Biomedical subjects

Brian M Casey

Publications and source records attributed to Brian M Casey.

10 recordsLinked to original sources

PubMed2006

Placental transfer of rosiglitazone in the ex vivo human perfusion model.

OBJECTIVE: The objective of the study was to determine transplacental passage of rosiglitazone (Avandia) using the ex vivo human placental model. STUDY DESIGN: Perfusion studies were performed on 10 placentas from term, uncomplicated deliveries. Concentrations typical for an 8-mg oral dose (216 to 692 ng/mL) as well as 2- to 3-fold increased concentrations were tested (734 to 1261 ng/mL). Transfer of rosiglitazone was assessed and accumulation was determined using the 14C-antipyrine reference method. RESULTS: The clearance index for low and high concentrations were 0.14 +/- 0.04 and 0.20 +/- 0.08, suggesting that the drug passes through the placenta at a relatively low rate. Fetal accumulation occurred in only 1 of 5 placentas at 16.4 ng/mL (5%) for the 8-mg dose and in 2 of 5 placentas ranging from 0 to 74 ng/mL (5% to 8%) at higher concentrations. CONCLUSION: There is minimal transfer and fetal accumulation of rosiglitazone according to the ex vivo human perfusion model.

Administration, Oral↗

PubMed2006

A randomized trial of coached versus uncoached maternal pushing during the second stage of labor.

OBJECTIVE: The objective of this study was to compare obstetrical outcomes associated with coached versus uncoached pushing during the second stage of labor. STUDY DESIGN: Upon reaching the second stage, previously consented nulliparous women with uncomplicated labors and without epidural analgesia were randomly assigned to coached (n = 163) versus uncoached (n = 157) pushing. Women allocated to coaching received standardized closed glottis pushing instructions by certified nurse-midwives with proper ventilation encouraged between contractions. These midwives also attended those women assigned to no coaching to ensure that any expulsive efforts were involuntary. RESULTS: The second stage of labor was abbreviated by approximately 13 minutes in coached women (P = .01). There were no other clinically significant immediate maternal or neonatal outcomes between the 2 groups. CONCLUSION: Although associated with a slightly shorter second stage, coached maternal pushing confers no other advantages and withholding such coaching is not harmful.

Adult↗

PubMed2006

Long-term fetal outcomes in pregnant trauma patients.

BACKGROUND: Trauma during pregnancy is associated with significant maternal and fetal morbidity and mortality, typically occurring during the hospital admission. Less is known about the delayed effects of trauma on pregnancy outcome once the patient has been discharged from the hospital with a viable fetus. METHODS: A retrospective cohort study was conducted of pregnant trauma patients who were discharged from the trauma center with a viable fetus. Risk of preterm delivery (PTD) and low birth weight (LBW) were compared between injured patients (Injury Severity Score > 0) and those without identified injury (Injury Severity Score = 0), for the remainder of pregnancy. RESULTS: Even after trauma center discharge, injured patients had a nearly 2-fold higher risk of PTD (relative risk, 1.9; 95% confidence interval, 1.1-3.3) and LBW (relative risk, 1.8; 95% confidence interval, 1.04-3.2) for the remainder of the pregnancy. The risk was higher with increasing injury severity and among those injured early in gestation. CONCLUSION: The risk of PTD and LBW in pregnant trauma patients who were discharged from trauma centers with a viable fetus remains increased throughout the remainder of the pregnancy. A history of trauma during gestation is a risk factor for poor pregnancy outcome.

Adolescent↗

PubMed2006

Subclinical hyperthyroidism and pregnancy outcomes.

OBJECTIVE: Subclinical hyperthyroidism has long-term sequelae that include osteoporosis, cardiovascular morbidity, and progression to overt thyrotoxicosis or thyroid failure. The objective of this study was to evaluate pregnancy outcomes in women with suppressed thyroid-stimulating hormone (TSH) and normal free thyroxine (fT(4)) levels. METHODS: All women who presented to Parkland Hospital for prenatal care between November 1, 2000, and April 14, 2003, underwent thyroid screening by chemiluminescent TSH assay. Women with TSH values at or below the 2.5th percentile for gestational age and whose serum fT(4) levels were 1.75 ng/dL or less were identified to have subclinical hyperthyroidism. Those women screened and delivered of a singleton infant weighing 500 g or more were analyzed. Pregnancy outcomes in women identified with subclinical hyperthyroidism were compared with those in women whose TSH values were between the 5th and 95th percentiles. RESULTS: A total of 25,765 women underwent thyroid screening and were delivered of singleton infants. Of these, 433 (1.7%) were considered to have subclinical hyperthyroidism, which occurred more frequently in African-American and/or parous women. Pregnancies in women with subclinical hyperthyroidism were less likely to be complicated by hypertension (adjusted odds ratio 0.66, 95% confidence interval 0.44-0.98). All other pregnancy complications and perinatal morbidity or mortality were not increased in women with subclinical hyperthyroidism. CONCLUSION: Subclinical hyperthyroidism is not associated with adverse pregnancy outcomes. Our results indicate that identification of subclinical hyperthyroidism and treatment during pregnancy is unwarranted. LEVEL OF EVIDENCE: II-2.

Adult↗

PubMed2006

Thyroid disease in pregnancy.

Thyroid testing during pregnancy should be performed on symptomatic women or those with a personal history of thyroid disease. Overt hypothyroidism complicates up to 3 of 1,000 pregnancies and is characterized by nonspecific signs or symptoms that are easily confused with complaints common to pregnancy itself. Physiologic changes in serum thyroid-stimulating hormone (TSH) and free thyroxine (T(4)) related to pregnancy also confound the diagnosis of hypothyroidism during pregnancy. If the TSH is abnormal, then evaluation of free T(4) is recommended. The diagnosis of overt hypothyroidism is established by an elevated TSH and a low free T(4). The goal of treatment with levothyroxine is to return TSH to the normal range. Overt hyperthyroidism complicates approximately 2 of 1,000 pregnancies. Clinical features of hyperthyroidism can also be confused with those typical of pregnancy. Clinical hyperthyroidism is confirmed by a low TSH and elevation in free T(4) concentration. The goal of treatment with thioamide drugs is to maintain free T(4) in the upper normal range using the lowest possible dosage. Postpartum thyroiditis requiring thyroxine replacement has been reported in 2% to 5% of women. Most women will return to the euthyroid state within 12 months.

Female↗

PubMed2005

Obstetric antecedents for postpartum pelvic floor dysfunction.

OBJECTIVE: The purpose of this study was to evaluate prospectively the association between selected obstetric antecedents and symptoms of pelvic floor dysfunction in primiparous women up to 7 months after childbirth. STUDY DESIGN: All nulliparous women who were delivered between June 1, 2000, and August 31, 2002, were eligible for a postpartum interview regarding symptoms of persistent pelvic floor dysfunction. Responses from all women who completed a survey at or before their 6-month contraceptive follow-up visit were analyzed. Obstetric antecedents to stress, urge, and anal incontinence were identified, and attributable risks for each factor were calculated. RESULTS: During the study period, 3887 of 10,643 primiparous women (37%) returned within 219 days of delivery. Symptoms of stress and urge urinary incontinence, were significantly reduced (P < .01) in women who underwent a cesarean delivery. Symptoms of urge urinary incontinence doubled in women who underwent a forceps delivery (P = .04). Symptoms of anal incontinence were increased in women who were delivered of an infant who weighed >4000 g (P = .006) and more than doubled in those women who received oxytocin and had an episiotomy performed (P = .01). CONCLUSION: The likelihood of symptoms of pelvic floor dysfunction up to 7 months after delivery was greater in women who received oxytocin, who underwent a forceps delivery, who were delivered of an infant who weighed >4000 g, or who had an episiotomy performed. Women who underwent a cesarean delivery had fewer symptoms of urge and stress urinary incontinence.

Adult↗

PubMed2005

Subclinical hypothyroidism and pregnancy outcomes.

BACKGROUND: Clinical thyroid dysfunction has been associated with pregnancy complications such as hypertension, preterm birth, low birth weight, placental abruption, and fetal death. The relationship between subclinical hypothyroidism and pregnancy outcomes has not been well studied. We undertook this prospective thyroid screening study to evaluate pregnancy outcomes in women with elevated thyrotropin (thyroid-stimulating hormone, TSH) and normal free thyroxine levels. METHODS: All women who presented to Parkland Hospital for prenatal care between November 1, 2000, and April 14, 2003, had thyroid screening using a chemiluminescent TSH assay. Women with TSH values at or above the 97.5th percentile for gestational age at screening and with free thyroxine more than 0.680 ng/dL were retrospectively identified with subclinical hypothyroidism. Pregnancy outcomes were compared with those in pregnant women with normal TSH values between the 5th and 95th percentiles. RESULTS: A total of 25,756 women underwent thyroid screening and were delivered of a singleton infant. There were 17,298 (67%) women enrolled for prenatal care at 20 weeks of gestation or less, and 404 (2.3%) of these were considered to have subclinical hypothyroidism. Pregnancies in women with subclinical hypothyroidism were 3 times more likely to be complicated by placental abruption (relative risk 3.0, 95% confidence interval 1.1-8.2). Preterm birth, defined as delivery at or before 34 weeks of gestation, was almost 2-fold higher in women with subclinical hypothyroidism (relative risk, 1.8, 95% confidence interval 1.1-2.9). CONCLUSION: We speculate that the previously reported reduction in intelligence quotient of offspring of women with subclinical hypothyroidism may be related to the effects of prematurity. LEVEL OF EVIDENCE: II-2.

Adult↗

PubMed2005

Thyroid-stimulating hormone in singleton and twin pregnancy: importance of gestational age-specific reference ranges.

OBJECTIVE: To estimate a normal reference range for thyroid-stimulating hormone (TSH) at each point in gestation in singleton and twin pregnancies. METHODS: All women enrolling for prenatal care from December 2000 through November 2001 underwent prospective TSH screening at their first visit. Separate nomograms were constructed for singleton and twin pregnancies using regression analysis. Values were converted to multiples of the median (MoM) for singleton pregnancies at each week of gestation. RESULTS: Thyroid-stimulating hormone was evaluated in 13,599 singleton and 132 twin pregnancies. Thyroid-stimulating hormone decreased significantly during the first trimester, and the decrease was greater in twins (both P < .001). Had a nonpregnant reference (0.4-4.0 mU/L) been used rather than our nomogram, 28% of 342 singletons with TSH greater than 2 standard deviations above the mean would not have been identified. For singleton first-trimester pregnancies, the approximate upper limit of normal TSH was 4.0 MoM, and for twins, 3.5 MoM. Thereafter, the approximate upper limit was 2.5 MoM for singleton and twin pregnancies. CONCLUSION: If thyroid testing is performed during pregnancy, nomograms that adjust for fetal number and gestational age may greatly improve disease detection. Values expressed as multiples of the median may facilitate comparisons across different laboratories and populations.

Adolescent↗

PubMed2004

Human myometrial gene expression before and during parturition.

Identification of temporal and spatial changes in myometrial gene expression during parturition may further the understanding of the coordinated regulation of myometrial contractions during parturition. The objective of this study was to compare the gene expression profiles of human fundal myometrium from pregnant women before and after the onset of labor using a functional genomics approach, and to further characterize the spatial and temporal expression patterns of three genes believed to be important in parturition. Fundal myometrial mRNA was isolated from five women in labor and five women not in labor, and analyzed using human UniGEM-V microarrays with 9182 cDNA elements. Real-time polymerase chain reaction using myometrial RNA from pregnant women in labor or not in labor was used to examine mRNA levels for three of the genes; namely, prostaglandin-endoperoxide synthase 2 (PTGS2), calgranulin B (S100A9), and oxytocin receptor (OXTR). The spatial expression pattern of these genes throughout the pregnant uterus before and after labor was also determined. Immunolocalization of cyclooxygenase-2 (also known as PTGS2) and S100A9 within the uterine cervix and myometrium were analyzed by immunohistochemistry. Few genes were differentially expressed in fundal myometrial tissues at term with the onset of labor. However, there appears to be a subset of genes important in the parturition cascade. The cellular properties of S100A9, its spatial localization, and dramatic increase in cervix and myometrium of women in labor suggest that this protein may be very important in the initiation or propagation of human labor.

Calgranulin B↗

PubMed2002

Maternal diabetes mellitus and infant malformations.

OBJECTIVE: To investigate the effects of pregestational, as opposed to gestational, diabetes on infant malformations. METHODS: All women delivering infants at Parkland Hospital between January 1, 1991, and December 31, 2000, were ascertained. Screening for gestational diabetes was methodically employed throughout the study period using National Diabetes Data Group criteria for diagnosis of pregestational and gestational diabetes. Standardized definitions of major infant malformations were specified before data analysis and subdivided according to the organ systems involved. RESULTS: A total of 145,196 women were delivered during the study period, and 2687 (1.9%) were diagnosed to have diabetes mellitus. Gestational diabetes was diagnosed in 2277 (1.6%) of whom 230 (10%) had fasting hyperglycemia diagnosed, and the remainder consistently demonstrated fasting serum levels less than 105 mg/dL. Pregestational diabetes was diagnosed in 410 (0.3%) women. Infant malformations occurred in 1.5% of nondiabetic women compared with 1.2% of women with normal fasting glucose gestational diabetes, 4.8% in women with gestational diabetes plus fasting hyperglycemia, and 6.1% in those with pregestational diabetes (P <.001, for comparison of the latter two groups with the nondiabetic population). CONCLUSION: Women with pregestational diabetes or gestational diabetes plus fasting hyperglycemia have a three- to four-fold increased risk of infant malformations, whereas women with mild gestational diabetes have malformation rates no different than the general nondiabetic obstetric population.

Adult↗