KEYWORDS trisomy 13 • trisomy 18 • neonate • congenital heart defects • neonatal intensive care • cardiac surgery ABSTRACTIntensive cardiac management such as pharmacological intervention for ductal patency (indomethacin and/or mefenamic acid for closure and prostaglandin E1 for maintenance) and palliative or corrective surgery is a standard treatment for congenital heart defects. However, whether it would be a treatment option for children with trisomy 13 or trisomy 18 syndrome is controversial because the efficacy on survival in patients with these trisomies has not been evaluated. We retrospectively reviewed 31 consecutive neonates with trisomy 13 or trisomy 18 admitted to our neonatal ward within 6 hr of birth between 2000 and 2005. The institutional management policies differed during three distinct periods. In the first period, both pharmacological ductal intervention and cardiac surgery were withheld. In the second, pharmacological ductal intervention was offered as an option, but cardiac surgery was withheld. Both strategies were available during the third period. The median survival times of 13, 9, and 9 neonates from the first, second, and third periods were 7, 24, and 243 days, respectively. Univariate and multivariate analyses confirmed that the patients in the third period survived significantly longer than the others. Intensive cardiac management consisting of pharmacological intervention for ductal patency and cardiac surgery was demonstrated to improve survival in patients with trisomy 13 or trisomy 18 in this series. Therefore, we suggest that this approach is a treatment option for cardiac lesions associated with these trisomies. These data are helpful for clinicians and families to consider in the optimal treatment of patients with these trisomies.

Cardiac surgery is infrequently but increasingly being used to repair congenital heart defects associated with trisomy 18. The clinical details of trisomy 18 patients undergoing cardiac surgery have rarely been reported. Seventeen patients with trisomy 18 and serious cardiac symptoms underwent cardiac surgery in our institution. Age at surgery ranged from 7 to 258 days (median, 66 days). One patient had an atrioventricular septal defect and coarctation of the aorta. The remaining patients had ventricular septal defects, including four patients with coarctation of the aorta. Fourteen patients had associated patent ductus arteriosus. Fourteen patients underwent palliative surgery without cardiopulmonary bypass, and four of these underwent a second-stage intracardiac repair. The other three patients underwent primary intracardiac repair. Postoperatively, 14 patients (82%) were discharged home with improved symptoms. Survival from birth ranged from 12 to 1384 days (median, 324 days). Eight patients survived longer than 1 year. Median postoperative survival was 179 days. Postoperative survival was significantly better after palliative surgery (0 to 1239 days; median, 257 days) than after primary intracardiac repair (1 to 179 days; median, 48 days). Only one patient died of heart failure, suggesting that cardiac surgery was effective in preventing heart failure-related death.

The effects of β-adrenoceptor agonists (β-agonists) on the production of tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β) and interleukin-8 (IL-8) by lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs) were investigated. The β-agonists, procaterol, clenbuterol, fenoterol and terbutaline, inhibited TNF-α and IL-1β production in a concentration-dependent manner, whereas they had no effect on IL-8 production. TNF-α production was inhibited more potently than IL-1β. Dibutyryl cyclic AMP (dbcAMP) also inhibited the production of TNF-α and IL-1β, but not IL-8. TNF-α production was almost completely inhibited by dbcAMP, whereas IL-1β production appeared to be partially refractory even at the highest concentration examined. Both procaterol and the-ophylline elevated cAMP levels in LPS-stimulated PBMCs, but the effect of procaterol was limited. The inhibition of TNF-α and IL-1β production by procaterol was additively potentiated with theophylline. dl-Propranolol, a β-adrenoceptor antagonist, abrogated the inhibition of TNF-α and IL-1β production by procaterol. These results indicate that β-agonists inhibit the production of proinflammatory cytokines, such as TNF-α and IL-1β, by elevating intracellular cAMP levels. These properties of β-agonists might be beneficial in the treatment of allergic inflammation.

IT IS WELL ESTABLISHED THAT apical migration of junctional epithelium (JE) along a root surface is an important factor in periodontal pocket formation and deepening. However, the exact mechanism and, more specifically, the role of inflammatory products in influencing the activity of cells within the JE is not known. To address this issue lipopolysaccharide (LPS) was applied topically into rat molar gingival sulcus and then tissues evaluated immunohistochemically for expression of proliferating cell nuclear antigen (PCNA). Tissues were prepared for histological analysis at designated times. Histologically, infiltration of neutrophils with associated edema was noted in JE and gingival connective tissues 6 hours after LPS application and was prominent at 12 hours. These inflammatory changes persisted in the 2- and 3-day specimens, and disappeared at 5 days. In normal gingiva, before the LPS application, the JE showed few PCNA positive cells, while almost all cells in the basal and suprabasal cell layers of the oral gingival epithelium and the oral sulcular epithelium were PCNA positive. No increase in the number of PCNA positive cells in the JE beyond zero time was observed at 6 and 12 hours after LPS application. One day after LPS application, PCNA positive cells appeared in the basal cell layer of the JE, with a continued increase number of PCNA positive cells in the JE continued at 2 and 3 days. By day 5 the number of PCNA positive cells were decreasing with return to a normal range by 7 days. These results showed that 1) under normal physiological conditions, cells within the JE have minimal mitotic activity and 2) the JE cells can enter the proliferating cell cycle when exposed to LPS, and suggest that the enhanced proliferating activity in the JE is an important factor for the deepening of the periodontal pocket, if the connective tissue attachment is broken down.

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Closure of VSDs in patients with trisomy 18 was found feasible and was associated with extended survival.

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Levofloxacin (LVFX), the bacteriologically active isomer of ofloxacin, is a fluorinated quinolone. LVFX suppressed the proliferative activity of peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin (PHA). LVFX increased interleukin-2 (IL-2) production by PBMC stimulated with PHA in a dose-dependent manner, with more than 10 μg/ml of LVFX causing a significant increase. The granulocyte-macrophage colony-stimulating factor and soluble IL-2 receptor production by PHA-stimulated PBMC was suppressed at high concentrations of LVFX. Interleukin-1β production by lipopolysaccharide-stimulated PBMC was suppressed in a concentration-dependent manner by LVFX, and tumor necrosis factor-α production was suppressed at only the highest concentration. In contrast, interleukin-8 production was little affected by LVFX. These results show that LVFX has an immunomodulatory action on cytokines production by PBMC independent of its antimicrobial activity.