Genetic polymorphism of cytomegalovirus strains responsible of congenital infections

OBJECTIVES: Congenital Cytomegalovirus (CMV) infection is the main cause of neurological handicap in young children. The objective for studying genetic polymorphism of strains responsible for congenital infection is to identify CMV strains or groups of strains which would be more frequent in this context and/or which would be responsible for more severe congenital infection. METHODS: In this paper, we report and analyze the literature concerning the genetic polymorphism of CMV strains responsible of congenital infection, in the genes coding for the envelop protein B and the non structural UL144 protein and in the CMV short tandem repeats. RESULTS AND CONCLUSION: All UL144 and gB genotypes can be vertically transmitted from mothers to fetuses, none of these studies has shown any link between the genotypes and the severity of congenital disease. Moreover, no link between short tandem repeats polymorphism and severity of congenital disease has been demonstrated. However, short tandem repeats analysis may be a powerful tool to study the epidemiology of CMV congenital infections.     

Effects of carotid sinus nerve transection on changes in neuropeptide Y and indolamines induced by long-term hypoxia in rats

 Long-term hypoxia induces changes in neuropeptide-Y-like immunoreactivity (NPY-LI) and/or in the content of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) at the central level. To determine whether these alterations depend on the integrity of carotid body (CB) chemoreceptors, intact rats or those whose carotid sinus nerve was transected (CSNT) were exposed to hypoxia (10% O₂) or to normoxia for 14 days. Thereafter, NPY-LI, 5-HT and 5-HIAA levels in discrete brain regions were determined. The increase in NPY-LI in the ventrolateral medulla oblongata (VLM) of intact hypoxic rats was mostly abolished after CSNT and therefore is mainly mediated by CB chemoreceptors. In contrast, other hypoxia-induced changes were similar or even enhanced in CSNT as compared to intact rats and therefore do not depend on the integrity of CB chemoreceptors. This was the case for the increase of NPY-LI in the striatum and the caudal dorsomedian medulla oblongata (DMM), as well as for all the changes in 5-HT and 5-HIAA in the DMM, the VLM, the raphe nuclei, the striatum and the frontal cortex. We propose that long-term hypoxia alters brain NPY-LI and indolamine content through the stimulation of CB chemoreceptors or ancillary chemoreceptors, as well as through local biochemical or morphological mechanisms. Received: 5 May 1998 / Received after revision: 27 July 1998 / Accepted: 3 September 1998     

Behavioral and neurochemical effects induced by subchronic combined exposure to toluene at 40 ppm and noise at 80 dB-A in rats

We investigated whether exposure to noise, in addition to its well-known potentiating effect on toluene-induced ototoxicity, may also exacerbate behavioral disturbances and brain neurochemical alterations produced by subchronic exposure to low toluene concentration. To test this hypothesis, we evaluated whether subchronic combined exposure (16 weeks, 104 h per week) to noise at 80 dB-A and toluene at 40 ppm potentiates the recently reported neurotoxic effects of subchronic exposure to 40 ppm toluene. Locomotor and rearing activities, sensitization to narcosis induced by acute toluene at high concentration, and tyrosine and tryptophan hydroxylase activities in the caudate-putamen and hippocampus were investigated in both male and female rats. Our results confirm that subchronic exposure to 40 ppm toluene significantly decreases rearing activity and leads to a sensitization to toluene-induced narcosis, as evaluated by loss of righting reflex, but fails to demonstrate any adverse effect of noise, alone or in combination with toluene. Given that toluene has addictive properties, the lack of potentiating behavioral and neurochemical effect of noise is discussed with regards to a recent study that has shown that methamphetamine neurotoxicity is potentiated by exposure to loud noise.     

Liver-First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients from the LiverMetSurvey Registry

Annals of Surgical Oncology - The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to...     

Endoscopic internal drainage for the management of leak,fistula, and collection after sleeve gastrectomy: our experience in 617 consecutive patients

BackgroundEndoscopy plays a pivotal role in the management of adverse events (AE) following bariatric surgery. Leaks, fistulae, and post-operative collection after sleeve gastrectomy (SG) may occur in up to 10% of cases.ObjectivesTo evaluate the efficacy and safety of endoscopic internal drainage (EID) for the management of leak, fistula, and collection following SG.SettingRetrospective, observational, single center study on patients referred from several bariatric surgery departments to an endoscopic referral center.MethodsEID was used as first-line treatment for the management of leaks, fistulae, and collections. Leaks and fistulae were treated with double pigtail stent (DPS) deployment in order to guarantee internal drainage and second intention cavity obliteration. Collections were treated with endoscropic ultrasound (EUS)–guided deployment of DPS or lumen apposing metal stents.ResultsA total of 617 patients (83.3% female; mean age, 43.1 yr) were enrolled in the study for leak (n = 300, 48.6%), fistula (n = 285, 46.2%), and collection (n = 32, 5.2%). Median follow-up was 19.5 months. Overall clinical success was 84.7% whereas 15.3% of cases required revisional surgery after EID failure. Clinical success according to type of AE was 89.5%, 78.5%, and 90% for leak, fistula, and collection, respectively. A total of 10 of 547 (1.8%) presented a recurrence during follow-up. A total of 28 (4.5%) AE related to the endoscopic treatment occurred. At univariate logistic regression predictors of failure were: fistula (OR 2.012), combined endoscopic approach (OR 2.319), need for emergency surgery (OR 1.755), and previous endoscopic treatment (OR 4.818).ConclusionEarly EID for the management of leak, fistula, and post-operative collection after SG seems a safe and effective first-line approach with good long-term results.     

Does crossing over repeated treatment with the dopamine reuptake inhibitors cocaine and BTCP modify their effects on cocaine-induced locomotion?

Because the dopamine reuptake inhibitors cocaine and BTCP produce different behavioral effects after repeated administration, we studied whether they could alter each other’s effects by examining the effects of crossing over repeated treatment with cocaine and BTCP on cocaine-induced locomotion. Male C57BL/6 mice were treated repeatedly with cocaine or BTCP during a first phase (days 1–3) and 3 days later, treated repeatedly with the same or the other compound during a second phase (days 7–9), after which they were administered one of several doses of cocaine on the next day. Locomotor activity was assessed after every daily treatment. The results show that 1) cocaine induced sensitization to its locomotor effects, 2) cocaine-induced sensitization was not altered by subsequent repeated treatment with BTCP, 3) initial repeated treatment with BTCP induced apparent cross-tolerance to cocaine, and 4) the initial effects of repeated BTCP were not markedly altered by subsequent repeated treatment with cocaine. The results indicate that the initial effects produced by repeated cocaine or BTCP are enduring and relatively difficult to alter by crossing over repeated treatment with the other compound. Thus, sensitization to the locomotor effects of cocaine in mice appeared to be attenuated by prior repeated treatment with BTCP but not reversed when followed by repeated treatment with BTCP. Received: 11 January 1998/Final version: 17 September 1998     

Vinflunine (20′,20′-difluoro- 3′,4′-dihydrovinorelbine), a novel Vinca alkaloid, which participates in P-glycoprotein (Pgp)-mediated multidrug resistance in vivo and in vitro

Vinflunine (VFL) is a novel derivative of vinorelbine (NVB, Navelbine®), which has shown markedly superior antitumor activity to NVB, in various experimental animal models. To establish whether this new Vinca alkaloid participates in P-glycoprotein (Pgp)-mediated multidrug resistance (MDR), VFL-resistant murine P388 cells (P388/VFL) were established in vivo and used in conjunction with the well established MDR P388/ADR subline, to define the in vivo resistance profile for VFL. P388/VFL cells proved cross-resistant to drugs implicated in MDR (other Vinca alkaloids, doxorubicin, etoposide), but not to campothecin or cisplatin and showed an increased expression of Pgp, without any detectable alterations in topoisomerase II or in glutathione metabolism. The P388/ADR cells proved cross-resistant to VFL both in vivo and in vitro, and this VFL resistance was efficiently modulated by verapamil in vitro. Cellular transport experiments with tritiated-VFL revealed differential uptake by P388 sensitive and P388/ADR resistant cells, comparable with data obtained using tritiated-NVB. In various in vitro models of human MDR tumor cells, whilst full sensitivity was retained in cells expressing alternative non-Pgp-mediated MDR mechanisms, cross resistance was identified in Pgp-overexpressing cells. Differences were, however, noted in terms of the drug resistance profiles relative to the other Vincas, with tumor cell lines proving generally least cross-resistant to VFL. Overall, these results suggest that VFL, like other Vinca alkaloids, participates in Pgp-mediated MDR, with tumor cells selected for resistance to VFL overexpressing Pgp, yet MDR tumor cell lines proved generally less cross resistant to VFL relative to the other Vinca alkaloids.     

Is a prophylactic treatment by erythropoietin relevant to reduce red blood cell transfusion in the pediatric intensive care unit?

OBJECTIVE: An adult trial reported the efficacy of recombinant human erythropoietin in critically ill patients with a 19% decrease in red blood cell transfusion. Our aim was to evaluate the relevance of this prophylactic treatment in children hospitalized in a pediatric intensive care unit (PICU). DESIGN: Cohort study from January 1995 to December 2004. SETTING: University hospital PICU. PATIENTS: Children between 1 month and 18 yrs of age. INTERVENTIONS: We searched through a prospective databank for all children hospitalized in the PICU for > or =4 days (potential recipients of erythropoietin, as proposed in the adult trial) and transfused with red blood cells after day 7 following PICU entry (in whom erythropoietin might prevent anemia, according to results of the adult trial). MEASUREMENTS AND MAIN RESULTS: We found that 799 of 2,578 children (31%) were hospitalized for > or =4 days. The study group comprised 787 patients who were hospitalized for > or =4 days in the PICU and for whom full records were available. One hundred eighty-three children in this study group were transfused during their stay in the PICU (median age, 7 months; weight, 6.60 kg). Hemoglobin levels before transfusion (mean +/- sd) were 7.7 +/- 1.5 g/dL. These transfused children represented 23% of the study group and 7% of the total PICU admissions. Forty-seven children (6% of the study group, 2% of the total PICU admissions) were transfused with red blood cells after 7 days of hospitalization and could have benefited from a prophylactic treatment with erythropoietin. Relative risk to benefit of a prophylactic treatment by erythropoietin was higher in cases of mechanical ventilation (relative risk, 1.18) and inotropic treatment (relative risk, 1.72) and if the main diagnosis involved dermatological (relative risk, 3.03) or oncologic disease (relative risk, 3.94). CONCLUSIONS: If we applied the results of the adult trial to our PICU, we would have to treat 31% of the children with prophylactic erythropoietin and thereby expect a reduction of one red blood cell transfusion for every 17 treated patients.