Degradation of Soluble Immunoglobulin Aggregates in Vitro by Monocytes from Normal Subjects and from Patients with Systemic Lupus Erythematosus

The capacity of human peripheral monocytes to degrade soluble immunoglobulin (IgG) aggregates (AIgG) was studied in vitro. Under serum-free conditions peripheral monocytes from normal donors were able to degrade soluble AIgG in a linear and time-dependent fashion. Addition of fresh human or fresh guinea-pig serum to the incubation mixtures caused a marked increase in degradation of the amount of soluble AIgG available. The stimulatory effect of fresh serum was complement-mediated, because it was abolished by heat treatment of the serum and was not seen when C4- or C3-deficient sera were tested. Functional inactivation of C3 receptors on the phagocytes by trypsin also abolished the complement-mediated stimulation, suggesting cooperation between Fc and C3 receptor in degradation of soluble AIgG. No significant differences were found between monocytes from normal donors and those from patients with systemic lupus erythematosus, as far as degradation is concerned in the presence of complement.     

Incidence and Predictors of Permanent Pacemaker Requirement after Transcatheter Aortic Valve Implantation with a Self‐Expanding Bioprosthesis

Background: Previous reports have suggested the occurrence of cardiac conduction disorders and permanent pacemaker (PPM) requirement after transcatheter aortic valve implantation (TAVI). Based on a single‐center experience, we aim to assess the incidence of postprocedural conduction disorders, need for PPM, and its determinants after TAVI with a self‐expanding bioprosthesis. Methods: From August 2007 to October 2009, 32 consecutive patients underwent TAVI with the Medtronic CoreValve (MCV) System (Medtronic Inc., Minneapolis, MN, USA). Three patients paced at baseline and two cases of procedure‐related mortality were excluded. We analyzed the 12‐lead electrocardiogram at baseline, immediately after procedure and at discharge. Requirements for PPM were documented and potential clinical, electrophysiological, echocardiographic, and procedural predictors of PPM requirement were studied. Results: After TAVI, eight patients (29.6%) required PPM implantation due to high‐grade atrioventricular (AV) block. The prevalence of left bundle branch block increased from 13.8% to 57.7% directly after implantation (P = 0.001). Need for PPM was correlated to the depth of prosthesis implantation (r = 0.590; P = 0.001). At a cutoff point of 10.1 mm, the likelihood of pacemaker could be predicted with 87.5% sensitivity and 74% specificity and a receiver operator characteristic curve area of 0.86 ± 0.07 (P = 0.003). Of the seven patients with preexisting right bundle branch block (RBBB), four (57.1%) required PPM implantation after TAVI. Conclusions: High‐grade AV block requiring PPM implantation is a common complication following TAVI and could be predicted by a deeper implantation of the prosthesis. Patients with preexisting RBBB also seem to be at risk for the development of high‐grade AV block and subsequent pacemaker implantation. (PACE 2010; 1364–1372)     

Initial clinical experience of real-time three-dimensional echocardiography in patients with ischemic and idiopathic dilated cardiomyopathy

The geometry of the left ventricle in patients with cardiomyopathy is often sub-optimal for 2-dimensional ultrasound when assessing left ventricular (LV) function and localized abnormalities such as a ventricular aneurysm. The aim of this study was to report the initial experience of real-time 3-D echocardiography for evaluating patients with cardiomyopathy. A total of 34 patients were evaluated with the real-time 3D method in the operating room (n = 15) and in the echocardiographic laboratory (n = 19). Thirteen of 28 patients with cardiomyopathy and 6 other subjects with normal LV function were evaluated by both real-time 3-D echocardiography and magnetic resonance imaging (MRI) for obtaining LV volumes and ejection fractions for comparison. There were close relations and agreements for LV volumes (r = 0.98, p <0.0001, mean difference = -15 +/- 81 ml) and ejection fractions (r = 0.97, p <0.0001, mean difference = 0.001 +/- 0.04) between the real-time 3D method and MRI when 3 cardiomyopathy cases with marked LV dilatation (LV end-diastolic volume >450 ml by MRI) were excluded. In these 3 patients, 3D echocardiography significantly underestimated the LV volumes due to difficulties with imaging the entire LV in a 60 degrees x 60 degrees pyramidal volume. The new real-time 3D echocardiography is feasible in patients with cardiomyopathy and may provide a faster and lower cost alternative to MRI for evaluating cardiac function in patients.     

Biochemical study and in vitro insect immune suppression by a trypsin‐like secreted protease from the nematode Steinernema carpocapsae

A trypsin‐like serine protease was purified by gel filtration and anion‐exchange chromatography from the excretory‐secretory products of parasitic phase Steinernema carpocapsae. The purified protease exhibited a molecular mass of about 29 kDa by SDS–PAGE and displayed a pI of 6·3. This protease exhibited high activity with trypsin‐specific substrate N‐Ben‐Phe‐Val‐Arg‐p‐nitroanilide and was highly sensitive to aprotinin and benzamidine. The purified trypsin protease digested the chromogenic substrate N‐Ben‐Phe‐Val‐Arg‐p‐nitroanilide with K_m, V_max and k_cat values of 594·2 μm , 0·496 μm /min and 22·8/s, respectively. The optimal pH and temperature for protease activity were 9 and 30°C, respectively. Internal amino acid sequencing yielded 150 amino acids and these were homologous to other trypsin sequences. In vitro investigation was carried out to monitor prophenoloxidase suppression in Galleria mellonella by the purified protease; about 38·9–52·6% suppression of prophenoloxidase was observed. The purified protease affected insect haemocyte spreading, causing cells to become spherical or round. Protease‐treated actin filaments were highly disorganized in haemocytes. In vitro, G. mellonella haemocytes recognized infective juveniles of Heterorhabditis bacteriophora; however, S. carpocapsae and Steinernema glaseri were not recognized. We provide experimental evidence that the purified trypsin has the potential to alter host haemocytes, actin filaments and to inhibit host haemolymph melanization.     

Association between CD226 polymorphism and soluble levels in rheumatoid arthritis: Relationship with clinical activity

Objective: To study the relation between CD226 rs763361 gene polymorphism and CD226 serum level and to evaluate their role in susceptibility and disease activity of RA in a cohort of Egyptian individuals.

Methods: The serum level of CD226 was measured using a suitable ELISA kit and the CD226 rs763361 gene polymorphism was typed by PCR-RFLP for 112 RA patients and 100 healthy controls.

Results: Significant association with RA was found with CD226 T allele (OR (95%CI) = 1.6 (1.04–2.4), P = 0.032), and higher CD226 serum level (P = 0.001). Higher CD226 levels were associated with higher ESR values (P = 0.035), positive CRP (0.048), increased number of tender joints (P = 0.045), and higher DAS score (P = 0.035). Serum CD226 is an independent risk factor for the prediction of RA (P = 0.001). No correlations were found between the serum level of CD226 and different CD226 genotypes and also between them and RA activity grades.

Conclusion: The CD226 T allele may be susceptibility risk factors for the development of RA and the higher serum level of CD226 may be involved in the pathogenesis of RA in Egyptian patients. The serum level of CD226 and not CD226 genotypes could be considered as an independent risk factor for the prediction of RA within healthy individuals and also for RA disease activity.     

Molecular epidemiology of macrolide resistance in neonatal bloodstream isolates of group B streptococci

Pulsed-field gel electrophoresis (PFGE) was performed on 122 neonatal bloodstream isolates of group B streptococci (GBS) to further examine the relationship between macrolide resistance and serotype V GBS (GBS-V). Over one-third (35%) of macrolide-resistant GBS belonged to a single PFGE subtype of GBS-V, which was also the most common GBS-V subtype noted in previous Centers for Disease Control and Prevention surveillance studies. Erm methylase (ermA and ermB) was the most common resistance mechanism detected, present in 12 of 20 macrolide-resistant GBS.     

Myocardial perfusion imaging with technetium-99m sestamibi SPECT in the evaluation of coronary artery disease

Technetium-99m hexakis-2-methoxy-isobutyl-isonitrile(^99mTc sestamibi) has been used for myocardial perfusion imaging in the evaluation of coronary artery disease (CAD) since 1990. The experience of its use in an Asian population with and without previous myocardial infarction (Ml), diabetes mellitus (DM), hypertension (HPT) and collateral circulation (COL) is reported. One hundred and thirty-nine patients who underwent treadmill exercise testing with ^99mTc sestamibi single photon emission computed tomography (SPECT) and coronary angiogram were studied. The overall sensitivity for the detection of CAD was 91.0% and specificity was 64.7%. For patients without previous myocardial infarction, the sensitivity was 83.8% and specificity was 83.3%. Patients with COL had a higher sensitivity while those with HPT had a lower specificity. Sensitivity was higher in patients with multi-vessel disease (MVD) than single vessel disease (SVD). The overall detection for individual artery stenosis was 74.1% with a specificity of 73.1 %. Amongst the three major coronary arteries, sensitivity was highest for the right coronary artery and specificity was highest for the left circumflex artery. Specificity was higher in patients without MI or COL. We found that the agreement between ^99mTc sestamibi SPECT and coronary angiogram for the extent of CAD was only 52.5%. The concordance rate was higher for patients with MVD than SVD. It is concluded that ^99mTc sestamibi SPECT is a sensitive and specific test for the detection of CAD and localization of disease to individual coronary arteries in our patients with some differences in the subgroups. Agreement between coronary angiogram and ^99mTc sestamibi for the extent of coronary artery disease was also satisfactory.