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Biomedical subjects

I D Frantz

Publications and source records attributed to I D Frantz.

At least 73 records · Page 4Linked to original sources

Lipids and atherosclerosis.

More than 50 years ago the observation was made that the prevalence of atherosclerosis is unusually low among some of the world's populations. Shortly thereafter came the suggestion that this circumstance is due to the low fat content of their diets and the low cholesterol concentration in their blood. Efforts to apply this thinking for the benefit of human health have taken various turns. The first approach was to recommend a low-fat diet. It was thought that the type of fat in the diet was immaterial and that the dietary cholesterol content made no difference either. Later, it was shown that excellent falls in blood cholesterol could be obtained with high-fat diets if most of the fat was polyunsaturated. Dietary cholesterol was found to play a role, but it must be held at exceptionally low levels before its importance becomes evident. Recently, we have become fearful of excessively high intakes of polyunsaturated fats because no population has consumed such a diet over a long period of time and because of suggestive experimental and epidemiological evidence that the incidence of some forms of cancer may be increased. A low-fat, low-cholesterol diet is the preferred prescription for hyperlipidemia.

Animals↗

Intercostal muscle reflexes and sleep breathing patterns in the human infant.

Breathing variability and apnea characteristic of rapid eye movement (REM) sleep was investigated in a newborn infant with complete interruption of intercostal to phrenic neural pathways due to intrapartem transection of the cervical spinal cord. Breath-to-breath variability in inspiratory duration (TI), breath duration (Ttot), tidal volume (VT), and ventilation (VI) was significantly greater in REM than in quiet sleep and was similar to the variability in these parameters seen in normal infants. In addition, brief periods of diaphragmeatic apnea were observed during REM sleep. The phenomenon of shortened TI during airway occlusion previously attributed to intercostal-to-phrenic reflexes was examined in the quadriplegic infant and in seven healthy term infants. The frequency of this response was increased when airway occlusion was delayed until after onset of inspiration. Shortening of TI by occlusion occurred no less frequently in the quadriplegic than in the control infants. The constant paradoxical inward movement of the rib cage during inspiration observed in the quadriplegic infant suggests that supraspinal innervation of intercostal muscle limits such paradoxical movements in the normal infant. The quadriplegic infant's end-expiratory volume was consistently above his passive functional residual capacity, as inferred from respiratory volume and pressure measurements.

Birth Injuries↗

Functional delay in lung maturation in fetuses of diabetic rabbits.

Lung maturation was studied in fetuses of rabbits made diabetic with alloxan. Lung maturation was examined functionally with pressure-volume curves and by determining surfactant content of lung lavage on a surface balance, and biochemically by measuring disaturated phosphatidylcholine content (DSPC) and lecithin: sphingomyelin ratio (L/S) of lung lavage and DSPC content of lung tissue. Pressure-volume curves of 27.5-day fetuses of diabetic does demonstrated less deflation stability. Functional assessment of pulmonary lavage surfactant measured on a surface balance was less in diabetic fetuses at both 27.5 and 29.5 days of gestation. There were no differences in DSPC content or L/S of lung wash or DSPC in whole-lung tissue between diabetic and control fetuses. The discordance between surfactant function and concentrations of major surfactant phospholipids suggests that surfactant in fetuses of diabetic animals is qualitatively different from that in the normal fetus. These findings may explain why analysis of amniotic fluid phospholipid content sometimes fails to predict risk of respiratory distressed syndrome correctly in human diabetic pregnancies.

Alloxan↗

Cortisol reversal of functional delay of lung maturation in fetuses of diabetic rabbits.

Lung maturation was examined in fetuses of rabbit does made diabetes with alloxan and then given cortisol or saline injections in late gestation. We have previously demonstrated decreased deflation stability and decreased functional surfactant by surface balance without change in lung lavage lecithin-to-sphingomyelin ratio (L/S) or disaturated phosphatidylcholine content (DSPC) in offspring of alloxan rabbits. Pressure-volume curves of fetuses of alloxan rabbits treated with cortisol demonstrated deflation stability intermediate between alloxan and control fetuses. Functional assessment of pulmonary lavage surfactant determined by surface balance was increased to control levels in fetuses of alloxan-cortisol does. There were no changes in DSPC content or L/S in lung lavage among fetuses from control does, those treated with alloxan, or those treated with alloxan than cortisol during late gestation. These findings suggest that maternal cortisol administration in the alloxan diabetic rabbit model produces a specific reversal of the functional delay of lung maturation caused by alloxan diabetes.

Air Pressure↗

Morphologic disturbance of lung maturation in fetuses of alloxan diabetic rabbits.

Maturation of lungs was studied morphologically in fetuses of does made diabetic with alloxan. The lungs of fetuses of does treated with alloxan 24 h after mating appeared to be less mature than control lungs, as shown by significant decrease in areal density of air space (p < 0.01) and by increases in areal density of alveolar epithelium and capillaries (p < 0.02). In alloxan fetuses, ultrastructural techniques revealed that type II cells had 10 times the control value for areal density of glycogen (p < 0.01) and 2.5 times that of rough endoplasmic reticulum (p < 0.05), but the proportion of type II cells and the number of lamellar bodies per type II cell profile were similar in both groups. Ultrastructural examination of capillaries demonstrated that their migration and the fusion of their basement membrane with that of alveolar epithelium did not occur as frequently in alloxan fetuses as in control fetuses. Biochemically, the lungs of alloxan fetuses contained significantly more glycogen and protein (p < 0.01) than control lungs, but the deoxyribonucleic acid was similar. The alloxan fetuses had a disturbance of lung structural maturation that was consistent with our previous findings of delayed functional maturation without accompanying change in disaturated phosphatidylcholine levels and ratio of lecithin to sphingomyelin.

Animals↗

Phospholipid synthesis in lung slices from fetuses of alloxan diabetic rabbits.

To investigate the effect of maternal diabetes on pulmonary phospholipid metabolism, we studied fetuses of rabbit does made diabetic with alloxan. Incorporation of radiolabeled choline into total and saturated phosphatidylcholine was measured in vitro in lung slices from 27.5 days gestation fetuses. No difference in choline incorporation was found between the diabetic and control groups even when disaturated phosphatidylcholine was measured. It was concluded that the previously described physiologic differences (i.e., decreases in lung deflation stability and surface activity of lung lavage) between fetuses of alloxan-diabetic and control rabbits must be due to some mechanism other than imparied phosphatidylcholine biosynthesis by the choline incorporation pathway.

Animals↗

Inhibition of cholesterol synthesis in mammary tissue, lung, and kidney following cholesterol feeding in the lactating rat.

Pregnant rats were randomly allocated to one of 3 experimental dietary groups: Group 1 -- 15.5% butter, 2% cholesterol, 0.78% sodium cholate purified diet; Group 2 -- standard rat diet with the addition of 10% lard and 2% cholesterol, and Group 3 -- standard rat diet. Plasma and milk cholesterol at 10 days postpartum were significantly elevated in dams fed exogenous cholesterol. The rat of incorporation of [1-14C] acetate into digitonin-precipitable sterols of mammary tissue slices from dams in Group 1 and Group 2 was eight-fold and two-fold, respectively, less than controls. Mammary tissue cholesterol was greater in dams fed detary cholesterol. Thus, our data, for the first time, demonstrate that cholesterol synthesis in lactating rat mammary tissue is suppressed following cholesterol feeding. In a second experiment, the rate of incorporation of [1-14C] acetate into digitonin-precipitable sterols in kidney and lung tissue of Group 1 rats was suppressed; however, this response was not as marked as that observed in lactating mammary tissue. The concentration of cholesterol in kidney and lung was greater than controls. These results suggest that extrahepatic inhibition of cholesterol synthesis exists in the rat with a concomitant increase in tissue cholesterol.

Animals↗

Muscle relaxation in mechanically ventilated infants.

We evaluated the effect of muscle paralysis on gas exchange and incidence of pneumothorax in 35 severely ill infants on mechanical ventilation. Pancuronium (0.1 mg/kg) was given repeatedly until spontaneous respirations ceased in infants with inadequate gas exchange with FIO2 greater than 0.60, or peak inspiratory pressure greater than 30 cm H2O, or who were breathing out of phase with the respirator. Of 27 infants who had an alveolar-arterial oxygen gradient greater than 300 torr before paralysis, AaDO2 improved by greater than 100 torr within one hour of paralysis in only two infants; it worsened in two infants within the same period. By six hours postparalysis, 12 of 27 infants had improved, five of whom had had a worsening AaDO2 before administration of pancuronium. Changes in oxygenation were unrelated to changes in arterial carbon dioxide tension in most infants. Peak transpulmonary pressures after paralysis were lower than during spontaneous breathing, and may explain the low incidence of pneumothorax (3 of 35) during paralysis. Since those who improved could not be distinguished by birth weight, gestational age, or diagnosis, pancuronium might be worthy of trial in a mechanically ventilated infant with severe lung disease who is at risk for pneumothorax.

Carbon Dioxide↗

The influence of early nutrition on the serum cholesterol of the adult rat.

In two experiments, young rats were preconditioned with dietary cholesterol by: 1) nursing from dams with a high cholesterol milk or, 2) receiving 10 mg cholesterol dissolved in 0.5 ml of corn oil daily from 6 to 30 days of age. When rats preconditioned with dietary cholesterol in early life were fed stock diet supplemented with 10% lard and 0.5% cholesterol ("cholesterol challenge diet") there was no protection against dietary induced hypercholesterolemia in adult life. In a third experiment, two groups of newborn rats were intubated with: 1) a cholesterol free formula, 2) the cholesterol free formula plus 50 mg% cholesterol. A third group of pups suckled normally. After weaning all pups were fed a stock diet supplemented with 10% lard and 0.5% cholesterol for 1 month. There was no difference in the serum cholesterol in either group of artificially reared rats after the "cholesterol challenge" (106 +/- 6 mg/100 ml). Suckled rats, however, had a lower serum cholesterol after the "cholesterol challenge" (75 +/- 2 mg/100 ml). All experiments conducted refute the hypothesis that early exposure to dietary cholesterol protects against dietary induced hypercholesterolemia in adult life. It appears, however, that cholesterol metabolic systems are affected in early life because of the decreased ability of artificially reared rats to handle a "cholesterol challenge." Possible factors include a component of the dam's milk, growth and development, and the psychological and emotional stress of the artificial rearing process.

Aging↗

Lung volume changes, occlusion pressure and chest wall configuration in human infants.

UNLABELLED: Measurements of respiration were compared in normal, full term and premature infants before and after application of 5 cm H2O continuous negative pressure (CNEG) around the body below the neck. Mean minute ventilation in the full term infants decreased when CNEG was applied, secondary to a decrease in respiratory rate, with tidal volume relatively unchanged. The premature infants showed no consistent ventilatory response to CNEG. There were variable changes in occlusion pressure at increased lung volume. Observation with rib cage and abdomen anterior-posterior (A-P) magnetometers showed that the increase in end-expiratory lung volume was accounted for largely by expansion of the rib cage so that the configuration of the diaphragm and its mechanical advantage were maintained. These results suggest that the diaphragm is the major determinant of mask occlusion pressure in infants. SPECULATION: The effects of increased lung volume on the configuration of the chest wall may relate to the success of continuous distending pressure in the treatment of respiratory disorders in infants, including apnea of prematurity.

Humans↗

Prolonged expiratory duration with elevated lung volume in newborn infants.

UNLABELLED: End-expiratory lung volume increased 17.5 +/- 5.4 ml (mean +/- SD) in full term infants and 7.7 +/- 2.1 ml in premature infants when 5--7 cm H2O continuous negative pressure (CNEG) was applied around the thorax. In the full term infants, respiratory rate decreased from 52--43 min-1 (P less than 0.001), mean inspiratory duration (ti) was unchanged, and mean duration of expiration (te) increased from 0.62 +/- 0.14 (SE)-0.84 +/- 0.22 sec (P less than 0.001) after application of CNEG. Te of occluded efforts on CNEG was also prolonged (P less than 0.005), although less than te of spontaneous breaths on CNEG (P less than 0.005). Te increased in four of eight premature infants when CNEG was applied. We conclude that phasic vagal feedback regulates Ti and te is controlled by tonic vagal activity. SPECULATION: Premature infants may have an optimum functional residual capacity (FRC) which can be achieved with continuous distending pressure, resulting in regularization of respiration.

Humans↗

Four electrophoretic methods compared for diagnosis of type III hyperlipoproteinemia.

Blood drawn from 192 probands and 1129 first-degree relatives who were participants in a collaborative family study of hyperlipoproteinemia at nine Lipid Research Clinics was used to prepare aliquots of whole plasma and top (d less than 1.006 g/mL) and bottom (d greater than 1.006 g/mL) ultracentrifugal fractions. Each aliquot was analyzed at a central laboratory by electrophoresis on paper, agarose, and polyacrylamide gel, and by a combined electrophoretic precipitation technique. The electrophoretograms were evaluated for the presence or absence of a "floating-beta" lipoprotein band. All four methods agreed completely for 92.3% of the samples. An additional 2.0% of the samples were in agreement for three electrophoretic methods, but the paper electrophoretic results were not interpretable. Another 1.9% were considered to be "floating-beta" positive by paper electrophoresis but negative by the other three electrophoretic methods.

Chemical Precipitation↗