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Biomedical subjects

K H Marks

Publications and source records attributed to K H Marks.

At least 19 recordsLinked to original sources

Parathyroid hormone gene expression in Hyp mice fed a low-phosphate diet.

BACKGROUND: The murine analogue of X-linked hypophosphataemia is the Hyp mouse; it has chronic phosphate depletion from an inherited defect of renal tubular reabsorption. Phosphate directly regulates the parathyroid (PT) in normal rats and it is of interest whether this regulation is intact in Hyp mice. METHODS: Hyp mice were fed either a low-phosphate diet or control diet and PTH mRNA levels were measured. In addition changes in NMR-visible kidney and muscle intracellular phosphate potentials in normal and Hyp mice were determined. Mice were maintained on a low-phosphate (0.02%) or normal-phosphate (0.6%) diet for 24 and 72 h. RESULTS: On the normal diet, Hyp mice had hypophosphataemia, normocalcaemia, and normal PTH mRNA levels. Phosphate deprivation for 72 h led to a profound fall in plasma phosphate, a slight but significant rise in plasma calcium, and a dramatic decrease in PTH mRNA, similar to that of normal mice fed this diet. Changes in kidney and muscle intracellular phosphate measured by NMR spectroscopy were not affected by diet or genotype. CONCLUSION: Dietary phosphate deprivation decreased Hyp mice PTH mRNA levels and caused no change in intracellular phosphate potentials. Therefore Hyp mice parathyroids' adapt appropriately to phosphate deprivation albeit at a lower threshold compared to normal mice.

Animals

Precise control of nitric oxide concentration in the inspired gas of continuous flow respiratory devices.

Inhaled NO has become widely used for diagnosis and therapy of pulmonary hypertension. The potential hazards of NO inhalation include the formation of methemoglobin, formation of NO2, and generation of free radicals in the presence of humidity and oxygen. Careful monitoring of NO and NO2 concentration, and titration of the dose according to a patient's clinical response is essential to minimize toxicity. This paper describes a formula and method that permits calculation and precise control of NO concentration in the inspired gas. The accuracy of the delivery system was assessed by a comparison of calculated and measured NO and NO2 concentrations in a continuous flow ventilator circuit. A comparison of electrochemical detector (ECD) versus chemiluminescence detector (CLD) monitoring techniques showed agreement between the instruments within approximately 2 ppm, with the ECD averaging a higher reading than the calculated or CLD measured values. We deemed a 2 ppm discrepancy between instruments clinically acceptable, and concluded that the instruments could be used interchangeably for clinical purposes to measure NO1 and that the ECD was preferable to CLD for measuring NO2. Details about the equipment are given and techniques are discussed to avoid the risk of inhalation of toxic concentrations of NO and NO2. This method provides the possibility of using inhaled NO with appropriate safety precautions in the range 0-60 ppm in a variety of continuous flow respiratory devices.

Electrochemistry

Calcium, phosphate, vitamin D, and the parathyroid.

The main factors which regulate parathyroid hormone (PTH) production are calcium, phosphate, vitamin D, and estrogens. Hypocalcemia leads to increased PTH secretion in seconds and minutes, gene expression in hours, and parathyroid (PT) cell number in weeks and months. Hypercalcemia leads to a decrease in PTH secretion by its action on the PT cell calcium receptor and no decrease in PTH mRNA levels. There is now convincing evidence that phosphate regulates the PT, independent of its effect on serum calcium and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. In vivo in rats hypophosphatemia markedly decreases PTH mRNA and serum intact PTH levels, independent of its effect on serum calcium and 1,25(OH)2D3. Clinical studies also indicate that phosphate regulates the PT independent of its effect on calcium and 1,25(OH)2D3; 1,25(OH)2D3 itself has a marked effect on the PT, where it decreases PTH gene transcription by a direct action on the PT. The application of basic science findings of how calcium, phosphate, and 1,25(OH)2D3 regulate the PT has led to an efficient and safe prescription for the management of the secondary hyperparathyroidism of chronic renal failure, which is the maintenance of a normal serum calcium and phosphate and the careful use of 1,25(OH)2D3.

Animals

Cardiorespiratory and stress hormone responses during first dose surfactant administration in neonates with RDS.

Our hypothesis was that surfactant instilled into the trachea, followed by body positioning maneuvers utilized to enhance drug distribution, could alter hemodynamic function and stimulate the release of catecholamines. We conducted a prospective randomized study designed to compare the immediate physiologic effects of the first dose of Exosurf Neonatal (5 mL/kg; n = 16) or Survanta (4 mL/kg; n = 18), when surfactant administration was standardized with strict adherence to drug company protocol. Physiologic variables were monitored continuously. Arterial blood gases (ABG) and plasma catecholamine concentrations were measured before, and 5 minutes after, surfactant administration. Both surfactants had an immediate effect on arterial oxygen saturation (SaO2), partial pressure of oxygen in arterial blood (PaO2), and oxygen index (OI). The improvement in oxygenation after surfactant therapy was similar in both groups. There was no significant difference in the mean umbilical arterial blood pressure (ABP) following surfactant therapy in both groups. High concentrations of plasma norepinephrine (reflecting activity of the sympathetic nerves) and epinephrine (a measure of secretion from the adrenal medulla) indicate that preterm infants with respiratory distress syndrome (RDS) prior to treatment mount a substantial stress response. The currently recommended techniques for instillation of surfactant appear not to trigger a significant further surge of plasma catecholamines or to acutely change mean ABP. Alternatively, it may be possible that the lack of response was because catecholamine release was already maximal.

Biological Products

Effects of dexamethasone and triiodothyronine on oligohydramnios-induced pulmonary hypoplasia.

We observed for differential effects of maternal treatment with dexamethasone, triiodothyronine (T3), or both in late gestation on the growth of fetal rat lungs during oligohydramnios-induced pulmonary hypoplasia (PH). Timed-pregnant mothers were randomly selected into four treatment groups: controls (no hormone treatment); dexamethasone only; T3 only; and both dexamethasone and T3. Each underwent amniocentesis of one uterine horn on day 15 of gestation. Untouched littermate on the opposite horn served as internal control. On days 19 and 20, treated mothers were given dexamethasone (0.2 mg/kg) or T3 (7 mg/kg intramuscularly), or both and were delivered on day 21 (term) by hysterotomy. Amniocentesis resulted in PH, defined as decreased wet lung weight to body weight ratio and lung DNA contents, 83% and 90% of control, respectively (P < 0.05). Body weight and lung weight decreased with hormone treatment for both with and without amniocentesis. Although hormone treatment resulted in smaller lungs, there was no significant difference in lung weight to body weight ratio for either group with or without amniocentesis. This suggests that hormone treatment resulted in proportionate growth retardation. All hormone treatments decreased the total lung DNA content during amniocentesis (P < 0.05). Growth suppression of fetal lung associated with maternal hormone treatment is superimposed on the pulmonary hypoplasia induced by oligohydramnios.

Amniocentesis

Electrically heated simulator for relative evaluation of alternative infant incubator environments.

A 10.9-cm diameter, copper ellipsoid was electrically heated to provide a simulation of sensible heat transfer from a newborn infant. The use of this simulator to determine mean radiant temperature and convective heat-transfer coefficient was demonstrated in three commercial incubators: the Isolette (Model C-86, Narco/Air Shields); the Armstrong Care-ette (Ohio Medical Products); and the I. C. (Ohmeda). The relative performance of these environmental therapeutic devices in shielding an infant against radiant heat loss was judged by the deviation of mean radiant temperature from incubator air temperature, which was varied from 32-36 degrees C. Whereas the I. C. incubator exhibited a radiant temperature always 0.5 degrees C less than air temperature, the Care-ette incubator showed radiant temperatures of 4.0-5.5 degrees C below air temperature, and the Isolette displayed radiant temperatures of 2.7-4.7 degrees C (inner wall removed) and 2.0-3.8 degrees C (inner wall inserted) below air temperature. The relative performance of the incubators in preventing convective heat loss was judged from the magnitude of the convective heat-transfer coefficient, hv. The I. C. incubator had an hv = 4.52 W/m2/degrees C; the Care-ette, 5.55 W/m2/degrees C; and the Isolette 7.19 W/m2/degrees C (inner wall removed) and 6.23 W/m2/degrees C (inner wall inserted). Although an ellipsoid simulator is not an anatomically correct substitute for an infant, it does provide a reliable and convenient comparison of steady-state heat transfer characteristics of alternative environmental devices.

Body Temperature Regulation

Effect of Intralipid infusion on transcutaneous oxygen and carbon dioxide tension in sick neonates.

We evaluated the change in transcutaneous oxygen (tcPo2) and carbon dioxide (tcPco2) tension in response to 60 minutes' infusion of Intralipid (Kabi Vitrum (Saphar] (mean dose (0.16 +/- 0.07 g/kg/h) in neonates with lung disease (hyaline membrane disease or bronchopulmonary dysplasia). The tcPo2 was 10% lower following Intralipid infusion (P less than 0.05), whereas no significant change occurred in tcPco2 measurements. The data confirm the need for limited use of Intralipid in this category of patients.

Blood Gas Monitoring, Transcutaneous

The accuracy and precision of an open-circuit system to measure oxygen consumption and carbon dioxide production in neonates.

We measured the oxygen consumption, carbon dioxide production, and respiratory quotient during the combustion of a known mass of anhydrous ethanol and methanol to assess the accuracy of an open-circuit flow-through system. Continuous measurements were made of the mass of alcohol burned, the velocity of gas flow through the apparatus, and simultaneous measurements of the fractional concentration of oxygen, carbon dioxide and nitrogen of the inlet and outlet gas using paramagnetic oxygen analyzer, infrared carbon dioxide meter, and mass spectrometer. Standard respiratory and stoichiometric equations were used to calculate the oxygen consumption, carbon dioxide production and RQ for the mass of absolute alcohol combustion per unit time. In a series of 12 consecutive laboratory experiments (on 7 days), the measured values of gas exchange (similar to the rate of respiratory gas exchange by an infant of 1-4 kg) were in agreement within 5% of the true values for ethanol and methanol combustion, confirming the validity of the open-circuit method. The paramagnetic oxygen analyzer and the mass spectrometer gave similar oxygen consumption results and differed very little when the rate of absolute alcohol combustion was used to quantify the accuracy of the complete measurement system. A positive measurement error was observed for the carbon dioxide production results from both the IR meter and mass spectrometer, with the result that the respiratory quotient measurements were 3.4-4.7% higher than the true value. The mass spectrometer gave more precise oxygen consumption results, whereas smaller variance of carbon dioxide production measurements was observed using the infrared CO2 meter.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Dioxide

Day-to-day energy expenditure variability in low birth weight neonates.

We estimated the metabolic rate of 13 low birth weight infants over a 9-day period, using indirect calorimetry in conjunction with serial measurements of oxygen consumption, carbon dioxide production, and total urinary nitrogen excretion. The mean percent error for oxygen consumption and carbon dioxide production measurements (determined by alcohol combustion experiments) assignable to the open-circuit system was 0.4 and 3.8%, respectively. Error in the total urinary nitrogen excretion measurement was less than 1% by the Kjeldahl technique. In the clinical setting, however, the range of deviation of measured oxygen consumption, carbon dioxide production and total urinary nitrogen excretion was +/- 12, 12, and 15% of the mean value respectively for an individual patient under standardized controlled conditions. The variability of metabolic rate between infants may be as much as 76%. Factors that had a small effect on metabolic rate were difficult to detect because of the variability inherent in the short-term measurement of metabolic rate. It was virtually impossible to control the sources of variation in the resting metabolism of low birth weight neonates over extended experimental periods. Day-to-day variations in resting energy expenditure may explain, in part, the widely different growth rates of premature infants receiving similar caloric intakes.

Carbon Dioxide

Incubators.

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Body Temperature

Energy metabolism and substrate utilization in low birth weight neonates under radiant warmers.

We evaluated the metabolic response to the thermal demands of an open radiant warmer device, as distinct from convection incubator, in 13 healthy premature infants (1.395 +/- 169 g, 28 +/- 12 days of age, mean +/- SD). Metabolic rate was 10% higher for infants under the radiant warmer than in the incubator (2.60 +/- 0.4 v 2.36 +/- 0.3 kcal/kg/h; P less than .05). The radiant warmer also induced a small (4%), but significant, increase in nonprotein respiratory quotient (0.94 +/- 0.1 v 0.90 +/- 0.1; P less than .05) and a 13% increase in carbon dioxide production (8.26 +/- 1.1 v 7.31 +/- 1.1 mL/kg/min; P less than .05). Subcutaneous fat accumulation (estimated from 60-second skin-fold thickness measurements) was greater under the radiant warmer than in the incubator (0.08 +/- 0.05 v 0.04 +/- 0.04 mm/d; P less than .05). Under the warmer, the infant's mean skin temperatures and core temperatures were normal and similar to those found in the incubator, but the foot temperature was on average 0.6 degrees C cooler. The average rate of weight gain (18 g/kg/d) was the same in the radiant environment. The pattern of the elevated metabolic rate, shift of respiratory quotient coupled with the accumulation of subcutaneous fat, and cool extremities of infants under the radiant warmer may represent a physiologic adaptive response to thermal stress. However, the reasons for the elevated metabolic rate are unclear, because activation of the sympathetic nervous system with the release of catecholamines is not apparently involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Calorimetry

Indirect BP monitoring in the newborn. Evaluation of a new oscillometer and comparison of upper- and lower-limb measurements.

We compared simultaneous direct (aortic) and indirect (oscillometric) BP measurements in 19 patients admitted to a newborn intensive care unit. Two hundred six indirect measurements were obtained from an upper extremity in 14 patients, and 50 from a lower extremity in five other patients. A regression analysis of paired data over a wide range of BPs showed excellent correlation between measurements obtained with the automated oscillometer and intra-arterial catheters. The oscillometric BP correlated equally well in both upper and lower extremities. Simultaneous upper- and lower-extremity BP measurements were taken in seven infants with low birth weights during the first 12 days of life and in ten normal term 2-to 5-day-old infants. Contrary to some previous reports, systolic, mean, and diastolic pressures were virtually identical at both sites.

Blood Pressure Determination

Focal necrosis of the spinal cord in utero.

We examined a child who suffered in utero necrosis of the spinal cord. Necrosis of this type typically occurs in the fetus with neck hyperextension and breech position and presumably results from focal ischemia of the spinal cord.

Cesarean Section

Frequency of transient hypothyroxinaemia in low birthweight infants. Potential pitfall for neonatal screening programmes.

Thyroid function was studied in 54 low birthweight infants during a 3-week period. Each infant was placed in one of three groups. Group 1 (n = 21), infants who were well and appropriately grown fro gestational age; group 2 (n = 23), infants who were appropriately grown but who had hyaline membrane disease; group 3 (n = 10), infants who were small-for-gestational-age. In group 1, 5 (24%) infants had at least one serum thyroxine value less than 3.0 micrograms/100 ml (39 nmol/l). There were 8 (35%) infants in group 2 who had similarly low serum thyroxine values as did 5 (50%) of the 10 infants in group 3. Serum thyrotropin levels and serum binding of the thyroid hormones, as measured by a T3-charcoal uptake test, were normal in all infants. In all instances but 2, serum thyroxine values were at least 4.0 micrograms/100 ml (51 nmol/l) by the end of the 3-week period. There is thus a high incidence of transient 'hypothyroxinaemia' in low birthweight infants, particularly if such infants have hyaline membrane disease or are small-for-gestational-age. These findings must be considered when interpreting results of screening programmes for congenital hypothyroidism and they lend further support to the use of a combination of serum thyroxine and thyrotropin determinations for optimum screening of such infants.

Aging

The metabolic effects of caffeine in the newborn infant.

We studied the effects of intravenous administration of 20 mg/kg caffeine citrate on glucose homeostasis, cardiorespiratory status, and urinary excretion of catecholamines and electrolytes in 12 premature infants with recurrent apnea. Six infants received intravenous dextrose (5% or 10% in 0.225% saline) during the study, and six were fed formula every 3-4 hours. In the intravenously fed infants, the plasma glucose concentration postcaffeine did not vary significantly from the precaffeine level of 73 +/- 3.2 mg/dl (mean +/- SEM) at 0.5, 1, and 1.5 hours. However, in the formula-fed infants, there was a consistent fall in plasma glucose levels after caffeine administration. This decrease from a precaffeine level of 99 +/- 12 mg/dl (mean +/- SEM) approached statistical significance at 0.5 hours (P = 0.07), and was significantly lower at 1 and 1.5 hours (P less than 0.02). In five infants, cardiorespiratory status and urinary excretion of catecholamines and electrolytes were evaluated for 12-hour periods before and after caffeine administration. There was a significant reduction in the number of apneic episodes following caffeine administration; however, caffeine did not appear to affect mean heart rate or urinary excretion of sodium, potassium, epinephrine, norepinephrine, or dopamine. Our data suggest that the effects of caffeine on glucose homeostasis may vary with the nature and/or route of substrate administration.

Apnea