinant of the reverse directionality and unusual motility of the motor. It is thought that each head of a two-headed myosin VI molecule binds one calmodulin (CaM) by means of a single "IQ motif". Using truncations of the myosin VI protein and electrospray ionization(ESI)-MS, we demonstrate that in fact each myosin VI head binds two CaMs. One CaM binds to a conventional IQ motif either with or without calcium and likely plays a regulatory role when calcium binds to its N-terminal lobe. The second CaM binds to a unique insertion between the converter region and IQ motif. This unusual CaM-binding site normally binds CaM with four Ca2+ and can bind only if the C-terminal lobe of CaM is occupied by calcium. Regions of the MD outside of the insert peptide contribute to the Ca(2+)-CaM binding, as truncations that eliminate elements of the MD alter CaM binding and allow calcium dissociation. We suggest that the Ca(2+)-CaM bound to the unique insert represents a structural CaM, and not a calcium sensor or regulatory component of the motor. This structure is likely an integral part of the myosin VI "converter" region and repositions the myosin VI "lever arm" to allow reverse direction (minus-end) motility on actin.