Karen D. Hendricks-Munoz, M.D.

Splanchnic-cerebral oxygenation ratio as a marker of preterm infant blood transfusion needs
Bailey SM; Hendricks-Munoz KD; Mally P
2011 Feb;52(2):252-60 L, Transfusion
BACKGROUND: Premature neonates often receive red blood cell (RBC) transfusions to improve tissue perfusion and oxygen delivery. Clinical and laboratory indicators used to guide transfusion therapy are inadequate to determine physiologic need with high predictability and transfusions frequently do not result in clinical improvement. The splanchnic-cerebral oxygenation ratio (SCOR) provides insight into overall tissue oxygen sufficiency and can be determined using near-infrared spectroscopy (NIRS). Our aim was to assess the usefulness of SCOR as a marker for transfusion need in preterm infants. STUDY DESIGN AND METHODS: This study was a prospective observational pilot study utilizing NIRS to analyze the SCOR in symptomatic anemic premature neonates receiving RBC transfusions and nontransfused asymptomatic premature neonates with similarly low hemoglobin (Hb) levels. Subject clinical status was determined based on frequency of apnea, bradycardia, pulse-oximetry desaturation events, heart rate, respiratory support, and feeding tolerance. We then assessed for any difference between baseline (pretransfusion) SCOR of 1) symptomatic subjects who improved after transfusion, 2) symptomatic subjects who did not improve, and 3) asymptomatic subjects. RESULTS: The study included 52 subjects (34 transfused, 18 asymptomatic): mean birth weight was 1164 g, mean gestational age was 28.6 weeks, and mean Hb level was 9.0 g/dL. Of 34 transfused subjects, 19 improved (56%). Mean baseline SCOR values were lower in neonates who improved with transfusion, 0.61 +/- 0.22, when compared to those without improvement, 0.75 +/- 0.17, and asymptomatic neonates, 0.77 +/- 0.16 (p = 0.03). Infants with a low baseline SCOR (</=0.73) were more likely to improve after transfusion (likelihood ratio, 2.8; 95% confidence interval, 1.1-6.7). CONCLUSION: SCOR may help identify premature infants who will benefit from RBC transfusion
— id: 138735, year: 2011, vol: 52, page: 252, stat: Journal Article,

Identification of a conserved glycan signature for microvesicles
Batista, Bianca S; Eng, William S; Pilobello, Kanoelani T; Hendricks-Munoz, Karen D; Mahal, Lara K
2011 Oct 7;10(10):4624-4633, Journal of proteome research
Microvesicles (exosomes) are important mediators of intercellular communication, playing a role in immune regulation, cancer progression, and the spread of infectious agents. The biological functions of these small vesicles are dependent on their composition, which is regulated by mechanisms that are not well understood. Although numerous proteomic studies of these particles exist, little is known about their glycosylation. Carbohydrates are involved in protein trafficking and cellular recognition. Glycomic analysis may thus provide valuable insights into microvesicle biology. In this study, we analyzed glycosylation patterns of microvesicles derived from a variety of biological sources using lectin microarray technology. Comparison of the microvesicle glycomes with their parent cell membranes revealed both enrichment and depletion of specific glycan epitopes in these particles. These include enrichment in high mannose, polylactosamine, alpha-2,6 sialic acid, and complex N-linked glycans and exclusion of terminal blood group A and B antigens. The polylactosamine signature derives from distinct glycoprotein cohorts in microvesicles of different origins. Taken together, our data point to the emergence of microvesicles from a specific membrane microdomain, implying a role for glycosylation in microvesicle protein sorting
— id: 138734, year: 2011, vol: 10, page: 4624, stat: Journal Article,

Cyclic GMP protects endothelial progenitors from oxidative stress
Curatola, Anna Maria; Xu, Jie; Hendricks-Munoz, Karen D
2011 Sep;14(3):267-279, Angiogenesis
Endothelial progenitor cells (EPCs) play a critical role in the repair of damaged blood vessels and/or in the growth of new ones in ischemic tissues. Elevated levels of oxygen radicals, which accumulate in the ischemic tissue, could compromise the angiogenic potential of EPCs. To determine if oxidative stress alters the angiogenic response of EPCs and to identify possible cellular targets that protect EPCs from the damaging effects of oxidative stress, we have investigated vascular development in embryonic bodies (EBs) under hyperoxic conditions. Murine EBs at differentiaton day 2 were cultured for 3 days under normoxic (21% O(2)) or hyperoxic (60% O(2)) conditions. Hyperoxic EBs showed a moderate reduction in Pecam-1, Vegfr-2, eNOS and Tie2 mRNA levels compared to normoxic EBs. However, immunostaining of hyperoxic EBs with antibodies against PECAM-1 after 1 week recovery at room air revealed a defective vasculature completely deficient in branches, while normoxic EBs developed a normal vascular plexus. Oxygen-induced defective vascular development correlated with a dramatic decrease in soluble guanylyl cyclase, phosphodiesterase (Pde) 4B and Pde4C mRNAs. Oxidative stress did not affect the expression of adenylyl cyclase 6 and Pde5. The abnormal vascular development caused by hyperoxia was reverted by pharmacological treatments that increased cGMP levels, such as 8-bromo-cGMP or 4-{[3',4'-(methylenedioxy)benzyl]amino}-6-methoxyquinazoline, a specific inhibitor of PDE5. These results indicated that oxidative stress inhibits vascular development from EPCs through its effects on levels of cyclic nucleotides and suggested that therapies that target cyclic nucleotide turnover may be useful in protecting vascular repair under oxidative conditions
— id: 136632, year: 2011, vol: 14, page: 267, stat: Journal Article,

Neonatal red blood cell transfusions: searching for better guidelines
Kasat, Kavita; Hendricks-Munoz, Karen D; Mally, Pradeep V
2011 Jan;9(1):86-94, Blood transfusion = Trasfusione del sangue
BACKGROUND: Packed red blood cell (RBC) transfusions are often administered to patients in the neonatal intensive care unit. The purpose of this study was to determine whether current blood transfusion guidelines are as useful as care givers' perception in identifying patients in need of a packed RBC transfusion. DESIGN AND METHODS: Health care providers were asked to complete a pre- and post-transfusion survey on neonates receiving a packed RBC transfusion. These patients were divided into three groups based on reasons for transfusion: (i) guidelines; (ii) care-givers' perceptions of need for packed RBC transfusion; or (iii) both. These three groups were further subdivided into two cohorts according to whether they had a clinical improvement or not. Demographic data and clinical variables were compared between the groups. RESULTS: Seventy-eight care-givers were surveyed. Eighteen patients (23%) were transfused based on guidelines, 36 (46%) based on care givers' perception and 24 (31%) based on both. Neonates transfused based on guidelines alone were more likely to have received the transfusion in the first week of life, had a higher pre-transfusion haematocrit, were less symptomatic and had a higher trend to require mechanical ventilation. Neonates transfused based on caregivers' perception were more likely to be on non-invasive ventilatory support and were more symptomatic. Neonates who improved after a transfusion had a lower pre-transfusion haematocrit (p=0.02), were more symptomatic (p=0.01) and were more likely to be on non-invasive ventilatory support (p=0.002) when compared to the group without a clinical improvement. The group without improvement had an increase in oxygen requirement (+2.8+/-6.4) after the transfusion (p=0.0004). Tachycardia was the most sensitive predictor of a benefit from packed RBC transfusion [OR 6.48: p=0.005]. DISCUSSION: Guidelines on when to transfuse stable growing neonates with packed RBC should be re-evaluated to include more care giver judgement and perhaps be more restrictive for critically ill neonates
— id: 134141, year: 2011, vol: 9, page: 86, stat: Journal Article,

Current management of the infant who presents with neonatal encephalopathy
Wachtel, Elena V; Hendricks-Munoz, Karen D
2011 May-Jun;41(5):132-153, Current problems in pediatric & adolescent health care
Neonatal encephalopathy after perinatal hypoxic-ischemic insult is a major contributor to global child mortality and morbidity. Brain injury in term infants in response to hypoxic-ischemic insult is a complex process evolving over hours to days, which provides a unique window of opportunity for neuroprotective treatment interventions. Advances in neuroimaging, brain monitoring techniques, and tissue biomarkers have improved the ability to diagnose, monitor, and care for newborn infants with neonatal encephalopathy as well as predict their outcome. However, challenges remain in early identification of infants at risk for neonatal encephalopathy, determination of timing and extent of hypoxic-ischemic brain injury, as well as optimal management and treatment duration. Therapeutic hypothermia is the most promising neuroprotective intervention to date for infants with moderate to severe neonatal encephalopathy after perinatal asphyxia and has currently been incorporated in many neonatal intensive care units in developed countries. However, only 1 in 6 babies with encephalopathy will benefit from hypothermia therapy; many infants still develop significant adverse outcomes. To enhance the outcome, specific diagnostic predictors are needed to identify patients likely to benefit from hypothermia treatment. Studies are needed to determine the efficacy of combined therapeutic strategies with hypothermia therapy to achieve maximal neuroprotective effect. This review focuses on important concepts in the pathophysiology, diagnosis, and management of infants with neonatal encephalopathy due to perinatal asphyxia, including an overview of recently introduced novel therapies
— id: 132577, year: 2011, vol: 41, page: 132, stat: Journal Article,

Packed red blood cell transfusion increases regional cerebral and splanchnic tissue oxygen saturation in anemic symptomatic preterm infants
Bailey, Sean M; Hendricks-Munoz, Karen D; Wells, John T; Mally, Pradeep
2010 Jun;27(6):445-453, American journal of perinatology
Preterm infants often receive multiple packed red blood cell (PRBC) transfusions that are intended to improve tissue oxygen levels. Near-infrared spectroscopy (NIRS) monitors regional cerebral tissue oxygen saturation (CrSO(2)) and splanchnic tissue oxygen saturation (SrSO(2)). Before such technology can be employed in neonatal transfusion management, it must first be established that transfusions result in an increase in tissue oxygen saturation. This prospective, observational study used NIRS to determine if PRBC transfusions increase the CrSO(2) and SrSO(2) of symptomatic anemic premature neonates. CrSO(2) and SrSO(2) values were compared for 20-minute duration immediately before, during, immediately after, and 12 hours after transfusion. As a secondary objective, CrSO(2) and SrSO(2) values were correlated with hemoglobin (Hgb) levels. One-way analysis of variance and Pearson correlation statistical tests were used for analysis. A statistically significant increase in CrSO(2) and SrSO(2) values were observed after transfusion in the 30 subjects included (CrSO(2): 62.8 +/- 1.6, 65.6 +/- 1.7, 68.0 +/- 1.3, 67.6 +/- 1.4, P < 0.001 and SrSO(2): 41.3 +/- 2.2, 46.7 +/- 3.0, 52.1 +/- 2.8, 48.2 +/- 2.5, P < 0.001). No correlation was found between CrSO(2) or SrSO(2) and Hgb values. NIRS identified increases in CrSO(2) and SrSO(2) in preterm neonates after PRBC transfusions and has the potential to become incorporated into neonatal transfusion management paradigms
— id: 109789, year: 2010, vol: 27, page: 445, stat: Journal Article,

Factors that influence neonatal nursing perceptions of family-centered care and developmental care practices
Hendricks-Munoz, Karen D; Louie, Moi; Li, Yihong; Chhun, Nok; Prendergast, Carol C; Ankola, Pratibha
2010 Mar;27(3):193-200, American journal of perinatology
The purpose of this study was to analyze the association of developmental care education and training and neonatal intensive care unit (NICU) developmental team structure in promoting neonatal nursing perception and beliefs of key characteristics of family-centered care (FCC), developmental care, and kangaroo mother care (KMC). A 24-item Likert scale survey of specific perceptions and beliefs of aspects of FCC, KMC, and developmental care characteristics was conducted with 59 neonatal nurses from three distinct level III NICUs in New York City where nurses had undergone recent reeducation and developmental team configuration. There was no difference in nursing beliefs of technical developmental care approaches to infant care at all three sites. Neonatal nurses who were supported by an on-site infant developmental specialist were more likely to have strong beliefs related to the affective areas of FCC and the technique of KMC. FCC and clinical care approaches that include a high level of parental participation such as KMC in the NICU are likely to be facilitated by a comprehensive approach of continuing training as well as a team structure that includes dedicated, specially trained infant developmental specialist personnel
— id: 107764, year: 2010, vol: 27, page: 193, stat: Journal Article,

Congenital diaphragmatic hernia: endothelin-1, pulmonary hypertension, and disease severity
Keller, Roberta L; Tacy, Theresa A; Hendricks-Munoz, Karen; Xu, Jie; Moon-Grady, Anita J; Neuhaus, John; Moore, Phillip; Nobuhara, Kerilyn K; Hawgood, Sam; Fineman, Jeffrey R
2010 Aug 15;182(4):555-561, American journal of respiratory & critical care medicine
RATIONALE: Endothelin-1 (ET1) is dysregulated in pulmonary hypertension (PH). It may be important in the pathobiology of congenital diaphragmatic hernia (CDH). OBJECTIVES: We hypothesized that ET1 levels in the first month would be higher in infants with CDH who subsequently expired or were discharged on oxygen (poor outcome). We further hypothesized that ET1 levels would be associated with concurrent severity of PH. METHODS: We sampled plasma at 24 to 48 hours, and 1, 2, and 4 weeks of age in 40 prospectively enrolled newborns with CDH. We performed echocardiograms to estimate pulmonary artery pressure at less than 48 hours of age and weekly to 4 weeks. PH was classified in relationship to systemic blood pressure (SBP): less than 2/3 SBP, 2/3 SBP-systemic is related to pressure, or systemic-to-suprasystemic pressure. MEASUREMENTS AND MAIN RESULTS: ET1 levels at 1 and 2 weeks were higher in infants with poor outcome compared with infants discharged on room air (median and interquartile range: 27.2 [22.6, 33.7] vs. 19.1 [16.1, 29.5] pg/ml, P = 0.03; and 24.9 [17.6, 39.5] vs. 17.4 [13.7, 21.8] pg/ml, P = 0.01 at 1 and 2 weeks, respectively). Severity of PH was significantly associated with increasing ET1 levels at 2 weeks (16.1 [13.7, 21.8], 21.0 [17.4, 31.1], and 23.6 [21.9, 39.5] pg/ml for increasing PH class, P = 0.03). Increasing severity of PH was also associated with poor outcome at that time (P = 0.001). CONCLUSIONS: Infants with CDH and poor outcome have higher plasma ET1 levels and severity of PH than infants discharged on room air. Severity of PH is associated with ET1 levels
— id: 138736, year: 2010, vol: 182, page: 555, stat: Journal Article,

Clinical issues in the management of late preterm infants
Mally, Pradeep V; Bailey, Sean; Hendricks-Munoz, Karen D
2010 Oct;40(9):218-233, Current problems in pediatric & adolescent health care
Prematurity is defined as birth before 37 weeks of gestation and is the major determinant of morbidity and mortality in newborns. The gestational ages known as near term or late preterm represent about 75% of preterm births and are the fastest growing subgroups of premature infants. These infants range in gestational age from 34 0/7 to 36 6/7 weeks and are at greater risk of morbidity, such as respiratory complications, temperature instability, hypoglycemia, kernicterus, feeding problems, neonatal intensive care unit admissions, and adverse neurological sequelae when compared with term infants. Long-term neurological and school-age outcomes of late preterm infants are concerns of major public health importance because even a minor increase in the rate of neurological disability and scholastic failure in this group can have a huge impact on the health care and educational systems. There is an urgent need to educate health care providers and parents about the vulnerability of late preterm infants, who are in need of diligent monitoring and care during the initial hospital stay and a comprehensive follow-up plan for post neonatal and long-term evaluations. Clinicians involved in the day-to-day care of late preterm infants, as well as those developing guidelines and recommendations, would benefit from having a clear understanding of the potential differences in risks faced by these infants, compared with their more mature counterparts
— id: 122106, year: 2010, vol: 40, page: 218, stat: Journal Article,

Maternal periodontal disease, pregnancy, and neonatal outcomes
Dasanayake, Ananda P; Gennaro, Susan; Hendricks-Munoz, Karen D; Chhun, Nok
2008 Jan-Feb;33(1):45-49, MCN: The American Journal of Maternal/Child Nursing
The purpose of this article is to review the current literature on the association between maternal periodontal disease and poor pregnancy and neonatal outcomes and outline the role nurses can play in improving the oral health of pregnant women. Maternal periodontal disease is linked to preterm birth, low birthweight, and preterm low birthweight, but treatment of periodontal disease during pregnancy has been shown to be safe and effective. Nurses, nurse practitioners, and nurse-midwives are in a position to educate pregnant women on the benefits of good oral health and identify and refer women who are in need of dental care for treatment
— id: 96617, year: 2008, vol: 33, page: 45, stat: Journal Article,

Quantification of impulse experienced by neonates during inter- and intra-hospital transport measured by biophysical accelerometery
Shah, Shetal; Rothberger, Adina; Caprio, Martha; Mally, Pradeep; Hendricks-Munoz, Karen
2008 ;36(1):87-92, Journal of perinatal medicine
BACKGROUND: Transport of premature infants incurs transfer-related morbidity, including intraventricular hemorrhage, a contributing factor to cerebral palsy. The force transmitted to the neonate during transport as a consequence of motion may be implicated in the increased morbidity in this population. Morbidity may occur via direct concussive force to a vulnerable germinal matrix, induction of an inflammatory reaction, or via transient desaturation via extubation. This transmitted force, measured as accelerations per unit time (impulse), is not well characterized. Any modification of a neonatal transporter which increases the time for a neonate in motion to come to rest may decrease the impulse experienced by the infant. OBJECTIVE: The objective of the study was to quantify the magnitude of impulse experienced by neonates during inter- and intra-hospital transport using a novel biophysical model and determine whether a specialized air-foam mattress can reduce the transmitted impulse on the neonate. METHODS: Five roundtrip trials were conducted for a transported neonate using a standard medical ambulance and transport isolette outfitted with an air-foam mattress. During the trials, measurements were made per second in the X (front-to-back), Y (side-to-side), and Z (up-and-down) planes using a computerized accelerometer attached to a neonatal resuscitation mannequin. Results were integrated over the trial time in each dimension to yield a measure of impulse (acceleration-per-unit-time). Total impulse for the trial was calculated. A second design included five trials from the delivery room to the NICU utilizing four different transport configurations with a standard neonatal isolette outfitted with a gel pillow, air-foam mattress, and air-foam mattress with gel pillow. RESULTS: Mean impulse for the transport model was statistically greater than at rest. In the X and Z dimensions, the mean impulse was significantly lower using the air-foam mattress. The impulse of the Z dimension with the air-foam mattress did not differ from that experienced by the experimental model at rest. For the intra-hospital trial, all experimental set-ups produced significantly less cumulative impulse than the standard isolette, though in each specific dimension, no significant differences were noted. For cumulative impulse, no significant differences between any of the three experimental designs were observed. A trend toward decreased transport time was seen with the addition of the air-foam mattress and gel pillow. CONCLUSIONS: The mechanical trauma induced by transport can be measured and quantified using this system. Neonates transported with the air-foam mattress experienced less impulse in the front-to-back and up-and-down dimensions. For transports between the delivery room and NICU, neonates transported using the air-foam mattress and gel pillow experienced significantly less total impulse
— id: 135331, year: 2008, vol: 36, page: 87, stat: Journal Article,

Barriers to provision of developmental care in the neonatal intensive care unit: neonatal nursing perceptions
Hendricks-Munoz, Karen D; Prendergast, Carol C
2007 Feb;24(2):71-77, American journal of perinatology
The role of the neonatal nurse is vital for the successful implementation of developmental care and the provision of an optimal neonatal intensive care unit (NICU) environment. The goal was to identify nurses' perceived barriers to implementation or improving developmental care in their NICUs. Nursing perceptions related to barriers for implementing developmental care were assessed using a 12-point questionnaire during two New York City Neonatal Nursing regional conferences. One hundred forty-six (86%) of 170 nurses representing 24 regional hospitals returned the survey. Developmental care was viewed as essential by 136 nurses (93%), yet 125 nurses (86%) believed that their NICU was not providing optimal developmental care. Light and sound standards were viewed as important to providing care by 71% and 91% of respondents, respectively, yet only four NICUs (3%) had light and sound meters to identify or standardize this environmental source of pain. As a group, the perceived barriers to provision of optimal developmental care in order of decreasing importance were staff nurses and staff physicians (53%) > NICU funds (42%) > physician leadership (37%) > facility limitations (31%) > registered nurse leadership (25%). In contrast, 90% of nurses whose NICU did not use developmental multidisciplinary team meetings or developmental care champions or advocates were significantly more likely to identify nursing or physician colleagues as barriers to implementing or improving developmental care, compared with 38% of nurses whose NICU used such activities ( P < 0.001). Developmental care is perceived by the neonatal nurse as a vital component to the care provided in the NICU. Use of simple light and sound measures may enhance perception of providing an optimal NICU environment. Neonatal nurses perceived barriers to care are often attributed to neonatal staff nursing and physician colleagues. This perception is decreased considerably in those NICUs in which multidisciplinary team meetings or champions are used to address the needs of caregivers by providing developmental care strategies
— id: 71418, year: 2007, vol: 24, page: 71, stat: Journal Article,

Transgenic expression of a dominant negative K(ATP) channel subunit in the mouse endothelium: effects on coronary flow and endothelin-1 secretion
Malester, Brian; Tong, Xiaoyong; Ghiu, Ioana; Kontogeorgis, Andrianos; Gutstein, David E; Xu, Jie; Hendricks-Munoz, Karen D; Coetzee, William A
2007 Jul;21(9):2162-2172, FASEB journal
K(ATP) channels are involved in regulating coronary function, but the contribution of endothelial K(ATP) channels remains largely uncharacterized. We generated a transgenic mouse model to specifically target endothelial K(ATP) channels by expressing a dominant negative Kir6.1 subunit only in the endothelium. These animals had no obvious overt phenotype and no early mortality. Histologically, the coronary endothelium in these animals was preserved. There was no evidence of increased susceptibility to ergonovine-induced coronary vasospasm. However, isolated hearts from these animals had a substantially elevated basal coronary perfusion pressure. The K(ATP) channel openers, adenosine and levcromakalim, decreased the perfusion pressure whereas the K(ATP) channel blocker glibenclamide failed to produce a vasoconstrictive response. The inducible endothelial nitric oxide pathway was intact, as evidenced by vasodilation caused by bradykinin. In contrast, basal endothelin-1 release was significantly elevated in the coronary effluent from these hearts. Treatment of mice with bosentan (endothelin-1 receptor antagonist) normalized the coronary perfusion pressure, demonstrating that the elevated endothelin-1 release was sufficient to account for the increased coronary perfusion pressure. Pharmacological blockade of K(ATP) channels led to elevated endothelin-1 levels in the coronary effluent of isolated mouse and rat hearts as well as enhanced endothelin-1 secretion from isolated human coronary endothelial cells. These data are consistent with a role for endothelial K(ATP) channels to control the coronary blood flow by modulating the release of the vasoconstrictor, endothelin-1
— id: 73407, year: 2007, vol: 21, page: 2162, stat: Journal Article,

Rationale for the administration of acellular pertussis vaccine to parents of infants in the neonatal intensive care unit
Shah, S; Caprio, M; Mally, P; Hendricks-Munoz, K
2007 Jan;27(1):1-3, Journal of perinatology
Pertussis infections in the United States are increasing as a consequence of waning immunity and increased surveillance. Those most at-risk of mortality include infants less than 6 months of age and premature infants. The 2006 immunization schedule emphasizes an adolescent pertussis booster at 12 years of age. However, of concern is the current generation of parents and grandparents who will still be un-immunized and therefore, available vectors of pertussis to vulnerable neonates. Given the proximity of parents to medical care in the Neonatal Intensive Care Unit (NICU), and the potential for severe disease in their children, NICU personnel should consider administration of acellular pertussis vaccine to parents of hospitalized infants
— id: 70828, year: 2007, vol: 27, page: 1, stat: Journal Article,

Administration of inactivated trivalent influenza vaccine to parents of high-risk infants in the neonatal intensive care unit
Shah, Shetal I; Caprio, Martha; Hendricks-Munoz, Karen
2007 Sep;120(3):e617-e621, Pediatrics
OBJECTIVE: Infants who are younger than 6 months and have influenza demonstrate significant morbidity and mortality. Trivalent inactivated influenza vaccine is indicated for parents and household contacts of these infants; however, the influenza vaccination rate in this population is estimated at 30%. The objective of this study was to determine the feasibility of trivalent inactivated influenza vaccine administration to parents in a tertiary-care, level III NICU and measure the effect of this program on vaccination rates among parents of this high-risk population. METHODS: For a 4-month period during influenza season, all parents of admitted patients were informed of the risks and benefits of trivalent inactivated influenza vaccine by placing an information letter at their infant's bedside. All staff were educated about the dangers of influenza and instructed to reinforce the need to obtain vaccination. Parents were screened, provided medical consent, and, when eligible, were immunized at their infant's bedside. RESULTS: During the study period, 158 children (273 parents) were admitted to the NICU with gestational ages ranging from 24 to 41 weeks; 220 parents (130 infants) were offered the vaccine, and 40 parents received the vaccine from their obstetrician. Overall vaccination rate was 95% (209 parents). A total of 23% of the parent population had never received trivalent inactivated influenza vaccine, despite having previous indications for immunization (smoking, asthma, or other children younger than 23 months, the indicated age for parental vaccination at the time of this study); 75% of the population received trivalent inactivated influenza vaccine for the first time. The 28 infants whose parents were not offered vaccine spent <72 hours in the NICU. CONCLUSIONS: Administration of trivalent inactivated influenza vaccine in the NICU is an effective means of increasing vaccination rates in parents of this population. In addition, the improved access and convenience allow for an increase in first-time vaccination of parents who were previously eligible to receive trivalent inactivated influenza vaccine but were never immunized
— id: 129066, year: 2007, vol: 120, page: e617, stat: Journal Article,

Computer-based multivariate economic analysis of neonatal-intensive-care-unit-based influenza vaccine administration to parents in a low-socio-economic, urban setting
Shah, Shetal I; Caprio, Martha; Sen, Alpana; Hendricks-Munoz, Karen
2007 May;2(3):158-164, Journal of hospital medicine
OBJECTIVE: Trivalent inactivated influenza vaccine has been shown to reduce the number of influenza-related outpatient visits and hospitalizations of children up to 24 months of age. The American Academy of Pediatrics, Centers for Disease Control, and Advisory Committee on Immunization Practices recommend that the influenza vaccine be administered to the first-person contacts of infants less than 6 months of age. However, the economic implications of increasing immunization rates by using the neonatal intensive care unit (NICU) as an arena to capture the parents of these infants has not been fully evaluated. We sought to examine the direct and indirect costs of a program to administer the influenza vaccine to parents in the NICUs of a cohort of tertiary-care units primarily serving a low socioeconomic population. METHODS: The probabilities of infants being hospitalized because of infection from contact and of the efficacy of prophylaxis used in the present study were based on published results where possible, with an estimated 10% reduction in hospitalization of patients whose parents had received the vaccine. Variables in the 3- and 4-tiered analyses included chronic lung disease status, estimation if patients had siblings, vaccination status of siblings, seroconversion rate of vaccine, and parental vaccination status. Two thousand six hundred and thirty-two patients were analyzed using 2003 admission data from the New York City Regional Perinatal Center, which encompasses 11 level III NICUs. Hospitalization costs, indirect costs, and outpatient costs were assessed using previously published standard calculations. RESULTS: On the basis of this computer model, costs were $188 per patient per influenza season, including $6.80 per patient in outpatient costs. Administration of an NICU-based influenza vaccine increased costs to $200 per patient per influenza season, but decreased outpatient costs to $1.40 per patient. For cost savings to equal costs of vaccine administration, there must be either a 20% reduction in influenza hospitalizations of NICU patients or an increase in the sample size per influenza season to 4000 patients. CONCLUSIONS: The cost of administration of the influenza vaccine to parents of NICU patients is higher than the financial burden of influenza in this population as long as the sibling immunization rate remains low. Cost savings do not occur until the treated cohort increases to 4000 patients or the incidence of lung disease in this population increases. Further studies are needed to validate the cost savings of this mode and more accurately assess the financial savings
— id: 102608, year: 2007, vol: 2, page: 158, stat: Journal Article,

The infant of the diabetic mother
Hendricks-Munos KD
Current pediatric therapy Edinburgh : Elsevier Saunders, 2006,
— id: 4063, year: 2006, vol: , page: 263, stat: Chapter,

Family centered and developmental care: improving outcome in the NICU
Hendricks-Munoz KD; Prendergast CC
Fetal & neonatal secrets Edinburgh : Elsevier Mosby, 2006,
— id: 4064, year: 2006, vol: , page: ?, stat: Chapter,

Nitric oxide-endothelin-1 interactions after surgically induced acute increases in pulmonary blood flow in intact lambs
Oishi, Peter; Azakie, Anthony; Harmon, Cynthia; Fitzgerald, Robert K; Grobe, Albert; Xu, Jie; Hendricks-Munoz, Karen; Black, Stephen M; Fineman, Jeffrey R
2006 May;290(5):H1922-H1932, American journal of physiology. Heart & circulatory physiology
Several congenital heart defects require surgery that acutely increases pulmonary blood flow (PBF). This can lead to dynamic alterations in postoperative pulmonary vascular resistance (PVR) and can contribute to morbidity and mortality. Thus the objective of this study was to determine the role of nitric oxide (NO), endothelin (ET)-1, and their interactions in the alterations of PVR after surgically induced increases in PBF. Twenty lambs underwent placement of an aortopulmonary vascular graft. Lambs were instrumented to measure vascular pressures and PBF and studied for 4 h. Before and after shunt opening, lambs received an infusion of saline (n = 9), tezosentan, an ETA- and ETB -receptor antagonist (n = 6), or Nomega-nitro-L-arginine (L-NNA), a NO synthase (NOS) inhibitor (n = 5). In control lambs, shunt opening increased PBF by 117.8% and decreased PVR by 40.7% (P < 0.05) by 15 min, without further changes thereafter. Plasma ET-1 levels increased 17.6% (P < 0.05), and total NOS activity decreased 61.1% (P < 0.05) at 4 h. ET-receptor blockade (tezosentan) prevented the plateau of PBF and PVR, such that PBF was increased and PVR was decreased compared with controls at 3 and 4 h (P < 0.05). These changes were associated with an increase in total NOS activity (+61.4%; P < 0.05) at 4 h. NOS inhibition (L-NNA) after shunt placement prevented the sustained decrease in PVR seen in control lambs. In these lambs, PVR decreased by 15 min (P < 0.05) but returned to baseline by 2 h. Together, these data suggest that surgically induced increases in PBF are limited by vasoconstriction, at least in part by an ET-receptor-mediated decrease in lung NOS activity. Thus NO appears to be important in maintaining a reduction in PVR after acutely increased PBF
— id: 66836, year: 2006, vol: 290, page: H1922, stat: Journal Article,

Inhaled nitric oxide induced NOS inhibition and rebound pulmonary hypertension: a role for superoxide and peroxynitrite in the intact lamb
Oishi, Peter; Grobe, Albert; Benavidez, Eileen; Ovadia, Boaz; Harmon, Cynthia; Ross, Gregory A; Hendricks-Munoz, Karen; Xu, Jie; Black, Stephen M; Fineman, Jeffrey R
2006 Feb;290(2):L359-L366, American journal of physiology. Lung cellular & molecular physiology
Previous in vivo studies indicate that inhaled nitric oxide (NO) decreases nitric oxide synthase (NOS) activity and that this decrease is associated with significant increases in pulmonary vascular resistance (PVR) upon the acute withdrawal of inhaled NO (rebound pulmonary hypertension). In vitro studies suggest that superoxide and peroxynitrite production during inhaled NO therapy may mediate these effects, but in vivo data are lacking. The objective of this study was to determine the role of superoxide in the decrease in NOS activity and rebound pulmonary hypertension associated with inhaled NO therapy in vivo. In control lambs, 24 h of inhaled NO (40 ppm) decreased NOS activity by 40% (P<0.05) and increased endothelin-1 levels by 64% (P<0.05). Withdrawal of NO resulted in an acute increase in PVR (60.7%, P<0.05). Associated with these changes, superoxide and peroxynitrite levels increased more than twofold (P<0.05) following 24 h of inhaled NO therapy. However, in lambs treated with polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) during inhaled NO therapy, there was no change in NOS activity, no increase in superoxide or peroxynitrite levels, and no increase in PVR upon the withdrawal of inhaled NO. In addition, endothelial NOS nitration was 18-fold higher (P<0.05) in control lambs than in PEG-SOD-treated lambs following 24 h of inhaled NO. These data suggest that superoxide and peroxynitrite participate in the decrease in NOS activity and rebound pulmonary hypertension associated with inhaled NO therapy. Reactive oxygen species scavenging may be a useful therapeutic strategy to ameliorate alterations in endogenous NO signaling during inhaled NO therapy
— id: 66837, year: 2006, vol: 290, page: L359, stat: Journal Article,

A computer-based multivariate, economic analysis of neonatal intensive-care-unit-based influenza vaccine administration to parents in a hospitalist setting
Shah SI; Caprio M; Hendricks-Munoz K
2006 ;1(Suppl. 2):25-25 #49, Journal of hospital medicine
— id: 66851, year: 2006, vol: 1, page: 25, stat: Journal Article,

Administration of inactivated trivalent influenza vaccine (TIV) to parents of high-risk infants in the neonatal intensive care unit (NICU): a novel strategy to increase vaccination rates
Shah SI; Caprio M; Hendricks-Munoz K
2006 ;1(Suppl. 2):47-47 #82, Journal of hospital medicine
— id: 66852, year: 2006, vol: 1, page: 47, stat: Journal Article,

Estimating peak inspiratory pressure to compensate for endotracheal tube length at neonatal ventilation settings in SIMV
Shah SI; Hendricks-Munoz K; Mally P
2006 ;42(1):34-38, Canadian journal of respiratory therapy : CJRT = Revue canadienne de la therapie respiratoire : RCTR
Introduction: Endotracheal tubes are shortened to various lengths to prevent tube obstruction (kinking). The degree of this remaining length in the ET tube contributes increased resistance and dead space in the mechanical ventilatory circuit. Knowing ET tube resistance, at laminar flow, is inversely related to the fourth power of the radius (Poiseuille's Law) of the tube and proportional to length, additional work of breathing is created at different tube lengths. Neonates are at high risk for lobar atelectasis and congenital lung abnormalities, which reduce the lung available for gas exchange and if not acutely compensated for, can cause significant barotrauma to the remaining, intact lung. Yet, the relation of these variables and their clinical impact has not yet been mathematically defined. Hypothesis: For neonates with small ET tube diameters, there is a linear mathematical relationship between ET tube length and the positive inspiratory pressure (PIP) required to sustain tidal volume. These relationships can be derived graphically and are described by the equation for a line: y = mx + b. (where m equals the slope of a linear plot of positive inspiratory pressure versus ET length and b is set to the positive end expiratory pressure). There also exists a linear relationship between the lobar volume lost which can be described by the same equation on a graph of tidal volume vs. percentage of isolated atelectasis. Methods: Four endotracheal tubes ranging from 2.5mm to 4.0mm in diameter were shortened at one centimeter intervals and the pressure required by a mechanical ventilator in a pressure regulated, volume control mode (with a positive end expiratory pressure of 5ml H<inf>2</inf>O and without pressure support) to generate a tidal volume of 10ml was monitored in a synthetic, pre-formed plastic respiratory test lung with normal lung compliance (Cd<inf>2</inf>O/Cd of 0.94). Successive measurements at each tube length were sampled in each of three combined trials, the average of which used for calculations. Lobar parenchymal lung losses were simulated by external compression of the compliant lung model using a 3.0 mm tube at 8cm using ventilatory settings of PIP 15, PEEP 5. Tidal volume measurements were made using the calibrated Pneumotac of a VIP GOLD ventilator (ViaSys, California, USA). Results: For endotracheal tubes of 2.5mm, a graphical linear relationship between tube length and pressure was observed using the least squares method as described by the equation: PIP = 0.67 ETL + PEEP (Positive Inspiratory Pressure equals 0.67 multiplied by Endotracheal Tube Length plus Positive End Expiratory Pressure) For ET tubes of 3.0 mm the equation described was: PIP = 0.5 ETL = PEEP (Positive Inspiratory Pressure equals 0.5 multiplied by Endotracheal Tube Length plus Positive End Expiratory Pressure) For patients with lobar lung loss due to congenital malformation or atelectasis: Tidal Volume Lost = 0.04 (Percentage of lobar loss) + Tidal Volume Measured at PEEP (3.5 cm3 in this model). Conclusions: For neonatal infants with ET tubes of small diameters but with acceptable lung compliance, small increases in pressure may be needed to overcome intrinsic resistance of the ET tube and deliver adequate tidal volume. Further studies are needed to observe if these changes are clinically significant or are maintained in a poorly compliant lung model
— id: 64074, year: 2006, vol: 42, page: 34, stat: Journal Article,

Retinal blood vessels develop in response to local VEGF-A signals in the absence of blood flow
Curatola, Anna Maria; Moscatelli, David; Norris, Asma; Hendricks-Munoz, Karen
2005 Aug;81(2):147-158, Experimental eye research
The role of hemodynamic forces and other signals from circulating blood in guiding the development of the retinal vasculature was examined by following the growth of these vessels in organ cultures. Retinal vascular development in organ cultures was monitored by immunofluorescent staining of retinal whole-mounts using antibodies against ICAM-2, a specific marker for endothelial cells and by vascular adenosine disphosphatase activity. Under culture conditions, the retinal vasculature from mice at postnatal day 3 (P3) grew from the optic nerve area to the edge of the retina in a manner similar to that observed in vivo. Both inner and outer vascular plexuses formed in retinal explants. Within the first few days of organ culture, the initial uniform meshwork of blood vessels was reorganized into arterioles, venules, and capillaries. As in animals, the initial retinal vascular plexus contained abundant vessels, and afterward some vessels regressed leading to the formation of a mature vascular bed. Changes in vascular density due to blood vessel growth and remodeling were confirmed by RT-PCR and Western blot analyses of ICAM-2 mRNA and protein levels, respectively. In addition, during in vitro retinal vascularization, arterioles acquired mural cell coverage, as shown by positive staining for alpha-smooth muscle actin. Thus, blood flow and blood-derived signals were not required for the development and maturation of retinal vessels. In contrast, stability of blood vessels in retinal explants was tightly regulated by endogenous levels of vascular endothelial growth factor-A (VEGF-A). VEGF-A was expressed in the explants throughout the culture period, and addition of neutralizing antibodies against VEGF-A to the organ culture caused a severe regression of blood vessels from the vascular front toward the optic nerve. In contrast, addition of anti-FGF-2 antibodies had no effect on the developing vasculature. Thus, retinal vascular development is dependent on local VEGF-A signals rather than systemic signals
— id: 58065, year: 2005, vol: 81, page: 147, stat: Journal Article,

Endothelial alterations during inhaled NO in lambs with pulmonary hypertension: implications for rebound hypertension
Ross, Gregory A; Oishi, Peter; Azakie, Anthony; Fratz, Sohrab; Fitzgerald, Robert K; Johengen, Michael J; Harmon, Cynthia; Hendricks-Munoz, Karen; Xu, Jie; Black, Stephen M; Fineman, Jeffrey R
2005 Jan;288(1):L27-L35, American journal of physiology. Lung cellular & molecular physiology
Clinically significant increases in pulmonary vascular resistance (PVR) have been noted upon acute withdrawal of inhaled nitric oxide (iNO). Previous studies in the normal pulmonary circulation demonstrate that iNO increases endothelin-1 (ET-1) levels and decreases endogenous nitric oxide synthase (NOS) activity, implicating an endothelial etiology for the increase in resistance upon iNO withdrawal. However, the effect of iNO on endogenous endothelial function in the clinically relevant pulmonary hypertensive circulation is unknown. The objective of this study was to determine the effects of iNO on endogenous NO-cGMP and ET-1 signaling in lambs with preexisting pulmonary hypertension secondary to increased pulmonary blood flow. Eight fetal lambs underwent in utero placement of an aortopulmonary vascular graft (shunt lambs). After delivery (4 wk), the shunt lambs were mechanically ventilated with iNO (40 ppm) for 24 h. After 24 h of inhaled NO, plasma ET-1 levels increased by 34.8% independently of changes in protein levels (P < 0.05). Contrary to findings in normal lambs, total NOS activity did not decrease during iNO. In fact, Western blot analysis demonstrated that tissue endothelial NOS protein levels decreased by 43% such that NOS activity relative to protein levels actually increased during iNO (P < 0.05). In addition, the beta-subunit of soluble guanylate cyclase decreased by 70%, whereas phosphodiesterase 5 levels were unchanged (P < 0.05). Withdrawal of iNO was associated with an acute increase in PVR, which exceeded baseline PVR by 45%, and a decrease in cGMP concentrations to levels that were below baseline. These data suggest that the endothelial response to iNO and the potential mechanisms of rebound pulmonary hypertension are dependent upon the underlying pulmonary vasculature
— id: 57726, year: 2005, vol: 288, page: L27, stat: Journal Article,

Effect of antenatal placental insufficiency on postnatal preterm infant gastrointestinal function
Wachtel, E; Hendrics-Munoz, K; Timor, I
2004 APR ;55(4):486A-486A, Pediatric research
— id: 46536, year: 2004, vol: 55, page: 486A, stat: Journal Article,

Emergence of smooth muscle cell endothelin B-mediated vasoconstriction in lambs with experimental congenital heart disease and increased pulmonary blood flow
Black, Stephen M; Mata-Greenwood, Eugenia; Dettman, Robert W; Ovadia, Boaz; Fitzgerald, Robert K; Reinhartz, Olaf; Thelitz, Stefan; Steinhorn, Robin H; Gerrets, Rene; Hendricks-Munoz, Karen; Ross, Gregory A; Bekker, Janine M; Johengen, Michael J; Fineman, Jeffrey R
2003 Sep 30;108(13):1646-1654, Circulation
BACKGROUND: Endothelin-1 (ET-1) has been implicated in the pathophysiology of pulmonary hypertension. In 1-month-old lambs with increased pulmonary blood flow, we have demonstrated early alterations in the ET-1 cascade. The objective of this study was to investigate the role of potential later alterations of the ET cascade in the pathophysiology of pulmonary hypertension secondary to increased pulmonary blood flow. METHODS AND RESULTS: Eighteen fetal lambs underwent in utero placement of an aortopulmonary vascular graft (shunt) and were studied 8 weeks after spontaneous delivery. Compared with age-matched control lambs, lung tissue ET-1 levels were increased in shunt lambs (317.2+/-113.8 versus 209.8+/-61.8 pg/g, P<0.05). In shunt lambs (n=9), exogenous ET-1 induced potent pulmonary vasoconstriction, which was blocked by the ETA receptor antagonist PD 156707 (n=3). This pulmonary vasoconstriction was mimicked by exogenous Ala1,3,11,15 ET-1 (4 Ala ET-1), the ETB receptor agonist, and was blocked by the ETB receptor antagonist BQ 788 (n=3). However, in control lambs (n=7), ET-1 and 4 Ala ET-1 did not change pulmonary vascular tone. In contrast to 4-week-old shunt lambs, immunohistochemistry revealed the emergence of ETB receptors on smooth muscle cells in the vasculature of 8-week-old shunt lambs. CONCLUSIONS: Over time, increased pulmonary blood flow and/or pressure results in the emergence of ETB-mediated vasoconstriction, which coincides with the emergence of ETB receptors on smooth muscle cells. These data suggest an important role for ETB receptors in the pathophysiology of pulmonary hypertension in this animal model of increased pulmonary blood flow
— id: 57727, year: 2003, vol: 108, page: 1646, stat: Journal Article,

Pilot study of in utero treatment of osteogenesis imperfecta (OI) with alendronate: Feasibility demonstrated in wildtype mouse model
McCarthy, EA; Camacho, NP; Raggio, CL; Lawrence, L; Rahman, M; Garcia, R; Hendricks-Munoz, K
2003 APR ;53(4):53A-54A, Pediatric research
— id: 38559, year: 2003, vol: 53, page: 53A, stat: Journal Article,

Developmental care: the impact of Wee Care developmental care training on short-term infant outcome and hospital costs
Hendricks-Munoz KD; Prendergast CC; Caprio MC; Wasserman RS
2002 ;2(1):39-45 Mar, Newborn & infant nursing reviews : NAINR
This article explores the effect of a comprehensive developmental care training program on the medical outcome and cost of care for premature infants. Premature infants less than 34 weeks' gestation admitted to 2 regional neonatal intensive care units were prospective studies 6 months before and after implementation of the Wee Care program (Children's Medical Ventures, Norwell, MA). Environment, medical outcome, and hospital charges were recorded. The sample consisted of 242 infants (139 pre- and 103 postintervention). Although the medical outcomes of chronic lung disease, infection rate, mild retinopathy of prematurity, and intraventricular hemorrhage were significantly decreased, there was no change in incidence of severe retinopathy of prematurity. Hospital stay and hospital costs were significantly decreased. The authors conclude that a multidisciplinary, structured program in developmental care can lead to alterations in the neonatal intensive care unit environment associated with improved medical outcome, decreased length of hospitalization, and decreased cost of care.
— id: 80322, year: 2002, vol: 2, page: 39, stat: Journal Article,

Nitric oxide-endothelin-1 interactions after acute ductal constriction in fetal lambs
Ovadia, Boaz; Bekker, Janine M; Fitzgerald, Robert K; Kon, Alexander; Thelitz, Stephan; Johengen, Michael J; Hendricks-Munoz, Karen; Gerrets, Rene; Black, Stephen M; Fineman, Jeffrey R
2002 Mar;282(3):H862-H871, American journal of physiology. Heart & circulatory physiology
Acute partial compression of the fetal ductus arteriosus (DA) results in an initial increase in pulmonary blood flow (PBF) that is followed by acute vasoconstriction. The objective of the present study was to determine the role of nitric oxide (NO)-endothelin-1 (ET-1) interactions in the acute changes in pulmonary vascular tone after in utero partial constriction of the DA. Twelve late-gestation fetal lambs (132-140 days) were instrumented to measure vascular pressures and left PBF. After a 24-h recovery period, acute constriction of the DA was performed by partially inflating a vascular occluder, and the hemodynamic variables were observed for 4 h. In control lambs (n = 7), acute ductal constriction initially increased PBF by 627% (P < 0.05). However, this was followed by active vasoconstriction, such that PBF was restored to preconstriction values by 4 h. This was associated with a 43% decrease in total NO synthase (NOS) activity (P < 0.05) and a 106% increase in plasma ET-1 levels (P < 0.05). Western blot analysis demonstrated no changes in lung tissue endothelial NOS, preproET-1, endothelin-converting enzyme-1, or ET(B) receptor protein levels. The infusion of PD-156707 (an ET(A) receptor antagonist, n = 5) completely blocked the vasoconstriction and preserved NOS activity. These data suggest that the fetal pulmonary vasoconstriction after acute constriction of the DA is mediated by NO-ET-1 interactions. These include an increase in ET(A) receptor-mediated vasoconstriction and an ET(A) receptor-mediated decrease in NOS activity. The mechanisms of these NO-ET-1 interactions, and their role in mediating acute changes in PBF, warrant further studies
— id: 66838, year: 2002, vol: 282, page: H862, stat: Journal Article,

Inhaled nitric oxide-induced rebound pulmonary hypertension: role for endothelin-1
McMullan DM; Bekker JM; Johengen MJ; Hendricks-Munoz K; Gerrets R; Black SM; Fineman JR
2001 Feb;280(2):H777-H785, American journal of physiology. Heart & circulatory physiology
Clinically significant increases in pulmonary vascular resistance have been noted on acute withdrawal of inhaled nitric oxide (NO). Endothelin (ET)-1 is a vasoactive peptide produced by the vascular endothelium that may participate in the pathophysiology of pulmonary hypertension. The objectives of this study were to determine the effects of inhaled NO on endogenous ET-1 production in vivo in the intact lamb and to determine the potential role of ET-1 in the rebound pulmonary hypertension associated with the withdrawal of inhaled NO. Seven 1-mo-old vehicle-treated control lambs and six PD-156707 (an ET(A) receptor antagonist)-treated lambs were mechanically ventilated. Inhaled NO (40 parts per million) was administered for 24 h and then acutely withdrawn. After 24 h of inhaled NO, plasma ET-1 levels increased by 119.5 +/- 42.2% (P < 0.05). Western blot analysis revealed that protein levels of preproET-1, endothelin-converting enzyme-1alpha, and ET(A) and ET(B) receptors were unchanged. On acute withdrawal of NO, pulmonary vascular resistance (PVR) increased by 77.8% (P < 0.05) in control lambs but was unchanged (-5.5%) in PD-156707-treated lambs. Inhaled NO increased plasma ET-1 concentrations but not gene expression in the intact lamb, and ET(A) receptor blockade prevented the increase in PVR after NO withdrawal. These data suggest a role for ET-1 in the rebound pulmonary hypertension noted on acute withdrawal of inhaled NO
— id: 66839, year: 2001, vol: 280, page: H777, stat: Journal Article,

Developmental delay in normal gastric wave pattern formation in neonates measured by electrography
Kim, Y; Javed, S; Shah, P; Hendricks-Munoz, K
2000 MAR ;48(2):215A-215A, Journal of investigative medicine
— id: 54586, year: 2000, vol: 48, page: 215A, stat: Journal Article,

The effect of a low discharge hematocrit on apnea and bradycardia during the first month at home
Parvez, N; Orsini, A; Hendricks-Munoz, K
2000 MAR ;48(2):213A-213A, Journal of investigative medicine
— id: 54585, year: 2000, vol: 48, page: 213A, stat: Journal Article,

Stress appraisal and coping in mothers of NICU infants
Reichman, SRF; Miller, AC; Gordon, RM; Hendricks-Munoz, KD
2000 ;29(4):279-293 FAL, Children's health care
In this study, we assessed the coping process in 35 mothers of premature and at-risk infants using a cognitive-behavioral theory to examine the relation among the stressful event, appraisal of the event, coping, and psychological symptomatology. Results show that 60% of the participants presented with clinically significant levels of distress. Tests of additional hypotheses and rt:search questions addressed the role of appraisals and coping strategies. Hierarchic;ar regression analysis revealed that 58% (adjusted R-2) Of the variance in distress was explained by four variables. The appraisal of uncontrollability, confrontive coping, and escape-avoidant coping were predictive of increased distress. The coping strategy of accepting responsibility was predictive of decreased distress. Satisfaction with the child's physician was a significant indicator of better functioning
— id: 54422, year: 2000, vol: 29, page: 279, stat: Journal Article,

Human endometrial endothelial cells: isolation, characterization, and inflammatory-mediated expression of tissue factor and type 1 plasminogen activator inhibitor
Schatz F; Soderland C; Hendricks-Munoz KD; Gerrets RP; Lockwood CJ
2000 Mar;62(3):691-697, Biology of reproduction
Binding of Ulex europaeus lectin to microvessels was used to isolate endothelial cells from cycling human endometrium. Cultured human endometrial endothelial cells (HEECs) exhibited endothelial cell-specific characteristics such as tube formation on a basement membrane matrix and sequestration of acetylated low-density lipoprotein. Markers for potentially contaminating epithelial, stromal, smooth muscle, and bone marrow-derived cells were not detected in the HEEC cultures. Basal and proinflammatory-stimulated immunostaining profiles for endothelial cell-specific adhesion markers, as exemplified by Von Willebrand's factor and E-selectin, were similar for cultured HEECs and human umbilical venous cord endothelial cells (HUVECs). However, HUVECs expressed several extracellular matrix proteins that were absent from cultured HEECs. In the latter, the protein kinase C agonist phorbol myristate acetate transiently enhanced tissue factor (TF) mRNA levels and elicited a more prolonged elevation in TF protein levels, but did not affect plasminogen activator inhibitor-1 (PAI-1) mRNA and protein levels. Inappropriate expression of TF, which initiates hemostasis by generating thrombin, and of PAI-1, which regulates hemostasis by acting as the primary inhibitor of fibrinolysis, can each lead to thrombosis. The differential regulation of TF and PAI-1 expression revealed in the current study emphasizes the importance of using HEECs to evaluate mechanisms regulating the hemostatic/thrombotic balance in human endometrium
— id: 11828, year: 2000, vol: 62, page: 691, stat: Journal Article,

Retinopathy of prematurity: lack of association with prenatal care
Higgins RD; Mendelsohn AL; DeFeo MJ; Ucsel R; Hendricks-Munoz KD
1999 Apr;3(2):114-116, Journal of AAPOS: American Association for Pediatric Ophthalmology & Strabismus
OBJECTIVES: The overall goal of this study was to prospectively assess risk factors for retinopathy of prematurity (ROP) in infants of birth weight <1250 g in an urban population at Bellevue Hospital Center, New York, New York. The hypothesis tested was that lack of prenatal care increases the incidence of ROP. METHODS: A consecutive sample of patients admitted to Bellevue Hospital Center's neonatal intensive care unit/special care nursery who weighed <1250 g at birth and survived until their ophthalmology screening examinations were included in the study. The main outcome measures were presence or absence of ROP and prenatal care. Additional relevant clinical information was collected on the patients. RESULTS: Ninety infants were evaluated. Sixty-one (68%) had ROP; 29 (32%) had no ROP. No differences in incidence or severity of ROP were detected with regard to prenatal care when the 2 groups were compared. In this population <1250 g, there were no differences in birth weight or gestational age with respect to prenatal care or lack of prenatal care. CONCLUSIONS: Lack of prenatal care was not associated with an increased risk for ROP in infants with birth weight <1250 g in this urban population
— id: 6103, year: 1999, vol: 3, page: 114, stat: Journal Article,

The effect of education, race and socioeconomic status on parental compliance and parental perception of documented home apnea monitors
Javed, F; Orsini, AJ; Carseni, L; Bank, S; Hendricks-Munoz, KD
1999 APR ;45(4):246A-246A, Pediatric research
— id: 54068, year: 1999, vol: 45, page: 246A, stat: Journal Article,

Effects of intrauterine exposure to cocaine, opium and methadone on gut myoelectrical activity of neonates
Javed, SZ; Kim, YS; Shah, P; Hendricks-Munoz, KD
1999 APR ;45(4):284A-284A, Pediatric research
— id: 54071, year: 1999, vol: 45, page: 284A, stat: Journal Article,

Very low birth weight infants - a new hypertensive population?
Kim, YS; Wang, J; Hendricks-Munoz, KD; Schacht, RG
1999 APR ;45(4):247A-247A, Pediatric research
— id: 54069, year: 1999, vol: 45, page: 247A, stat: Journal Article,

Developmental delay in normal gastric wave pattern formation in neonates measured by electrogastrography
Kim, YS; Zayed, SZ; Shah, P; Hendricks-Munoz, KD
1999 APR ;45(4):113A-113A, Pediatric research
— id: 54066, year: 1999, vol: 45, page: 113A, stat: Journal Article,

The incidence of apnea after discharge in infants less than 34 weeks gestation with normal pre-discharge pneumocardiograms
Orsini, AJ; Pohl, CA; Gibson, E; Epstein, ML; Carseni, L; Hendricks-Munoz, KD
1999 APR ;45(4):252A-252A, Pediatric research
— id: 54070, year: 1999, vol: 45, page: 252A, stat: Journal Article,

Endothelin receptor blockade prevents the rise in pulmonary vascular resistance after cardiopulmonary bypass in lambs with increased pulmonary blood flow
Petrossian E; Parry AJ; Reddy VM; Akkersdijk GP; McMullan DM; Thompson L; Hendricks-Munoz KD; Hallak H; Hanley FL; Fineman JR
1999 Feb;117(2):314-323, Journal of thoracic & cardiovascular surgery
BACKGROUND: Children with increased pulmonary blood flow may experience morbidity as the result of increased pulmonary vascular resistance after operations in which cardiopulmonary bypass is used. Plasma levels of endothelin-1, a potent vasoactive substance implicated in pulmonary hypertension, are increased after cardiopulmonary bypass. OBJECTIVES: In a lamb model of increased pulmonary blood flow after in utero placement of an aortopulmonary shunt, we characterized the changes in pulmonary vascular resistance induced by hypothermic cardiopulmonary bypass and investigated the role of endothelin-1 and endothelin-A receptor activation in postbypass pulmonary hypertension. METHODS: In eleven 1-month-old lambs, the shunt was closed, and vascular pressures and blood flows were monitored. An infusion of a selective endothelin-A receptor blocker (PD 156707; 1.0 mg/kg/h) or drug vehicle (saline solution) was then begun 30 minutes before cardiopulmonary bypass and continued for 4 hours after bypass. The hemodynamic variables were monitored, and plasma endothelin-1 concentrations were determined before, during, and for 6 hours after cardiopulmonary bypass. RESULTS: After 90 minutes of hypothermic cardiopulmonary bypass, both pulmonary arterial pressure and pulmonary vascular resistance increased significantly in saline-treated lambs during the 6-hour study period (P <.05). In lambs pretreated with PD 156707, pulmonary arterial pressure and pulmonary vascular resistance decreased (P <. 05). After bypass, plasma endothelin-1 concentrations increased in all lambs; there was a positive correlation between postbypass pulmonary vascular resistance and plasma endothelin-1 concentrations (P <.05). CONCLUSIONS: This study suggests that endothelin-A receptor-induced pulmonary vasoconstriction mediates, in part, the rise in pulmonary vascular resistance after cardiopulmonary bypass. Endothelin-A receptor antagonists may decrease morbidity in children at risk for postbypass pulmonary hypertension. This potential therapy warrants further investigation
— id: 66841, year: 1999, vol: 117, page: 314, stat: Journal Article,

Role of the endothelium in placental dysfunction after fetal cardiac bypass
Reddy VM; McElhinney DB; Rajasinghe HA; Liddicoat JR; Hendricks-Munoz K; Fineman JR; Hanley FL
1999 Feb;117(2):343-351, Journal of thoracic & cardiovascular surgery
BACKGROUND: Fetal cardiac bypass causes placental dysfunction, characterized by increased placental vascular resistance, decreased placental blood flow, hypoxia, and acidosis. Vasoactive factors produced by the vascular endothelium, such as nitric oxide and endothelin 1, are important regulators of placental vascular tone and may contribute to this placental dysfunction. METHODS: To investigate the role of the vascular endothelium in placental dysfunction related to fetal cardiac bypass, we studied 3 groups of fetal sheep. In the first group (n = 7) we determined placental hemodynamic responses before and after bypass to an endothelium-dependent vasodilator (acetylcholine), an endothelium-independent vasodilator (nitroprusside), and endothelin 1. In the second group (n = 8) a nonspecific endothelin receptor blocker (PD 145065) was administered and placental hemodynamic values were measured before and after bypass. In the third group (n = 5) endothelin 1 levels were measured before and after bypass. RESULTS: Before fetal cardiac bypass exogenous endothelin 1 decreased placental blood flow by 9% and increased placental resistance by 9%. After bypass endothelin 1 decreased placental flow by 47% and increased resistance by 106%. There was also a significant attenuation of the placental vascular relaxation response to acetylcholine after bypass, whereas the response to nitroprusside was not significantly altered. In fetuses that received the PD 145065, placental vascular resistance increased significantly less than in control fetuses (28% versus 62%). Similarly, placental blood flow decreased significantly more (from 6. 3 +/- 3.1 to 28.3 +/- 10.4 pg/mL; P =.01) in control fetuses than in fetuses receiving PD 145065 (33% versus 20%). Umbilical venous endothelin 1 levels increased significantly in fetuses exposed to fetal bypass but did not change in control fetuses. CONCLUSIONS: The basal endothelial regulatory mechanisms of placental vascular tone were deranged after fetal cardiac bypass. Endothelin receptor blockade, which substantially reduced postbypass placental dysfunction, and other interventions aimed at preserving endothelial function may be effective means of optimizing fetal outcome after cardiac bypass
— id: 66840, year: 1999, vol: 117, page: 343, stat: Journal Article,

Hyperoxia stimulates endothelin-1 secretion from endothelial cells; modulation by captopril and nifedipine
Higgins RD; Hendricks-Munoz KD; Caines VV; Gerrets RP; Rifkin DB
1998 May;17(5):487-493, Current eye research
PURPOSE: Retinopathy of prematurity (ROP) is a vasoproliferative condition that can result in severe visual impairment and blindness in preterm babies. Two conditions seen very early in radioimmunoassay (ROP) are vasoconstriction and vaso-obliteration. A potent vasoconstrictor secreted by endothelial cells is endothelin-1 (ET-1). Premature birth results in a relative systemic hyperoxia, compared to the in utero oxygen milieu. We tested the hypothesis that hyperoxia increases ET-1 expression as a possible mechanism for vasoconstriction in the retinal vasculature. METHODS: Bovine retinal endothelial cells and adrenal capillary endothelial cells were isolated and maintained in culture. Cells were exposed to control or hyperoxic culture conditions for 24 h, with and without addition of captopril and nifedipine. Media was collected and assayed for ET-1 by ROP. In addition, cell counts and secreted LDH assays were performed. RESULTS: Conditioned media from cultured bovine retinal and adrenal endothelial cells exposed to hyperoxic culture conditions for 24 h were found to have higher levels of ET-1 than conditioned media from normoxic control cells. Captopril (10(-6) M and 10(-4) M) and nifedipine (10(-6) M and 10(-4) M) inhibited ET-1 release from hyperoxia-exposed endothelial cells. Under normoxic conditions, ET-1 release was inhibited by 10(-4) M captopril or 10(-4) M nifedipine. CONCLUSIONS: These results demonstrate that (1) hyperoxia stimulates in vitro ET-1 secretion in bovine retinal and adrenal capillary endothelial cells, and (2) captopril and nifedipine downregulate ET-1 secretion under normoxic and hyperoxic culture conditions, in a dose-dependent fashion. We speculate that ET-1 may be involved in retinal vessel vasoconstriction seen early in the development of ROP. Further, ACE inhibitors and calcium-channel blocking agents, such as captopril and nifedipine, may provide an avenue for blocking vasoconstriction in ROP
— id: 42356, year: 1998, vol: 17, page: 487, stat: Journal Article,

Antenatal dexamethasone and decreased severity of retinopathy of prematurity
Higgins RD; Mendelsohn AL; DeFeo MJ; Ucsel R; Hendricks-Munoz KD
1998 May;116(5):601-605, Archives of ophthalmology
OBJECTIVE: To assess risk factors associated with the development of retinopathy of prematurity (ROP) in an urban population. DESIGN: Observational cohort study. SETTING: Bellevue Hospital Center, a regional perinatal referral center in New York City. PATIENTS: Surviving inborn infants with birth weight less than 1250 g undergoing an ophthalmologic screening examination. MAIN OUTCOME MEASURES: Screening examination results for ROP were obtained. Additional data included birth weight, gestational age, maternal factors, and common neonatal diagnoses and exposures. RESULTS: Sixty-three infants were included in the analysis. Mean +/- SD birth weight was 981+/-179 g and mean gestational age was 27.8+/-2.4 weeks. Infants whose mothers received antenatal dexamethasone developed significantly less ROP that was stage 2 or higher than infants without a history of antenatal dexamethasone exposure--8.7% (2/23) vs 35% (14/40), respectively (P=.04). Birth weight, gestational age, respiratory distress syndrome, bronchopulmonary dysplasia, and patent ductus arteriosus were also significantly associated with the development of ROP that was stage 2 or higher. After controlling for these confounders by multiple logistic regression analysis, antenatal dexamethasone administration was associated with a significantly decreased risk of development of ROP stage 2 or higher (adjusted odds ratio [OR], 0.14; 95% confidence interval [CI], 0.02-0.93). The association was stronger when the analysis was restricted to the 36 infants who were 24 to 28 weeks of gestational age (adjusted OR, 0.02; 95% CI, 0.00-0.76). CONCLUSION: Antenatal dexamethasone administration appears to be associated with a decreased incidence of development of ROP of stage 2 or higher in this urban population
— id: 7597, year: 1998, vol: 116, page: 601, stat: Journal Article,

Post-cardiopulmonary bypass pulmonary hypertension in lambs with increased pulmonary blood flow. A role for endothelin 1
Reddy VM; Hendricks-Munoz KD; Rajasinghe HA; Petrossian E; Hanley FL; Fineman JR
1997 Feb 18;95(4):1054-1061, Circulation
BACKGROUND: After cardiopulmonary bypass (CPB), pulmonary hypertension and its associated increased vascular reactivity are a major source of morbidity, particularly for children with increased pulmonary blood flow. Although post-CPB pulmonary hypertension is well described, its mechanisms remain incompletely understood. Plasma levels of endothelin 1. a potent vasoactive substance implicated in pulmonary hypertension, are increased after CPB. The purpose of the present study was threefold: to characterize the changes in pulmonary vascular resistance and vascular reactivity induced by hypothermic CPB; to investigate the effects of preexisting increased pulmonary blood flow on these changes; and to better define the role of endothelin 1 in the pathogenesis of post-CPB pulmonary hypertension. METHODS AND RESULTS: Vascular pressures and blood flows were monitored in 14 1-month-old lambs with increased pulmonary blood flow (after in utero placement of an aortopulmonary shunt) and 6 age-matched control lambs. During the 2-hour study period after 105.3 +/- 20.6 minutes of hypothermic CPB the increase in pulmonary vascular resistance was significantly augmented in lambs with increased pulmonary blood flow compared with control lambs (P < .05). Pretreatment with PD 145065 (a nonselective endothelin receptor blocker; 50 micrograms.kg-1.min-1) completely blocked this increase in pulmonary vascular resistance and blocked the increase in pulmonary vascular resistance in response to acute alveolar hypoxia after CPB (96.3 +/- 88.5% versus -9.7 +/- 16.4%; P < .05). Plasma endothelin 1 levels increased after CPB in all lambs. CONCLUSIONS: Preexisting increased pulmonary blood flow alters the response of the pulmonary circulation to hypothermic CPB; the increase in pulmonary vascular resistance induced by CPB is augmented in lambs with increased pulmonary blood flow. Pretreatment with endothelin 1 receptor blockers eliminated the increase in pulmonary vascular resistance and the pulmonary vasoconstricting response to alveolar hypoxia, suggesting a role for endothelin 1 in post-CPB pulmonary hypertension. Endothelin 1 receptor blockers may decrease morbidity in children at risk for pulmonary hypertension after surgical repair with CPB and warrants further study
— id: 66842, year: 1997, vol: 95, page: 1054, stat: Journal Article,

Rapid estimation of insertional length of endotracheal intubation in newborn infants
Shukla HK; Hendricks-Munoz KD; Atakent Y; Rapaport S
1997 Oct;131(4):561-564, Journal of pediatrics
OBJECTIVE: To create a simple and accurate method of predicting the correct insertional length of endotracheal intubation during resuscitation of neonates. STUDY DESIGN: Phase I of the study enrolled infants that required either orotracheal or nasotracheal intubations. The endotracheal tube position was confirmed by auscultation and radiographic images. Three regression equations were then created using nasal-tragus length, sternal length, and birth weight on insertional length. In phase II of the study, the modified regression equations of nasotracheal and sternal length were used to predict endotracheal tube insertional length in 50 infants (40 orotracheal and 10 nasotracheal). RESULTS: Nasal-tragus length and sternal length are good parameters to estimate insertional length for endotracheal intubation (p < 0.005 for both the parameters). The modified prediction equation for insertional length of the endotracheal tube for the orotracheal route is NTL or STL + 1. For the nasotracheal route the equation is NTL or STL + 2. CONCLUSION: During resuscitation of the neonate when vital parameters are difficult to obtain, the insertional length of endotracheal intubation can be quickly and accurately predicted by nasal-tragus length or sternal length
— id: 12219, year: 1997, vol: 131, page: 561, stat: Journal Article,

Cocaine-stimulated endothelin-1 release is decreased by angiotensin-converting enzyme inhibitors in cultured endothelial cells
Hendricks-Munoz KD; Gerrets RP; Higgins RD; Munoz JL; Caines VV
1996 Jan;31(1):117-123, Cardiovascular research
OBJECTIVE: The primary aim was to determine the action of pathophysiologically relevant cocaine concentrations (10(-7)-10(-5) M) on endothelin-1 (ET-1) release from cultured endothelial cells under various cellular conditions. Further aims were to evaluate the effect of angiotensin-converting enzyme inhibitors on cocaine-treated endothelial cells, to assess their potential for inhibition of ET-1-stimulated release. METHODS: Endothelin-1 release into the media was evaluated by radioimmunoassay under basal conditions and after 24 h treatment of endothelial cells with cocaine hydrochloride (HCl), or cocaine HCl and ACE inhibitors, captopril and lisinopril. The effect of serum and plasma under these conditions was also investigated. RESULTS: Cocaine HCl stimulated ET-1 release in a dose response fashion that was independent of plasma or serum factors. Furthermore, cocaine-stimulated ET-1 release was inhibited by administration of angiotensin-converting enzyme inhibitors captopril and lisinopril. CONCLUSIONS: These findings suggest that cocaine can directly stimulate endothelial cells to release ET-1 and that the observed increase is independent of serum or plasma factors. Furthermore, cocaine-stimulated endothelin-1 release appears to be mediated at least in part by the angiotensin system. These observations provide a framework for understanding the cellular mechanisms involved in cocaine-induced vasoconstriction
— id: 12677, year: 1996, vol: 31, page: 117, stat: Journal Article,

Association of antenatal dexamethasone with decreased severity of retinopathy of prematurity
Higgins, RD; Mendelsohn, AL; DeFeo, MJ; Ucsel, R; HendricksMunoz, KD
1996 APR ;39(4):1277-1277, Pediatric research
— id: 52993, year: 1996, vol: 39, page: 1277, stat: Journal Article,

Endothelin-1 vasoactive responses in lambs with pulmonary hypertension and increased pulmonary blood flow
Wong J; Reddy VM; Hendricks-Munoz K; Liddicoat JR; Gerrets R; Fineman JR
1995 Dec;269(6 Pt 2):H1965-H1972, American journal of physiology
Increased concentrations of endothelin-1 (ET-1) are found in children with congenital heart diseases that produce increased pulmonary blood flow and pulmonary hypertension, but the role of ET-1 in the pathophysiology of pulmonary hypertension is unclear. Therefore, we investigated ET-1-induced vasoactive responses and ET-1 concentrations in an animal model of pulmonary hypertension and increased pulmonary blood flow. Vascular shunts were placed between the ascending aorta and main pulmonary artery in seven late-gestation fetal sheep. Four weeks after spontaneous delivery, ET-1 increased pulmonary vascular resistance by 29.7 +/- 34.4% (P < 0.05), the ETb-receptor agonist [Ala1,3,11,15]ET-1 (4AlaET-1) had no effect, and the ETa-receptor antagonist cyclo(D-Asp-L-Pro-D-Val-L-Leu-D-Trp) (BQ-123) decreased pulmonary vascular resistance by -16.0 +/- 5.6% (P < 0.05). In contrast, in six control lambs with a similar degree of pulmonary hypertension induced by U-46619, ET-1 and 4AlaET-1 decreased pulmonary vascular resistance by 24.8 +/- 17.6, and 20.0 +/- 13.8%, respectively (P < 0.05). In addition, systemic arterial concentrations of immunoreactive ET-1 were elevated in lambs with pulmonary hypertension (29.2 +/- 9.6 vs. 15.2 +/- 10.7 pg/ml, P < 0.05). Pulmonary hypertension and increased pulmonary blood flow alters the response of ET-1 from pulmonary vasodilation to vasoconstriction. These altered responses suggest a role for ET-1 and its receptors in the pathogenesis of pulmonary hypertension secondary to increased pulmonary blood flow
— id: 66843, year: 1995, vol: 269, page: H1965, stat: Journal Article,

Profile and stability of sensorineural hearing loss in persistent pulmonary hypertension of the newborn
Walton JP; Hendricks-Munoz K
1991 Dec;34(6):1362-1370, Journal of speech & hearing research
The purpose of this study was to examine the incidence, profile, and stability of sensorineural hearing loss (SNHL) in infants diagnosed with persistent pulmonary hypertension of the newborn (PPHN). Over a five-year period, 19 of 51 infants (37%) with PPHN were diagnosed with SNHL: 16 with bilateral and 3 with unilateral impairment. This incidence of SNHL is approximately 25 times greater than observed in graduates of our intensive care nursery. The profile of SNHL in the group of 19 children was typically downward sloping. However, there was considerable variation with respect to degree of loss. In addition, progressive SNHL was identified in 5 children whose hearing worsened an average of 55 dB at 2 to 4 kHz. On retrospective analysis, the perinatal variables associated with PPHN were comparable between hearing-impaired and normal-hearing infants. In contrast, the two groups were significantly different when treatment variables, such as the duration of mechanical ventilation or amikacin, were compared. Children with SNHL were treated for longer durations as compared to normal-hearing infants. Children with SNHL were subdivided into two groups, mild and severe, based on degree of loss and treatment variables, and compared again to the normal-hearing group. Two findings emerged from this analysis. First, the duration of hyperventilation was now the only variable significantly different between children with mild SNHL and children with normal hearing. Second, comparison of the mild with the severe SNHL groups showed that the duration of hyperventilation was similar. The pathophysiology and underlying mechanisms resulting in SNHL in PPHN survivors are discussed
— id: 66844, year: 1991, vol: 34, page: 1362, stat: Journal Article,

The effects of indomethacin on renal function and intracranial hemorrhage in infants with patent ductus arteriosus
Davis JM; Hendricks-Munoz KD; Hagberg D; Manning JA
1990 ;14(1):15-19, Developmental pharmacology & therapeutics
The effects of indomethacin on patent ductus arteriosus (PDA) were retrospectively studied by evaluating 1,600 consecutive infants less than 36 weeks gestation from 1983 to 1986. Two hundred thirteen infants were diagnosed with a PDA, and 102 infants received indomethacin. Indomethacin was associated with successful PDA closure in 81 infants (79%), with 59 infants (58%) closing after a single dose. No cases of renal failure were observed after indomethacin. Nine infants were treated despite a creatinine (Cr) value greater than or equal to 1.5 mg/dl. Cr improved in all these infants after therapy. Blood urea nitrogen values were greater than or equal to 30 mg/dl in 22 infants at the time of treatment; 18 infants (82%) improved. An intracranial hemorrhage (ICH) was detected in 23 infants (22%) by cranial ultrasound prior to indomethacin; there was no progression after treatment. Data suggest that indomethacin is highly associated with closure of a PDA, and therapy did not result in prolonged renal dysfunction or worsening ICH
— id: 66846, year: 1990, vol: 14, page: 15, stat: Journal Article,

The role of the lumbar puncture in the admission sepsis evaluation of the premature infant
Hendricks-Munoz KD; Shapiro DL
1990 Mar;10(1):60-64, Journal of perinatology
Premature infants with respiratory distress commonly receive evaluation for sepsis, including a lumbar puncture, within a short time after admission to a neonatal intensive care unit. We questioned the use of the lumbar puncture during the early sepsis evaluation, and since 1979, have omitted this procedure as part of the initial evaluation for sepsis (within 6 hours of birth) of premature infants. We monitored this policy to detect any change in the incidence of meningitis, and now report results accumulated over a 7-year period. From 1979 to 1986, 1390 inborn premature infants of 34 weeks' gestation or less were evaluated for early sepsis within 6 hours of birth. Thirty-two infants (2.3%) were diagnosed with sepsis. Fifteen of these infants died in the first 24 hours of life. Meningitis was not demonstrated by autopsy evaluation. The surviving 17 infants diagnosed with sepsis did not have meningitis. One hundred twenty-three infants whose initial blood cultures were negative developed infection later in their hospital course. Eleven of these 123 infants had infections with perinatally acquired organisms; two had group B streptococcus (GBS) meningitis. Their cases were not compatible with missed meningitis. The remaining 112 infants developed nosocomial infections of which 38.3% developed meningitis without associated bacteremia. These results suggest that the omission of the lumbar puncture in the early sepsis evaluation of the premature infant did not result in any missed meningitis and spared many infants the procedure shortly after birth. The lumbar puncture, however, continues to be vital in the assessment of late infections of the neonate
— id: 66845, year: 1990, vol: 10, page: 60, stat: Journal Article,

Membrane phospholipid methylation is associated with surfactant secretion in rabbit type II alveolar epithelial cells
Hendricks-Munoz KD; Finkelstein JN; Shapiro DL
1989 ;15(1):63-76, Experimental lung research
We investigated the involvement of membrane phospholipid methylation in receptor-mediated secretion of surfactant in adult rabbit type II alveolar epithelial cells (type II pneumocyte). Phospholipid methyltransferase activity was found in type II pneumocyte microsomes. Cell cultures of adult rabbit type II pneumocytes were then used to assay methyltransferase activity in the presence of the beta-adrenergic agonist, terbutaline, and the methyltransferase inhibitor, 3-deazaadenosine. Terbutaline predictably stimulated adenylate cyclase activity and surfactant secretion. It was also found to stimulate incorporation of methyl groups into phosphatidylcholine and to increase beta-adrenergic receptor availability as assayed by binding of dihydroalprenolol (DHA). Surfactant secretion, as well as adenylate cyclase activity, were stimulated by terbutaline and were inhibited by 3-deazaadenosine. 3-Deazaadenosine did not inhibit DHA binding. These results suggest that phospholipid methylation plays a role in stimulus-secretion coupling in adult rabbit type II pneumocytes
— id: 66847, year: 1989, vol: 15, page: 63, stat: Journal Article,

Spontaneous focal gastrointestinal perforation in very low birth weight infants
Aschner JL; Deluga KS; Metlay LA; Emmens RW; Hendricks-Munoz KD
1988 Aug;113(2):364-367, Journal of pediatrics
Spontaneous, focal gastrointestinal perforation occurred in six very low birth weight infants. The first recognized clinical sign of perforation in five of the six infants was striking blue-black discoloration of the abdominal wall. In all cases the clinical and radiographic presentations, as well as the histologic findings, were distinct from those associated with necrotizing enterocolitis. All 4 infants who underwent exploratory laparotomy and repair had excellent surgical outcomes
— id: 66849, year: 1988, vol: 113, page: 364, stat: Journal Article,

Hearing loss in infants with persistent fetal circulation
Hendricks-Munoz KD; Walton JP
1988 May;81(5):650-656, Pediatrics
Infants with the diagnosis of persistent fetal circulation were evaluated for hearing loss. From Jan 1, 1982, to Jan 1, 1984, 28 infants with this diagnosis were retrospectively identified, and 18 were evaluated by formal audiologic testing. Additionally, 22 infants were prospectively followed by serial auditory evaluation from Jan 1, 1984, to Jan 1, 1986. Of the 40 infants evaluated, 21 were identified as having hearing impairment (52.5%), 14 of whom required hearing aids. For 82% of those retrospectively identified hearing-impaired infants who required hearing aids, parental concern was expressed for their lack of hearing acuity. This factor could have aided in the earlier recognition of these infants' impairment. Among those infants followed prospectively, formal audiologic testing, in some cases serially, was needed to diagnose a progressive hearing loss that was expressed at 6 to 8 months after discharge from the neonatal intensive care unit. Perinatal factors associated with the development and management of persistent fetal circulation were identified and compared in infants with confirmed hearing loss and those with normal hearing. Variables related to those infants with hearing loss were as follows: degree of alkalosis, duration of ventilation, and possibly use of furosemide. We concluded from these results that infants with persistent fetal circulation have an extremely high incidence of sensorineural hearing loss and suggest serial formal audiologic evaluations to aid in detection of hearing-impaired infants
— id: 66850, year: 1988, vol: 81, page: 650, stat: Journal Article,

Surfactant replacement therapy at birth: final analysis of a clinical trial and comparisons with similar trials
Kendig JW; Notter RH; Cox C; Aschner JL; Benn S; Bernstein RM; Hendricks-Munoz K; Maniscalco WM; Metlay LA; Phelps DL; et al.
1988 Nov;82(5):756-762, Pediatrics
A randomized trial of surfactant replacement therapy at birth was conducted at the University of Rochester between June 1983 and November 1985. Thirty-four premature infants, 25 to 29 weeks' gestational age, received a preventilatory dose of a calf lung surfactant extract in saline prepared at the University of Rochester. A control group of 31 infants received a preventilatory dose of saline alone. The major finding of this trial is that a single preventilatory dose of calf lung surfactant extract reduces the severity of the respiratory distress syndrome during the first 24 hours of life. The beneficial effects, however, are not sustained in many infants and diminish after 24 hours of life. The survival rate was 71% in both the control and surfactant-treated groups. There was a lower incidence of pneumothorax in the surfactant-treated group. There were no differences in the incidence of bronchopulmonary dysplasia, patent ductus arteriosus, and intraventricular hemorrhage. No adverse effects of surfactant replacement therapy were identified. Results of this study suggest that multiple postventilatory doses of surfactant will be required for optimal therapy
— id: 66848, year: 1988, vol: 82, page: 756, stat: Journal Article,