Corticosteroids for the Enhancement of Fetal Lung Maturity: Impact on the Gravida with Preeclampsia and the HELLP Syndrome

Summary: This study was undertaken to determine maternal impact of corticosteroids administered for the promotion of fetal lung maturity in mothers with the HELLP syndrome. Twenty-seven of 427 women with the HELLP syndrome treated between 1980–1991 received a full course of steroids prior to preterm delivery. This group was compared to 27 matched control patients with the HELLP syndrome who received no corticosteroids. Subjects were matched for maternal age, race, sex of the fetus, and severity of the HELLP syndrome. The antepartum platelet count stabilized or increased in 25 of 27 steroid-treated women in contrast to 0 of 15 control women (p <0.00001). In comparison to control patients, LDH serum concentrations in steroid-treated patients stabilized or decreased and the SGOT/AST and SGPT/ALT stabilized or decreased during therapy (p < 0.005). The interval from delivery to platelet nadir in patients with Class III HELLP syndrome was shorter in the steroid-treated group (p<0.008) than in untreated patients.     

A behavioral group procedure for parents of severely troubled and troubling youth in out-of-home care: Alternative to conventional parent training

Many youth, their parents, and social services regard the unification of the family as the most desirable outcome for youth in out-of-home placements. This goal is often difficult to achieve because the families of these troubled/troubling youths are often severely dysfunctional, with multiple problems. A group process model for serving natural parents of youth in placement is described which, in conjunction with one-on-one interactions with professionals, appears to have a positive impact on these families and on youths' return home. Group components that seem particularly important are described, including attendance by invitation only, public commitment to attend and participate, reminder prompts, transportation support, babysitting support, refreshments, opportunity to visit with their child, defined staff roles, an empowering approach, and starting where the parent is. The group process maintained a relatively high level of both attendance and participation by the targeted parents. Participants tended to achieve most goals that they set in the group. Our experience indicates that interventions with natural parents of troubled youth can enable even a very dysfunctional family to improve enough to receive youth back into their home.The authors are grateful for the assistance of Sharon Estill, Jim Bernardo, Anita Mentzer, Dave Walker, and Suni Dague-Lyman for assistance in collecting the data reported here. Debbie Buchanan and others have been a great assistance in transporting families.     

Generation and comparative analysis of approximately 3.3 Mb of mouse genomic sequence orthologous to the region of human chromosome 7q11.23 implicated in Williams syndrome.

Williams syndrome is a complex developmental disorder that results from the heterozygous deletion of a approximately 1.6-Mb segment of human chromosome 7q11.23. These deletions are mediated by large (approximately 300 kb) duplicated blocks of DNA of near-identical sequence. Previously, we showed that the orthologous region of the mouse genome is devoid of such duplicated segments. Here, we extend our studies to include the generation of approximately 3.3 Mb of genomic sequence from the mouse Williams syndrome region, of which just over 1.4 Mb is finished to high accuracy. Comparative analyses of the mouse and human sequences within and immediately flanking the interval commonly deleted in Williams syndrome have facilitated the identification of nine previously unreported genes, provided detailed sequence-based information regarding 30 genes residing in the region, and revealed a number of potentially interesting conserved noncoding sequences. Finally, to facilitate comparative sequence analysis, we implemented several enhancements to the program, including the addition of links from annotated features within a generated percent-identity plot to specific records in public databases. Taken together, the results reported here provide an important comparative sequence resource that should catalyze additional studies of Williams syndrome, including those that aim to characterize genes within the commonly deleted interval and to develop mouse models of the disorder.     

Relationship between numbers of beta adrenergic receptors in lymphocytes and disease severity in asthma

In order to assess the status of beta adrenergic receptors in bronchial asthma, binding studies using (−) [³H] dihydroalprenolol (DHA) were performed on lymphocytes of 10 control subjects and 11 stable asthmatic patients. Specific DHA binding was generally lower at all DHA concentrations in asthmatics. At 12 nM DHA concentration, specific DHA binding was 391 ± 40 fM/mg protein in controls and 263 ± 35 fM/mg protein for asthmatic subjects (p < 0.05). A highly statistically significant positive correlation between specific DHA binding (at 12 nM DHA) and FEV₁/FVC% was observed (r = 0.93, p < 0.01), with those asthmatic subjects with the more severe airway obstruction and disease severity showing lower DHA binding. The results of the study suggest that a lymphocyte beta adrenergic receptor defect may be present among some patients with asthma. The magnitude of the receptor abnormality appears to be related to disease severity and degree of airway obstruction as measured by FEV₁/FVC%. Documentation of drug consumption was made, and restriction of beta adrenergic agonists was attempted; theophylline and corticosteroids were the predominant drugs used in the study. Even with these precautions, it is possible that the differences in DHA binding observed among subjects are the results of greater drug (e.g., theophylline and corticosteroids) consumption by the clinically more severe patients. On the other hand, the lymphocyte receptor alteration noted may reflect a more general beta adrenergic receptor abnormality in bronchial asthma.     

Socioeconomic position and cardiovascular and neuroendocrine responses following cognitive challenge in old age

Social disparities in health persist into old age, and differences in psychophysiological responsivity may contribute to this pattern. We assessed whether higher socioeconomic status (SES) is associated with attenuated cardiovascular and neuroendocrine responses elicited by cognitive tasks in old age. We tested 132 community-dwelling men and women aged 65-80 years, divided on the basis of educational attainment into higher and lower SES groups, and compared them with 26 higher educated participants aged 27-42 years. Blood pressure, hemodynamic variables and salivary cortisol were assessed in response to the performance of three cognitive tasks, and then during recovery. Older groups showed smaller heart rate and larger cortisol changes than younger participants. Post-task recovery in heart rate, stroke volume, pre-ejection period, and systolic blood pressure was greatest in the younger group, least in the older/lower education group, and intermediate in the older/higher education group. SES did not influence the increased cortisol responsivity of older participants. The results are consistent with the notion that higher SES protects against age-related changes in cardiovascular response profiles, particularly during recovery.     

Contributions of parental alcoholism, prenatal substance exposure, and genetic transmission to child ADHD risk: a female twin study

BACKGROUND: Genetic influences have been shown to play a major role in determining the risk of attention-deficit hyperactivity disorder (ADHD). In addition, prenatal exposure to nicotine and/or alcohol has also been suggested to increase risk of the disorder. Little attention, however, has been directed to investigating the roles of genetic transmission and prenatal exposure simultaneously. METHOD: Diagnostic telephone interview data from parents of Missouri adolescent female twin pairs born during 1975-1985 were analyzed. Logistic regression models were fitted to interview data from a total of 1936 twin pairs (1091 MZ and 845 DZ pairs) to determine the relative contributions of parental smoking and drinking behavior (both during and outside of pregnancy) as risk factors for DSM-IV ADHD. Structural equation models were fitted to determine the extent of residual genetic and environmental influences on ADHD risk while controlling for effects of prenatal and parental predictors on risk. RESULTS: ADHD was more likely to be diagnosed in girls whose mothers or fathers were alcohol dependent, whose mothers reported heavy alcohol use during pregnancy, and in those with low birth weight. Controlling for other risk factors, risk was not significantly increased in those whose mothers smoked during pregnancy. After allowing for effects of prenatal and childhood predictors, 86% of the residual variance in ADHD risk was attributable to genetic effects and 14% to non-shared environmental influences. CONCLUSIONS: Prenatal and parental risk factors may not be important mediators of influences on risk with much of the association between these variables and ADHD appearing to be indirect.     

Antibodies to squalene in recipients of anthrax vaccine

We previously reported that antibodies to squalene, an experimental vaccine adjuvant, are present in persons with symptoms consistent with Gulf War Syndrome (GWS) (P. B. Asa et al., Exp. Mol. Pathol 68, 196-197, 2000). The United States Department of Defense initiated the Anthrax Vaccine Immunization Program (AVIP) in 1997 to immunize 2.4 million military personnel. Because adverse reactions in vaccinated personnel were similar to symptoms of GWS, we tested AVIP participants for anti-squalene antibodies (ASA). In a pilot study, 6 of 6 vaccine recipients with GWS-like symptoms were positive for ASA. In a larger blinded study, only 32% (8/25) of AVIP personnel compared to 15.7% (3/19) of controls were positive (P > 0.05). Further analysis revealed that ASA were associated with specific lots of vaccine. The incidence of ASA in personnel in the blinded study receiving these lots was 47% (8/17) compared to an incidence of 0% (0/8; P < 0.025) of the AVIP participants receiving other lots of vaccine. Analysis of additional personnel revealed that in all but one case (19/20; 95%), ASA were restricted to personnel immunized with lots of vaccine known to contain squalene. Except for one symptomatic individual, positive clinical findings in 17 ASA-negative personnel were restricted to 4 individuals receiving vaccine from lots containing squalene. ASA were not present prior to vaccination in preimmunization sera available from 4 AVIP personnel. Three of these individuals became ASA positive after vaccination. These results suggest that the production of ASA in GWS patients is linked to the presence of squalene in certain lots of anthrax vaccine.