Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery: Diagnoses and Surgical Results in 12 Pediatric Patients

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital condition. It responds well to early diagnosis and treatment, but otherwise the prognosis is poor. We present our case series of 12 patients (mean age, 2 ± 2.58 yr; age range, 2 mo–8 yr), emphasizing the diagnostic process and discussing our surgical results. The diagnosis of ALCAPA should be suspected in infants who have dilated cardiomyopathy with electrocardiographic changes that suggest ischemia, and in older children who have isolated mitral regurgitation. When clinical suspicion is high, the results of 2-dimensional echocardiography combined with color-flow Doppler studies in expert hands can establish the diagnosis, thus avoiding angiography in critically ill infants. The treatment of choice in our patients was transfer and reimplantation of the left coronary artery onto the ascending aorta. There were 2 deaths: both were infants in extremis who underwent emergency surgery. An older child with severe ventricular dysfunction was given mechanical ventricular assistance and then heart transplantation. As of this report, all 10 survivors remained well and asymptomatic.     

Arachidonic acid-stimulated platelet tests: Identification of patients less sensitive to aspirin treatment

Serum thromboxane-B2 (TxB2), together with arachidonic acid (AA)-induced platelet aggregation, are, at the moment, the most used tests to identify patients displaying high on-aspirin treatment platelet reactivity (HAPR). Both tests are specific for aspirin action on cyclooxygenase-1. While the correlation between serum TxB2 assay and clinical outcome is established, data are conflicting with regard to aspirin treatment and a possible association with AA-stimulated platelet markers and clinical outcome. To understand such discrepancy, we performed a retrospective study to compare both assays. We collected data from 132 patients receiving a daily dose of aspirin (100?mg/day) and data from 48 patients receiving aspirin on alternate days. All Patients who received a daily dose of aspirin were studied for AA-induced platelet aggregation together with serum TxB2 levels and AA-induced TxB2 formation was also studied in 71 patients out of entire population. Consistent with recommendations in the literature, we defined HAPR by setting a cut-off point at 3.1?ng/ml for serum levels of thromboxane B2 and 20% for AA-induced platelet aggregation. According to this cut-off point, we divided our overall population into two groups: (1) TxB2?<?3.1?ng/ml and (2) TxB2?>?3.1?ng/ml. We found low agreement between such tests to identify patients displaying HAPR. Our results show that AA-induced platelet aggregation >20% identify a smaller number of HAPR patients in comparison with TxB2. A good correlation between serum TxB2 and arachidonic acid-induced TxB2 production was found (r?=?0.76619).     

Early embryonic loss associated with immune activation in cattle and sheep

Increased peripheral NK cells in aborting women are considered as a predictor of immunological miscarriages. Here, we investigated the diagnostic value of the NK count at the time of abortion. Peripheral NK cells were counted by flow cytometry in 44 women undergoing therapeutic termination of first trimester missed pregnancy (A = 24) or elective abortion (B = 20). Histology of the extracted material was performed and immunological lesions (villitis, intervillositis, vascular thrombosis, increased fibrinoid necrosis) were recorded. Twenty first trimester pregnant women (C1) and 20 nonpregnant women (C2) served as controls. In 20 women of groups A and B (A1 = 10, B2 = 10) count was repeated after 5 days. At abortion time, the NK percentage and number did not differ between groups A and B (18.18%, 360 versus 15.61%, 374), but there was a statistically significant difference between A and C1 (18.18% versus 13.6%, P < 0.03). When histology negative (11) and positive (8) cases were excluded from groups A and B, respectively, NKs were slightly higher in group A (18.18–19.76%) and significantly lower in B (15.61–13.07%, P < 0.05). At the time of second count, aborters' NKs decreased (A1 = 16.64 versus 13.6 and 10.6 in groups C1 and C2 –P = 0.01, respectively). In group B, NK percentage was equal to that of nonpregnant women (10.94 versus 10.6). At the time of abortions, NKs increase only in cases of immune‐mediated miscarriages. Their – in time – count may contribute to the diagnosis of immmunological abortions.     

Opioid receptor binding in parahippocampus of patients with temporal lobe epilepsy: its association with the antiepileptic effects of subacute electrical stimulation.

Opioid receptor binding was evaluated in parahippocampal cortex (PHC) obtained from patients with intractable mesial temporal lobe epilepsy (MTLE) with and without subacute high frequency electrical stimulation (HFS) in this brain area. Mu, delta and nociceptin receptor binding was determined by autoradiography in PHC of five patients (ESAE group) with MTLE history of 14.8 +/- 2.5 years and seizure frequency of 11 +/- 2.9 per month, two of them (40%) with mesial sclerosis. This group demonstrated antiepileptic effects following subacute HFS (130 Hz, 450 micros, 200-400 microA), applied continuously during 16-20 days in PHC. Values were compared with those obtained from patients with severe MTLE (history of 21.7 +/- 2.8 years and seizure frequency of 28.2 +/- 14 per month) in whom electrical stimulation did not induce antiepileptic effects (ESWAE group, n = 4), patients with MTLE in whom no electrical stimulation was applied (MTLE group, n = 4) and autopsy material acquired from subjects without epilepsy (n = 4 obtained from three subjects). Enhanced 3H-DAMGO (MTLE, 755%; ESAE, 375%; ESWAE, 693%), 3H-DPDPE (MTLE, 242%; ESAE, 80%; ESWAE, 346%) and 3H-nociceptin (MTLE, 424%; ESAE, 217%; ESWAE, 451%) binding was detected in the PHC of all epileptic groups. However, tissue obtained from ESAE group demonstrated lower opioid receptor binding (3H-DAMGO, 44.5%, p < 0.05; 3H-DPDPE, 47%, p < 0.05; 3H-nociceptin, 39.3%, p < 0.5) when compared with MTLE group. The present results indicate that a high effectiveness to the antiepileptic effects induced by HFS is associated with reduced opioid peptide binding.     

Priming with a very low dose of DNA complexed with cationic block copolymers followed by protein boost elicits broad and long-lasting antigen-specific humoral and cellular responses in mice

Cationic block copolymers spontaneously assemble via electrostatic interactions with DNA molecules in aqueous solution giving rise to micellar structures that protect the DNA from enzymatic degradation both in vitro and in vivo. In addition, we have previously shown that they are safe, not immunogenic and greatly increased antigen-specific CTL responses following six intramuscular inoculations of a very low dose (1 μg) of the vaccine DNA as compared to naked DNA. Nevertheless, they failed to elicit detectable humoral responses against the antigen. To gain further insight in the potential application of this technology, here we show that a shorter immunization protocol based on two DNA intramuscular inoculations of 1 μg of DNA delivered by these copolymers and a protein boost elicits in mice broad (both humoral and cellular) and long-lasting responses and increases the antigen-specific Th1-type T cell responses and CTLs as compared to priming with naked DNA. These results indicate that cationic block copolymers represent a promising adjuvant and delivery technology for DNA vaccination strategies aimed at combating intracellular pathogens.