Non-invasive detection of coronary artery disease by dobutamine-stress echocardiography in children after heart transplantation.

BACKGROUND: Coronary vasculopathy is the main cause of cardiac graft failure. Because yearly coronary angiography is invasive in children, a non-invasive method for detecting graft vasculopathy is needed. The aim of this study was to test dobutamine-stress echocardiography in a pediatric population to determine its feasibility, safety and reliability in the detection of graft coronary artery disease. METHODS: Eighteen patients, aged 2 days to 16.8 years at transplantation (mean 8.4 years), underwent 44 dobutamine-stress echocardiography (DSE) exams, at a follow-up of 1.1 to 11.8 years (mean 5.1 years). Selective coronary angiography was performed for comparison. Echocardiographic recordings were obtained in 4 standard views of the left ventricle and measurements carried out within the frames of a 16-segment model. Segmental scores of contractility were obtained for each segment and a total segmental contractility index was calculated at each stage. RESULTS: All patients reached the maximum dose stage. Maximum heart rate was 57% to 90% of predicted maximum. Maximum systolic blood pressure reached 190 mmHg. Segmental scores were normal in 37 and abnormal in 7 cases. Echographic results were concordant with angiography in 82% and discordant in 18% of the cases (4 negative DSEs with minor angiographic lesions, 2 positive DSEs with normal angiography), but there was no significant angiographic lesion with normal DSE. CONCLUSIONS: DSE is a safe and highly feasible non-invasive technique in transplanted children. A normal DSE study successfully predicts the absence of significant coronary artery disease in the post-transplant population.     

HepG2 cell binding activities of different hepatitis b virus isolates: inhibitory effect of anti-HBs and anti-preS1(21–47)

The antigenic relationships among different hepatitis B virus (HBV) isolates were investigated by using monoclonal antibodies (MAbs) specific for HBs, preS2 (pHSA binding site), and preS1 (hepatocyte receptor-binding site) epitopes in a double immunoradiometric assay. In order to define possible functional differences resulting from structural and antigenic differences in the HBV env protein, the HBV isolates were compared in an in vitro cell-binding assay based on the attachment of 125I-labeled HBV to human hepatoma HepG2 cells. We provided evidence for a variability of the expression of preS1 and preS2 specificities in the peplomer (glyco)protein of HBV depending on d/ysubtype of HBsAg, which could affect the viral infectivity. We showed that the integrity of the HBV envelope structure associated with a large expression of preS1(21–47) epitopes is an essential factor for effective binding to HepG2 cells. Interestingly, the HBs-specific MAbs directed to disulfide-bond-dependent epitopes were found to be the best inhibitors of the preS1-HepG2 cell interaction (>50% at the final concentration of 0.5 μg/ml). The MAb F35.25 directed to the preS1(21–47) sequence corresponding to the hepatocyte receptor recognition site was, however, also found to inhibit binding. Thus, our results demonstrate the abilities of both anti-HBs and anti-preS(21–41) to block the attachment of complete HBV particles to HepG2 cells, suggesting that these antibodies should be virus neutralizing and would be expected to confer protection against reinfection.     

Major vascular injuries during gynecologic laparoscopy

Background:This study was undertaken to report our experience with major vascular injuries in gynecologic laparoscopy in order to specify the circumstances under which they occurred, the means of diagnosis, the risk factors, and the means for prevention.Study Design:Retrospective case review study.Results:Seventeen patients with 21 major vascular injuries were identified. The average age of the patients was 33.8 ± 11.6 years, and the mean body index mass was 21.6 ± 3.08 kg/m². Three of four of the accidents occurred during the set-up phase of laparoscopy (13 cases; 76.5%), and in 4 cases (23.5%) the accident occurred during the laparoscopic surgery procedure. Eleven (84.6%) of the complications occurring during the set-up phase were secondary to insertion of the umbilical trocar and 2 (15.4%) to insertion of the needle used to create the pneumoperitoneum (P-needle). Half (6 cases; 54.5%) of the major vascular injuries secondary to insertion of the umbilical trocar were observed when reusable trocars were used. In every case, the diagnosis was made during the operation. Two patients died, and two others presented a serious complication (phlebitis; acute ischemia requiring reoperation).Conclusions:Major vascular injuries are rare but serious complications of laparoscopic surgery. Prevention of these accidents relies on the surgeon’s experience and scrupulous respect of the safety rules. In the vast majority of cases, it is necessary to convert to laparotomy immediately, calling in a vascular surgeon.     

Healthy choices: motivational enhancement therapy for health risk behaviors in HIV-positive youth.

This study piloted a brief individual motivational intervention targeting multiple health risk behaviors in HIV-positive youth aged 16-25. Interviews about sexual behavior and substance use and viral load testing were obtained from 51 HIV-positive youth at baseline and post intervention. Youth were randomized to receive a four-session motivational enhancement intervention (N = 25) or to a wait-list control (N = 26). Of the eligible youth approached, 88% agreed to participate, and 80% percent of participants completed at least three of four sessions. The treatment group showed significantly greater reductions in unprotected sex acts and in viral load compared with controls. Although change scores for substance use were not significantly different between the two groups, paired t tests demonstrated that reductions in alcohol use and marijuana use were significant for the treatment group at the trend level. There were no significant differences in substance use from baseline to posttest for the control group. Findings demonstrate the potential of a brief motivational enhancement intervention to improve health risk behaviors in HIV-positive youth. Larger randomized clinical trials are warranted. Resources required for retention should not be underestimated.     

Radioiodinated tracers for the evaluation of dopamine receptors in the neonatal rat brain after hypoxic-ischemic injury

In order to evaluate in vivo single-photon emission tomography (SPET) method of assessing cerebral function after hypoxic-ischemic injury in human neonates, we studied D₁ and D₂ dopamine receptors in a rat model. Seven-day-old rats underwent permanent unilateral common carotid ligation followed by exposure to 8% O₂. Two weeks later, in brains with no visible loss of hemispheric volume, striatal dopaminergic receptors were studied, with [¹²⁵I]TISCH and [1251]IBZM for the D₁ and D₂ dopamine receptors, respectively. Using [¹²⁵I]TISCH, we observed no modifications of D₁ receptors, but in contrast, ex vivo and in vitro autoradiographic experiments showed a 40% decrease in the striatal binding of [¹²⁵I]IBZM on both the ipsilateral and the contralateral side to the carotid ligation. These alterations were detected with IBZM, a D₂ dopamine receptor ligand usable for SPET imaging. Therefore, exploration of D₂ receptors by SPET in human neonates suffering from perinatal hypoxia-ischemia may be valuable for the diagnosis and follow-up of cerebral function damages. Correspondence to: D. Guilloteau     

In vitro metabolism of ferroquine (SSR97193) in animal and human hepatic models and antimalarial activity of major metabolites on Plasmodium falciparum.

Ferroquine (SSR97193) has been shown to be a promising antimalarial, both on laboratory clones and on field isolates. So far, no resistance was documented in Plasmodium falciparum. In the present work, the metabolic pathway of ferroquine, based on experiments using animal and human hepatic models, is proposed. Ferroquine is metabolized mainly via an oxidative pathway into the major metabolite mono-N-demethyl ferroquine and then into di-N,N-demethyl ferroquine. Some other minor metabolic pathways were also identified. Cytochrome P450 isoforms 2C9, 2C19, and 3A4 and, possibly in some patients, isoform 2D6, are mainly involved in ferroquine oxidation. The metabolites were synthesized and tested against the 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant) P. falciparum strains. According to the results, the activity of the two main metabolites decreased compared with that of ferroquine; however, the activity of the mono-N-demethyl derivative is significantly higher than that of chloroquine on both strains, and the di-N-demethyl derivative remains more active than chloroquine on the chloroquine-resistant strain. These results further support the potential use of ferroquine against human malaria.