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OBJECTIVE:To examine prospective parents' perceptions of management options and outcomes in the context of threatened periviable delivery, and the values they apply in making antenatal decisions during this period. STUDY DESIGN:Qualitative analysis of 46 antenatal interviews conducted at three tertiary-care hospitals with 54 prospective parents (40 pregnant women, 14 partners) who had received counseling for threatened periviable delivery (40 cases). RESULTS:Participants most often recalled being involved in resuscitation, cerclage, and delivery mode decisions. Over half (63.0%) desired a shared decision-making role. Most (85.2%) recalled hearing about morbidity and mortality, with many reiterating terms like "brain damage", "disability", and "handicap". The potential for disability influenced decision making to variable degrees. In describing what mattered most, participant spoke of giving their child a "fighting chance"; others voiced concerns about "best interest", a "healthy baby", "pain and suffering", and religious faith. CONCLUSIONS:Our findings underscore the importance of presenting clear information on disability and eliciting the factors that parents deem most important in making decisions about periviable birth.

Objective. No uniform method for calculating growth velocity (GV) (grams per kilogram per day) among extremely low birth weight (ELBW) infants has been reported. Because the calculation of actual GV is so labor intensive, investigators have estimated GV with varying approaches, making comparisons across studies difficult. This study compares the accuracy of 3 mathematical methods used for estimating average GV, namely, 2-point models using the difference between weights at 2 time points divided by time and weight (either birth weight [BW] or average weight), linear regression models that are normalized for either BW or average weight, and an exponential model. The accuracy of all models was compared with actual GVs calculated from daily weight measures for a group of ELBW infants. Methods. Actual GVs were calculated from daily weights for 83 ELBW infants admitted to the special care nursery and were compared with estimated GVs from each of the 5 models for the same infants. Results. The exponential model, using weights from 2 time points, ie, GV = [1000 x ln([W.sub.n]/[W.sub.1])]/([D.sub.n] - [D.sub.1]), was extremely accurate, with mean absolute errors of 0.02% to 0.10%. The 2-point and linear models were highly inaccurate when BW was used in the denominator, with mean absolute errors of 50.3% to 96.4%. The 2-point and linear models were fairly accurate when average weight was used in the denominator, with mean absolute errors of 0.1% to 8.97%. Additional analyses showed that the accuracy of the 2-point and linear model estimates was affected significantly by the combination of BW, length of stay, and chronic lung disease, whereas the exponential model was not affected by these combined factors. Conclusions. GV estimates calculated with 3 commonly used models varied widely, compared with actual GVs; however, the exponential model estimates were extremely accurate. The exponential model provides the accuracy and ease of use that are lacking in current methods applied to infant growth research. Pediatrics 2005; 116:1466-1473; infant, extremely low birth weight, growth velocity, mathematical model prematurity. ABBREVIATIONS. BW, birth weight; ELBW, extremely low birth weight; GV, growth velocity; LOS, length of stay; ANCOVA, analysis of covariance., In the United States, 22 845 extremely low birth weight (ELBW) infants (birth weight [BW] of The measurement of postnatal growth is central to clinical care and research for ELBW [...]

The source of the elevation of endogenous stress hormones was investigated in experimental protocols with attenuated endotoxin-induced tumor necrosis factor-alpha (TNF-alpha) response. A chronically catheterized rat model was used. Baseline concentrations of corticosterone and catecholamines were significantly lower in the nonsurgical-stressed group. The findings suggest that the surgical and nonsurgical stresses inherent in experimental protocols increase baseline stress hormones, masking the endotoxin-induced TNF-alpha response.

Background Previous studies have established an association between low birthweight (LBW) and future kidney disease, but few have explored the progression of kidney dysfunction through the pediatric years leading up through adolescence and young adulthood. Methods To better understand the temporal effects of birthweight on kidney disease progression, we conducted a retrospective cohort study comparing the glomerular filtration rate (GFR) between LBW (<2500 grams) and normal birthweight (NBW) infants who were admitted to the neonatal intensive care unit (NICU) at our institution from 1992 to 2006. Results Age at follow-up ranged 1–26 years old. GFR was found to be significantly lower in participants born with LBW than those born with NBW, with a mean difference of 5.5 mL/min/1.73m2 (P < 0.01). These differences were found in the adolescent and young adult age group over 9 years of age, specifically in the extremely low birthweight group (ELBW) whose birthweight was less than 1000 grams. Conclusions We recommend screening for CKD in ELBW individuals starting at the age of 9 years old, regardless of their previous medical history. [ABSTRACT FROM AUTHOR]

Patients with severe trauma injury are transiently exposed to increased serum concentrations of tumor necrosis factor-[Alpha] (TNF-[Alpha]). These patients are susceptible to the development of multisystem organ failure (MSOF) triggered by subsequent exposure to bacterial toxins either via infection or increased intestinal permeability. We simulated the cytokine response of trauma by infusing 0.8 or 8.0 [micro]g/kg of TNF-[Alpha] (priming dose) into chronically catheterized rats. After 48 h, rats were challenged with endotoxin [lipopolysaccharide (LPS); 10 or 1,000 [micro]g/kg]. Animals primed with either dose of TNF-[Alpha] and then challenged with 1,000 [micro]g/kg of LPS demonstrated significantly increased mortality, mean peak serum concentrations of interferon-[Gamma] (IFN-[Gamma]), and blood lactate concentrations (P [is less than] 0.05) compared with nonprimed animals. Mean peak serum concentrations of IFN-[Gamma] and blood lactate concentrations were increased after challenge with 10 [micro]g/kg of LPS only in animals primed with 8.0 [micro]g/kg of TNF-[Alpha]. Priming with TNF-[Alpha] did not increase mortality after challenge with 10 [micro]g/kg of LPS. These data suggest that both TNF-[Alpha] release and the subsequent exposure to bacterial toxins mediate the pathophysiological progression from trauma to subsequent MSOF. septic shock; priming; interferon-[Gamma]; endotoxin; lactate

Staphylococcal enterotoxin B potentiates LPS-induced hepatic dysfunction in chronically catheterized rats. Am J Physiol Gastrointest Liver Physiol 280: G866-G872, 2001.--Most models of liver dysfunction in sepsis use endotoxin (lipopolysaccharide; LPS) to induce a pathophysiological response. In our study published in this issue (Beno DWA, Uhing MR, Goto M, Chen Y, Jiyamapa-Serna VA, and Kimura RE. Am J Physiol Gastrointest Liver Physiol 280: G858-G865, 2001), the adverse effect of LPS on hepatic function in vivo was only significant at relatively high LPS doses despite high tumor necrosis factor-[Alpha] concentrations. However, many patients with sepsis are exposed to multiple bacterial toxins that may augment the immune response, resulting in increased hepatic dysfunction. We have developed a model of polymicrobial sepsis by parentally administering a combination of staphylococcal enterotoxin B (SEB) and LPS. Using this model, we demonstrate that SEB (50 [micro]g/kg) potentiates the effect of LPS-induced hepatic dysfunction as measured by decreased rates of biliary indocyanine green clearance and bile flow. These increases were most pronounced with doses of 10 and 100 [micro]g/kg LPS, doses that by themselves do not induce hepatic dysfunction. This may explain the seemingly increased incidence and severity of liver dysfunction in sepsis, and it suggests that the exclusive use of LPS for replicating septic shock may not be relevant for studies of hepatic dysfunction. interferon-[Gamma]; hepatocellular dysfunction; sepsis; cholestasis; in vivo studies

Endotoxin-induced reduction in biliary indocyanine green excretion rate in a chronically catheterized rat model. Am J Physiol Gastrointest Liver Physiol 280: G858-G865, 2001.--Using a nonstressed chronically catheterized rat model in which the common bile duct was cannulated, we studied endotoxin-induced alterations in hepatic function by measuring changes in the maximal steady-state biliary excretion rate of the anionic dye indocyanine green (ICG). Biliary excretion of ICG was calculated from direct measurements of biliary ICG concentrations and the bile flow rate during a continuous vascular infusion of ICG. Despite significant elevations in mean peak serum tumor necrosis factor-[Alpha] (TNF-[Alpha]) concentrations (90.9 [+ or -] 16.2 ng/ml), there was no effect on mean rates of bile flow or biliary ICG clearance after administration of 100 [micro]g/kg endotoxin at 6 or 24 h. Significant differences from mean baseline rates of bile flow and biliary ICG excretion did occur after administration of 1,000 [micro]g/kg endotoxin (mean peak TNF-[Alpha] 129.6 [+ or -] 24.4 ng/ml). Furthermore, when rats were treated with up to 16 [micro]g/kg of recombinant TNF-[Alpha], there was no change in mean rates of bile flow or ICG biliary clearance compared with baseline values. These data suggest that the complex regulation of biliary excretion is not mediated solely by TNF-[Alpha]. tumor necrosis factor-[Alpha]; hepatocellular dysfunction; sepsis; cholestasis; in vivo studies

1. A catheterized rat model was used to define the intestinal and hepatic components of oral bioavailability for an 11β-HSD1 inhibitor, AMG 221. These data were integrated with standard in vivo metabolism studies to elucidate the components contributing to the oral disposition of a novel drug candidate. 2. Intestinal and hepatic extraction ratios of AMG 221 obtained using a five-catheter rat model were 0.56 and 0.32, respectively. Therefore, both intestinal and hepatic extraction contributed to the first-pass component of oral bioavailability. There was no evidence for significant gut extraction of systemically administered drug. 3. Mass balance data and in vivo metabolite characterization obtained after administration of [14C] AMG 221 to rat showed that AMG 221 was completely absorbed from the gut lumen following an oral dose, primarily excreted in urine and was almost completely metabolized prior to excretion. 4. Hepatic bioavailability (FH), measured in two animals at various time points after oral dose administration was somewhat variable but generally characterized by an initial reduction during the absorption phase followed by an increase during the elimination phase, consistent with hepatic distribution of AMG 221. 5. The five-catheter rat model afforded estimates of hepatic and intestinal contribution to oral bioavailability that were used with other data to define the preclinical ADME characteristics of a drug candidate. [ABSTRACT FROM AUTHOR]