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Human Infant Physiology Laboratory
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.
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.
Divisional Core-Lab of Developmental Biology
Vadim Ten
The main focus is research on role of mitochondrial dysfunction in pathogenesis of cellular injury in neonatal diseases: asphyxia, BPD, NEC. Specifically, we study changes in mitochondrial production of ATP and formation of reactive oxygen species, membrane potential, Ca++ upload capacity in response to the modeling of the disease of our interest.
The goal is to identify a molecular target for attenuation of mitochondrial dysfunction and to offer clinically relevant strategy to protect cells from injurious factors (ischemia, oxidative stress, inflammation).
Prognosis, Risk Perception, Informed Consent and Decision Making in Neonatal Care
K. Orfali
In neonatal care many crucially important decisions involve assessing long term consequences in terms of impairments and disabilities, and reliable medical and statistical evidence on the probabilities of the various outcomes often fail to be available. In such a context, the prerequisite of informed consent for parents, a crucial aspect of medical ethics and bedside care, may become elusive because of the potentially subjective nature of the neonatologists prognosis. Dr Orfali's interdisciplinary and international research focuses on risk perception and assessment, exploring how neonatologists elaborate a prognosis and make decisions in critical uncertain cases, when statistical evidence does not exist and probabilistic assessments cannot even be derived from a consensual professional opinion. Among the outcomes of the study, she hopes to develop a practical tool for physician to assess their optimism and pessimism index compared to peers. Other topics of interest are related to ethical dilemmas, parental choices and life and death decision-making as well as shifting paradigms in neonatal care in a cross-cultural perspective.
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.
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