The reference range and within-person variability of thyroid stimulating hormone during the first and second trimesters of pregnancy.

OBJECTIVE: To further explore first and second trimester reference ranges for thyroid stimulating hormone (TSH) and examine within-person variability of TSH and thyroid peroxidase (TPO) antibody. SETTING: Women coming for routine prenatal care in early pregnancy agreed to participate in a trial of integrated serum screening for Down's syndrome. Two serum samples were obtained from each woman, one each in the first and second trimesters. These samples were also available for TSH and TPO measurements in the present study. METHODS: TSH and TPO antibody measurements were performed in 1126 women with ultrasound-dated pregnancies who provided serum samples in both trimesters. TSH reference ranges were established for the entire cohort and for the antibody-negative subgroup. Within-person variability of TSH measurements between trimesters was examined. RESULTS: Median TSH values are lower in the first trimester than in the second (1.00 versus 1.29 mIU/l), but 98th centile values are higher (5.20 versus 4.18 mIU/l). High correlation exists between individual women's first and second trimester TSH measurements (r=0.75, r2=0.56, p<0.001). Among 23 women with TSH values above the 98th centile in the second trimester, 17 (74%) were over the 95th centile in the first trimester. TPO antibody measurements are also highly correlated between trimesters (r=0.97, r)=0.94). CONCLUSION: Proper interpretation of TSH measurements during pregnancy requires that laboratories establish and monitor appropriate reference ranges. TSH levels show high within-person consistency between trimesters.

Association between exposure to environmental tobacco smoke and exacerbations of asthma in children.

BACKGROUND: Exposure to environmental tobacco smoke, as reported by parents, has been linked to diminished pulmonary function and more frequent exacerbations of asthma in children with the disease. Further insight into this association might be gained by using urine cotinine levels to measure actual exposure. METHODS: We measured urine cotinine levels in 199 children with asthma; 145 also underwent pulmonary-function studies. A parent answered questions about each child's exposure to environmental tobacco smoke. Acute exacerbations of asthma during the preceding year were documented through blinded review of medical records. Possible confounding factors were accounted for by the use of multivariate analysis and by comparisons of serum theophylline levels in exposed and unexposed children. RESULTS: The median urine cotinine levels were 5.6 ng per milliliter in the 116 children reported not to have been exposed to tobacco smoke, 13.1 ng per milliliter in the 53 children exposed to cigarette smoking by the mother or other persons, and 55.8 ng per milliliter in the 30 children exposed to cigarette smoking by the mother and other persons. Acute exacerbations of asthma increased with exposure, whether such exposure was reported by a parent or identified on the basis of the cotinine level; the relative risks for the highest as compared with the lowest exposure category were 1.8 (95 percent confidence interval, 1.4 to 2.2) for reported exposure and 1.7 (95 percent confidence interval, 1.4 to 2.1) for exposure indicated by cotinine levels. The forced expiratory volume in one second (FEV1), the forced expiratory flow between 25 and 75 percent of vital capacity, and the ratio of FEV1 to forced vital capacity also decreased with increases in both measures of exposure. CONCLUSIONS: Measurement of urine cotinine levels provides further evidence of an association between exposure to environmental tobacco smoke and pulmonary morbidity in children with asthma. These data emphasize the need for systematic, persistent efforts to stop the exposure of children with asthma to environmental tobacco smoke.

Lack of an association between late fetal death and antiphospholipid antibody measurements in the second trimester.

To examine the relationship between elevated antiphospholipid antibody levels in the maternal circulation and late fetal death, we carried out a case-control study in which levels of anticardiolipin and antiphosphatidylserine antibodies were measured in banked second-trimester sera from 309 pregnancies ending in fetal death and from 618 viable control pregnancies. The sera were obtained from a population base of approximately 22,000 pregnancies enrolled for maternal alpha-fetoprotein screening between 15 and 20 weeks' gestation. The anticardiolipin immunoglobulin G level was markedly elevated (15.6 SD) in one serum sample associated with a fetal death. Otherwise, the anticardiolipin and antiphosphatidylserine measurements were similar in the two populations. Several other factors known to be associated with fetal death were also examined, and these all demonstrated the expected relationship. Antiphospholipid antibody measurements obtained at 15 weeks' gestation or later in the general pregnancy population are not helpful in identifying pregnancies at risk for fetal death.

Environmental tobacco smoke exposure during infancy.

We collected information about household smoking habits from 518 mothers when they made their first well child visit with a 6 to 8-week old infant. A urine sample was also collected from the infant, the cotinine concentration measured, and the measurement correlated with data provided by the mother. Eight percent of the infant urine cotinine values fell at or above 10 micrograms/L in the 305 households where no smoking was reported. Corresponding rates were 44 percent in the 96 households where a member other than the mother smoked, 91 percent in the 43 households where only the mother smoked, and 96 percent in the 74 households where both the mother and another household member smoked. In households where the mother smoked, infant urine cotinine levels were lower in the summer, and higher when the infant was breast-fed. A screening question about family smoking habits in conjunction with well child care could effectively define a group of infants exposed to environmental tobacco smoke and thus be at greater risk for respiratory diseases.

Ketoacids and the insulin receptor.

The binding of insulin to a specific receptor on IM-9-cultured human lymphocytes was studied in vitro under conditions simulating diabetic ketoacidosis. Compared with control incubations at pH 7.4, binding was reduced by 19 per cent at pH 7.1 and by 48 per cent at pH 6.8. Addition of beta-hydroxybutyrate, at concentrations similar to those seen clinically, "restored" insulin binding toward normal. We suggest that, by counteracting the effects of acidosis, ketoacids themselves maintain normal insulin-receptor binding in diabetic ketoacidosis. These data also illustrate that small molecules, present in vivo, can significantly alter the interactions between a hormone and its receptor in vitro.

Sex variations in free fatty acids and ketones during fasting: evidence for a role of glucagon.

Women differ markedly from men in their metabolic response to caloric deprivation. To determine if these differences could be attributed solely to changes in insulin concentration, a group of 8 women was matched with a group of 7 men so that the mean fall in serum insulin during a 72-h fast did not differ between the groups. Glucose levels fell to a greater degree in the women than in the men. The serum concentrations of free fatty acids and ketone bodies rose more rapidly in the women and closely paralleled the earlier rise in glucagon concentrations. Over the first 36 h of fasting the change in free fatty acids was positively correlated to the change in glucagon and negatively correlated to the change in insulin. For the second 36 h of fasting, only changes in glucagon correlated with changes in free fatty acids. These correlations were true for both sexes and support the hypothesis that glucagon plays a physiologically significant role the regulation of lipolysis during starvation.

Increased insulin binding by lymphocyte receptors induced by beta-OH butyrate.

The serum concentration of ketones increases in both fasting and diabetic ketoacidosis. Whether ketones alter, independent of changes in pH, in number and affinity of insulin receptors is not known. The binding of insulin 125I by 24 X 10(6)IM-9 lymphocyte cells was examined in both the presence and absence of 8 mM beta-OH butyrate. Studies were conducted at multiple concentrations of insulin. A consistent increase of insulin binding was induced by beta-OH butyrate. The mean maximum increase of insulin binding was 35%, which achieved significance at the 1% level.

Diet-induced alterations of hGH secretion in man.

Studies were designed to determine whether variations in diet composition could modify the secretion of human growth hormone. Eight men and seven women ingested experimental diets for 10-12 days. Each experimental diet was preceded by a control diet for five days. Experimental diets studied in men were a) 2300 calorie, 80% carbohydrate (8 men); b) 2300 calorie, 75% high-fat (7 men); c) 2300 calorie, 70% high-protein (5 men); d) 3600 calorie, "control" (40% carbohydrate, 40% fat, 20% protein) (5 men); and e) 3600 calorie, 80% high-carbohydrate (5 men). A control diet and a high-carbohydrate (5 men). A control diet and a high-carbohydrate diet at the 2300 calorie level were studied in women. Each diet study was terminated by a 72 hour fast. Serum samples were collected hourly for 24 hours after each control period, on the eigth, ninth, or tenth day of each study, and during the final day of each fast. High-carbohydrate diets at the 2300 calorie level caused a significant decrease of growth hormone values in serum in each of eight men (sign test of significance, P less than .01). The mean figures were likewise significantly decreased. Isocaloric diets of high fat and high protein did not alter growth hormone concentrations in serum. A high-caloric diet similar to the control diet in composition was without effect on growth hormone secretion in men; however, a high-carbohydrate diet at the higher caloric level again depressed growth hormone values in plasma. On the third day of a 72 hour fast, growth hormone values in serum increased 287% in men, from a mean control serum concentration of 4.4 +/- 0.8 ng/ml to 11.9 +/- 5.0 ng/ml (P less than .01). Women, unlike men, had no significant decrease in growth hormone concentrations in serum over a 24 hour period after the high-carbohydrate diet, and the increase after starvation was significantly less than that in men, achieving significance only when evaluated by paired analysis. Growth hormone values in serum after the infusion of arginine followed a similar pattern, i.e., decreased after high carbohydrate but unaffected by other diets in men; high carbohydrate diets did not alter the growth hormone response of women to arginine.

Ecology of human oral lactobacilli.

Lactobacilli were found in saliva, on teeth, and on the dorsum of the tongue, the vestibular mucosa, and the hard palate in humans. Their proportions in saliva, expressed as percentage of the anaerobically cultivable flora, were 10- to 100-fold higher than those on the tooth surface, but were comparable to those on the epithelial surfaces. The adherence of Lactobacillus casei and L. fermenti to oral surfaces was compared with that of streptomycin-labeled Streptococcus sanguis and S. salivarius by using in vitro-cultivated cells. The affinity of both Lactobacillus species for the tooth surface was very low compared with that of S. sanguis but was somewhat higher than that of S. salivarius. The lactobacilli and both Streptococcus species adhered to a similar extent to the dorsum of the tongue, whereas the affinity of the lactobacilli and S. salivarius for the vestibular mucosa was about one-half of that of S. sanguis. The results suggest that the affinity of lactobacilli for oral surfaces significantly influences their proportional distribution in the mouth. The relatively low affinity of lactobacilli for the tooth surface suggests that their recognized association with carious lesions and mechanical appliances under certain conditions may be due primarily to mechanical retention rather than unique growth conditions.

Plaque size heterogeneity: a genetic trait of lymphocytic choriomeningitis virus.

All of the ten strains of lymphocytic choriomeningitis virus assayed on BHK 21/13S cells showed various degrees of plaque size heterogeneity. The amount of virus released from these plaques was usually very small because of rapid photodynamic inactivation by neutral red. When virus from large and small plaques of a specific strain was plated, the same distribution of plaque size was obtained from each clone. Although it was shown that surface virus could possibly be randomly distributed at the time of addition of neutral red overlays, no virus could be isolated from nonplaque areas. Two different strains of virus (CA1371 and WE) with markedly different plaque size ranges were separated by plaque excision from plates infected with a mixture of both viruses.