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Biomedical subjects

I R Holzman

Publications and source records attributed to I R Holzman.

At least 19 recordsLinked to original sources
PubMed1998

Gestational age-dependent extravillous cytotrophoblast osteopontin immunolocalization differentiates between normal and preeclamptic pregnancies.

PROBLEM: Normal placentation requires modulation of proliferative cytotrophoblast to an invasive phenotype. Preeclampsia is characterized by failed cytotrophoblast invasion and arterial remodeling. Osteopontin (OPN) is an extracellular matrix protein implicated in cell adhesion, spreading, and invasion. METHOD OF STUDY: To investigate gestational age-related OPN expression, placental immunostaining was performed. To investigate the role of OPN in uteroplacental vascular pathology, placental immunostaining from pregnancies with preeclampsia (n = 12), fetal growth retardation (FGR) (n = 8), or both (n = 4) was compared with gestational age-matched controls (n = 24). RESULTS: In non-preeclamptic pregnancies, OPN immunolocalized to basal plate and intervillous cytotrophoblasts from 24-30 weeks (n = 13). In preeclampsia, OPN immunoreactivity was detected from 24-40 weeks. Cytotrophoblasts from FGR placentas were OPN-positive until 30 weeks, unless preeclampsia accompanied the FGR. In this case, cytotrophoblasts were OPN-positive from 24-40 weeks. CONCLUSIONS: The data suggest a role for OPN in cytotrophoblast invasion of the maternal vasculature/extracellular matrix during non-preeclamptic placentation, and OPN may serve as a marker for placental bed remodeling.

Diagnosis, Differential↗
PubMed1998

Noninvasive estimation of serum bilirubin.

OBJECTIVE: The aim of this study was to evaluate the accuracy and clinical usefulness of a new computer-driven, hand-held device (Chromatics Colormate III) to estimate serum bilirubin from skin-reflectance (skin color) of neonates. STUDY DESIGN: A total of 2441 infants (both term and premature) at two hospitals had repeated measurements of transcutaneous bilirubin. Of these infants, 900 had one or more laboratory determinations of serum bilirubin. Many of the infants had early measurements of skin color before the onset of jaundice. A visual estimate of the degree of jaundice was made by a health care worker when the laboratory study was drawn. A subgroup of 61 infants was also studied while undergoing phototherapy with a total of 284 comparisons obtained. The reproducibility of the instrument was assessed separately using standardized color tiles and repeated measurements by multiple operators. RESULTS: The range of serum bilirubin measurements that had concurrent skin color measurements was 3.22 to 338.1 micromol/L (0.2 to 21 mg/dL). The linear regression indicated an r = 0.956, and 95% of the skin color measurements were within 32.2 micromol/L (2.0 mg/dL). There was no interference with the accuracy of the device because of infant race or weight, or because of the use of phototherapy. The device provided reproducible information when infants were tested repeatedly over 30 minutes; the coefficient of variation for the transcutaneous bilirubin measurement was 3.1% around a mean estimate of 135.32 micromol/L (8.4 mg/dL). CONCLUSION: The Chromatics Colormate III allows for a clinically useful estimate of serum bilirubin in a wide variety of infants. By using a color discrimination algorithm and obtaining a skin measurement before the onset of icterus, this instrument can provide valuable clinical information that obviates the need for serum bilirubin determinations. Its use in newborn nurseries may allow physicians to shorten length of stay more safely and decrease the use of invasive blood tests.

Algorithms↗
PubMed1997

Comparison of Infasurf (calf lung surfactant extract) to Survanta (Beractant) in the treatment and prevention of respiratory distress syndrome.

OBJECTIVE: To compare the relative safety and efficacy of Infasurf (calf lung surfactant extract; ONY, Inc, Amherst, NY, IND #27169) versus Survanta (Beractant, Ross Laboratories, Columbus, OH) in reducing the acute severity of respiratory distress syndrome (RDS) when given at birth and to infants with established RDS. DESIGN: A prospective, randomized, double-blind, multicenter clinical trial. SETTING: Thirteen neonatal intensive care units participated in the treatment arm: seven of these concurrently participated in the prevention arm. PATIENTS: The treatment arm enrolled infants of </=2000 g birth weight with established RDS, and the prevention arm enrolled infants of </=29 weeks' gestation with birth weights <1250 g. INTERVENTION: Infants were randomly assigned to receive Infasurf (n = 303, treatment arm; n = 180, prevention arm) or Survanta (n = 305, treatment arm; n = 194, prevention arm) in accordance with the Survanta package insert instructions. OUTCOME MEASURES: We projected a 25% reduction between groups in the need for a third dose of surfactant for infants with established RDS, and a 25% reduction in the need for a second dose of surfactant for infants who received prophylactic surfactant. Secondary outcomes included the severity of RDS measured by inspired oxygen concentrations and mean airway pressure, air leaks, complications associated with surfactant administration, and survival to 36 weeks' postmenstrual age without the need for oxygen supplementation. RESULTS: In the treatment arm, there was no difference between groups in the number of infants requiring more than two doses of surfactant. The interval between doses was significantly longer for Infasurf, suggesting an increased duration of treatment effect. The inspired oxygen concentration and mean airway pressure were lower in the Infasurf infants during the first 48 hours in the treatment arm. In the prevention arm, there were no differences with respect to the number of surfactant doses. The dosing intervals were longer for Infasurf infants after the second dose. No difference in inspired oxygen or mean airway pressure was noted during the first 72 hours. There were no significant differences in the incidence of air leaks, complications associated with dosing, complications of prematurity, mortality, or survival without chronic lung disease in the prevention or treatment arm. CONCLUSIONS: Infants treated with Infasurf have a modest benefit in the acute phase of RDS. Infasurf seems to produce a longer duration of effect than Survanta.

Age Factors↗
PubMed1996

Neonatal jaundice: when to treat, when to watch and wait.

What clinical circumstances call for aggressive treatment of jaundice in newborns? Is cessation of breast-feeding necessary to help bring down the high bilirubin concentration? When should phototherapy be started--and stopped? The authors address these and other questions in this thorough guide to differential diagnosis and management of neonatal jaundice.

Bilirubin↗
PubMed1995

Metabolic correlates of neurologic and behavioral injury after prolonged hypothermic circulatory arrest.

Thirty-two inbred weanling puppies were divided into four groups to study the effect on cerebral blood flow and metabolism of different hypothermic strategies for cerebral protection similar to those used during cardiac operations in infancy. All animals were cooled to 18 degrees C. The animals in the hypothermic control group were immediately rewarmed. One group underwent 30 minutes of hypothermic circulatory arrest at 18 degrees C; another group had 90 minutes of hypothermic circulatory arrest at 18 degrees C, and the final group had low-flow cardiopulmonary bypass (25 ml/kg per minute) at 18 degrees C for 90 minutes. All animals had preoperative and postoperative neurologic and behavioral evaluation and extensive intraoperative monitoring of cerebral blood flow, cerebral vascular resistance, and oxygen and glucose uptake and metabolism: quantitative electroencephalography was also monitored before, during and after operation, but those results are reported separately. Two animals in the 90-minute arrest group died, and all the survivors showed evidence of clinical, neurologic, and behavioral impairment on postoperative day 1, with residual abnormalities in all but one animal on day 6. In contrast, the survivors in all the other groups showed no significant clinical or behavioral sequelae. Cerebral metabolism was reduced only to 32% to 40% of baseline values at 18 degrees C in all groups, although systemic metabolism was only 16% of normal. Cerebral metabolism returned promptly to baseline in all groups during rewarming and remained at baseline levels throughout the 8 hours of follow-up. Cerebral blood flow showed marked hyperemia in the hypothermic arrest groups during rewarming but then significant reductions below baseline values in all groups except the controls at 2 and 4 hours after the operation, lasting as late as 8 hours after the operation in the 90-minute arrest group. Cerebral vascular resistance showed increases in all groups at 2 and 4 hours after the operation, which persisted in the 90-minute arrest group at 8 hours. Cerebral metabolism was maintained at baseline levels despite postoperative decreases in cerebral blood flow and increases in cerebral vascular resistance by increases in oxygen and glucose extraction. The result was very low sagittal sinus oxygen saturations in all groups, most marked in the 90-minute arrest groups, which had a saturation of only 24% 8 hours after the operation. Our data show a severe, prolonged disturbance in cerebral blood flow and cerebral vascular resistance after 90 minutes of hypothermic circulatory arrest at 18 degrees C, which correlates with clinical evidence of cerebral injury.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Maternal and neonatal risk factors for cryptorchidism.

We assessed risk factors for cryptorchidism in a prospective hospital-based cohort study at Mount Sinai Hospital in New York City. We examined at birth 6,699 singleton male neonates who were delivered between October 1987 and October 1990. Follow-up examinations were undertaken at 3 months and 1 year for those diagnosed as cryptorchid at birth. We calculated prevalence ratios and adjusted odds ratios according to selected maternal and neonatal characteristics for those who remained cryptorchid at the 1-year assessment. We found elevated risks for maternal obesity [prevalence ratio = 2.42; 95% confidence interval (CI) = 1.11-5.27], for infants delivered by cesarean section (adjusted odds ratio = 2.17; 95% CI = 1.29-3.65), for low birthweight (adjusted odds ratio = 2.29; 95% CI = 1.12-4.70), for preterm birth (adjusted odds ratio = 2.25; 95% CI = 1.16-4.35), and for infants with congenital malformations (prevalence ratio = 13.97; 95% CI = 1.27-26.67). We observed a seasonal effect, with a peak in births of cryptorchid infants during September through November and a smaller peak during the months of March through May. We found no evidence that young women, white women, or primiparas were at increased risk.

Birth Weight↗
PubMed1994

New perspectives on neonatal hyperbilirubinemia.

Notwithstanding a number of advances in the understanding of hyperbilirubinemia and its treatment in the newborn, controversy continues. The trend has been to decrease interventions and observe and manage infants with jaundice as outpatients. This trend will probably prove to be both medically and economically sound. In the absence of significant hemolysis or other underlying medical conditions such as infection, many physicians are now comfortable with expectant observation for those healthy full-term infants with serum bilirubin measurements of less than 18 mg/dL. New thinking about this condition and advances in treatment may transform hyperbilirubinemia in neonates into a medical curiosity.

Bilirubin↗
PubMed1993

Prevalence and natural history of cryptorchidism.

OBJECTIVE: A prospective hospital-based cohort study was conducted to determine the prevalence rates of cryptorchidism at birth, 3 months, and 1 year of age. DESIGN: A total of 6935 consecutive male neonates delivered at Mount Sinai Hospital in New York City between October 1987 and October 1990 were examined at birth for cryptorchidism. Standardized examination and classification criteria were used. Infants classified as cryptorchid at birth were reexamined at 3 months and 1 year after the expected date of delivery. RESULTS: Of 6935 neonates assessed at birth, 255 (3.7%) were found to be cryptorchid at birth. The rates were significantly elevated for low birth weight, preterm, small-for-gestational age, and twin neonates. The overall rate had declined to 1.0% by the 3-month assessment and 1.1% at the 1-year assessment. Although the rates at the 1-year assessment tended to be higher for low birth weight and preterm infants, no significant group differences were observed. CONCLUSIONS: Since the prevalence rates in this study are similar to those reported several decades ago, these data provide no evidence that the rate of cryptorchidism has increased either at birth or by 1 year of age. Furthermore, most testes that descend spontaneously do so within the first 3 months after the expected date of delivery.

Confidence Intervals↗
PubMed1992

Cerebral blood flow and metabolism in hypothermic circulatory arrest.

Although hypothermic circulatory arrest has been accepted for use in cardiovascular operations, the potential for cerebral injury exists. The mechanism of the cerebral injury remains unclear. To address these questions we studied cerebral blood flow and metabolism. Sixteen puppies were randomly assigned to undergo either 45 or 90 minutes of hypothermic circulatory arrest after perfusion/surface cooling to 13 degrees C. Cerebral blood flow, cerebral oxygen and glucose metabolism, and cerebral vascular resistance measurements were obtained at 37 degrees C, 13 degrees C, 10 minutes after reperfusion, 30 degrees C and 2 and 4 hours after hypothermic circulatory arrest. No neurologic or behavioral changes were observed in any of the long-term survivors (11/16). Metabolic and cerebral blood flow data did not differ between groups. Cerebral blood flow was significantly lower in the late postarrest measurements, whereas oxygen and glucose consumption had returned to baseline values. In the presence of low cerebral blood flow and high cerebral vascular resistance it is notable that control levels of oxygen consumption were attained by abnormally high oxygen extraction. These data strongly suggest a vulnerable interval after hypothermic circulatory arrest in which cerebral metabolism is limited by cerebral blood flow.

Animals↗
PubMed1992

Effect of prazosin on hypoxemia-induced blood flow redistribution in the newborn piglet.

We examined the effect of the alpha 1-adrenergic antagonist prazosin on blood pressure, left ventricular output and blood flow redistribution during normoxemia and mild hypoxemia in the chronically instrumented, unanesthetized newborn piglet employing the radiolabeled microsphere technique. Prior to prazosin, hypoxemia caused increases in aortic pressure and blood flows to the brain, myocardium and diaphragm, accomplished by small, statistically insignificant decreases in flows to the carcass and viscera without an increase in cardiac index. Prazosin treatment during normoxemia caused a fall in blood pressure and resulted in greater blood flows of left ventricular origin to the carcass, myocardium and lung. Hypoxemia after prazosin administration increased not only aortic pressure and blood flows to the brain, myocardium and diaphragm, but also, unlike the situation before drug treatment, cardiac index. Thus, in the newborn piglet, the maintenance of critical organ oxygen delivery during hypoxemia is not blocked by prazosin, but is accomplished by an increase in cardiac index rather than simply by redistribution of blood flow.

Animals↗
PubMed1990

Evolving issues in surrogate motherhood.

Surrogate mothering is an arrangement whereby a woman who gives birth to an infant intends--through a contractual agreement--to give that baby to another couple. The recent Baby M case in the United States has raised numerous legal concerns causing many legislative bodies to consider possible statutes to regulate or prohibit surrogacy. The competing interests among and between the individuals involved in this relationship (i.e., the surrogate mother, the couple, the baby, and society) suggest various ethical issues related to benefits, risks, and autonomy. Legal and ethical concerns surrounding the technologically possible procedure of surrogate motherhood are discussed.

Adoption↗
PubMed1989

The effect of aminophylline on gastrointestinal blood flow and oxygen metabolism in the conscious newborn lamb.

Aminophylline, widely used in the neonatal period, has been reported to be associated with necrotizing enterocolitis. We hypothesized that aminophylline might alter gastrointestinal blood flow and oxygen delivery. The effects of this drug on gastrointestinal (GI) blood flow and oxygen delivery, consumption, and extraction were examined using the radioactive microsphere method in ten chronically catheterized, unanesthetized lambs aged 5-12 days. While cardiac output and systemic oxygen consumption did not change, we found statistically significant increases (p less than 0.05) in small intestinal blood flow as a function of lamb weight and as a percentage of cardiac output. Splanchnic oxygen consumption also increased significantly. The oxygen reserve available to the GI tract can be compromised by aminophylline at levels similar to those used in the human neonate for treatment of apnea.

Aminophylline↗