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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
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 cardiovascualar 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;
- 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.
- 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 ofÊ chronic lung disease among babies
born in a setting of chorioamnionitis vs no evidence of a perinatal
infectious process.
- 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 RNA)
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