High-dose oral erythromycin decreased the incidence of parenteral nutrition-associated cholestasis in preterm infants

BACKGROUND & AIMS: Feeding intolerance because of functional gastrointestinal dysmotility and parenteral nutrition-associated cholestasis (PNAC) are common problems in preterm, very-low-birth-weight (VLBW) infants. This double-blind, randomized, placebo-controlled study aimed to assess the effectiveness of "high-dose" oral erythromycin as a prokinetic agent in decreasing the incidence of PNAC. Two secondary end points, including the time to achieve full enteral feeding and the duration of parenteral nutrition, were also evaluated. METHODS: Infants consecutively admitted to the neonatal unit were randomized to receive erythromycin (12.5 mg/kg/dose every 6 hours for 14 days) or an equivalent volume of normal saline (placebo) if they attained less than half the total daily fluid intake (<75 mL/kg/day) as milk feeds on day 14 of life. RESULTS: Of 182 VLBW infants enrolled, 91 received erythromycin. The incidence of PNAC was significantly lower in erythromycin-treated infants (18/91) compared with placebo infants (37/91; P = .003). Treated infants achieved full enteral nutrition significantly earlier (mean, 10.1; SE, 1.7 days; P < .001), and the duration of parenteral nutrition was also significantly decreased by 10 days (P < .001). Importantly, fewer infants receiving erythromycin had 2 or more episodes of septicemia (n = 4) compared with placebo patients (n = 13, P = .03). No serious adverse effect was associated with erythromycin treatment. CONCLUSIONS: High-dose oral erythromycin can be considered as a rescue measure for VLBW infants who fail to establish adequate enteral nutrition and in whom anatomically obstructive pathologies of the gastrointestinal tract have been excluded.     

新生儿难治性腹泻采用周围静脉营养辅助治疗的报告

对本院新生儿病房自１９９２年３月－１９９３年３月的新生儿腹泻病程在５－１０天者及新生儿坏死性小肠结肠炎，经口喂养热卡不足需要量的６０％者，采用周围静脉供给营养，共１１例，并与１９９２年以前病情相同未用静脉营养的９例作对照。结果：用静脉营养组疗效明显优于对照组，主要表现在腹泻好转时间缩短，治疗后的体重较治疗前明显增加，住院天数缩短。     

Immunohistochemical expression of fibronectin and tenascin in human tooth pulp capped with mineral trioxide aggregate and a novel endodontic cement

Introduction

The purpose of the present study was the immunohistochemical study of fibronectin (FN) and tenascin (TN) in human tooth pulp capped with mineral trioxide aggregate (MTA) and novel endodontic cement (NEC) (calcium enriched mixture cement) after 2 and 8 weeks.

Methods

Thirty-two premolar teeth that were scheduled for extraction for orthodontic reasons were exposed and capped with either MTA or NEC. The teeth were randomly divided into 4 groups: group 1 (NEC for 2 weeks), group 2 (NEC for 8 weeks), group 3 (MTA for 2 weeks), and group 4 (MTA for 8 weeks). After capping the exposed pulps with either NEC (groups 1 and 2) or MTA (groups 3 and 4), half of the specimens underwent extraction and were prepared for histologic and immunohistochemical evaluation for FN and TN after 2 weeks, and the remaining half were assessed after 8 weeks. FN and TN expression was scored by a blinded pathologist on a scale of I-IV, and the results were analyzed by the Wilcoxon and Mann-Whitney U statistical tests.

Results

FN and TN staining was observed in all 4 experimental groups, and there was no significant difference between expression of FN and TN in any groups. FN and TN staining was observed in the dentinal bridge matrix after 2 weeks under MTA. Expression of both markers reduced significantly after 8 weeks under MTA, and staining was observed only in unmineralized parts of dentinal bridge. FN and TN expression was observed in the matrix of the dentinal bridge after 2 weeks under NEC, and staining of both markers was reduced after 8 weeks compared with 2 weeks. The staining pattern of TN in NEC groups was higher than in MTA groups in both time intervals. However, the difference was not significant.

Conclusions

The present study demonstrated that both MTA and NEC are suitable biomaterials for direct pulp capping and are able to stimulate dentinal bridge formation. Moreover, the role of FN and TN as 2 major components of the matrix of a reparative dentinal bridge was observed.     

Early identification of the risk for free radical-related diseases in preterm newborns

Background

Despite recent advances in preterm newborns healthcare, perinatal pathologies and disabilities are increasing. Oxidative stress (OS) is determinant for the onset of an unbalance between free radicals (FRs) production and antioxidant systems which plays a key role in pathogenesis of pathologies such as retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), grouped as ‘free radical-related diseases’ (FRD).

Aim

This study tests the hypothesis that OS markers levels in cord blood may predict the onset of FRD pathologies.

Patients and methods

168 preterm newborns of GA: 24-32 weeks (28.09 ± 1.99); and BW: 470-2480 gr (1358.11 ± 454.09) were consecutively recruited. Markers of potential OS risk (non-protein bound iron, NPBI; basal superoxide anion, BSA; under stimulation superoxide anion, USSA) and markers of OS-related damage (total hydroperoxides, TH; advanced oxidation protein products, AOPP) were assessed in cord blood. Associations between FRD onset and OS markers were checked through inferential analysis (univariate logistic regression).

Results

The development of FRD was significantly associated to high cord blood levels of TH, AOPP and NPBI (respectively p = 0.000, OR = 1.025, 95%CI = 1.013-1.038; p = 0.014, OR = 1.092, 95%CI = 1.018-1.172; p = 0.007, OR = 1.26995%CI = 1.066-1.511).

Conclusions

Elevated levels of TH, AOPP and, above all, NPBI, in cord blood are associated with increased risk for FRD. OS markers allow the early identification of infants at risk for FRD because of perinatal oxidant exposure. This can be useful in devising strategies to prevent or ameliorate perinatal outcome.     

Bile acids induce ileal damage during experimental necrotizing enterocolitis

BACKGROUND & AIMS: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants. While the effect of bile acids (BAs) on intestinal mucosal injury is known, we investigated the contribution of BAs during the development of NEC in neonatal rats. METHODS: Premature rats were fed with cow's milk-based formula and subjected to asphyxia and cold stress to develop NEC. Jejunal and ileal luminal BAs, portal blood BAs, and messenger RNA and protein for the apical sodium-dependent bile acid transporter, the ileal bile acid binding protein, and the heteromeric organic solute transporter (Ostalpha/Ostbeta)were evaluated. RESULTS: Ileal luminal BAs levels were increased significantly during disease development and the removal of ileal BAs significantly decreased the incidence and severity of disease. Furthermore, when NEC was reduced via treatment with epidermal growth factor (EGF), BA levels were reduced significantly. Jejunal luminal BA levels were similar between animals with NEC and controls, but portal/ileal luminal BA ratios were decreased significantly in animals with NEC. The apical sodium-dependent bile acid transporter was up-regulated at the site of injury in animals with NEC and decreased after EGF treatment; however, the ileal bile acid binding protein was up-regulated only in the NEC and EGF group. Ostalpha/Ostbeta expression was low in all groups, and only slightly increased in the NEC group. CONCLUSIONS: These data strongly suggest that BAs play a role in the development of ileal damage in experimental NEC and that alterations in BA transport in the neonatal ileum may contribute to disease development.     

The role of chemotherapy and/or octreotide in patients with metastatic gastroenteropancreatic and hepatobiliary neuroendocrine carcinoma

Background

Neuroendocrine carcinomas (NECs) of the gastro-entero-pancreatic (GEP) and hepatobiliary (HB) tract are rare and a heterogenous group of malignancies. Octreotide showed the anti-tumor activity in functional and nonfunctional well differentiated metastatic midgut neuroendocrine tumors (NETs). However, the effect of octreotide on survival has not been evaluated.

Patients and methods

We analyzed 17 patients (6 HB- and 11 GEP- tract) with metastatic NEC diagnosed between January 2009 and June 2012. All patients had one or more cytotoxic chemotherapy and nine patients had received octreotide as single agent (n=3) or combination of cytotoxic chemotherapy (n=6).

Results

The median age was 68 years (range, 23-79 years) and median Eastern Cooperative Oncology Group performance status (ECOG PS) was 1. Sixteen of all patients (n=17) received cytotoxic chemotherapy with or without octreotide as the first line therapy and 10 of 16 patients who experienced disease progression to the first line therapy received the second line therapy. Overall response rates (RR) and disease control rates (DCR) to the 1^st line therapy were 41.2% and 76.5%, respectively. The median overall survival (OS) was 16 months [95% confidence interval (CI), 12.8-19.2] and the median OS in patients receiving octreotide during treatment was 40.2 months. In univariate analysis, any clinico-pathologic features including sex, the location of primary tumor, the number of metastatic sites, the debulking operation and the liver metastasis did not have prognostic value regarding OS. However, the use of octreotide offered favorable trend for OS (P=0.091).

Conclusions

The use of octreotide may benefit for patients with GEP- and HB- NECs as a single agent or a combination therapy.     

Differential regulation of HCN channel isoform expression in thalamic neurons of epileptic and non-epileptic rat strains

Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels represent the molecular substrate of the hyperpolarization-activated inward current (I_h). Although these channels act as pacemakers for the generation of rhythmic activity in the thalamocortical network during sleep and epilepsy, their developmental profile in the thalamus is not yet fully understood. Here we combined electrophysiological, immunohistochemical, and mathematical modeling techniques to examine HCN gene expression and I_h properties in thalamocortical relay (TC) neurons of the dorsal part of the lateral geniculate nucleus (dLGN) in an epileptic (WAG/Rij) compared to a non-epileptic (ACI) rat strain. Recordings of TC neurons between postnatal day (P) 7 and P90 in both rat strains revealed that I_h was characterized by higher current density, more hyperpolarized voltage dependence, faster activation kinetics, and reduced cAMP-sensitivity in epileptic animals. All four HCN channel isoforms (HCN1-4) were detected in dLGN, and quantitative analyses revealed a developmental increase of protein expression of HCN1, HCN2, and HCN4 but a decrease of HCN3. HCN1 was expressed at higher levels in WAG/Rij rats, a finding that was correlated with increased expression of the interacting proteins filamin A (FilA) and tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b). Analysis of a simplified computer model of the thalamic network revealed that the alterations of I_h found in WAG/Rij rats compensate each other in a way that leaves I_h availability constant, an effect that ensures unaltered cellular burst activity and thalamic oscillations. These data indicate that during postnatal developmental the hyperpolarizing shift in voltage dependency (resulting in less current availability) is compensated by an increase in current density in WAG/Rij thereby possibly limiting the impact of I_h on epileptogenesis. Because HCN3 is expressed higher in young versus older animals, HCN3 likely does not contribute to alterations in I_h in older animals.     

Rare case of disseminated neonatal zygomycosis mimicking necrotizing enterocolitis with necrotizing fasciitis

A set of monochorionic male twins presented with intestinal perforation. The smaller twin was diagnosed with necrotizing enterocolitis followed by sepsis, disseminated intravascular coagulation, and necrotizing fasciitis of the abdominal wall. The infant died on the fourth day after surgery, 16 days after birth. Surgical specimens and autopsy revealed a disseminated zygomycotic infection. Gastrointestinal zygomycosis followed by necrotizing fasciitis in premature infants is a rare condition and mimics necrotizing enterocolitis clinically. Necrotizing fasciitis after gastrointestinal zygomycosis in premature infants is considered a poor prognostic sign. Gastrointestinal zygomycosis should be considered in the differential diagnosis of necrotizing enterocolitis.