Radiologic diagnosis of an intra-abdominal abscess. Do multiple tests help?

A review was made of the charts of 94 patients who underwent ultrasonography (US), computed tomography (CT), and gallium citrate Ga 67 (Gall) scan to rule out intra-abdominal abscesses. Of all the clinical and laboratory data, only the presence of pain and tenderness differentiated patients with and without abscesses. A review of radiologic data showed that CT was superior to US, and that US was superior to Gall scan with regard to sensitivity, specificity, accuracy, and positive and negative predictive values. When multiple radiologic tests were performed, results agreed in 72% of cases; therefore, the additional tests were essentially redundant. When radiologic test results disagreed, accuracy rates were CT, 0.86; US, 0.00; and Gall scan, 0.44. These findings suggest that, except to rule out pelvic abscesses in the presence of pelvic inflammatory disease, CT is usually the only special radiologic test that should be performed to localize a suspected intra-abdominal abscess.     

Some mechanical properties of polypropylene sutures: relationship to the use of polypropylene in vascular surgery

This study was performed to examine some mechanical properties of Polypropylene sutures. Fifty segments of 3-0, 4-0, 5-0, 6-0, and 7-0 sutures were mounted in clamps and were subjected to stepwise elongation. Results showed that suture stiffness (elastic modulus) and breaking stress (tensile strength) correlated directly and linearly with the circumference or "skin" of the filaments and inversely with the cross-sectional area or "core" of the filaments. These data suggest that the strength of the suture may reside in the outer skin. These findings are related to the handling of Polypropylene in surgery, and to suture motion in grafts in patients.     

Treatment of renal diseases with plasma exchange: a single center experience

Over the last decades, plasma exchange (PE) has been applied in the treatment of over 150 different diseases including nephrological, hematological, neurological, and rheumatological. Clinical benefit has been demonstrated in only about 40 of them and the best results were achieved in diseases with pathogenic autoimmune mechanisms. We used PE most frequently in patients with immune and autoimmune nephropathies aiming to decrease pathologically elevated antibody levels, autoantibodies and immune complexes. PE was applied in 40 patients with chronic glomerulonephritis, 29 patients with lupus nephritis, and 9 patients with Schoenlein‐Henoch nephritis. After 3 to 4 PE sessions, continuous immunosuppressive drug therapy was initiated. Significant reduction of antibody titers and immune complexes was achieved. PE was also applied in 45 plasmacytoma patients with nephropathy to reduce plasma viscosity and slow down the progression of myeloma nephropathy. The result was a significant reduction of pathologically elevated plasma viscosity and a detoxification effect. In our clinic plasma exchange procedures were performed by either centrifugal method with Haemonetics M‐30 device or by plasma filtration. An average of 1316 mL plasma was removed during a PE session. For substitution purposes donor plasma and saline solutions were used. Clinical remission was achieved in 61.3% of all patients without slowing the progression of renal failure, however.     

Sex differences in face processing are mediated by handedness and sexual orientation

Previous research has demonstrated sex differences in face processing at both neural and behavioural levels. The present study examined the role of handedness and sexual orientation as mediators of this effect. We compared the performance of LH (left-handed) and RH (right-handed) heterosexual and homosexual male and female participants on a face recognition memory task. Our main findings were that homosexual males have better face recognition memory than both heterosexual males and homosexual women. We also demonstrate better face processing in women than in men. Finally, LH heterosexual participants had better face recognition than LH homosexual participants and also tended to be better than RH heterosexual participants. These findings are consistent with differences in the organisation and laterality of face-processing mechanisms as a function of sex, handedness, and sexual orientation.     

Transition towards antigen-binding promiscuity of a monospecific antibody

Polyspecificity is defined as the ability of a given antibody molecule to bind a large panel of structurally diverse antigens. A fraction of circulating IgG in all healthy individuals acquires promiscuous antigen-binding activity only after a transient exposure to certain protein destabilizing factors. The molecular mechanisms of this phenomenon are not well understood. Exposures to protein destabilizing agents are common steps in immunoglobulin isolation and purification processes. We performed kinetic and thermodynamic analyses using surface plasmon resonance-based technique in order to characterize the interactions of a single mouse monoclonal antibody to its cognate antigen before and after induction of promiscuous antigen-binding activity. The obtained results, suggest that enhanced antigen binding activity induced by exposure to mild denaturing condition resulted from an increase in the structural flexibility of the antigen-binding site. Further pH and ionic strength-dependence analyses of the antibody/antigen interactions demonstrated that the transition to promiscuous antigen-binding was accompanied by a change in the type of non-covalent forces involved in the complex formation. Moreover, from this study, it is evident that an antibody molecule could use two distinct thermodynamic pathways for binding to the same antigen while retaining the same value of the binding affinity. The obtained results may contribute to the understanding of the molecular mechanisms that lay behind natural antibody polyspecificity.     

Five‐year Follow‐up of Intracardiac Echocardiography‐assisted Transcatheter Closure of Complex Ostium Secundum Atrial Septal Defect

Objective. We sought to prospectively evaluate long‐term follow‐up results of intracardiac echocardiography‐aided transcatheter closure of complex atrial septal defects (ASD) in the adults. Design and Settings. Prospective multicenter registry in tertiary care hospitals. Patients and Interventions. Over a 5‐year period, we prospectively enrolled 56 patients (mean age 49 ± 16.7 years, 24 females) who have been referred to our center for catheter‐based closure of complex secundum ASD (>25 mm diameter, deficiency of ≥1 rim, multiple secundum ASD, multiperforated ASD, associated incomplete floor of the fossa ovalis with or without aneurysm, embryonic remnants of incomplete atrial septation). All patients were screened by means of transesophageal echocardiography before the operation. Eligible patients underwent intracardiac echocardiography study and closure attempt. Results. Forty patients underwent a transcatheter closure attempt: transesophageal echocardiography‐planned device type and size were modified in 32 patients (64%). Rates of procedural success, predischarge occlusion, and major complications rate were 100%, 90%, and 2%, respectively. On mean follow‐up of 5.4 ± 1.8 years, the follow‐up occlusion rate was 98%. During follow‐up, only one case of permanent atrial fibrillation was observed. There were no cases of aortic/atrial erosion, device thrombosis, or new atrioventricular valve dysfunction. Conclusions. Intracardiac echocardiography‐guided complex secundum ASD transcatheter closure is safe and effective and appears to have excellent long‐term results, thus minimizing potential complications resulting from the complex anatomy.     

Activation of the p53 pathway by small-molecule-induced MDM2 and MDMX dimerization

Activation of p53 tumor suppressor by antagonizing its negative regulator murine double minute (MDM)2 has been considered an attractive strategy for cancer therapy and several classes of p53-MDM2 binding inhibitors have been developed. However, these compounds do not inhibit the p53-MDMX interaction, and their effectiveness can be compromised in tumors overexpressing MDMX. Here, we identify small molecules that potently block p53 binding with both MDM2 and MDMX by inhibitor-driven homo- and/or heterodimerization of MDM2 and MDMX proteins. Structural studies revealed that the inhibitors bind into and occlude the p53 pockets of MDM2 and MDMX by inducing the formation of dimeric protein complexes kept together by a dimeric small-molecule core. This mode of action effectively stabilized p53 and activated p53 signaling in cancer cells, leading to cell cycle arrest and apoptosis. Dual MDM2/MDMX antagonists restored p53 apoptotic activity in the presence of high levels of MDMX and may offer a more effective therapeutic modality for MDMX-overexpressing cancers.     

Influence of vascular muscle tone upon isogravimetric capillary pressure

Isogravimetric capillary pressure (P_ci) was determined in vitro in the perfused, skinned dog forearm preparation. Two procedures were employed. In one, arterial pressure was lowered before venous pressure was elevated (A, V sequence). In the second procedure, venous pressure was elevated before arterial pressure was lowered (V,A sequence). If the composition of the blood perfusing the preparation remains constant, the capillary pressure determined by both procedures should be equal. However, it was found that the A,V sequence resulted in a lower estimate of P_ci and a higher value for venous resistance than did the V,A sequence. A deliberate filtration of 2–5 g of fluid elevated the mean P_ci values but did not abolish the A,V and V,A difference. Addition of KCN to relax smooth muscle, yielded a single P_ci value for both the A,V and V,A sequences. This value was higher than the values obtained prior to KCN treatment. Moreover, A,V and V,A KCN isogravimetric sequences exhibited no differences in venous resistance or venous pressure at comparable levels of flow, whereas differences were present before treatment with KCN. Therefore, it was concluded that the double set of data in the untreated state was due to the presence of active and/or myogenic postcapillary smooth muscle. Because of the influence of venous smooth muscle, most estimates of P_ci underestimate plasma colloid osmotic pressure. Moreover, calculations of venous resistance employing this P_ci would be underestimated, since these calculations involve P_ci.     

Selective silencing of DNA-specific B lymphocytes delays lupus activity in MRL/lpr mice

The pathological DNA-specific B lymphocytes in lupus are logical targets for a selected therapeutic intervention. We have hypothesized that it should be possible to suppress selectively the activity of these B cells in lupus mice by administering to them an artificial molecule that cross-links their surface immunoglobulins with the inhibitory FcgammaIIb surface receptors. A hybrid molecule was constructed by coupling the DNA-mimicking DWEYSVWLSN peptide to a monoclonal anti-mouse FcgammaRIIb antibody. This chimeric antibody was added to cultured spleen cells from sick MRL/lpr mice, immunized with diphtheria toxoid, resulting in reduction of the numbers of anti-DNA but not of anti-diphtheria IgG antibody-producing cells. Intravenous infusions with the DNA-peptide antibody chimera to 7-wk-old animals prevented the appearance of IgG anti-DNA antibodies and of albuminuria in the next 2 months. The administration of the DNA-peptide chimeric antibody to 18 wk-old mice with full-blown disease resulted in the maintenance of a flat level of IgG anti-DNA antibodies and in delay of the aggravation of the lupus glomerulonephritis. The use of chimeric antibodies targeting inhibitory B lymphocyte receptors represents a novel approach for the selective suppression of autoreactive disease-associated B cells in autoimmune diseases.