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Biomedical subjects

L Eisenfeld

Publications and source records attributed to L Eisenfeld.

At least 19 recordsLinked to original sources

Hypoplastic left heart syndrome: factors influencing therapeutic choice.

Parent's choices among therapeutic options for their infants born with hypoplastic left heart syndrome are difficult and controversial. Currently, management options include surgical reconstruction, cardiac transplantation, and comfort measures only. We retrospectively reviewed medical records of 47 patients (1989-1999) to create a database of clinical features of infants who received either an operation or comfort care only. Eleven families were interviewed by means of a structured questionnaire pertaining to their experience and reasons for their choice. Of the 47, 20 were prenatally diagnosed and nine of these (45%) aborted. The remaining 38 of the 47 were liveborns. Of the 38, 20/38 (53%) chose comfort care only. The other 18 chose operation. Although 17 were able to survive until first stage repair, only 8/17 (47%) survived beyond five months. At the time of last contact (ages one to 4.5 years), 5/17 (29%) remained alive. Over the nine years an increasing proportion of parents chose operative reconstruction; 8/11 (73%) for 1996-99 vs 10/27 (37%) for 1989-1995. Interviewed families who chose comfort care were more likely to believe the rate of survival following operation was poor, quality of life was diminished, and seemed concerned that their infant would suffer. Influence by optimistic physicians at surgical centers seemed important for an operative choice. Most suggested that provision of written materials, professional family counseling, and support groups of hypoplastic left heart syndrome families are or would be helpful.

Abortion, Induced↗

New syndrome of hydrocephalus, endocardial fibroelastosis, and cataracts (HEC syndrome).

We report on two unrelated male infants with similar findings of communicating hydrocephalus, endocardial fibroelastosis (EFE) and congenital cataracts, who died at 4 months of age. Both mothers reported an upper respiratory infection during the first trimester of pregnancy which was further complicated by polyhydramnios in the third trimester. The infants were diagnosed with bilateral congenital nuclear cataracts at birth. Serologic tests for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, syphilis, and galactosemia screens were negative. Chromosome analyses were normal. Both children developed communicating hydrocephalus between one and three months after birth. Patient 1 died suddenly at 4 months following an upper respiratory infection. Patient 2 developed congestive heart failure and also died at 4 months. At autopsy, both infants had enlarged hearts with endocardial fibroelastosis. No identifiable organism could be isolated. We discuss the association of birth defects in widely separated organ systems in these patients and suggest that this may represent a genetic syndrome; however, a viral etiology cannot entirely be excluded. We believe this is a distinct disorder and propose the acronym HEC for hydrocephalus, EFE and cataracts.

Abnormalities, Multiple↗

Lack of compliance with influenza immunization for caretakers of neonatal intensive care unit patients.

BACKGROUND: Both the Centers for Disease Control and Prevention and the American Academy of Pediatrics have recommended influenza immunizations for neonatal intensive care unit staff. Compliance rates for influenza immunization among neonatal intensive care unit staff have not yet been reported. METHODS: To determine both the rates and the associated factors for compliance between 1990 and 1993 among neonatal intensive care unit nursing staff, interviews were conducted at three Hartford area hospitals by means of a structured questionnaire. RESULTS: Compliance rates at the three hospitals were 15% in 1990 to 1991, 20% in 1991 to 1992, and 17% in 1992 to 1993 (89% sampling of all nurses with direct patient care). Sixty-three percent were not immunized between 1991 and 1993, 26% were vaccinated once, 9% were vaccinated twice, and 2% were vaccinated three times within the 3-year period. Convictions regarding vaccine safety and effectiveness, concern about getting influenza, and awareness of national recommendations for annual influenza immunization were shown to be associated with vaccination compliance. Concern over exposing neonates, peer influence, pain from injection, and previous adverse reaction were not statistically significant factors differentiating compliers from noncompliers. CONCLUSIONS: There is a poor acceptance of the influenza vaccine among our neonatal intensive care unit nursing staff. Educational and research efforts directed toward influenza risks among neonates and vaccine safety and effectiveness, along with incentives to comply, may improve compliance rates.

Attitude of Health Personnel↗

Effect of corticosteroids on the maturation of neutrophil motility in very low birthweight neonates.

Neutrophil (PMN) chemotaxis and chemokinesis were longitudinally studied in a group of 17 neonates with birthweights between 750 and 1250 g. Five of the 17 neonates were treated with prenatal betamethasone to attempt to prevent hyaline membrane disease, six received postnatal dexamethasone in an effort to reduce bronchopulmonary dysplasia, three received both, and three were not treated with corticosteroids. The group of 17 neonates were tested on four separate occasions: (1-2, 3-4, 7-8, and 10-14 postnatal days). PMN chemotaxis and chemokinesis were determined using a standard micropore filter assay. A group of 36 adults was used as additional controls. There were no significant differences noted in PMN chemotaxis or chemokinesis for the corticosteroid vs the noncorticosteroid-treated groups. In the total group of 17 neonates, there was depression in PMN chemotaxis compared with adult values, which lasted at least through postnatal day 8. By day 13 to 14, PMN chemotactic values were similar to those of adults. In contrast, chemokinesis, was depressed during the initial 14 days (except for the first 2 postnatal days). These data suggest that perinatal corticosteroid administration does not affect PMN motility in newborn infants.

Betamethasone↗

Surveillance for influenza in a newborn intensive care unit.

Although influenza may cause fatal neonatal infections, the current prevalence of disease in newborn intensive care units (NICU) is unknown. Furthermore, because compliance of NICU staff with annual influenza immunization is poor, absence of antibody may provide an indication of influenza susceptibility for neonatal patients and staff. We studied our NICU staff and patients during the winter of 1992-93 to determine seroprevalence of influenza antibody and attempted to document infection serologically or by culture in symptomatic staff and by culture in neonatal patients. Before the influenza season commenced or at birth (using cord blood), antibody to influenza A was absent in 9% (4/43) of the staff and 11% (9/83) of the neonatal patients. Antibody to influenza B was absent in 26% (11/43) of the staff and in 37% (31/83) of the neonates. We were able to document influenza serologically in only one nurse during the study. None of our staff or patients had positive cultures; however, we demonstrated a susceptible population of both staff and particularly neonates who need protection. There were study limitations of sampling and a low incidence of influenza in Connecticut for 1993. Nevertheless, continuing surveillance for influenza in NICUs could provide a more rational basis for immunization and prevention practices.

Adult↗

Variable clinical expression of mosaic trisomy 16 in the newborn infant.

Trisomy 16 is common in embryos and fetuses aborted early during development. Mosaicism for trisomy 16 is sometimes encountered during prenatal diagnosis, particularly with chorionic villi biopsy specimens, and, until recently, was thought to be confined to the placenta. However, recently, several liveborn infants with trisomy 16 mosaicism have been described. We report on an additional liveborn infant with trisomy 16 mosaicism and compare the clinical findings with those of the previously reported cases in an attempt to delineate a mosaic trisomy 16 syndrome. Cytogenetic analysis from our patient showed that there was a different proportion of abnormal cells in different tissues and that the anomaly was undetectable in blood lymphocyte cultures. This observation was consistent with some of the previous reports. DNA analysis of parents and child was carried out using a polymorphic dinucleotide marker that maps to the long arm of chromosome 16. This analysis showed that the extra chromosome 16 in the infant was maternal in origin and suggested that the nondisjunction was probably a first meiotic division error. Our results suggest that an investigation of multiple tissues is required before concluding that mosaicism is confined to the placenta. We conclude that a finding of trisomy 16 mosaicism at prenatal diagnosis should be regarded with extreme caution. This diagnosis may be associated with a highly variable phenotype that may occasionally be compatible with extrauterine life.

Abnormalities, Multiple↗

Cytomegalovirus antibody detection in blood donors and mothers of very low birth weight neonates by using three serologic methods.

We compared three serologic methods for cytomegalovirus (CMV) antibody detection and determined the CMV antibody seroprevalence of blood donors and mothers of very low birth weight (less than 1250 g) neonates in the Greater Hartford region. CMV serology was determined for 577 healthy blood donors as well as for 147 mothers of premature infants. Plasma from blood donors and sera from mothers were tested by either latex agglutination (LA) or by an immunofluorescent antibody assay (IFA), and results were compared with those from an enzyme-linked immunosorbent assay (ELISA). Sensitivity and specificity for LA to ELISA were significantly better than for IFA to ELISA [sensitivity 79/81 (97%) vs 171/202 (85%), and specificity 90/94 (96%) vs 257/347 (74%), p less than 0.01]. These differences remained whether plasma or sera were tested. Borderline values explained only two (33%) of six LA-ELISA as well as only 70 (58%) of 121 IFA-ELISA discordance. CMV seroprevalence rate for the donor blood population was 38%, and for the mothers was 53%. The LA assay is superior to the IFA assay for CMV screening of blood donors and maternal populations.

Antibodies, Viral↗

Enhancement of neonatal neutrophil motility (chemotaxis) with adult fresh frozen plasma.

We examined the effect of adult fresh frozen plasma (FFP) on neonatal neutrophil (PMN) motility (chemotaxis) using a micropore filter assay. Adult FFP was transfused into 13 neonates receiving FFP transfusion for suspected life-threatening sepsis. Blood was obtained from neonates before and after FFP transfusion for assessment of PMN chemotaxis. An increase in PMN chemotaxis was noted in 12 of the 13 neonates following FFP transfusion, with a mean percentage increase of 12 +/- 3% (p less than 0.01). PMN chemotaxis increased 13 +/- 2% (p less than 0.01) in four bacteremic infants and 11 +/- 5% (p = 0.06) in nine infants without bacteremia. Adult FFP transfusion may enhance impaired neonatal PMN motility and improve outcome from infection in newborn infants.

Adult↗

Modulation of neonatal neutrophil function by pentoxifylline.

Immunomodulating agents are being investigated for treatment of infection in newborn infants where morbidity and mortality remain high despite the continued development of new antibiotics. We studied the effect of the methylxanthine pentoxifylline on polymorphonuclear leukocyte (PMN) chemotaxis, F-actin content, and phagocytic activity as measured by nitroblue tetrazolium reduction and H2O2 production in neonates and adults to determine whether pentoxifylline might be useful in augmenting PMN function. The drug was found to have a dose-dependent effect on both neonatal and adult PMN function with enhancement at lower concentrations and suppression at higher concentrations. PMN chemotaxis increased 42% (p less than 0.01) in neonates and 16% (p less than 0.05) in adults at 100 micrograms/mL of pentoxifylline and it decreased 4 and 25%, respectively, at 4000 micrograms/mL. PMN nitroblue tetrazolium reduction increased by 34% in neonates and 23% (p less than 0.05) in adults at 100 micrograms/mL of pentoxifylline and decreased by 52 (p less than 0.01) and 74% (p less than 0.01), respectively, at 2000 micrograms/mL. Similar dose-dependent responses were noted with F-actin content and H2O2 production. These and other observations support the hypothesis that pentoxifylline has a broad range of effects on PMN but that a primary effect is alteration of PMN deformability. Pentoxifylline has potential clinical use as an immunomodulator in augmenting impaired PMN function in neonates and other immunocompromised hosts or in suppressing excessive PMN activity in certain disease processes.

Actins↗

Enhancement of neutrophil function for treatment of neonatal infections.

Newborn infants are at increased risk of morbidity and mortality from infection despite the continued development of new antibiotics. Because impairment of such host defense mechanisms as PMN function is thought to be largely responsible for this problem, correction of these defects in neonates offers a new and potentially important therapy against infection. Further studies are necessary to determine whether transfusion of either adult PMNs, antibody or fresh frozen plasma; administration of immunomodulating drugs; or some combination of these will provide maximum therapeutic benefit for the newborn infant with infection.

Humans↗

Characterization of nonmotile neutrophil subpopulations in neonates and adults.

Previous studies have demonstrated that polymorphonuclear leukocytes (PMN) are not a homogeneous population of cells but differ significantly in their structure and function. PMN move at varying rates, and a fraction estimated from 20 to 70% do not move at all in response to chemotactic stimuli. To characterize this PMN subpopulation better, we studied PMN motility in neonates and adults using a polycarbonate micropore filter chemotactic assay and the 31D8 MAb. Most PMN strongly bind 31D8 MAb (31D8 "bright"), but a minority (31D8 "dull") weakly bind the antibody and in this respect are similar to immature PMN precursors. The 31D8 "dull" PMN have impaired function compared with 31D8 "bright" PMN. In the present study, a PMN subpopulation that failed to migrate using the micropore filter assay accounted for 58 +/- 7% of adult PMN and was similar to the migrating subpopulation in regard to viability and phagocytic function. The nonmotile subpopulation had a higher percentage of bands (5 +/- 3% versus 1 +/- 2%, p less than 0.01) and decreased binding of 31D8 MAb compared with the motile subpopulation. Neonates had a larger nonmigrating PMN subpopulation and 31D8 "dull" PMN subpopulation than those of adults (76 +/- 3% versus 58 +/- 7%, p = 0.04 and 26 +/- 11% versus 8 +/- 2%, p less than 0.01, respectively). These data indicate that although PMN appear morphologically as a homogeneous population of cells, there exists a viable, nonmotile PMN subpopulation that may be less mature than the motile PMN subpopulation. They also indicate that impaired neonatal PMN motility may be attributable in part to an increased size of the nonmotile PMN subpopulation.

Adult↗

The effect of betamethasone on neonatal neutrophil chemotaxis.

Antenatal maternal glucocorticoid administration has been widely used to accelerate fetal lung maturation. Glucocorticoids have also been used postnatally in selected neonates as antiinflammatory agents. Numerous studies have shown that glucocorticoids inhibit multiple components of the immune system including neutrophil (PMN) function in children and adults. Since PMNs are of critical importance in host defense against bacterial infection, impaired PMN function in newborn infants is thought to be an important cause of their increased morbidity and mortality from bacterial infection. Further compromise of neonatal PMN function by exogenous factors such as glucocorticoids may therefore be of significant clinical importance. A micropore filter chemotactic assay was used to determine the in vitro effect of betamethasone on the random migration and directed migration (chemotaxis) of PMNs from 18 neonates. The addition of a concentration of betamethasone (0.01 microgram/ml) similar to that found in cord blood following a standard dose administered to the mother resulted in a significant (p less than 0.01) inhibition in mean neonatal PMN random migration (-15.0 +/- 0.8%) and chemotaxis (-23.5 +/- 3.0%). A similar inhibition was not found when PMNs from 14 adults were exposed to the same concentrations of betamethasone. Betamethasone administration to pregnant women or their newborn infants may further impair PMN motility and lead to an increased morbidity and mortality from bacterial infection in neonates.

Bacterial Infections↗

Pentoxifylline enhancement of defective neutrophil function and host defense in neonatal mice.

Decreased neutrophil (PMN) chemotaxis is thought to contribute to the increased morbidity and mortality from infection in newborn infants. Pentoxifylline, a methylxanthine, has previously been shown to augment PMN chemotaxis in vitro. The authors therefore investigated the effects of pentoxifylline on 1) in vitro PMN chemotaxis, 2) in vivo leukocyte accumulation, and 3) protection against Staphylococcus aureus infection in newborn mice. Using a modified Boyden chamber system, they demonstrated that pentoxifylline significantly enhanced neonatal PMN chemotaxis in a dose-dependent manner. Additionally, pentoxifylline was found to increase PMN accumulation in vivo in a proteose peptone-induced peritonitis model. Finally, the survival rate in experimentally induced S aureus infection was 51% in neonatal mice given pentoxifylline, compared with 17% in a control (nonpentoxifylline) group (P less than 0.01). These data demonstrate pentoxifylline modulation of PMN migration and enhancement of host defense against bacterial infection.

Animals↗

Polymorphonuclear leukocyte adherence and chemotaxis in stressed and healthy neonates.

Defects in polymorphonuclear neutrophil (PMN) adherence and chemotaxis in neonates are thought to be an important cause of their increased susceptibility to overwhelming bacterial infection. Few studies of these functions have been carried out in stressed neonates who are at even greater risk of infection. PMN adherence and chemotaxis were examined in 33 stressed neonates with acute lower respiratory illness, 13 healthy neonates, and 43 healthy adults using whole blood PMN adherence and chemotaxis assays. PMN chemotaxis was significantly decreased in stressed neonates (locomotion index of 38.4 +/- 9.7 micron) compared with that of healthy neonates (48.9 +/- 12.8 micron, p less than 0.01) or adults (61.6 +/- 11.9 micron, p less than 0.001). PMN chemotaxis was studied during illness and recovery in 13 of the 33 stressed neonates and showed significant improvement during recovery (41.6 +/- 9.9 and 53.2 +/- 11.9 micron, respectively, p = 0.012). PMN adherence was decreased in stressed neonates (1.4 +/- 1.6%) compared with that of adults (12.3 +/- 11.4%, p less than 0.01) but was similar to that of healthy neonates (1.1 +/- 1.4%). These findings suggest that further impairment of PMN chemotaxis in stressed neonates helps account for their increased susceptibility to overwhelming bacterial infection.

Adult↗