Biomedical subjects
Publications and source records attributed to I Kohane.
A total of 37 girls with a history of benign premature pubarche were followed into puberty; a disproportionate number of girls experienced early menarche. Twenty-five had some degree of acne, 14 had hirsutism, and 5 had acanthosis nigricans. Body mass index (BMI) at initial presentation correlated with postpubertal BMI and was weakly correlated with postpubertal hirsutism.
World Wide Web (Web) technology has become increasingly popular and successful, because it uses standard communication protocols and Hyper Text Markup Language(HTML), and is supported on multiple platforms. Innovations such as server push, secure socket layer and Java make it possible to use the Web as the basis for creating monitoring systems of dynamic processes. This paper presents a project, whose goal is to develop a Web based Intelligent on-line Monitoring system for Intensive Care Units (IMI). IMI has been tested and evaluated in an intensive care unit since October 1995, and the results are promising. After presenting the motivations of using Web technology, we present the system structure and the functionality of IMI as well as the testing and evaluation results. Security issues are also addressed.
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OBJECTIVE: Corticotrophin releasing hormone, a hypothalamic neuropeptide also made in placenta, may regulate fetal maturation in a stress-responsive manner. The objectives of this study were: (1) to determine if levels of corticotrophin releasing hormone in the amniotic fluid correlate with fetal lung maturation; (2) to confirm that third trimester plasma levels of corticotrophin releasing hormone are increased in patients with pregnancy-induced hypertension compared to normotensives, and (3) to increase the recovery of extracted corticotrophin releasing hormone from plasma and amniotic fluid. DESIGN: (1) Levels of corticotrophin releasing hormone in amniotic fluid during the third trimester were compared with those of saturated phosphatidyl choline. (2) Corticotrophin releasing hormone levels were measured in a group of normotensive pregnant women during the entire gestation period. Corticotrophin releasing hormone levels during the third trimester were compared in normotensives and patients with pregnancy-induced hypertension. PATIENTS: Twenty-one non-pregnant normal volunteers and 63 pregnant women. MEASUREMENTS: Blood pressure, corticotrophin releasing hormone in plasma and amniotic fluid, and saturated phosphatidyl choline in amniotic fluid. RESULTS: Corticotrophin releasing hormone levels in amniotic fluid samples during the third trimester ranged from 12 to 98 pmol/l and positively correlated with the saturated phosphatidyl choline levels, but not with gestational age. A significant difference existed in plasma corticotrophin releasing hormone concentration between gestational age-matched third trimester normotensive and hypertensive gravids: corticotrophin releasing hormone levels were significantly lower in normotensives (223 +/- 65 pmol/l) than in patients with pregnancy-induced hypertension (544 +/- 106 pmol/l, P = 0.001). Plasma corticotrophin releasing hormone increased with gestational age from 51 pmol/l (range 8.4-85) at 25-32 weeks to 375 pmol/l (range 35-1386) at 33-40 weeks. During the third trimester the rise in plasma corticotrophin releasing hormone conformed to an exponential mathematical model of a positive feedback loop between placental corticotrophin releasing hormone and fetal adrenal cortisol. CONCLUSIONS: During the third trimester of pregnancy there is a positive correlation between the level of amniotic fluid corticotrophin releasing hormone and that of saturated phosphatidyl choline. The positive correlation between amniotic fluid corticotrophin releasing hormone and saturated phosphatidyl choline, but not between amniotic fluid corticotrophin releasing hormone and gestational age, suggests that a factor(s), such as stress, may affect both amniotic fluid corticotrophin releasing hormone and saturated phosphatidyl choline in parallel. Furthermore, our data are consistent with the hypothesis that the rise in placental corticotrophin releasing hormone is coupled to an increase in fetal glucocorticoid and lung maturation, and that stresses such as pregnancy-induced hypertension may accelerate this process.
This paper describes the construction of a computer model that simulates the hypothalamic-pituitary-adrenal axis (HPA axis) regulation of cortisol production. It is presented to illustrate the process of physiological modeling using standard "off the shelf" technologies. The model simulates components of the HPA axis involved in the continuous secretion and elimination of cortisol, adrenocorticotropin (ACTH), and corticotropin releasing hormone (CRH). The physiological relations of these component pieces were modeled based on the current knowledge of their functioning. Rate constants, half lives, and receptor affinities were assigned values derived from the experimental literature. At its current level of development the model is able to accurately simulate the timing, magnitude and decay of the ACTH and cortisol concentration peaks resulting from the ovine-CRH stimulation test in normal and hypercortisolemic patients. The model will be used to predict the effects of lesions in different components of the HPA axis on the time course of cortisol and ACTH levels. We plan to use the model to explore the experimental conditions required to distinguish mechanisms underlying various disorders of the HPA axis, particularly depression. Efforts are currently underway to validate the model for a large variety of normal and pathological perturbations of the HPA axis.
The control of oxygen delivery to mechanically ventilated newborn infants is a time intensive process that must balance adequate tissue oxygenation against possible toxic effects of oxygen exposure. Investigation in computer assisted control of mechanical ventilation is increasing, although very few studies involve newborn infants. We have implemented a fuzzy controller for the adjustment of inspired oxygen concentration (FIO2) in ventilated newborns. The controller utilizes rules produced by neonatologists, and operates in real-time. A clinical trial of this controller is currently taking place in the neonatal intensive care unit (NICU) of Children's Hospital, Boston, MA.
Exhaustive display of all available clinical data, particular in data-rich environments like the intensive care unit, can easily overwhelm the ability of clinicians to comprehend the clinical status and evolution of their patients and may reduce their ability to detect pathological trends in a reliable and timely manner. SmartDisplay is a system we have designed that restricts the data sets displayed to time-lines of those parameters that are relevant to the patient context and to the particular care provider. The relevance criteria are provided by monitoring programs which may range in complexity from simple threshold alarms to full-fledged diagnostic engines. SmartDisplay can specify which parameters to display and the time intervals during which they should be displayed.
One-, two- and three-locus models of selection and mutation in completely self-fertilizing populations are examined. Equilibrium frequencies can be determined for these systems. Numerical analyses indicate that random genetic drift attributable to selfing plays a major role in determining equilibrium frequencies, even when strong directional selection is operating. Linkage has no effect on marginal gene frequencies or single-locus heterozygosity at equilibrium. The only model of those examined which leads to linkage disequilibrium is disruptive selection. In that model, selection reinforced the effect of selfing in favoring the homozygous genotypes.
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