Michael A. Simmons

Hypernatremia and intracranial hemorrhage in neonates.

Abstract Records of all newborn admissions over a two-year period were reviewed for the occurrence of hypernatremia and intracranial hemorrhage. When restrictive criteria for the use of sodium bica...

Bronchodilator effects of terbutaline and aminophylline alone and in combination in asthmatic patients.

In 17 patients with moderate to severe asthma, we compared acute bronchodilator effects of the following drugs or drug combinations using a double-blind crossover design: terbutaline, 5; aminophyline 400; terbutaline, 5, plus aminophyline, 400; terbutaline, 2.5; aminophylline, 200; terbutaline, 2.5, plus aminophyline, 200 mg; and placebo. The higher doses of terbutaline and aminophylline alone produced comparable bronchodilation and similarly frequent adverse side effects; low doses of each drug also had comparable effects. The high-dose combination produced significantly (P less than 0.05) greater bronchodilatation than either drug alone. The low dose combination had bronchodilator effects comparable to those produced by the higher dose of either drug alone. These findings suggest therapeutic advantages in combining high doses of theophylline and an oral beta adrenergic agonist (terbutaline) in asthma not well controlled on high doses of either drug alone and in combining these drugs in lower doses in patients experiencing intolerable side effects from a high dose of either drug.

Low positioning of umbilical-artery catheters increases associated complications in newborn infants.

We performed a randomized prospective study of the effect of placement position of umbilical-artery catheters on complication rates in high-risk newborn infants. A higher complication rate (31 of 40 vs. 13 of 33) (P less than 0.005) occurred in the group with the catheter tip at the third to fourth lumbar segment, as compared to those with the tip at the seventh to eighth thoracic segment, owing to more episodes of blanching and cyanosis of the extremities. There was no difference between groups in the rate of complications requiring catheter removal. Aortography revealed thrombosis in 21 of 23 patients studied, but there was no clinical evidence of impaired circulation. In retrospect, we found that, independently of catheter position, administration of antibiotics through the catheter was associated with an increased rate of complications (63 vs. 20 per cent). Umbilical-artery catheterization entails potential risks regardless of the position of the catheter; placement of the catheter with its tip at the seventh to eighth thoracic segment may be associated with fewer complications than at lower positions.

Longitudinal changes in lung function and respiratory symptoms in progressive systemic sclerosis: Prospective Study

Most patients with progressive systemic sclerosis (PSS) exhibit lung involvement. However, the natural history of lung disease in PSS remains poorly defined. To evaluate lung function over time in PSS, a battery of lung function tests were prospectively performed serially between 1973 and 1982 in 61 patients with PSS. Functional indexes of restriction (vital capacity and total lung capacity) and diffusion impairment (diffusing capacity) showed greater-than-expected annual rates of change. Male subjects showed a trend toward faster declines in forced vital capacity, forced expired volume in one second, total lung capacity, and functional residual capacity and a more rapid increase in static recoil pressure at 90 percent of total lung capacity than did female subjects. Nonsmokers had greater rates of decline in total lung capacity and static lung compliance (but not in forced vital capacity or diffusing capacity) and a greater rate of increase in static recoil pressure than did current and former smokers. Level of lung function at initial study visit, age, race, and chlorambucil therapy had no significant effect on the annual rates of change in lung function, whereas longer duration of disease prior to study entry was associated with a slower annual decrease in lung volumes. Between the first and last visits (mean interval 3.1 years, maximum nine years), the frequency of abnormality in pulmonary function test results showed significant change only in the diffusing capacity (60 percent increasing to 82 percent) and static lung compliance (40 percent increasing to 54 percent), whereas the frequency of respiratory symptoms showed little change. These findings indicate an overall indolent progression of PSS-related lung disease, with substantial individual variability.

Fetal metabolic response to maternal starvation.

Extract: In the pregnant ewe in the fed state, higher maternal protein intake does not lead to increased protein catabolism by the fetus. Total maternal starvation results in a prompt fall in fetal glucose concentrations (by 35%) to a stable plateau by 48 hr of starvation. Transplacental glucose uptakes during prolonged starvation are less than 40% of normal fed state values. Fetal urea production rates (a reflection of amino acid catabolism) increase to a level twice the fed state values by the 4th day of starvation and then return to base-line values by the 7th day of starvation. Fetal glucose concentrations remain stable throughout prolonged starvation, even after urea production rates have returned to base-line values.Speculation: At the peak of urea production, amino acid catabolism by the fetus can account for at least 80% of fetal oxygen consumption. However, the mechanisms and substrates available for homeostasis during the first 2 days (and after the 7th day of starvation) are unknown and, in the face of depressed transplacental glucose uptakes, may put the fetus at significant risk.

Nicotine blood levels and short-term smoking reduction with an electronic nicotine delivery system.

OBJECTIVES To evaluate nicotine delivery from the NJOY® King Bold Electronic Nicotine Delivery System (ENDS) and its short-term potential for smoking reduction or cessation. METHODS One week of ad libitum use was followed by measurements of plasma nicotine, heart rate, and craving and withdrawal after 12 hours of nicotine abstinence in 25 adult smokers not interested in quitting. RESULTS After 5 minutes of use, blood nicotine levels increased by a mean of 3.5 ng/mL (p < .001), heart rate increased, and craving was reduced by 55%. Cigarettes per day were reduced by 39% during the test week, and perceptions of use for reduction or cessation were positive. CONCLUSIONS The NJOY® King Bold ENDS delivers nicotine and led to short-term smoking reduction.

Coagulation Studies in Extremely Premature Infants

Summary: Evidence of developmental evolution of coagulation can be seen when the studies of 10 thriving extremely premature (EPT) infants are compared to normal full-term (FT) infants. The prothrombin time, partial thromboplastin time, and thrombin time all became shorter with increasing gestational age. Fibrinogen levels and platelet counts appear to be comparable to term infant and adult levels. Fibrin degradation products (FDP) of 10 μg/ml or less were found in the thriving EPT infants. When compared to healthy full-term infants, there is a definite gestational dependency of anti-thrombin III levels. Factors II and VII appear to be related to intrauterine maturation after the age of viability (24 wk), but factor VII-X complex does not. The contact factors XI, XII, high molecular weight kininogen (Fitzgerald factor), and prekallikrein (Fletcher factor) are all markedly decreased in thriving EPT infants. The mean factor V level is lower than that found in FT infants. This study confirms a gestational age dependency of factor VIII activity. The ratio of factor VIII antigen to factor VIII clotting activity is increased (2.8 vs 1.01 in FT and adults). Thriving small for gestational age (SGA) infants had coagulation studies which were not statistically different from those of thriving EPT infants. The coagulation changes which occurred in severely ill EPT were mainly in the factors which decrease during intravascular coagulation (factors I, V, and VIII). The present study suggests that because of the high antigen to activity ratio seen in thriving EPT infants, a dysfunctional or fetal factor VIII may have been produced. However, the further elevation of this ratio in the severely ill EPT infants is in keeping with a pathologic proteolysis or increased endothelial release of factor VIII antigen.Speculation: Prevention of and prompt therapeutic intervention for asphyxia, sepsis, hypovolemia, hypotension, hypothermia, hypoxia, and acidosis may prevent the occurrence of the coagulation changes seen in the severely ill EPT infants. A distinction between abnormal proteolysis versus production of dysfunctional proteins is essential before specific therapies can be designed.

Insulin effect on fetal glucose utilization.

Summary: Insulin infused into a sheep fetus over a 3-hr period at the rate of ∼0.24 U·kg-1·h-1 increased fetal glucose uptake (utilization) from 4.4 ± 0.7 mg·min-1·kg-1 to 6.9 ± 0.9 mg·min-1·kg-1 as compared to a noninsulin control period. Insulin administration did not alter fetal oxygen consumption (8.6 ± 0.7 ml·min-1·kg-1 vs. 7.7 ± 0.7 ml·min-1·kg-1), umbilical blood flow (220 ± 1 ml·min-1·kg-1 vs. 209 ± 16 ml·min-1·kg-1), or the placental clearances of antipyrine (114 ± 7 ml·min-1·kg-1 vs. 109 ± 8ml·min-1·kg-1) and urea (24.5 ± 2.2 ml·min-1·kg-1 vs. 25.0 ± 2.1 ml·min-1·kg-1). Fetal plasma glucose concentration fell significantly (0.22 ± 0.01 mg·ml-1 to 0.16 ± 0.01 mg·ml-1) during insulin infusion. The insulin effect on fetal glucose uptake occurred over a range of maternal glucose concentrations (0.32 → 0.78 mg·ml-1), which were not altered by the infusion of insulin in the fetal compartment.Insulin has a specific effect on increasing fetal glucose uptake and utilization.Speculation: The effect of insulin on increasing transplacental fetal glucose uptake is consistent with a growth-promoting role for insulin in the fetus. This action of insulin might be due to a direct effect of insulin on the mechanisms of placental glucose transport, to an alteration of placental glucose catabolism, or simply to the effect of insulin on the transplacental gradient of glucose.

1024 APGAR SCORES IN INFANTS LESS THAN 1500 GRAMS (LBW)

Apgar scores have been used to assess intrapartum asphyxia and to predict the association of perinatal insult with ultimate outcome. We tested the association of the one-minute Apgar Score and intrapartum asphyxia in LBW infants (n-38) by measuring umbilical artery pH and base excess (BE) from double clamped cord and by comparing infant survival with One- and Five-minute Apgar scores (n=153).There was no correlation between Apgar score and cord pH or BE. pH varied from 6.91 to 7.55 and BE from -18 to -3 in the LBW infants with one-minute Apgar scores of 3 or less. In infants with Apgars of 4-7, pH varied from 7.13 to 7.50 and BE from -13 to -4. No consistent effect of anesthesia was apparent Survival was not predicted by cord pH or BE.85% of LBW infants with one minute Apgars of 7 or greater survived. 46% of LBW infants with Apgars of 3 or less survived. The 5 minute Apgar score was also imprecise in predicting survival, since 25% of LBW infants with Apgars <3 survived and 14% with Apgars >7 expired.The Apgar score is not a reliable reflection of the intrapartum condition in LBW infants and is an imprecise predictor of survival. Low Apgar scores in LBW infants should not be used, formally or informally, to decide intervention in the delivery room.

257 THE INDUCTION OF OXIDATION BY THROXINE AND CORTISONE IN RAT PUP JEJUNUM

We determined if increased jejunal glucose oxidation is related to physiologic surges of glucocorticoids (16–20 days) and thyroxine (T4) (20–24 days) during weaning. We administered cortisone (15 μg/gm body wt IP) on days 10, 11, 12 and 13. Thyroxine (1.0 μg/gm body wt SubQ) was given on days 14 and 15, or day 15. Littermate controls received saline injections on the same days. At sacrifice on day 16, jejunal slices were incubated with [1–14C] glucose, and CO2, production was measured.Cortisone-T4 (14,15d) group is significantly higher when compared to all other groups (p<.05). Thyroxine given on day 15 produces no change in glucose oxidation. Treatment with cortisone increases oxidation of CO2 (35%). Thyroxine given at 14 and 15 days increases oxidation (200%). Administering T4 on days 14 and 15 to cortisone treated pups increases oxidation in 16 day old suckling pups to postwean levels (23 day old; 2.24±0.10 n=6). We conclude cortisone and T4 have a synergistic effect on the early induction of glucose oxidation which was not seen when either hormone is given separately. We speculate metabolic changes during the weaning period in rat jejunum are mediated by the combined effect of glucocorticoids and thyroxine.