Higher estrogen levels during pregnancy in Andean than European residents of high altitude suggest differences in aromatase activity.

CONTEXT: Uteroplacental hypoxia has been reported to lower estrogen levels in preeclampsia as the result of reduced aromatase activity. OBJECTIVE: We asked whether the chronic hypoxia of residence at high altitude in the absence of preeclampsia lowered estrogen, whether such effects differed in Andean vs European high-altitude residents, and whether such effects were related to uterine artery diameter or blood flow. DESIGN, SETTING, AND PARTICIPANTS: Studies at weeks 20 and 36 of pregnancy were conducted in 108 healthy Bolivian low- (400 m, n = 53) or high-altitude (3600 m, n = 55) residents of European (n = 28 low and 26 high altitude) or Andean (n = 25 low and 29 high altitude) ancestry. All groups were similar in age, nonpregnant body mass index, and pregnancy weight gain. RESULTS: High-altitude residence increased circulating progesterone, cortisol, estrone, 17ß-estradiol, and estriol levels (all P < .01). High-altitude Andeans vs Europeans at week 36 had higher progesterone, estrone, 17ß-estradiol, and estriol levels as well as product to substrate ratios for the reactions catalyzed by aromatase, whereas week 36 cortisol levels were greater in the European than Andean women (all P < .05). Lower cortisol, higher estriol (both P < .01), and trends for higher progesterone and 17ß-estradiol levels were associated with greater uterine artery diameters and blood flow at high altitude. CONCLUSIONS: Chronic hypoxia does not lower but rather raises estrogen levels in multigenerational Andeans vs shorter-term Europeans, possibly as the result of greater aromatase activity. Because hypoxia alone does not lower estrogen, other attributes of the disease may be responsible for the lower estrogen levels seen previously in preeclamptic women.

Sedation in children: adequacy of two-hour fasting.

OBJECTIVES: (1) To investigate the relationship between the duration of time that children fasted before a procedure and their gastric volume and pH at the time of the procedure. (2) To compare the variables of gastric pH and volume with historical standards. METHODS: We performed 285 gastroscopies for children aged 0.1 to 18.6 years (mean, 7.5 +/- 5.3) between October 1991 and January 1995. Duration of fasting was 0.5 to 24 hours (mean, 6.7 +/- 5.3) after ingestion of clear liquids. Immediately after intravenously administered sedation, the gastric contents were removed endoscopically with suction and direct visualization to ensure complete evacuation. The volume and pH of the gastric contents were measured and analyzed in comparison with the duration of fasting. The values obtained were also compared with historical standards thought to minimize the risk of aspiration pneumonia: gastric volume 0.4 ml or less per kilogram of body weight and pH of 2.5 or greater. RESULTS: There was no significant correlation between duration of fasting and either gastric volume divided by body weight (mean, 0.68 +/- 1.31 ml/kg; range, 0 to 15.23 ml/kg) or pH (mean, 2.03 +/- 1.40; range, 1 to 8). There was less no significant difference in the percentage of children with gastric volume of 0.4 ml/kg or less or with pH of 2.5 or greater between the groups with the following fasting times: 30 minutes to 3 hours, more than 3 hours to 8 hours, and more than 8 hours. CONCLUSIONS: On the basis of the data in this study and a review of the literature, we concluded that (1) fasting longer than 2 hours after ingesting clear liquids does not significantly change gastric volume or pH, (2) there is no advantage in requiring children to fast for longer than 2 hours after clear liquid ingestion before sedation or anesthesia for any procedure, and (3) fewer than half of pediatric patients actually achieve the "desirable" values of a gastric volume of 0.4 ml/kg or less and a pH value of 2.5 pH units or more, regardless of fast duration, even though these values are presented in the literature as a goal to minimize the risk of aspiration pneumonia.

The prevalence of akathisia in patients receiving stable doses of clozapine.

BACKGROUND: Akathisia is a common side effect of traditional neuroleptic drugs and is associated with medication refusal and impulsive behavior. While our previous experience indicates that clozapine is effective in treating persistent akathisia, two controlled studies indicate vastly different prevalence rates of akathisia (7% vs. 40%) in patients receiving clozapine. METHOD: We used the Barnes Rating Scale for Drug-Induced Akathisia to estimate the prevalence of akathisia in patients receiving stable doses of clozapine alone (N = 29) in a state hospital. Measurements were also made of manifest psychopathology (Brief Psychiatric Rating Scale) and tardive dyskinesia (Abnormal Involuntary Movement Scale). RESULTS: Two patients (6.8%) receiving clozapine were rated as having akathisia. Only 4 (28.6%) of the 14 subjects with a history of moderate-to-severe tardive dyskinesia on traditional neuroleptic drugs continued to show current evidence of tardive dyskinesia, and in 10 patients (71.4%) there was no evidence of the syndrome (p < .002). In the 4 subjects with tardive dyskinesia there was amelioration to a milder form of the syndrome. There were no new cases of tardive dyskinesia among clozapine-treated subjects. CONCLUSION: These data support the low prevalence of akathisia in patients receiving stable doses of clozapine monotherapy. There is further support that clozapine has an ameliorating effect on tardive dyskinesia associated with traditional neuroleptic drugs. These and other data indicate the need for a controlled trial of clozapine in patients experiencing persistent and disabling akathisia on traditional neuroleptic drugs.

Charting infant distress: an aid to defining colic.

The value of a 24-hour distress diary, previously validated against a voice-activated audiotape record, was investigated in 30 infants with colic and 30 control infants. The infants with colic had significantly more distress behavior (300.0 minutes vs 102.5 minutes; p < 0.001), although overlap of duration of distress was noted. On the basis of a clinical definition of colic--total distress lasting 180 minutes in a 24-hour period--the diary had a sensitivity of 77% and a specificity of 87%. The sensitivity of the chart was confirmed in a separate study of another 90 infants with colic.

Manifestations of milk allergy in infancy: clinical and immunologic findings.

In a study of the manifestations of cow milk allergy in 100 young children (mean age 16 months), 30 items of historical data and information relating to the effects of a standardized milk challenge were entered into a computer data base. Three clusters of patients were derived using a K-means algorithm. In group 1 were 27 patients with predominantly urticarial and angioedematous eruptions, which developed within 45 minutes of ingesting cow milk. They had positive skin test reactions to milk and elevated total and milk specific IgE serum antibody levels. In group 2, 53 patients had pallor, vomiting, or diarrhea between 45 minutes and 20 hours after milk ingestion. These children were relatively IgA deficient. The 20 patients in group 3 had eczematous or bronchitic or diarrheal symptoms; in 17 symptoms developed more than 20 hours after commencing milk ingestion. Of the patients in group 3, only those with eczema had a positive skin test reaction and elevated IgE antibodies to milk. The patients in group 3 were the most difficult to identify clinically; they had a history of chronic ill health, and symptoms developed many hours or days after commencing milk ingestion in the challenge situation. In view of the heterogeneous clinical and immunologic findings in our patients, it is unlikely that a single laboratory test will identify cow milk allergy in all susceptible patients.