Ventricular Aneurysm Repair: A New Approach

Repair of chronic left ventricular aneurysm or acute rupture of the heart after myocardial infarction is associated with technical difficulties and major morbidity and mortality. We describe a new endoventricular repair for both conditions. The repair consists of externally covering a Duran ring with Dacron and internally lining it with autologous pericardium. The modified ring is then sewn into the neck of the lesion. The technique is rapid, simple, and hemostatic. After repair of the chronic aneurysm, ventricular hemodynamics are improved during both diastole and systole. We have performed this technique in two patients with chronic aneurysm and one with subacute rupture.     

Neonatal nonbacterial thrombotic endocarditis]

Nonbacterial thrombotic endocarditis is not widely known in neonates. CASE REPORTS: We report three new cases which illustrate some specific aspects of this pathology. Respiratory distress with severe pulmonary hypertension, systemic hypotension and disseminated intravascular coagulopathy in a full-term newborn were characteristic findings. CONCLUSION: An early echocardiography should lead to accurate diagnosis. Hypoxemia and genetic factors could be determining factors in its pathogenesis.     

The Receptor Binding Domain of Botulinum Neurotoxin Serotype A (BoNT/A) Inhibits BoNT/A and BoNT/E Intoxications In Vivo

The receptor binding domain of botulinum neurotoxin (BoNT), also designated the C terminus of the heavy chain (H_C), is a promising vaccine candidate against botulism. In this study, a highly efficient expression system for the protein was developed in Escherichia coli, which provided yields that were 1 order of magnitude higher than those reported to date (350 mg H_C per liter). The product was highly immunogenic, protecting mice from a challenge with 10⁵ 50% lethal dose (LD₅₀) after a single vaccination and generating a neutralizing titer of 49.98 IU/ml after three immunizations. In addition, a single boost with H_C increased neutralizing titers by up to 1 order of magnitude in rabbits hyperimmunized against toxoid. Moreover, we demonstrate here for the first time in vivo inhibition of BoNT/A intoxication by H_C/A, presumably due to a blockade of the neurotoxin protein receptor SV2. Administration of H_C/A delayed the time to death from 10.4 to 27.3 h in mice exposed to a lethal dose of BoNT/A (P = 0.0005). Since BoNT/A and BoNT/E partially share SV2 isoforms as their protein receptors, the ability of H_C/A to cross-inhibit BoNT/E intoxication was evaluated. The administration of H_C/A together with BoNT/E led to 50% survival and significantly delayed the time to death for the nonsurviving mice (P = 0.003). Furthermore, a combination of H_C/A and a subprotective dose of antitoxin E fully protected mice against 850 mouse LD₅₀ of BoNT/E, suggesting complementary mechanisms of protection consisting of toxin neutralization by antibodies and receptor blocking by H_C/A.     

Physicochemical properties that enhance discriminative antibacterial activity of short dermaseptin derivatives

Antimicrobial peptides are widely believed to exert their effects by nonspecific mechanisms. We assessed the extent to which physicochemical properties can be exploited to promote discriminative activity by manipulating the N-terminal sequence of the 13-mer dermaseptin derivative K(4)-S4(1-13) (P). Inhibitory activity determined in culture media against 16 strains of bacteria showed that when its hydrophobicity and charge were changed, P became predominantly active against either gram-positive or gram-negative bacteria. Thus, conjugation of various aminoacyl-lysin moieties (e.g., aminohexyl-K-P) led to inactivity against gram-positive bacteria (MIC(50) > 50 microM) but potent activity against gram-negative bacteria (MIC(50), 6.2 microM). Conversely, conjugation of equivalent acyls to the substituted analog M(4)-S4(1-13) (e.g., hexyl-M(4)-P) led to inactivity against gram-negative bacteria (MIC(50) > 50 microM) but potent activity against gram-positive bacteria (MIC(50), 3.1 microM). Surface plasmon resonance experiments, used to investigate peptides' binding properties to lipopolysaccharide-containing idealized phospholipid membranes, suggest that although the acylated derivatives have increased lipophilic properties with parallel antibacterial behavior, hydrophobic derivatives are prevented from reaching the cytoplasmic membranes of gram-negative bacteria. Moreover, unlike modifications that enhanced the activity against gram-positive bacteria, which also enhanced hemolysis, we found that modifications that enhanced activity against gram-negative bacteria generally reduced hemolysis. Thus, compared with the clinically tested peptides MSI-78 and IB-367, the dermaseptin derivative aminohexyl-K-P performed similarly in terms of potency and bactericidal kinetics but was significantly more selective in terms of discrimination between bacteria and human erythrocytes. Overall, the data suggest that similar strategies maybe useful to derive potent and safe compounds from known antimicrobial peptides.     

Delayed signs and symptoms after oropharyngeal trauma in a child

Injury to the oropharynx can be potentially life threatening. Innocent-looking injuries of the oropharynx may result in intravascular thrombosis of the internal carotid artery. The symptoms often appear some time after the initial injury. We present a case in which an apparently minor injury of the oropharynx developed into a life-threatening thrombus stretching from the internal carotid to the brain. Our patient underwent endarterectomy and thrombectomy. The case is presented with a review of the literature.     

Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease

HER-2 overexpression, a predictive marker of tumour aggressiveness and responsiveness to therapy, occurs in 20-30% of breast cancer. Although breast cancer is a heterogeneous disease, HER-2 measurement is carried out in primary tumour. This study aims to evaluate HER-2 overexpression in primary and metastases and its effect on treatment decisions. Biopsies from primary breast cancer and corresponding metastases from 58 patients were studied. HER-2 overexpression was evaluated immunohistochemically in all primary and metastatic sites. Positive overexpression in primary and/or metastases was confirmed by fluorescence in situ hybridisation (FISH). Discordance in HER-2 overexpression between primary and metastatic sites was 14% (eight of 58 patients). Concordance was found in 50 (86%) of patients (95% CI: 77-95). In one patient (2%), HER-2 was negative in metastasis but positive in primary. In seven (12%) patients, HER-2 was positive in metastases and negative in primary (95% CI: 3.7-20), and three of them responded to trastuzumab. Gene amplification by FISH was found in all cases with HER-2 positive (+2 and +3) by immunohistochemistry. Our data suggest that a possible discordance of HER-2 overexpression between primary and metastases should be considered when making treatment decisions in patients with primary HER-2-negative tumours.     

Therapeutic communities for drug addicts: prediction of long-term outcomes

The study, conducted among 167 heroin addicts from three therapeutic communities (TCs) in Israel, examined their drug use 15 months after their departure from the community and the contribution of sociodemographic characteristics, time in community, psychopathology, self-esteem, and locus of control to successful outcome. The findings show that about half the clients were clean at follow-up, that over 90% of those who completed the program were clean, and that the longer the client stayed in the TC, the more likely he or she was to be clean later. Drug use at follow-up was positively associated with prior criminal activity and negatively associated with living with a partner before entering the TC. In addition, high self-esteem and an independent locus of control (not believing that one's life was controlled by powerful others) were also associated with being clean at follow-up.