Reanalysis of the data--science at its best and always informative.
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Biomedical subjects
Publications and source records attributed to Robert J Sokol.
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This study examined the relative importance of caregiver substance abuse as a correlate of child-reported exposure to violence. A total of 407 female African-American primary caregivers and their children age 6 to 7 were evaluated. The association between child report of violence and exposure to substance abuse by others (both within and outside the home) was considered after controlling for variance accounted for by child characteristics, caregiver characteristics, home environment, and neighborhood environment (including neighborhood crime). Caregiver alcohol abuse, children's witnessing of drug use in the home, and children's witnessing of drug deals all explained significant additional variance in violence exposure. These findings suggest that for early elementary-age children, meaningful prevention of violence exposure may be possible via addressing their exposure to substance abuse in their home and community.
Children in the United States are exposed to considerable community violence that has been linked to child functioning. However, not all those exposed, experience negative outcomes. Recent research has focused on factors that "buffer" or protect children from negative consequences of violence exposure. The purpose of this investigation was to examine the potential buffering or moderating role of maternal acceptance in the relationship between community violence exposure and internalizing and externalizing problems. Subjects were 268 urban African American first graders. Community violence exposure was significantly related to symptoms of post-traumatic stress, but did not correlate with either internalizing or externalizing problems for all children, after control for demographics, maternal mental health, and general life stress. However, children's perceptions of maternal acceptance moderated the relationship between violence exposure and internalizing and externalizing problems which included being withdrawn, anxious-depressed, and demonstrating delinquent behavior. Children with the lowest levels of self-reported maternal acceptance were most impacted by community violence. In this sample of urban first graders, low levels of maternal acceptance placed children at greater risk for adverse outcomes associated with community violence exposure compared to moderate and high levels of maternal acceptance.
OBJECTIVE: The release of nitric oxide by tumor cells, through the stimulation of inducible nitric oxide synthase expression, may play a critical role in ovarian cancer progression. In this study we have sought to determine the effects of inhibiting inducible nitric oxide synthase on angiogenesis that was induced by 2 ovarian cancer cell lines, SKOV and MDAH2774. STUDY DESIGN: Real-time polymerase chain reaction and enzyme-linked immunosorbent assay techniques were used to determine the expression levels of inducible nitric oxide synthase and vascular endothelial growth factor in the ovarian cancer cell lines in response to treatments with L-NAME, an inhibitor of nitric oxide synthase, and SNAP, and nitric oxide donor. Ovarian cancer-induced angiogenesis was assessed in vitro with an established assay that is based on the ability of human umbilical vein endothelial cells to form a tubular network in response to angiogenic agents. RESULTS: SKOV and MDAH2774 cell lines exhibited over-expression of inducible nitric oxide synthase and have high baseline nitric oxide levels. This was associated with high levels of vascular endothelial growth factor production and angiogenesis induction. Treatment of the ovarian cancer cell lines with L-NAME significantly reduced vascular endothelial growth factor levels production and completely inhibited angiogenesis. In contrast, treatment with SNAP significantly increased vascular endothelial growth factor levels and increased angiogenesis in both cell lines. CONCLUSION: Our data suggest that the inhibition of inducible nitric oxide synthase may form a basis for a novel therapeutic treatment option for ovarian cancer therapy.
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OBJECTIVES: To examine alcohol use for mothers with and without an ADH1B*3 allele and the moderating effects of the maternal and child ADH1B*3 allele on a broad range of infant and 7.5-year outcomes. STUDY DESIGN: Blood samples from 263 black mother/child pairs (217 mothers and 239 children) were analyzed to determine incidence of the ADH1B allele and the relation of the maternal allele to pregnancy drinking assessed at every prenatal clinic visit. Moderating effects of ADH1B were examined by dichotomizing the moderator variable and performing regression analyses on the 2 groups. RESULTS: Pregnancy drinking at conception was less frequent in the presence of the ADH1B*3 allele, and virtually no adverse effects were found in children whose mothers had at least one ADH1B*3 allele. By contrast to the maternal allele, we found no consistent pattern of greater vulnerability in children lacking the ADH1B*3 allele. CONCLUSIONS: These data are consistent with the hypothesis that the maternal ADH1B*3 allele provides some protection to the fetus from prenatal alcohol exposure.
BACKGROUND: Biomarkers of fetal exposure to alcohol are important to establish so that early detection and intervention can be made on these infants to prevent undesirable outcomes. The aim of this study was to analyze long-chain fatty acid ethyl esters (FAEEs) in meconium as potential biomarkers of fetal alcohol exposure and effect. METHODS: Fatty acid ethyl esters were analyzed in the meconium of 124 singleton infants by positive chemical ionization gas chromatography/mass spectrometry (GC/MS) and correlated to maternal ethanol use. RESULTS: A total of 124 mother/infant dyads were enrolled in the study: 31 were in the control group and 93 were in the alcohol-exposed group. The incidence (28% vs 9.7%, p = 0.037) of ethyl linoleate detected in meconium was significantly higher in the alcohol-exposed groups than the control groups. Similarly, when the concentrations of ethyl linoleate in meconium were grouped (trichotomized), there was a significant linear by linear association between alcohol exposure and group concentrations of ethyl linoleate (p = 0.013). Furthermore, only alcohol-exposed infants were found in the group with the highest ethyl linoleate concentration. The sensitivity of ethyl linoleate in detecting prenatal alcohol exposure was only 26.9%, and its specificity and positive predictive value were 96.8 and 96.2%, respectively. There was no significant correlation between the concentration of ethyl linoleate in meconium and absolute alcohol consumed (oz) per drinking day across pregnancy, although a trend toward a positive correlation is seen at lower amounts of alcohol consumed. Among the polyunsaturated, long-chain FAEEs, there was weak evidence that the incidence (21.5% vs 6.5%, p = 0.057) and concentration (p = 0.064) of ethyl arachidonate (AA) were significantly higher in the alcohol-exposed groups than the control groups. Ethyl linolenate and ethyl docosahexanoate (DHA) in meconium were found only in the alcohol group, although not at statistically significant levels. Highly significant correlations were found among the concentrations of ethyl linoleate, ethyl linolenate, ethyl AA, and ethyl DHA in meconium (correlations ranged between rs = 0.203, p = 0.024; and rs = 0.594, p < 0.001). CONCLUSION: We conclude that FAEEs in meconium, particularly ethyl linoleate and ethyl AA, are biomarkers of high specificity for prenatal exposure to alcohol in newborn infants. We also propose that ethyl AA and DHA could be potential biomarkers of fetal alcohol effects on the developing fetal brain and should be investigated further.
OBJECTIVE: To determine the effects of sildenafil citrate on fetal growth in maternal rats exposed to hypoxia. METHODS: Timed pregnant rats were randomized to either hypoxia or control on gestational days (GD) 18-20, and received either sildenafil (45 mg/kg) orally every 12 h on GD 18-21 or an equal volume of sterile water. Fetal pups were retrieved by laparotomy on GD 21. Pup weight and length were evaluated and cGMP measured in maternal and fetal blood. RESULTS: In the non-hypoxic rats, sildenafil exposure was associated with a decrease in size(4.75 +/- 0.43 vs. 5.11 +/- 0.34 g, p = 0.00). In contrast, in the hypoxic rat model, sildenafil exposure was associated with increased size of the offspring (5.48 +/- 0.45 vs. 5.16 +/- 0.36 g, p = 0.016). Maternal cGMP levels were increased in the presence of both sildenafil and hypoxia (23.0 +/- 10.5 vs. 15.6 +/- 2.7 pmol/ml, p = 0.001). CONCLUSION: Exposure to sildenafil in a non-hypoxic setting results in a decrease in fetal size. Sildenafil in the presence of a stimulus, hypoxia, will lead to increased fetal size. These results suggest that sildenafil may have some influence on fetal growth. How these effects occur and by what mechanism remain to be determined.
Systemic lupus erythematosus is a chronic multi-system autoimmune disease that occurs predominantly in women of childbearing age. The risk of complications and adverse fetal outcomes in pregnant women with lupus is high. Moreover, pregnancy can cause flares of lupus disease activity necessitating maternal immunosuppressive intervention. Interestingly, many potential complications of pregnancy present as symptoms of lupus making diagnosis and treatment a challenge. Advancing technology and better understanding of the maternal-fetal dyad in lupus have improved outcomes in lupus pregnancies over the last 40 years. This article will briefly review the important issues in pregnancies complicated by lupus and provide a general guideline to physicians for monitoring and treatment.
OBJECTIVE: This study was undertaken to determine whether there is any difference in the rate of error of estimated fetal weight (EFW) in cases of shoulder dystocia compared with controls. STUDY DESIGN: Women whose delivery was complicated by shoulder dystocia were studied and compared with a control group matched for parity, race, labor type (spontaneous or induced), and birth weight (BW). Accuracy (%) was defined as [(EFW-BW)/BW] x 100. The primary outcome of the study was rate of EFW underestimation error 20% or greater. RESULTS: During the 5-year study period, there were 206 cases of shoulder dystocia that met all study criteria. There was no difference in the number of patients that had EFW underestimation error 20% or greater (shoulder dystocia 9.8% vs control 12.8%; P = .38). There was also no difference in the number of patients that had EFW underestimation error 20% or greater between shoulder dystocia with and without injury (injury 8.3% vs no injury 7.1%; P = .79). CONCLUSION: EFW underestimation error in cases of shoulder dystocia is an infrequent event and does not occur more often than in deliveries without shoulder dystocia.
OBJECTIVE: The purpose of this study was to evaluate pregnancy outcomes before and after diagnosis of lupus. STUDY DESIGN: Successive selection criterion applied to 148 lupus and 78,905 non-lupus pregnancies, generated 3 groups: lupus group, 84 pregnancies (not-yet-diagnosed group, 15 women; already-diagnosed group, 69 women), and control group, 51,000 pregnancies. Three-way analysis of variance and the chi-squared test were used for analyses. RESULTS: Stillbirth outcome was increased in the lupus group compared with the control group (odds ratio, 4.84 [95% CI, 1.72,11.08]); the not-yet-diagnosed group (odds ratio, 9.89 [95% CI, 1.09,42.63]), and the already-diagnosed group (odds ratio, 3.85 [95% CI, 1.02,10.31]). Considering >1 pregnancy per patient would have overestimated the stillbirth rate. Stillbirth risk was increased significantly in severe maternal disease that was marked by central nervous system involvement. The already-diagnosed group had more hypertensive complications (P = .001 and .0001). Both lupus groups showed a significantly greater proportion of preterm births (P = .03), growth restriction (P = .019), and infants in the very low birth weight category (P = .021) compared with the control group. CONCLUSION: Poor fetal outcomes are seen in pregnancies that are complicated by lupus, even before clinical appearance of disease, which supports a predisease state.
OBJECTIVE: The purpose of this study was to explore the relationship between residency program selection factors and placements we received on candidates' match lists. STUDY DESIGN: An annual (2001-2004) telephone survey of applicants (n = 140) ranked for acceptance to the department's residency program addressed 16 program selection factors important in choosing our site. Candidates' comments about these program selection factors were recorded. Logistic regression was conducted with program selection factors as independent variables and program receipt of candidates' top quartile match list rankings as the dependent variable. RESULTS: The overall response rate was 68% (n = 95). Applicants' positive ratings on 3 program selection factors were related to our receipt of top quartile match list rankings: 1) our capacity to meet personal career goals (odds ratio [OR] 4.59); 2) positive faculty-resident relationships (OR 1.97); and 3) suitable location (OR 1.96). CONCLUSION: The single most important factor contributing to receipt of candidates' top quartile match list placements was positive perceptions of our program's abilities to meet their personal career goal needs.
The purpose of this study was to determine the frequency of prescription and over-the-counter (OTC) medications, and herbal remedies used by pregnant women. A prospective observational study was performed at a single tertiary-care hospital. Postpartum women completed a questionnaire that included a list of more than 120 medications, herbal remedies, and alternative therapies listed by both brand and common name. Patients were asked to identify any and all medications or treatments used during pregnancy. Of 418 patients who completed questionnaires, 96.9% took at least one medication during their pregnancy. After excluding prenatal vitamins and iron supplements, 76.5% took at least one other medication; 62.8% used OTC medications, and 4.1% used herbal and/or alternative remedies. Multiple drug use occurred in 33.5% of patients, with up to 13.6% consuming four or more medications. The use of prescribed and OTC, medications, and herbal/alternative therapy, is common in pregnancy, with many patients consuming more than one agent at a time.
BACKGROUND: African American women and socioeconomically challenged women are at risk of compromised folate status and, thus, of folate-related birth defects. Data are limited on circulating folate concentrations in pregnant African American women after folic acid fortification of the food supply was implemented. OBJECTIVE: The objective was to determine the influence of smoking and alcohol consumption on plasma 5-methyltetrahydrofolic acid (5-MTHFA) concentrations in pregnant African American women. DESIGN: Alcohol consumption, smoking exposure, and other characteristics of pregnant African American women reporting to an inner-city antenatal clinic were assessed. At 24 wk of gestation, blood samples and food-frequency intake data were collected. Plasma 5-MTHFA concentrations were determined by liquid chromatography-mass spectrometry for 116 subjects and examined in a correlational study design. RESULTS: Dietary folate and markers of alcohol consumption were positively associated, whereas exposure to smoke was negatively associated with plasma 5-MTHFA. More than one-half of the participants in this population failed to meet the recommended dietary allowance for dietary folate equivalents of 600 microg/d during pregnancy. CONCLUSIONS: Most inner-city African American women are not meeting the recommended dietary allowance for dietary folate during pregnancy, and smoking may further compromise their folate status. Programs to reduce smoking and raise awareness about the importance of folate and multivitamin supplementation during pregnancy need to target this population.
Somatic complaints of children in primary care settings often go unexplained despite attempts to determine a cause. Recent research has linked violence exposure to stress symptomatology and associated somatic problems. Unknown, however, is whether specific physical symptom complaints can be attributed, at least in part, to violence exposure. Urban African-American 6- and 7-year-old children (N = 268), residing with their biological mothers, recruited before birth, and without prenatal exposure to hard illicit drugs participated. Children and mothers were evaluated in our hospital-based research laboratory, with teacher data collected by mail. Community violence exposure (Things I Have Seen and Heard), stress symptomatology (Levonn), and somatic complaints (teacher-and self-report items) were assessed. Additional data collected included prenatal alcohol exposure, socioeconomic status, domestic violence, maternal age, stress, somatic complaints and psychopathology, and child depression, abuse, and gender. Community violence witnessing and victimization were associated with stress symptoms (r = .26 and .25, respectively, p < .001); violence victimization was related to decreased appetite (r = .16, p < .01), difficulty sleeping (r = .21, p < .001), and stomachache complaints (r = .13, p < .05); witnessed violence was associated with difficulty sleeping (r = .13, p < .05) and headaches (r = .12, p < .05). All associations remained significant after control for confounding. Community violence exposure accounted for 10% of the variance in child stress symptoms, and children who had experienced community violence victimization had a 28% increased risk of appetite problems, a 94% increased risk of sleeping problems, a 57% increased risk of headaches, and a 174% increased risk of stomachaches. Results provide yet another possibility for clinicians to explore when treating these physical symptoms in children.
BACKGROUND: Inner-city, black women are among those groups that are at higher risk for having infants with fetal alcohol spectrum disorders that can include life-long neurobehavioral and cognitive impairments. Chronic alcohol consumption can decrease amounts of docosahexaenoic acid (DHA), a fatty acid that is essential for optimal infant neural and retinal development in a variety of tissues. METHODS: Black women who presented at an inner-city antenatal clinic for their first prenatal visit were recruited into a longitudinal, observational study. Alcohol intake was determined by a structured interview. Participants provided blood specimens and completed food frequency surveys at 24 weeks of gestation, infant delivery, and 3 months postpartum. Fatty acid composition analyses were completed on 307, 260, and 243 for plasma and 278, 261, and 242 erythrocyte specimens at 24 weeks of gestation, delivery, and 3 months postpartum, respectively. RESULTS: Proportion of drinking days at the first prenatal visit was associated with decreased DHA in plasma and erythrocytes throughout the study. This association was the strongest at 24 weeks of gestation. In addition, an interaction between proportion of drinking days at the time of conception and ounces of absolute alcohol per drinking day at the time of conception was detected and demonstrated that, in daily drinkers, high intakes of alcohol are associated with decreased DHA and arachidonic acid (AA) concentrations in plasma. CONCLUSIONS: Frequent and high intakes of alcohol that have been previously associated with fetal alcohol spectrum disorders are also associated with decreased maternal DHA and AA plasma concentrations. The present findings indicate that maternal DHA deficiency is associated with high-risk drinking and may contribute to the mechanism(s) of alcohol-related neurodevelopmental disorders.
BACKGROUND: A broad range of attentional and neuropsychological impairments have been demonstrated in children with fetal alcohol exposure. This study was designed to investigate which specific aspects of attentional function are most directly affected by moderate to heavy doses of prenatal alcohol exposure. METHODS: A total of 337 black children who were aged 7.5 years and recruited prospectively to overrepresent prenatal alcohol exposure at moderate to heavy levels were assessed on a diverse battery of neuropsychological tests. Principal components analyses were used to replicate and extend Mirsky et al.'s (1991) four-component model of attention. The relation of prenatal alcohol exposure to empirically derived attentional constructs was examined. RESULTS: Both the replicated and the extended attentional models produced solutions similar to the original Mirsky et al. model, reflecting elements of encode (working memory), shift, and focused and sustained attention, as well as a distinct component reflecting impulsivity. Adverse effects of maternal drinking across pregnancy were found primarily for working memory, and these effects were exacerbated when mothers were aged 30 or older at the time of the child's birth. CONCLUSIONS: These data confirm previous studies using diverse methods that suggest that working memory may be the most important aspect of attention that is adversely affected by prenatal alcohol exposure.
Alcohol use among women of childbearing age is prevalent in the United States, with approximately 1 in 5 nonpregnant women reporting binge drinking (5 or more drinks on any one occasion) and 1 in 25 pregnant women reporting binge drinking. Alcohol use during pregnancy results in a spectrum of adverse outcomes known as fetal alcohol spectrum disorders. Fetal alcohol syndrome (FAS) is one of these disorders. Fetal alcohol syndrome is characterized by specific facial abnormalities and significant impairments in neurodevelopment and physical growth. Early identification of children with FAS has been shown to enhance their long-term outcomes. In an effort to improve clinical recognition of children with this condition, Centers for Disease Control and Prevention (CDC) was directed by Congress in 2002 to lead the development of uniform diagnostic criteria for FAS and other prenatal alcohol-related conditions. The purpose of this commentary is to provide clinicians a summary of the report released by CDC describing the current diagnostic criteria for FAS. In addition, advancements have been made in screening and brief interventions for alcohol use disorders in women who have the potential to make significant strides in the prevention of FAS spectrum disorders. Knowledge of the diagnostic criteria for FAS can lead to increased identification of the syndrome in infants and children and the provision of appropriate medical and support services. Screening for and intervening with women at risk for an alcohol-exposed pregnancy can prevent FAS and other fetal alcohol spectrum disorders.