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Ian R Holzman

Publications and source records attributed to Ian R Holzman.

17 recordsLinked to original sources
PubMed2007

Effects of butyrate on intestinal barrier function in a Caco-2 cell monolayer model of intestinal barrier.

Production of short-chain fatty acids (SCFA) in the intestinal lumen may play an important role in the maintenance of the intestinal barrier. However, overproduction/accumulation of SCFA in the bowel may be toxic to the intestinal mucosa and has been hypothesized to play a role in the pathogenesis of neonatal necrotizing enterocolitis (NEC). By using a Caco-2 cell monolayer model of intestinal barrier, we report here that the effect of butyrate on the intestinal barrier is paradoxical. Butyrate at a low concentration (2 mM) promotes intestinal barrier function as measured by a significant increase in transepithelial electrical resistance (TER) and a significant decrease in inulin permeability. Butyrate at a high concentration (8 mM) reduces TER and increases inulin permeability significantly. Butyrate induces apoptosis and reduces the number of viable Caco-2 cells in a dose-dependent manner. Intestinal barrier function impairment induced by high concentrations of butyrate is most likely related to butyrate-induced cytotoxicity due to apoptosis. We conclude that the effect of butyrate on the intestinal barrier is paradoxical; i.e. whereas low concentrations of butyrate may be beneficial in promoting intestinal barrier function, excessive butyrate may induce severe intestinal epithelial cell apoptosis and disrupt intestinal barrier.

Apoptosis↗
PubMed2005

Is there an advantage of using pressure support ventilation with volume guarantee in the initial management of premature infants with respiratory distress syndrome? A pilot study.

OBJECTIVE: To evaluate the feasibility of using the pressure support ventilation with volume guarantee (PSV-VG) as an initial ventilatory mode in preterm infants with respiratory distress syndrome (RDS) after surfactant treatment to achieve accelerated weaning of peak inspiratory pressure (PIP) and mean airway pressure (MAP). STUDY DESIGN: Initial 24-hour ventilatory parameters were compared in two groups of preterm infants managed by PSV-VG and the synchronized intermittent mandatory ventilation (SIMV) mode in a randomized controlled pilot study after surfactant treatment for RDS. A total of 16 babies were randomized to PSV-VG (1198+/-108 g [mean+/-SEM]; 27.9+/-0.6 weeks) and 18 babies to SIMV (birth weight 1055+/-77 g; gestational age 27.4+/-0.5 weeks). Repeated measures analysis of variance was used to compare serial values of PIP and MAP in the two groups. RESULTS: The PIP and MAP decreased over time (p<0.001) during the first 24 hours after surfactant administration in both groups but the decrease in MAP was faster in the SIMV group compared to PSV-VG group (p=0.035). The median numbers of blood gases during the first 24 hours were four and two in the SIMV and PSV-VG groups, respectively (p<0.001). The overall outcomes were not significantly different between the two groups. CONCLUSION: PSV-VG did not offer any ventilatory advantage over SIMV in the initial management of surfactant-treated premature newborns with RDS except for minimizing the number of blood gases.

Blood Gas Analysis↗
PubMed2005

Acidosis in newborns with nuchal cords and normal Apgar scores.

OBJECTIVE: Apgar scores and cord blood gases (BG) and pH were compared between a group of babies with nuchal cords and a group without nuchal cords and uncomplicated deliveries. STUDY DESIGN: We collected umbilical arterial (UA) and umbilical venous (UV) blood samples from the placentas of term infants from both normal deliveries (NORM, n=29) and nuchal cords (NUCH, n=33). BG/pH and hematocrit were measured; base deficits and oxygen contents were calculated; and a member of the study assigned Apgar scores and demographic data were collected from the babies' charts. RESULTS: Median Apgar scores in the NUCH babies at 1 and 5 minutes were 9 and 9 respectively, which did not differ from the NORM infants. The pH, PCO(2), and oxygen content obtained from UV of the NUCH infants was not statistically different from the NORM. The pH and oxygen content of the NUCH UA was significantly lower than that of the NORM. The UA PCO(2) in the NUCH was greater than the NORM. Veno-arterial (VA) differences (Delta VA) in pH and PCO(2) of the NUCH infants were greater than that of the NORM. CONCLUSION: The Apgar score is not a sensitive indicator of acid-base changes in nuchal cord patients; UV samples alone may be misleading. UA must be sampled to detect the hypercapnia and diminished oxygen content that is a result of the nuchal cord.

Acidosis↗
PubMed2005

Short-chain fatty acid induces intestinal mucosal injury in newborn rats and down-regulates intestinal trefoil factor gene expression in vivo and in vitro.

BACKGROUND: Luminal administration of short-chain fatty acids (SCFAs) induces dose-dependent intestinal mucosal injury in newborn rats. However, the mechanism underlying the injurious effects of SCFAs on intestinal mucosa in neonates is unclear. Intestinal trefoil factor (ITF) is a factor important for the maintenance and repair of the intestinal mucosal barrier. Regulation of ITF gene expression by SCFAs may be involved as one of the mechanisms. OBJECTIVES: To examine the effect of butyrate-induced colonic injury on ITF gene expression in vivo and to determine the molecular mechanisms underlying the butyrate regulation of ITF gene expression in vitro. METHODS: Whole-section colonic tissues from 9- to 10-day-old Sprague-Dawley rats that have received butyric acid at two different concentrations (150 mmol/L and 300 mmol/L) and for different time periods were processed for total RNA extraction and Northern blot analysis. Littermates that received normal saline or lactic acid at 300 mmol/L served as controls. The effect of butyrate on ITF gene expression was also examined in vitro with human colonic epithelial LS 174T cells. To further define ITF gene regulation by butyrate, transient transfection assays were performed on a 930 bp human ITF promoter-luciferase reporter gene plasmid in LS174T cells with or without the presence of butyrate. RESULTS: Concurrent with mucosal injury, butyric acid inhibited ITF gene expression in colonic tissues of newborn rats as well as in intestinal epithelial cells in a dose- and time-dependent manner. Furthermore, butyrate reduced ITF promoter report gene activity in transfected LS174T cell, suggesting that butyric acid regulation of ITF gene is by way of a specific ITF promoter. CONCLUSIONS: Butyric acid induced-intestinal mucosal injury in newborn rats is associated with down-regulation of ITF gene expression. The changes in ITF gene expression in vivo may play a role in the pathogenesis of SCFA-induced intestinal mucosal injury.

Animals↗
PubMed2004

Short-chain fatty acids induce colonic mucosal injury in rats with various postnatal ages.

Short chain fatty acids (SCFAs) may play a role in the pathogenesis of neonatal necrotizing enterocolitis. To evaluate the injurious effect of SCFAs on the colonic mucosa of rats at various postnatal developmental stages, we studied a total of 170 newborn Sprague-Dawley rats at postnatal ages days 3, 9, and 23. A 1.8-F silastic catheter or umbilical catheter was inserted rectally deep into the proximal colon of the rats. Rats from each of the three postnatal age groups were randomly divided to receive one of the following distinct SCFA solutions: acetic acid, butyric acid, propionic acid, or a mixture of above SCFAs solutions. An additional subgroup of rats from each of the age groups received normal saline as a control. The concentration of each SCFA solution was 300 mM, and the pH of all solutions was adjusted to 4.0. The volume of administered solution was 0.1 mL/10 g of body weight. After 24 h, all rats were killed and the daily weight change was recorded and proximal colon was collected for histologic examination. A histologic injury score was used to quantify the severity of mucosal injury. The severity of mucosal injury induced by luminal SCFAs administration decreased as the rats matured; by postnatal day 23, the injury caused by SCFAs was minimal. Thus, the severity of the colonic mucosal injury induced by luminal SCFAs is maturation dependent; the immature state of the mucosal defense in early postnatal age in newborn rat may explain its greater vulnerability to luminal SCFAs.

Acetic Acid↗
PubMed2004

The not unreasonable standard for assessment of surrogates and surrogate decisions.

Standard views on surrogate decision making present alternative ideal models of what ideal surrogates should consider in rendering a decision. They do not, however, explain the physician's responsibility to a patient who lacks decisional capacity or how a physician should regard surrogates and surrogate decisions. The authors argue that it is critical to recognize the moral difference between a patient's decisions and a surrogate's and the professional responsibilities implied by that distinction. In every case involving a patient who lacks decisional capacity, physicians and the treatment team have to make judgments about the appropriateness of both the surrogate and the surrogate's decision. They have to assess the surrogate's decisional capacity and attitude toward the patient as well as the reasons that support the surrogate's decision. This paper provides a model for acceptable surrogate decisions and a standard for blocking inappropriate surrogates. Only decisions based on widely shared reasons are allowable for surrogate refusal of highly beneficial treatment.

Decision Making↗
PubMed2004

In utero pesticide exposure, maternal paraoxonase activity, and head circumference.

Although the use of pesticides in inner-city homes of the United States is of considerable magnitude, little is known about the potentially adverse health effects of such exposure. Recent animal data suggest that exposure to pesticides during pregnancy and early life may impair growth and neurodevelopment in the offspring. To investigate the relationship among prenatal pesticide exposure, paraoxonase (PON1) polymorphisms and enzyme activity, and infant growth and neurodevelopment, we are conducting a prospective, multiethnic cohort study of mothers and infants delivered at Mount Sinai Hospital in New York City. In this report we evaluate the effects of pesticide exposure on birth weight, length, head circumference, and gestational age among 404 births between May 1998 and May 2002. Pesticide exposure was assessed by a prenatal questionnaire administered to the mothers during the early third trimester as well as by analysis of maternal urinary pentachlorophenol levels and maternal metabolites of chlorpyrifos and pyrethroids. Neither the questionnaire data nor the pesticide metabolite levels were associated with any of the fetal growth indices or gestational age. However, when the level of maternal PON1 activity was taken into account, maternal levels of chlorpyrifos above the limit of detection coupled with low maternal PON1 activity were associated with a significant but small reduction in head circumference. In addition, maternal PON1 levels alone, but not PON1 genetic polymorphisms, were associated with reduced head size. Because small head size has been found to be predictive of subsequent cognitive ability, these data suggest that chlorpyrifos may have a detrimental effect on fetal neurodevelopment among mothers who exhibit low PON1 activity.

Adult↗
PubMed2003

Sodium and potassium clearances by the maturing kidney: clinical-molecular correlates.

A temporal dissociation exists between the early appearance of sodium absorptive and later detection of potassium secretory processes in the maturing rabbit collecting duct. To extend the latter findings to the human, we sought to correlate developmental changes in renal sodium and potassium clearances with the molecular expression of corresponding ion channels in kidneys of premature infants. In a longitudinal prospective study of 23- to 31-week gestational age (GA) infants, sodium, potassium, and creatinine clearances were measured weekly for 5 weeks and the absolute and fractional excretions of sodium (FE(Na)) and potassium (FE(K)) calculated. Gene-specific probes were used to assess steady-state abundance of mRNA encoding the sodium channel ENaC and potassium channel ROMK in homogenates of human kidneys (obtained from the Anatomic Gift Foundation). Although urinary losses of sodium in infants /=28 weeks and all infants >approximately 32 weeks GA achieved a state of positive balance, a maturational process associated with a decrease in FE(Na )and increase in ENaC. Infants >approximately 30 weeks GA maintained a state of positive potassium balance. We noted a twofold reduction in FE(K )after approximately 26 weeks GA and no change in ROMK abundance during the developmental window studied. We speculate that the developmental regulation of renal ENaC expression contributes, at least in part, to the decrease in FE(Na )observed with advancing GA, and that in the human, as in the rabbit, there is a delay between the maturation of sodium absorptive and potassium secretory pathways.

Creatinine↗
PubMed2003

Ontogeny and prenatal expression of trefoil factor 3/ITF in the human intestine.

BACKGROUND: Trefoil factor 3 (TFF3) or intestinal trefoil factor (ITF), a peptide normally expressed and secreted by goblet cells at the mucosal surface of the small intestine and colon, is important for the maintenance and repair of the intestinal mucosal barrier. AIM: To study the ontogeny and developmental expression of TFF3 in human intestine. SUBJECTS: We examined TFF3 expression in formalin-fixed and paraffin-embedded intestinal tissues from 24 fetuses (gestational age [GA] 12-23 weeks) and 5 adults by immunohistochemical staining. To determine whether TFF3 is excreted into the fetal intestinal tract, first-passed meconium samples were collected from 43 newborn infants (gestational age 24-41 weeks). The presence of TFF3 was examined by Western blot analysis and the relative levels of TFF3 in the meconium were quantified with a slot blot assay. RESULTS: TFF3 can be detected by immunohistochemistry in human intestine as early as 12 weeks gestation. TFF3 is present in the meconium of newborn infants; no significant difference exists in TFF3 levels in the meconium of premature infants with birth weight (BW) less than 1500 g compared to those with birth weight equal to or more than 1500 g. CONCLUSION: Premature infant's susceptibility to intestinal mucosal injury is unlikely to be explained by developmental expression of TFF3 in human intestine since secreted TFF3 is not deficient in premature infants.

Adult↗
PubMed2003

A trial of vitamin A therapy to facilitate ductal closure in premature infants.

OBJECTIVE: To determine whether postnatal vitamin A therapy increased ductal closure rate in premature infants. STUDY DESIGN: This was a prospective, double-blind, placebo-controlled trial. Subjects (n=40) were recruited on day of life 1. Inclusion criteria were premature neonates weighing 500 to 1500 g with an indwelling umbilical line. Vitamin A was administered intramuscularly on days 1, 3, and 7. Blood vitamin A and retinol binding protein levels were obtained on days 1 and 3. Echocardiography was performed on days 1, 3, 7, and 14. Failure of ductal closure was defined as the presence of a moderate to large patent ductus arteriosus on day 14, indomethacin therapy, or surgical ligation. RESULTS: Comparison between the treatment and placebo groups revealed no differences in gestational age, weight, or oxygenation index. Vitamin A and retinol binding protein levels did not differ between the groups at entry but increased significantly after vitamin A treatment. Failure of ductal closure occurred in 22 of 40 babies without any difference between the groups (12/22 vs 10/18, P=NS). Four infants required surgical ligation, all in the treatment group (P=.04). Clinical outcome did not vary between groups. CONCLUSION: Postnatal vitamin A therapy did not improve ductal closure rates in premature infants.

Birth Weight↗
PubMed2003

Midaortic syndrome in the fetus and premature newborn: a new etiology of nonimmune hydrops fetalis and reversible fetal cardiomyopathy.

Nonimmune hydrops fetalis is the final common pathway of many conditions that ultimately result in fetal anasarca. Even after extensive evaluation, the etiology of a small percentage of cases of hydrops remains unknown. We present a case of midaortic syndrome, also known as abdominal coarctation syndrome, in a fetus with hydrops and a severe cardiomyopathy. The clinical manifestations of midaortic syndrome in this fetus and premature newborn, including malignant hypertension and reversible cardiomyopathy, are detailed. The fetal pathophysiology of midaortic syndrome remains speculative, but likely includes fetal hypertension as the cause of cardiac dysfunction. To our knowledge, this is the first report of midaortic syndrome as an etiology for nonimmune hydrops fetalis.

Adult↗
PubMed2003

Meconium enhances the growth of perinatal bacterial pathogens.

OBJECTIVE: To demonstrate the effects of meconium on growth of bacterial pathogens, which are common causes of intra-amniotic infection and neonatal sepsis. METHODS: Meconium collected from 9 healthy neonates was suspended as a 20% solution using sterile saline. In experiment 1, separate test tubes of meconium solution and sterile saline (the control) were individually inoculated with 10(6) colony-forming units of a single species of the following test pathogens: Escherichia coli, Enterococcus faecalis, Group B Streptococcus, Staphylococcus aureus, Pseudomonas aeruginosa, and Listeria monocytogenes. After incubation at 37 degree C for 24 hours, 1 L each of the bacterial-meconium and bacterial-saline solutions was inoculated onto 5% sheep blood agar. After 24 hours of incubation, the number of developing colonies was counted. In experiment 2, equal volumes of meconium and saline solutions were inoculated with 10(5) colony-forming units of either E. coli or Group B Streptococcus. At intervals of 6, 9, and 24 hours post-incubation, 1 L each of the bacterial-meconium and bacterial-saline solutions was inoculated onto 5% sheep blood agar plates, and colonies were counted after overnight incubation. RESULTS: In the first experiment, 24 hours of incubation resulted in bacterial amplification in the meconium solution from an initial inoculum of 10(6) colony-forming units/mL to 10(9) colony-forming units/mL. In contrast, the same inoculation of saline solution (control) showed no increase in colony counts over the same time interval. For E. coli and Group B Streptococcus in experiment 2, growth enhancement in meconium was seen as early as 6 hours, as colony counts of a test species increased from 105 colony-forming units/mL to 10(9)-10(10) colony-forming units/mL. CONCLUSION: Enhanced growth of perinatal pathogens in meconium was constantly observed, and can occur as early as 6 hours after bacterial interaction of meconium.

Bacteria↗
PubMed2002

Variable effects of short chain fatty acids and lactic acid in inducing intestinal mucosal injury in newborn rats.

BACKGROUND: Short chain fatty acids and lactic acid are colonic bacterial fermentation products. METHODS: To evaluate the effects of these organic acids on the intestinal mucosa, a total of 72 newborn Sprague-Dawley rats (10 days old) were studied. A 3.5F catheter was inserted per rectum 4.0 cm deep into the proximal colon for organic acid administration at a volume of 0.1 ml/10 g body weight. The pH of organic acid solutions and normal saline was adjusted to 4.0. Group 1 (n = 10) received normal saline as a control. Group 2 (n = 11) received 150 mM acetic acid. Group 3 (n = 11) received 300 mM acetic acid. Group 4 (n = 10) received 150 mM butyric acid. Group 5 (n = 11) received 300 mM butyric acid. Group 6 (n = 7) received 150 mM lactic acid, and group 7 (n = 12) received 300 mM lactic acid. Animals were killed 24 hours after colonic installation of test solutions. RESULTS: Both 300 mM acetic acid and 300 mM butyric acid were associated with impaired weight gain, increased colon wet weight, and increased histologic injury scores in the colon and distal ileum (P < 0.05, analysis of variance). Both 150 mM acetic acid and butyric acid at 150 mmol/L induced minimal injury in the colon and distal ileum. Neither 150 mM nor 300 mM lactic acid induced any identifiable gross or microscopic intestinal mucosal injury. CONCLUSION: Luminal short chain fatty acids can induce dose-dependent intestinal mucosal injury in newborn rats, resembling the pathology seen in neonatal necrotizing enterocolitis. Overproduction/accumulation of short chain fatty acids, but not lactic acid, in the proximal colon and/or distal ileum may play a role in the pathogenesis of necrotizing enterocolitis in premature infants.

Acetic Acid↗
PubMed2002

Vitamin A supplementation ameliorates butyric acid-induced intestinal mucosal injury in newborn rats.

Vitamin A (vit A) plays an important role in wound healing and therefore may help in repairing of intestinal mucosal injury. The purpose of this study was to determine if vit A supplementation could promote healing in intestinal mucosal injury as commonly seen in neonatal necrotizing enterocolitis (NEC). Mild intestinal mucosal injury was induced in 10-day-old Sprague-Dawley rats by luminal administration of 1.5% butyric acid (BA) at pH 4.0. Normal saline at the same pH was administered as control. Immediately after administrations of BA or normal saline, animals were randomly assigned to receive high dose vit A (20,000 IU/kg for one dose, i.p.), low dose vit A (5,000 IU/kg for two doses) or vehicle. Animals were followed for 48 hours and then sacrificed for histological examination. Rats with BA-induced intestinal mucosal injury had a reduction in daily weight gain (p < 0.05). Vit A supplementation significantly improved the daily weight gain in the rats with BA-induced intestinal mucosal injury and the effect is dose dependent. At sacrifice, the colon wet weight was significantly heavier and the histological injury scores from both ileum and proximal colon higher in the rats with BA-induced intestinal mucosal injury. All of those parameters were improved with vit A supplementation. We conclude that vit A supplementation ameliorates BA induced-intestinal mucosal injury in newborn rats.

Animals↗
PubMed2002

Changes in upper extremity position cause migration of peripherally inserted central catheters in neonates.

OBJECTIVE: The migration of peripherally inserted central catheters (PICCs) from the superior or inferior vena cava into the right atrium can pose a significant risk of lethal pericardial effusion and tamponade secondary to myocardial perforation. Arm movement has been reported to cause displacement of the catheter tip toward the heart and lead to ventricular tachycardia in adults. The objective of this study was to investigate whether adduction or abduction at the shoulder and flexion or extension at the elbow affect the position of PICCs placed via upper limb veins. We also hypothesized that arm movements can be used to reposition malpositioned catheters. METHODS: A total of 280 radiographs of 60 neonates with PICCs inserted via upper limb veins from July 2000 through June 2001 were reviewed. Differences in catheter tip position as a result of abduction versus adduction at the shoulder, flexion versus extension at the elbow, and combination changes in arm posture were determined by measurements in paired radiographs. Correction of malpositioned catheters was attempted in 10 patients by using arm movements without any alterations at the site of insertion. RESULTS: Arm movements were associated with significant displacement of catheters. Catheters that were placed via the basilic or axillary vein migrated toward the heart with adduction of the arm, whereas those that were placed via the cephalic vein moved away from the heart with adduction. Flexion of the elbow displaced catheters that were placed in the basilic or cephalic vein below the elbow toward the heart but did not have any effect on catheters that were placed via the axillary vein. For catheters that were placed in the basilic vein, simultaneous shoulder adduction and elbow flexion caused the greatest movement toward the heart (15.11 +/- 1.22 mm). We were able to reposition correctly inappropriately placed catheters in 9 of 10 patients by using arm movements. CONCLUSIONS: Arm movements significantly affect the position of the tip of the PICCs. Prevention of catheter migration into the right atrium requires radiographic determination of vein of insertion and monitoring of catheter tip position with upper extremity in position of maximum inward movement of catheter for that vein. Arm movements can be used to correct the malpositioned catheters.

Arm↗