Mutual inhibition of the binding of Clq and protein A to rabbit IgG immune complexes

A complex of rabbit IgG antibody with horseradish peroxidase covalently linked to Sepharose 4B was used as an insoluble immune complex for studying the binding of complement factor C1q protein A from Staphylococcus aureus, and its IgG-binding fragments AB and B, to rabbit IgG. It was shown that protein A (mol. wt approx. 42,000) and fragments AB and B (mol. wts approx. 14,000 and 7000, respectively) inhibited the binding of C1q to insoluble immune complex at 4 degrees C. However, at 37 degrees C fragment B did not inhibit this binding. On the other hand, C1q, when bound to an insoluble immune complex, almost completely blocked the binding of protein A and fragment B at both temps. The higher affinity of C1q for its CH2-binding site than of fragment B for its CH2-binding site may explain the displacement of the latter from the CH2 domain. The mutual inhibition of the binding of C1q and protein A (and its smaller fragments) indicates that the binding sites for C1q and protein A are closely located in the CH2 domain.     

The Influence of Food Intake on Liver Stiffness Values Assessed by Acoustic Radiation Force Impulse Elastography—Preliminary Results

The present study assessed the influence of food intake on acoustic radiation force impulse elastography (ARFI) measurements. Seventy-three healthy volunteers were included: 57 subjects in the study group (on whom ARFI measurements were performed first in fasting condition, followed by measurements made 1h and 3h after food intake); and 16 subjects in the control group (on whom ARFI measurements were performed 3 times during a 3-h interval without eating). All subjects included in the study group received the same standard solid meal. In the study group, the mean liver stiffness (LS) values by ARFI increased significantly 1 h after food intake (1.51 ± 0.40 m/s vs. 1.27 ± 0.23, p = 0.003), but 3 h after the meal the differences were no longer significant (1.46 ± 0.51 vs. 1.27 ± 0.23, p = 0.06). In the control group, the mean LS values were similar in all 3 measurements. In conclusion, food intake significantly increased the LS values, thus ARFI measurements should be performed in fasting conditions.     

Kin KeeperSM: Design and baseline characteristics of a community-based randomized controlled trial promoting cancer screening in Black,Latina, and Arab women

BackgroundAlthough breast and cervical cancer deaths have declined due to early screening, detection, and more effective treatment, racial and ethnic disparities persist. This paper describes the study design and baseline characteristics of a randomized controlled trial (RCT) evaluating the effectiveness of the Kin Keeper^SM Cancer Prevention Intervention, a family-focused educational intervention for underserved women applied in a community-based setting to promote health literacy and screening adherence to address cancer disparities.MethodsFemale public health community health workers (CHWs) were trained to administer the intervention. They recruited female clients from their public health program caseload and asked each to assemble two to four adult female family members for the breast and cervical cancer home-based education sessions the CHWs would deliver in English, Spanish or Arabic. We randomized the clients into the kin keeper group (treatment) or the participant client group (control).ResultsComplete data were obtained on 514 Black, Latina, and Arab women. Close to half were unemployed and had yearly family income below $20,000. Thirty-four percent had no medical insurance, and 21% had diabetes. Almost 40% had no mammography in the last year. Treatment and control groups were similar on most sociodemographics but showed differences in breast and cervical screening history.ConclusionsThis innovative study demonstrates the implementation of an RCT using community-based participatory research, while delivering cancer prevention education across woman's life span with women not connected to the health care system.     

Import of malaria in a Romanian Western County

BACKGROUND: Malaria is not a serious concern in Romania nowadays although 30-60 imported cases are diagnosed yearly, especially in travellers from Africa. Timis, the most extensive of the Romanian counties, is the western gate of the country from where a lot of people travel abroad. The aim of this study is to overview all the imported cases of malaria diagnosed in our county and to describe two recent severe cases. METHODS: We retrospectively analyzed both the medical records of 28 malaria patients treated between 1974 and 2007 at Victor Babes Hospital of Infectious Disease from Timisoara, Romania, and the results of 6 blood examinations performed in the last decade in the parasitological laboratory of Victor Babes University of Medicine and Pharmacy from Timisoara. A comparison between the two recent severe cases was made, emphasizing on the clinical aspects, complications and the laboratory test results. RESULTS: Most of the patients (55.38%) were in the age group of 20-29 years; 85.71% of the patients were males; Plasmodium falciparum was found in 75% of the cases. CONCLUSIONS: Findings of our study have shown that P. falciparum is the main malaria species in Timis County, outlining the difficulties in the diagnosis and management of the imported cases.     

Right Ventricular Function Predicts Clinical Response to Specific Vasodilator Therapy in Patients with Pulmonary Hypertension

Introduction: We followed patients with pulmonary arterial hypertension (PAH) receiving specific vasodilator therapy and tested for predictors of clinical outcome. Methods: Thirty‐two patients (mean age 39 ± 15 years, 22 women, diagnosed with pulmonary hypertension; PH): 29 with PAH and 3 patients with inoperable chronic thromboembolic PH received therapy with either bosentan, sildenafil, or both and were evaluated with clinical parameters, biomarkers (B‐type natriuretic peptide values), and echocardiography before receiving specific medication and every 3 months thereafter. A right heart catheterization was performed at baseline. A composite endpoint of death, worsening of functional class, or the need of a second vasodilator agent was used to define the clinical nonresponders. Results: Patients were followed for 14 months (7.5–21). The endpoint was reached by 15 patients: four patients died (two idiopathic PAH and two PAH in context of Eisenmenger syndrome), seven patients showed 1 functional class worsening, and four patients needed to be switched to combination therapy. Patients who remained clinically stable or improved had at baseline a better cardiac output with a less remodeled right ventricle (RV) and better functioning RV (all P < 0.05). A RV fractional area change (RVFAC) lower than 25.7% and a RV global strain value higher than ?13.4% predict with 87% sensitivity and 83% specificity (AUC 87.3%, P = 0.001) and 73% sensitivity and 91% specificity (AUC 84.2%, P = 0.003), respectively, patients who will deteriorate clinically under specific vasodilator therapy. A multivariate model showed RVFAC to be the only independent predictor of the endpoint with a HR of 0.87 (0.8–0.96), P = 0.007. Conclusions: Over an average period of 1 year, almost half of patients showed signs of clinical deterioration despite specific vasodilator therapy. Parameters of right ventricular morphology and function had prognostic value in these patients.     

The influence of aminotransferase levels on liver stiffness assessed by Acoustic Radiation Force Impulse Elastography: A retrospective multicentre study

BackgroundAcoustic Radiation Force Impulse Elastography is a new method for non-invasive evaluation of liver fibrosis.AimTo evaluate the impact of elevated alanine aminotransferase levels on liver stiffness assessment by Acoustic Radiation Force Impulse Elastography.MethodsA multicentre retrospective study including 1242 patients with chronic liver disease, who underwent liver biopsy and Acoustic Radiation Force Impulse. Transient Elastography was also performed in 512 patients.ResultsThe best Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis was 1.29 m/s in cases with normal alanine aminotransferase levels and 1.44 m/s in patients with alanine aminotransferase levels > 5× the upper limit of normal. The best cut-off for predicting liver cirrhosis were 1.59 and 1.75 m/s, respectively.Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis and cirrhosis were relatively similar in patients with normal alanine aminotransferase and in those with alanine aminotransferase levels between 1.1 and 5× the upper limit of normal: 1.29 m/s vs. 1.36 m/s and 1.59 m/s vs. 1.57 m/s, respectively.For predicting cirrhosis, the Transient Elastography cut-offs were significantly higher in patients with alanine aminotransferase levels between 1.1 and 5× the upper limit of normal compared to those with normal alanine aminotransferase: 12.3 kPa vs. 9.1 kPa.ConclusionLiver stiffness values assessed by Acoustic Radiation Force Impulse and Transient Elastography are influenced by high aminotransferase levels. Transient Elastography was also influenced by moderately elevated aminotransferase levels.     

Diagnostic and prognostic values of B-type natriuretic peptides (BNP) and N-terminal fragment brain natriuretic peptides (NT-pro-BNP)

Abstract

B-type natriuretic peptide (BNP) is a member of a four-natriuretic peptide family that shares a common 17-peptide ring structure. The N-terminal fragment (NT-pro-BNP) is biologically inert, but both are secreted in the plasma in equimolar quantities and both have been evaluated for use in the management of congestive heart failure. BNP and NT-pro-BNP are frequently used in the diagnosis of congestive heart failure and distinguishing between patients with dyspnoea of cardiac or pulmonary origin. Values of NT-pro-BNP are affected by age or the presence of one or several co-morbidities such as chronic renal failure, type 2 diabetes, and acute coronary syndrome. ‘Normal’ values of these peptides also vary depending on the type of test used. The performance characteristics of these tests vary depending on the patients on whom they are used and the manufacturer. For this reason, the determination of reference values for this peptide represents such a challenge.     

Severe adverse events during antiviral therapy in hepatitis C virus cirrhotic patients: A systematic review

AIM: To identify severe adverse events (SAEs) leading to treatment discontinuation that occur during antiviral therapy in hepatitis C virus (HCV)-infected cirrhotic patients.METHODS: We identified all the articles published prior to December 2011 in the PubMed, Medline, Lilacs, Scopus, Ovid, EMBASE, Cochrane and Medscape databases that presented these data in cirrhotic patients. These studies evaluated the rate of SAEs leading to discontinuation of standard care treatment: Pegylated interferon (PegIFN) alpha 2a (135-180 μg/wk) or PegIFN alpha 2b (1 or 1.5 μg/kg per week) and ribavirin (800-1200 mg/d). Patients with genotype 1 + 4 underwent treatment for 48 wk, whereas those with genotypes 2 + 3 were treated for 24 wk.RESULTS: We included 17 papers in this review, comprising of 1133 patients. Treatment was discontinued due to SAEs in 14.5% of the patients. The most common SAEs were: severe thrombocytopenia and/or neutropenia (23.2%), psychiatric disorders (15.5%), decompensation of liver cirrhosis (12.1%) and severe anemia (11.2%). The proportion of patients who needed to discontinue their therapy due to SAEs was significantly higher in patients with Child-Pugh class B and C vs those with Child-Pugh class A: 22% vs 11.4% (P = 0.003). A similar discontinuation rate was found in cirrhotic patients treated with PegIFN alpha 2a and those treated with PegIFN alpha 2b, in combination with ribavirin: 14.2% vs 13.7% (P = 0.96). The overall sustained virological response rate in cirrhotic patients was 37% (95%CI: 33.5-43.1) but was significantly lower in patients with genotype 1 + 4 than in those with genotype 2 + 3: 20.5% (95%CI: 17.9-24.8) vs 56.5% (95%CI: 51.5-63.2), (P < 0.0001).CONCLUSION: Fourteen point five percent of HCV cirrhotic patients treated with PegIFN and ribavirin needed early discontinuation of therapy due to SAEs, the most common cause being hematological disorders.     

Identification of citrullinated vimentin peptides as T cell epitopes in HLA–DR4–positive patients with rheumatoid arthritis

Objective

Antibodies directed against citrullinated proteins (ACPAs) are highly specific for rheumatoid arthritis (RA). The production of ACPAs is most likely dependent on the presence of T cells, since ACPAs undergo isotype switching and are associated with the shared epitope (SE)–containing HLA–DRB1 alleles. Vimentin is a likely candidate protein for T cell recognition, since >90% of patients positive for ACPAs that are reactive with (peptides derived from) citrullinated vimentin carry SE‐containing HLA–DRB1 alleles. The aim of this study was to identify citrullinated vimentin peptides that are presented to HLA–DRB1*0401–restricted T cells.

Methods

HLA–DR4–transgenic mice were immunized with all possible citrulline‐containing peptides derived from vimentin, and T cell reactivity was analyzed. Peptides recognized in a citrulline‐specific manner by T cells were selected and analyzed for their ability to be processed from the entire vimentin protein. A first inventory of the selected epitopes recognized by T cells was performed using peripheral blood mononuclear cells (PBMCs) from ACPA+, HLA–DR4+ patients with RA.

Results

A citrulline‐specific response was observed for 2 of the peptides analyzed in DR4‐transgenic mice. These peptides were found to be naturally processed from the vimentin protein, since citrullinated vimentin was recognized by peptide‐specific T cells. T cell reactivity against these peptides was also observed in cultures of PBMCs from RA patients.

Conclusion

This study identifies, for the first time, 2 naturally processed peptides from vimentin that are recognized by HLA–DRB1*0401–restricted T cells in a citrulline‐specific manner. These peptides can be recognized by T cells in ACPA+, HLA–DR4+ patients with RA, as shown in a first inventory.