Neonatal facial coding system scores and spectral characteristics of infant crying during newborn circumcision.

OBJECTIVE: To determine the relations between Neonatal Facial Coding System (NFCS) scores and measures of infant crying during newborn circumcision. METHODS: Video and audio recordings were made of infant facial activity and cry sounds, respectively, during the lysis phase of circumcisions of 44 healthy term males (<3 d of age). All infants received topical analgesia before circumcision. NFCS scores were determined by blinded assistant from video recordings of facial activity. Measures of infant crying were determined via spectrum analysis of audio recordings by a blinded, independent researcher. Pearson product-moment correlations were used to examine relationship between NFCS scores and measures of crying. Principal component factor analysis detected dimensions underlying related measures of crying. Factor scores from a factor analysis were used in stepwise linear regression to predict NFCS scores. RESULTS: Higher NFCS scores correlated with lower peak fundamental frequency of crying (P<0.01) and with higher amplitudes of crying at peak fundamental frequency and dominant frequency and in overall cry sample (P<0.01). The factor analysis showed 3 significant orthogonal dimensions underlying measures of crying: Power and Velocity (amplitude and rapidity), Pitch of Crying (frequency characteristics), and Infant Arousal (turbulence and intensity) accounting for 42.3%, 17.8%, and 14.6% of variance, respectively. A regression analysis showed all 3 factor scores accounted for significant and separate portions of variance (P<0.001). The best predictor of NFCS score was Power and Velocity (P<0.002), followed by Infant Arousal (P<0.002), and Pitch of Crying (P<0.007). DISCUSSION: These data provide some of the first known evidence linking specific measures of infant crying with an independent, validated measure of pain.

Nitric oxide and prostaglandin response to group B streptococcal infection in the lung.

Group B streptococcus (GBS) causes a complex inflammatory process that involves prostaglandins (PG) and nitric oxide (NO). The goal of this study was to examine the inflammatory response to GBS in the lung and the co-regulation of the PG and NO pathways, if any, both in vitro and in vivo. Sprague Dawley rats were treated with various combinations of GBS, aminoguanidine (AG), a selective inducible nitric oxide synthase (iNOS) inhibitor, and L-arginine (LA), a NO donor. The mRNA expression of the COX 2 gene was studied by reverse transcriptase polymerase chain reaction (RTPCR) in rat lung tissue. The studies were confirmed in vitro using human lung epithelial (A549) cells treated with GBS, AG, and LA (in combinations similar to the rats) for 3 and 24 hr, after which PG E2 levels in the media were measured by enzyme linked immunosorbent assay (ELISA). COX 2 mRNA in rat lung tissue was significantly induced by GBS (p = 0.04), an effect that was suppressed by AG (p = 0.02). In the A549 cell line, PG E2 levels increased with GBS treatment at 3 and 24 hr (p <0.001). When AG was added, PG E2 levels were suppressed (p = 0.03) after 24 hr; LA partly reversed the suppression of PG E2 levels (p = 0.039). These data indicate that GBS infection causes significant COX 2 induction and PG E2 synthesis in lung tissue, regulated at least partly by the NO pathway. The interaction between the 2 pathways may play a pathogenic role in GBS lung infections and could be a potential target for pharmacological manipulation.

Combined treatment with a nonselective nitric oxide synthase inhibitor (l-NMMA) and indomethacin increases ductus constriction in extremely premature newborns.

Studies in premature animals suggest that 1) prolonged tight constriction of the ductus arteriosus is necessary for permanent anatomic closure and 2) endogenous nitric oxide (NO) and prostaglandins both play a role in ductus patency. We hypothesized that combination therapy with an NO synthase (NOS) inhibitor [N(G)-monomethyl-L-arginine (L-NMMA)] and indomethacin would produce tighter ductus constriction than indomethacin alone. Therefore, we conducted a phase I and II study of combined treatment with indomethacin and L-NMMA in newborns born at <28 weeks' gestation who had persistent ductus flow by Doppler after an initial three-dose prophylactic indomethacin course (0.2, 0.1, 0.1 mg/kg/24 h). Twelve infants were treated with the combined treatment protocol [three additional indomethacin doses (0.1 mg/kg/24 h) plus a 72-hour L-NMMA infusion]. Thirty-eight newborns received three additional indomethacin doses (without L-NMMA) and served as a comparison group. Ninety-two percent (11/12) of the combined treatment group had tight ductus constriction with elimination of Doppler flow. In contrast, only 42% (16/38) of the comparison group had a similar degree of constriction. L-NMMA infusions were limited in dose and duration by acute side effects. Doses of 10-20 mg/kg/h increased serum creatinine and systemic blood pressure. At 5 mg/kg/h, serum creatinine was stable but systemic hypertension still limited L-NMMA dose. We conclude that combined inhibition of NO and prostaglandin synthesis increased the degree of ductus constriction in newborns born at <28 weeks' gestation. However, the combined administration of L-NMMA and indomethacin was limited by acute side effects in this treatment protocol.

Nitric oxide-dependent regulation of pro-inflammatory cytokines in group B streptococcal inflammation of rat lung.

Group B Streptococcus (GBS) infection leading to sepsis and lung injury is a major cause of neonatal morbidity and mortality. Lung injury may result from overproduction of pro-inflammatory mediators (cytokines), caused by nitric oxide (NO). Our objective was to characterize the molecular signaling events involving the pro-inflammatory mediators interleukin-6 (IL-6) and macrophage inflammatory protein (MIP-2) in the presence of aminoguanidine (AG), an inducible nitric oxide synthase (iNOS) specific inhibitor, in lung tissue from GBS-treated young rats. Changes in iNOS mRNA, lactic acid, and rectal temperature were determined as markers of the inflammatory response. Expression and regulation of IL-6 and MIP-2 mRNA in lung tissue were studied by RT-PCR with densitometry analysis. GBS treatment of young rats induced the expression of pro-inflammatory mediators IL-6 (6-fold) and MIP-2 (3-fold) in lung tissue compared to controls. AG decreased IL-6 and MIP-2 expression. Addition of L-arginine (L-arg) reversed the AG effect on IL-6 and MIP-2 expression. These data suggest a role for the nitric oxide pathway in the overproduction of pro-inflammatory mediators IL-6 and MIP-2 during GBS-induced lung inflammation. This pathway may be responsible for the initiation of lung injury.