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Faculty
Research Collaborations
Human Infant Physiology Laboratory
Sheep and Primate Research
Molecular Biology Laboratory
Epidemiology Studies
Decision Making in the Care of Extremely
Premature Infants
Special Laboratory Tests
Human Infant Physiology Laboratory
Karl Schulze, Rakesh Sahni, Sudha Kashyap, Helen Towers
Despite the many exciting advances being made daily in molecular
biology and molecular genetics, investigation of intact, functioning
human beings still forms the foundation of clinical research.
This is particularly true of developmental human biology.
In some ways, studies of human infants are inordinately difficult.
Each infant is biologically unique, measurements must be noninvasive
and are often unsystematic, important variables are necessarily
uncontrolled or unmeasurable, and studies are often performed
while infants are receiving aggressive and confounding therapies.
But there are advantages as well. Growing low birth weight
infants are available for long periods of observation, their
intake and output can be very accurately measured and controlled,
physical activity is much easier to quantify, and they can
be studied serially across a wide window of development, during
which time body mass may double, or even triple.
Our former director, Dr. Stanley James was among the first
neonatologists to appreciate that a special patient care site(s),
complete with pre-configured, hard-wired instrumentation would
facilitate clinical research in the NICU without impeding
nursing care. Over the last two decades the Human Infant Physiology
Laboratory at Babies & Children's Hospital has focused
on the study of low birth weight infants under actual nursing
conditions. The theme that ties together all studies from
this facility is the measurement of energy expenditure. Energy
expenditure must be investigated from both sides of the equation.
Over the last few years we have studied the relationships
between alterations in the amount and quality of dietary intake
and the associated changes in gaseous metabolism (oxygen consumption
and carbon dioxide consumption). Recently, as evidence accumulates
that early dietary intake may influence cardiovascular health
in adulthood, we have expanded our focus to include studies
of the effects of diet on cardiovascular and metabolic function
with an eye on possible mechanisms for "metabolic programming."
Another major area of interest for our group is the effect
of prone vs supine positioning on the autonomic control of
the heart and lungs.
Sheep and Primate Research
Buddy Stark, Marianne Garland
In the tradition of its founder Dr. Stanley James, the Perinatal
Physiology Laboratory continues as a multidisciplinary center
of research emphasizing investigations into the causes and
consequences of oxygen and substrate deprivation during early
development. Raymond Stark is the principal investigator of
the multidisciplinary Perinatal Emphasis Research Center from
the NICHD. Dr. Stark's project evaluates fetal cardiorespiratory
and neurobehavioral function associated with sleep state and
circadian rhythm to understand differences between the normal
variation in and the adaptive alterations induced by oxygen
deprivation. In separate grants, Dr. Marianne Garland has
defined kinetic models to define the fetal drug exposure from
maternal drug levels through research on the placental transfer
and fetal metabolism of anti-AIDS drugs and opiates in the
non-human primate model. Further studies in this model evaluate
the potential for newly developed antigen delivery system
to induce immune response in the fetus and the possibility
of intrauterine immunization against specific infectious agents
that risk fetal well-being.
Molecular Biology Laboratory
Robert Vosatka
The Division of Neonatology's Molecular Biology Laboratory
is a state-of -the-art facility for advanced molecular techniques.
The laboratory resides in recently renovated space in the
Black Building within room 411. Research within the laboratory
focuses on gene regulation relevant to perinatal physiology.
Currently, the laboratory is investigating the mechanisms
whereby maternal and neonatal diets regulate the adult physiology
of newborns and fetuses. The facility includes extensive gel
electrophoresis and photodocumentation equipment, a PCR thermocycler,
a laminar flow hood for tissue culture and preparation of
PCR reactions, CO2 incubator and support equipment, reverse
osmosis water and glass distillation is readily available.
The laboratory complements the extensive physiologic expertise
of our collaborators both within the Division and in the Department
of Developmental Psychobiology.
Epidemiology Studies
David Bateman
Dr. Bateman has participated in several observational epidemiological
studies related to infants born at Harlem Hospital. These
include descriptions of the effect of intrauterine cocaine
exposure on the growth and neurological status of newborns,the
neurodevelopment of children exposed to cocaine in utero,the
risk factors associated with maternal HIV infection and congenital
syphilis, and the outcome of unattended out of hospital births.
Related studies include cost estimates of intrauterine cocaine
exposure and congenital syphilis.
Decision Making in the Care of
Extremely Premature Infants
J.M. Lorenz
There are many complex issues involved in balancing maternal
and neonatal risks and benefits of intrapartum and neonatal
care of the extremely premature fetus or newborn. These include
maternal morbidity attendant to interventions to prolong pregnancy
in the face of premature labor or complications of pregnancy,
long-term survival and morbidity of the infant, suffering
of the infant and family, parental values and autonomy, and
consumption of limited communal resources. Informed decisions
about whether to administer intensive care to extremely premature
infants require the best data that is feasibly available,
as well as presentation of this information to the parents
in a way that is most comprehendable. Because communal resources
are invariably expended in the care of these infants and because
infants are valued in and of themselves, physicians also need
more explicit direction from the larger community about the
range of options that may be reasonably offered to parents
regarding the care of their extremely premature infant. Dr.
Lorenz' research focuses on these related issues: first, defining
long-term outcomes of the extremely premature infant and exploring
the effect of difference in the application of intensive care
on these outcomes; second, investigating the effect on parental
decisions of varying methods of presenting relevant information
to parents; and, thirdly, developing a systematic approach
to applying cost-effectiveness data and balancing competing
moral values in policy formulation.
Special Laboratory Tests
Joan Regan
Our current laboratory investigations involve use of PCR,
microbiological culture techniques and cytokine assays to
address the following research questions;
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Role of Ureaplasma urealyticum colonization of Very
low birth weight infants in the development of chronic
lung disease. By serially sampling the respiratory tract
of infants< 1500 g by PCR and culture for evidence
of Uu colonization on days 1, 3, 7 and weekly thereafter
until discharge, we have identified three patterns of
colonization among VLBW infants: Persistent, Early Transient
and Nosocomial Colonization. Ours is the first study to
confirm that the later two patterns occur. These patterns
account for 50 % of all Uu colonization in the nursery.
However only Persistent Uu colonization carries a high
risk of developing chronic lung disease. Our future directions
in this area of research include studies to identify factors
which cause persistent colonization and to determine if
the association between persistent Uu colonization and
chronic lung disease is causal or a marker for concurrent
physiological processes which lead to CLD.
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Role of cytokines in tracheal aspirates in the development
of chronic lung disease in VLBW infants. In conjunction
with the Uu studies described above we are collecting
serial samples of tracheal aspirates among intubated VLBW
infants to measure cytokine levels (IL-1B, Il-6, Il-8)
. Our objectives in this study are to relate these levels
to the presence or absence of Uu, and to study the natural
history of the cytokine levels with respect to the development
of chronic lung disease among babies born in a setting
of chorioamnionitis Vs no evidence of a perinatal infectious
process.
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Role of genital co-Colonization in the progression of
maternal HIV infection. By performing serial cultures
for BV, GBS, Chlamydia trachomatis, and Candida species
and monitoring the course of HIV infected mothers we have
demonstrated a significant association with high titer
Candida colonization and Low CD4 counts.
Laboratory Capabilities:
Bacterial cultures-aerobic and anerobic
Fungal cultures-Candida species
Mycoplasma cultures-Ureaplasma urealyticum and
Mycoplasma hominis
Trichomonas vaginalis- Diamond's media cultures
Bacterial Vaginosis-gram stain scoring
Chlamydia trachomatis-tissue culture and Micotrak
Rapid identification methods
GBS-Latex coagglutination and optical immuno assay
Trichomonas and Chlamydia by immunoflourescence
Cytokine assays by ELISA (sera, CSF, Amniotic fluid, cervico
vaginal secretions, tracheal aspirates)
IL-1 beta
TNF alfa
IL-6
I1-8
PCR
Ureaplasma urealyticum
Universal bacterial antigen (16S ribosomal RN)
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