Constructing a relevant decision aid for parents of children with bronchopulmonary dysplasia.

BACKGROUND: To develop and test a decision aid for counseling parents of children with bronchopulmonary dysplasia (BPD).Local problem:Parental education about complex conditions is not standardized and communication and understanding may not be adequate. METHODS: Semi-structured interviews were conducted with 33 neonatal clinicians and 12 parents of children with BPD using a qualitative research design. The interviews were used to identify education topics that were felt to be important in BPD education. These topics were then used to create a visual decision aid to be used in counseling sessions with parents. The decision aid was then used in mock counseling sessions with 15 'experienced' participants and 7 'naïve' participants to assess its efficacy. The participants completed a pre and post test to assess change in knowledge as well as an 11-question Likert style acceptability survey. INTERVENTION: Implementation of a decision aid while educating parents about BPD. RESULTS: Topics identified during the interviews were used to create eight educational cards which included pictures, pictographs and statistics. Overall, participants thought the decision aid contained an appropriate amount of information, were easy to understand and improved their knowledge about BPD. Testing demonstrated a significant increase in knowledge in both the 'experienced' (P<0.0001) and 'naïve' group (P=0.0064). CONCLUSION: A decision aid for parents of children with BPD may improve understanding of the condition and help facilitate communication between parents and doctors.

Tollip SNP rs5743899 modulates human airway epithelial responses to rhinovirus infection.

BACKGROUND: Rhinovirus (RV) infection in asthma induces varying degrees of airway inflammation (e.g. neutrophils), but the underlying mechanisms remain unclear. OBJECTIVE: The major goal was to determine the role of genetic variation [e.g. single nucleotide polymorphisms (SNPs)] of Toll-interacting protein (Tollip) in airway epithelial responses to RV in a type 2 cytokine milieu. METHODS: DNA from blood of asthmatic and normal subjects was genotyped for Tollip SNP rs5743899 AA, AG and GG genotypes. Human tracheobronchial epithelial (HTBE) cells from donors without lung disease were cultured to determine pro-inflammatory and antiviral responses to IL-13 and RV16. Tollip knockout and wild-type mice were challenged with house dust mite (HDM) and infected with RV1B to determine lung inflammation and antiviral response. RESULTS: Asthmatic subjects carrying the AG or GG genotype (AG/GG) compared with the AA genotype demonstrated greater airflow limitation. HTBE cells with AG/GG expressed less Tollip. Upon IL-13 and RV16 treatment, cells with AG/GG (vs. AA) produced more IL-8 and expressed less antiviral genes, which was coupled with increased NF-κB activity and decreased expression of LC3, a hallmark of the autophagic pathway. Tollip co-localized and interacted with LC3. Inhibition of autophagy decreased antiviral genes in IL-13- and RV16-treated cells. Upon HDM and RV1B, Tollip knockout (vs. wild-type) mice demonstrated higher levels of lung neutrophilic inflammation and viral load, but lower levels of antiviral gene expression. CONCLUSIONS AND CLINICAL RELEVANCE: Our data suggest that Tollip SNP rs5743899 may predict varying airway response to RV infection in asthma.

A comparison of the direct cost of care in an open-bay and single-family room NICU.

OBJECTIVE: This research examined the proposition that the direct costs of care were no different in an open-bay (OPBY) as compared with a single-family room (SFR) neonatal intensive care (NICU) environment. STUDY DESIGN: This was a sequential cohort study. RESULT: General linear models were implemented using clinical and cost data for all neonates admitted to the two cohorts studied. Costs were adjusted to year 2007 U.S. dollars. Models were constructed for the unadjusted regression and subsequently by adding demographic variables, treatment variables, length of respiratory support and length of stay. With the exception of the last, none were found to achieve significance. The full model had R(2)=0.799 with P=0.0095 and predicted direct costs of care less in the SFR NICU. CONCLUSION: For the time, location and administrative practices in place, this study demonstrates that care can be provided in the SFR NICU at no additional cost as compared with OPBY NICU.

Blood stream infection (BSI) and acute GVHD after hematopoietic SCT (HSCT) are associated.

Blood stream infection (BSI) and acute GVHD (aGVHD) are serious complications of hematopoietic SCT (HSCT). We hypothesized that the two events were not independent of one another. We studied (1) associations between BSI and aGVHD; and (2) the impact of BSI and/or aGVHD on death within 100 days after HSCT, using a retrospective cohort analysis. Risk factor analysis was carried out using multivariable Cox proportional hazards analyses. Of 211 patients who underwent allogeneic HSCT from January 2000 to December 2005 (58% of whom underwent reduced intensity transplantation), 82 (39%) developed BSI. In 49 patients (23%), grade (gr) 2-4 aGVHD occurred. Early BSI was independently associated with an increased occurrence of subsequent aGVHD gr 2-4. CMV seropositivity was independently associated with decreased occurrence of aGVHD. aGVHD gr 2-4 independently predicted subsequent first BSI. Both BSI and aGVHD gr 2-4 were significant independent predictors of death within 100 days after HSCT. There is a strong, independent association between BSI and aGVHD. Potential explanations include the elaboration of cytokines during BSI favoring the development of aGVHD and/or the immunosuppressive treatment of aGVHD favoring the development of BSI. Future studies should be directed at the mechanistic investigations of this association.

Neonatal intensive care nursery staff perceive enhanced workplace quality with the single-family room design.

OBJECTIVE: To compare perceived workplace quality in an open-bay neonatal intensive care unit (NICU) and a single-family room (SFR) NICU. STUDY DESIGN: Prospective non-randomized, non-controlled cohort study. RESULT: Staff workplace quality perceptions assessed included the following: the quality of being a Sanford Health System employee (NS-not significant), the quality of the NICU physical work environment, the quality of NICU patient care, the job quality in the NICU, the quality of health and safety in the NICU (NS), the quality of safety and security in the NICU, the quality of interaction with other members of the NICU health-care team (NS; in subanalysis nurse scores significantly declined), the quality of interaction with NICU technology and the off-job quality of life (NS). Scores for each category and the total scores were statistically greater in the SFR, except as noted (NS). CONCLUSION: Staff perceptions of workplace quality were significantly greater in the SFR than the open-bay NICU.

The impact of architectural design upon the environmental sound and light exposure of neonates who require intensive care: an evaluation of the Boekelheide Neonatal Intensive Care Nursery.

OBJECTIVES: To evaluate the differences in environmental sound, illumination and physiological parameters in the Boekelheide Neonatal Intensive Care Unit (BNICU), which was designed to comply with current recommendations and standards, as compared with a conventional neonatal intensive care unit (CNICU). STUDY DESIGN: Prospectively designed observational study. RESULT: Median sound levels in the unoccupied BNICU (37.6 dBA) were lower than the CNICU (42.1 dBA, P<0.001). Median levels of minimum (6.4 vs 48.4 lux, P<0.05) and maximum illumination (357 vs 402 lux, P<0.05) were lower in the BNICU. A group of six neonates delivered at 32 weeks gestation showed significantly less periodic breathing (14 vs 21%) and awake time (17.6 vs 29.3%) in the BNICU as compared to the CNICU. CONCLUSION: Light and sound were both significantly reduced in the BNICU. Care in the BNICU was associated with improved physiological parameters.

Congenital cardiomyopathy and pulmonary hypertension: another fatal variant of cytochrome-c oxidase deficiency.

Biventricular hypertrophy was noted at 24 weeks' gestation in a fetus with isolated cytochrome-c oxidase (COX) deficiency. Shock, caused by hypertrophic cardiomyopathy and severe pulmonary hypertension, led to the patient's death on day 6. His phenotype defines a new lethal variant of COX deficiency characterized by prenatal-onset cardiopulmonary pathophysiology.

Androgen inhibits, while oestrogen enhances, restraint-induced activation of neuropeptide neurones in the paraventricular nucleus of the hypothalamus.

The hormonal response to stress is enhanced by oestrogen but inhibited by androgens. To determine underlying changes in activity of neuropeptide neurones in the paraventricular nucleus of the hypothalamus (PVN), we examined the effect of oestrogen and androgen treatment on restraint-induced c-fos mRNA, corticotropin-releasing hormone (CRH) heteronuclear RNA, and arginine vasopressin hnRNA expression in the PVN. Male rats were gonadectomized and injected with oestradiol benzoate (EB) or dihydrotestosterone propionate (DHTP; s.c., daily for 4 days). Rats were stressed by restraint for 10 min or 30 min before killing. Other rats were stressed for 30 min and then returned to their home cage for 20 min before killing. Corticosterone and adrenocorticotropic hormone responses to restraint stress were significantly greater in EB-treated rats and lower in DHTP-treated rats at the 30-min timepoint compared to controls. c-fos mRNA increases following stress were augmented by EB but inhibited by DHTP. CRH hnRNA expression increased significantly in the PVN in response to restraint stress, and this increase was augmented by EB treatment, but decreased by DHTP treatment. Vasopressin hnRNA expression was also increased in response to stress, and this increase was attenuated by DHTP. These findings indicate that gonadal hormones influence the reactivity of the hypothalamic-pituitary adrenal axis to stress.

Sn-Mesoporphyrin interdiction of severe hyperbilirubinemia in Jehovah's Witness newborns as an alternative to exchange transfusion.

OBJECTIVE: The religious convictions of parents who are Jehovah's Witness adherents lead them to reject the use of exchange transfusions as therapy for severe hyperbilirubinemia in newborns in whom intensive phototherapy has failed to control this problem. Consequently, physicians caring for such infants may be obliged to initiate legal action to compel use of the procedure when severe hyperbilirubinemia not sufficiently responsive to phototherapy warrants an exchange transfusion. Our goal was to determine if we could use the potent inhibitor of bilirubin production, Sn-Mesoporphyrin (SnMP), to resolve the troubling medical-legal issues in such situations in 2 infants with hemolytic disease of the newborn who required exchange transfusions for severe hyperbilirubinemia but whose Jehovah's Witness parents rejected the procedure. SnMP was administered in a single dose, as in previous studies, at the time when exchange transfusion would have been initiated and plasma bilirubin levels were monitored at close intervals thereafter. METHODS: SnMP is a potent inhibitor of heme oxygenase, the rate-limiting enzyme in catabolism of heme to bilirubin. We found in earlier studies that in single doses of 6 micromol/kg birth weight, SnMP is extremely effective in moderating the course of hyperbilirubinemia and in eliminating the need for supplemental phototherapy in jaundiced newborns. In the 2 cases described, a single dose of SnMP (6 micromol/kg birth weight) was administered intramuscularly to severely jaundiced infants with immune hemolysis at a time when clinical circumstances dictated the need for exchange transfusion. CASE 1: This patient was a preterm male infant (gestational age: 35 5/7 weeks; birth weight: 2790 g) whose plasma bilirubin concentration (PBC) at 1 hour after birth was 5.0 mg/dL. Despite intensive phototherapy with 3 banks of lights and 1 biliblanket, the PBC increased steadily with no diminution in the rate of increase for 75 hours. In view of the problems of immune hemolysis, and prematurity, and the inability of phototherapy to stop progression of hyperbilirubinemia, a decision to carry out an exchange transfusion was made; the decision was, however, rejected by the Jehovah's Witness parents. Pending legal action to compel use of the procedure, a request to this (Rockefeller) laboratory for SnMP was made; its use was approved by the Food and Drug Administration; and the inhibitor was delivered to the physician-in-charge (D.P.M.) in Sioux Falls, South Dakota. The single dose of SnMP was administered to the infant at 75 hours after birth; the course of hyperbilirubinemia before and after the use of the inhibitor is shown in Fig 1. [figure: see text]. CASE 2: This female term infant (gestational age: 38-39 weeks; birth weight: 4140 g) with immune hemolysis was delivered by cesarean section and because of problems related to meconium aspiration required helicopter transfer to the Special Care Nursery in Abilene, Texas, where 10 hours after birth the first PBC was determined to be 18.0 mg/dL. Double-bank phototherapy plus a biliblanket was initiated; a third bank of lights was later ordered. The PBC fluctuated in the ensuing 2 days between 13.8 to 25.8 mg/dL during which suggestive clinical signs of possible bilirubin encephalopathy became manifest. In view of the clinical circumstances and the continued severe hyperbilirubinemia, permission for a double-exchange transfusion was requested. The parents, who were Jehovah's Witness adherents, refused the procedure. While preparing legal action to compel use of the exchange, a request was made to this (Rockefeller) laboratory for use of SnMP to attempt control of hyperbilirubinemia. With FDA approval, the SnMP was delivered to the attending neonatologist (J. R. M.) in Abilene and administered in a single dose (6 micromol/kg birth weight) at 56 hours after birth when the PBC was 19.5 mg/dL. The course of bilirubinemia before and after SnMP use is shown in Fig 2. [figure: see text]. RESULTS AND CONCLUSIONS: The use of SnMP to moderate or prevent the development of severe hyperbilirubinemia in newborns (preterm, near-term, term with high PBCs [15-18 mg/dL], ABO-incompatibility; glucose-6-phosphate dehydrogenase deficiency) has been extensively studied in carefully conducted clinical trials the results of which have been reported earlier. This inhibitor of bilirubin production has demonstrated marked efficacy in moderating the course of hyperbilirubinemia in all diagnostic groups of unconjugated neonatal jaundice. The 2 cases described in this report confirmed the efficacy of SnMP in terminating progression of hyperbilirubinemia in infants in whom phototherapy had failed to sufficiently control the problem and whose parents, for religious reasons, would not permit exchange transfusions. Interdiction of severe hyperbilirubinemia by inhibiting the production of bilirubin with SnMP can be an effective alternative to the use of exchange transfusion in the management of severe newborn jaundice that has not responded sufficiently to light treatment to ease concern about the development of bilirubin encephalopathy.

Targeting acute ischemic stroke with a calcium-sensitive opener of maxi-K potassium channels.

During ischemic stroke, neurons at risk are exposed to pathologically high levels of intracellular calcium (Ca++), initiating a fatal biochemical cascade. To protect these neurons, we have developed openers of large-conductance, Ca++-activated (maxi-K or BK) potassium channels, thereby augmenting an endogenous mechanism for regulating Ca++ entry and membrane potential. The novel fluoro-oxindoles BMS-204352 and racemic compound 1 are potent, effective and uniquely Ca++-sensitive openers of maxi-K channels. In rat models of permanent large-vessel stroke, BMS-204352 provided significant levels of cortical neuroprotection when administered two hours after the onset of occlusion, but had no effects on blood pressure or cerebral blood flow. This novel approach may restrict Ca++ entry in neurons at risk while having minimal side effects.

Cone-beam tomography with a digital camera.

We show that x-ray computer tomography algorithms can be applied with minimal alteration to the three-dimensional reconstruction of visible sources. Diffraction and opacity affect visible systems more severely than x-ray systems. For camera-based tomography, diffraction can be neglected for objects within the depth of field. We show that, for convex objects, opacity has the effect of windowing the angular observation range and thus blurring the reconstruction. For concave objects, opacity leads to nonlinearity in the transformation from object to reconstruction and may cause multiple objects to map to the same reconstruction. In x-ray tomography, the contribution of an object point to a line integral is independent of the orientation of the line. In optical tomography, however, a Lambertian assumption may be more realistic. We derive an expression for the blur function (the patch response) for a Lambertian source. We present experimental results showing cone-beam reconstruction of an incoherently illuminated opaque object.

Acoustic imaging of objects buried in soil.

In this study, we demonstrate an acoustic system for high-resolution imaging of objects buried in soil. Our goal is to image cultural artifacts in order to assess in a rapid manner the historical significance of a potential construction site. We describe the imaging system and present preliminary images produced from data collected from a soil phantom. A mathematical model and associated computer software are developed in order to simulate the signals acquired by the system. We have built the imaging system, which incorporates a single element source transducer and a receiver array. The source and receiver array are moved together along a linear path to collect data. Using this system, we have obtained B-mode images of several targets by using delay-and-sum beamforming, and we have also applied synthetic aperture theory to this problem.

Spatially variant apodization for image reconstruction from partial Fourier data.

Sidelobe artifacts are a common problem in image reconstruction from finite-extent Fourier data. Conventional shift-invariant windows reduce sidelobe artifacts only at the expense of worsened mainlobe resolution. Spatially variant apodization (SVA) was previously introduced as a means of reducing sidelobe artifacts, while preserving mainlobe resolution. Although the algorithm has been shown to be effective in synthetic aperture radar (SAR), it is heuristically motivated and it has received somewhat limited analysis. In this paper, we show that SVA is a version of minimum-variance spectral estimation (MVSE). We then present a complete development of the four types of two-dimensional SVA for image reconstruction from partial Fourier data. We provide simulation results for various real-valued and complex-valued targets and point out some of the limitations of SVA. Performance measures are presented to help further evaluate the effectiveness of SVA.

Tomographic imaging of foam.

The morphology of three-dimensional foams is of interest to physicists, engineers, and mathematicians. It is desired to image the 3-dimensional structure of the foam. Many different techniques have been used to image the foam, including magnetic resonance imaging, and short-focal length lenses. We use a camera and apply tomographic algorithms to accurately image a set of bubbles. We correct for the distortion of a curved plexiglas container using ray-tracing.

High-resolution planetary imaging via spotlight-mode synthetic aperture radar.

We consider the application of a spotlight-mode synthetic aperture radar (SAR) imaging technique to the problem of high-resolution lunar imaging and other related radar astronomy problems. This approach offers improved image quality, compared with conventional processing, at the expense of slightly increased computational effort. Results of the processing of lunar data acquired with the 12.6 cm wavelength radar system at Arecibo Observatory are presented, and compared with the best available published result, by Stacy (1993), which uses focusing techniques from stripmap SAR.

Partial Radon transforms.

This article formally defines partial Radon transforms for functions of more than two dimensions. It shows that a generalized projection-slice theorem exists which connects planar and hyperplanar projections of a function to its Fourier transform. In addition, a general theoretical framework is provided for carrying out n-dimensional backprojection reconstruction in a multistage fashion through the use of the partial Radon transform.

Phenotypic alteration of a human BK (hSlo) channel by hSlobeta subunit coexpression: changes in blocker sensitivity, activation/relaxation and inactivation kinetics, and protein kinase A modulation.

A human homolog of the large-conductance calcium-activated potassium (BK) channel beta subunit (hSlobeta) was cloned, and its effects on a human BK channel (hSlo) phenotype are reported. Coexpression of hSlo and hSlobeta, in both oocytes and human embryonic kidney 293 cells, resulted in increased Ca2+ sensitivity, marked slowing of BK channel activation and relaxation, and significant reduction in slow inactivation. In addition, coexpression changed the pharmacology of the BK channel phenotype: hSlo-mediated currents in oocytes were more sensitive to the peptide toxin iberiotoxin than were hSlo + hSlobeta currents, and the potency of blockade by the alkaloid BK blocker tetrandrine was much greater on hSlo + hSlobeta- mediated currents compared with hSlo currents alone. No significant differences in the response to charybdotoxin or the BK channel opener NS1619 were observed. Modulation of BK channel activity by phosphorylation was also affected by the presence of the hSlobeta subunit. Application of cAMP-dependent protein kinase increased P(OPEN) of hSlo channels, but decreased P(OPEN)of most hSlo + hSlobeta channels. Taken together, these altered characteristics may explain some of the wide diversity of BK channel phenotypes observed in native tissues.

Effects of channel modulators on cloned large-conductance calcium-activated potassium channels.

Through expression of the cloned mouse (mSlo) or human (hSlo) large-conductance (BK) Ca(2+)-activated K+ channel in Xenopus laevis oocytes and HEK 293 cells, we characterized the effects of reported blockers and openers of BK channels to initiate the study of the molecular determinants of BK channel modulation. In oocytes, iberiotoxin and charybdotoxin, peptidyl scorpion toxins, were both equally effective blockers of BK current, although iberiotoxin was significantly more potent than charybdotoxin. The structurally related peptide kaliotoxin was not a potent blocker of BK current. Paxilline, a fungal tremorgenic alkaloid, was an effective but complex blocker of BK current. Tetrandrine, a putative blocker of type II BK channels, and ketamine were relatively ineffective. The putative BK openers NS004 and NS1619, phloretin, niflumic acid, flufenamic acid, and 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) increased BK current in oocytes at microM concentrations; many of these produced biphasic concentration-response relationships. Coapplication of representative blockers and openers revealed several patterns of interaction, including competitive and noncompetitive antagonism. NS1619, niflumic acid, and phloretin were tested by using excised inside-out membrane patches from HEK 293 cells and were found to increase the activity of hSlo BK channels and produce a leftward shift in the G/Gmax-versus-voltage relationship of these channels. These results represent the first comprehensive examination of the molecular pharmacology of BK channels.

Bilateral fetal chylothorax: results of unilateral in utero therapy.

The optimal method for antenatal treatment of pleural effusions from congenital chylothorax unknown. A fetus with bilateral congenital chylothorax and hydrops had a pleural catheter placed in utero on only one side of the fetal chest for 14 days prior to delivery. The fetal hydrops partially resolved. After birth there was significantly less drainage from the pleural space that had been antenatally drained. This case demonstrates potential neonatal advantages of pleuro-amniotic shunt placement.

Polyhydramnios-oligohydramnios in a twin pregnancy complicated by fetal glomerulocystic kidney disease.

Polyhydramnios and oligohydramnios in twin gestation is most often caused by twin-twin transfusion syndrome. Presented is a monozygotic twin pair with polyhydramnios and oligohydramnios, in which both twins had glomerulocystic kidney disease of differing severity. The more severely affected donor twin died of renal failure in the neonatal period. The surviving twin is well following unilateral nephrectomy. This case illustrates the varied spectrum of pathology in glomerulocystic kidney disease.