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Biomedical subjects

M W Varner

Publications and source records attributed to M W Varner.

At least 37 records · Page 2Linked to original sources
PubMed1996

Dose-related effects of low dose aspirin on hemostasis parameters and prostacyclin/thromboxane ratios in late pregnancy.

BACKGROUND: The purpose of this study was to determine which low dose of low dose aspirin (LDA) optimized the urinary prostacyclin (PGI2)/thromboxane (TXA2) ratio and minimized evidence of platelet aggregation during normal late pregnancy. METHODS: Twelve women with uncomplicated singleton pregnancies between 28 and 34 weeks gestation participated in a randomized blinded study. Blood samples for salicylate levels were obtained pretreatment, 4 hours and 7 days after administration of placebo, 20mg, 40mg or 80mg of aspirin. Twenty-four hour urine specimens collected at the same intervals were assayed for PGI2 and TXA2 metabolites. In addition, bleeding time and platelet aggregation studies were performed prior to and after 7 days of LDA or placebo. RESULTS: A dose-related increase in bleeding time occurred with 40 mg and 80 mg of LDA, but not with the 20 mg dose or placebo. Platelet aggregation studies changed progressively from a normal baseline to abnormal with an increasing dose of LDA. The PGI2/TXA2 ratio increased with aspirin doses as low as 20mg, with a decrease in TXA2 metabolites but not in PGI2 metabolites. Serum salicylate was not detectable in any sample from any patient. CONCLUSION: There are dose-related changes in platelet aggregation and bleeding times with progressively increasing doses of LDA. A lower dose of LDA, such as 20-40 mg per day, may be as efficacious as higher doses in the prophylaxis of pre-eclampsia in high risk populations.

Adolescent↗
PubMed1996

Elevations of serum interleukin-12 concentrations in women with severe pre-eclampsia and HELLP syndrome.

The objective is to test the hypothesis that serum IL-12 concentrations would be elevated in women with severe pre-eclampsia and HELLP syndrome. The Methods used were as follows: Serum was obtained from women admitted to our Labor and Delivery unit diagnosed with severe pre-eclampsia or HELLP syndrome and normal control patients. IL-12 concentrations in these samples were determined by the use of two different and specific enzyme-linked immunosorbent assays for the p40 subunit and the intact p75 dimer. It was found that serum IL-12 (p40 subunit) concentrations were elevated in women with both severe pre-eclampsia (p = 0.011) or HELLP syndrome (= 0.004). Similar findings were noted for these patients when matched with control patients for maternal age, gestational age, and parity. Eleven women had elevations of serum IL-12 p75 dimer, and 10 of these 11 patients had severe pre-eclampsia or HELLP syndrome. In conclusion, we found that women with severe pre-eclampsia and HELLP syndrome commonly have detectable concentrations of the IL-12 p40 monomer and were more likely than normal control women to have detectable serum IL-12 p75 dimer. While the exact role of IL-12 in hypertensive disease during pregnancy is unclear, our data support the hypothesis that the regulation of IL-12 production and metabolism is abnormal in women with pre-eclampsia and HELLP syndrome, perhaps contributing to the immunologic alterations characteristic of these disorders.

Adult↗
PubMed1996

Very advanced maternal age: pregnancy after age 45.

OBJECTIVE: Our purpose was to describe the maternal and fetal outcomes of pregnancies in women > or = 45 years old at delivery. STUDY DESIGN: A retrospective review of in-hospital deliveries after 20 weeks of gestation was performed in four Utah tertiary care hospitals for the 10-year period between 1985 and 1994. RESULTS: Seventy-nine cases were identified among 126,500 births, with an incidence of 0.63 per 1000 births. Maternal ages were 45 (n = 44), 46 (n = 21), and > or = 47 (n = 14) years. Three of the conceptions were assisted, including both twin gestations. Thirty-seven (46.8%) had obstetric complications during pregnancy; the most frequent complications were gestational diabetes (12.7%) and preeclampsia (10.1%). Median (range) gestational age at delivery was 39 (22.9 to 41.7) weeks; 12 (15.2%) deliveries occurred before 37 weeks. Eight (9.9%) karyotype abnormalities were diagnosed. The cesarean section rate was 31.7%; the most frequent indications were abnormal lie (n = 9), fetal distress (n = 5), and previous cesarean delivery (n = 5). There were no maternal deaths. Median (range) birth weight was 3466 (397 to 5085) gm; 14 (17.3%) were < 2500 gm and 16 (19.8%) were > 4000 gm. Twelve (14.8%) infants were admitted to the neonatal intensive care unit. The corrected perinatal mortality rate was 1.3% (1/78). CONCLUSIONS: In women > 45 years old at delivery maternal and fetal outcomes were generally good, but there was a high incidence of pregestational (chronic hypertension, hypothyroidism) and gestational (karyotype abnormalities, gestational diabetes, cesarean section, macrosomia) complications. This information may be helpful for counseling women between 45 and 50 years old who are considering pregnancy.

Apgar Score↗
PubMed1996

Elevation of amniotic fluid interleukin-4 concentrations in women with preterm labor and chorioamnionitis.

Preterm labor associated with intrauterine infection is characterized by increased amniotic fluid concentrations of various proinflammatory cytokines, including interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-8, and macrophage inflammatory protein-1alpha (MIP-1alpha). The purpose of this study was to determine if preterm labor in women with clinically evident chorioamnionitis is marked by elevations of the anti-inflammatory cytokine interleukin-4 (IL-4) and the T cell growth factor IL-2. Amniotic fluid samples were obtained from (1) women at term, not in labor (n = 10); (2) women at term, in labor (n = 10); (3) women with preterm contractions but undelivered within 1 week of amniotic fluid collection (n = 10); (4) women with preterm labor and delivery without clinically evident chorioamnionitis (n = 10); (5) women with preterm labor associated with chorioamnionitis (n = 8); and (6) women with preterm labor and delivery without infection matched with patients with chorioamnionitis (n = 8). Amniotic fluid concentrations of IL-4 and IL-2 were determined for each sample with a specific and sensitive enzyme-linked immunoassay. We found that women with infection-associated preterm labor and delivery had significantly higher concentrations of IL-4 when compared to appropriately matched controls (p < 0.05). Additionally, women with preterm labor and delivery not associated with infection had higher amniotic fluid IL-4 concentrations than women with preterm contractions but no labor (p < 0.05). Women with term labor had rare modest elevations of amniotic fluid IL-4. No IL-2 was detected in any sample. Our data indicate that amniotic fluid IL-4 is elevated in women with preterm labor and delivery, particularly in association with chorioamnionitis. We suggest that IL-4, although previously considered an anti-inflammatory agent, may have a paradoxical proinflammatory role in the pathogenesis of infection-associated preterm labor.

Adult↗
PubMed1996

Significant decrease in parathyroid hormone-related protein concentrations in amniotic fluid with labour at term but not preterm.

It has been determined whether amniotic fluid concentrations of parathyroid hormone-related protein (PTHrP) change with labour. An evaluation of which cells from intrauterine tissues might produce PTHrP has also been conducted. Amniotic fluid was obtained by amniocentesis from women: (1) at term, not in labour; (2) in normal term labour; (3) in preterm labour, undelivered within one week; (4) in preterm labour, delivered within one week; (5) in preterm labour associated with clinical chorioamnionitis; and (6) who were gestation-matched controls for chorioamnionitis patients-women in this group were similar to those in Group 4 but were different patients. Amnion, chorion, and decidual cells were grown by standard techniques and incubated with interleukin-1 beta (IL-1 beta). PTHrP was assayed in duplicate samples of amniotic fluid or tissue culture media using an immunoradiometric assay. There was a significant reduction in amniotic fluid concentrations of PTHrP during labour at term. Preterm labour was not associated with significant changes in amniotic fluid concentrations of PTHrP although a trend for reduced concentrations was observed. Amnion and chorion produced measurable quantities of PTHrP and rates of production were increased by treatment with IL-1 beta. Decidual cells did not produce detectable amounts of PTHrP. Hence, labour at term is associated with a decrease in amniotic fluid PTHrP concentrations that may reflect reduced amnion production, which in turn may play a permissive or active role in the mechanism(s) of parturition. These data support the view that the mechanisms that control term and preterm labour may be regulated differently.

Amniocentesis↗
PubMed1994

Cervical ripening before induction of labor: a randomized trial of prostaglandin E2 gel versus low-dose oxytocin.

OBJECTIVE: The purpose of this study was to compare prostaglandin E2 gel and a low-dose infusion of oxytocin for cervical ripening before labor induction. STUDY DESIGN: A total of 158 women were randomized to receive either two intracervical doses of 0.5 mg prostaglandin E2 gel 6 hours apart or 12 hours of intravenous oxytocin up to 4 mlU/min. After cervical ripening labor was induced with high-dose oxytocin infusion and amniotomy. RESULTS: There was no difference between the prostaglandin E2 and low-dose oxytocin groups in the likelihood of being in labor or having a Bishop score favorable for induction after ripening (64.2% vs 52.0%, p = 0.12) or in the incidence of vaginal delivery (75.9% vs 74.7%). Prostaglandin E2-treated patients were delivered sooner (20.2 +/- 8.1 hours vs 25.0 +/- 10.5 hours, p = 0.002). Among delivered patients the likelihood of vaginal delivery within 24 hours was greater with prostaglandin E2 ripening (63.7% vs 47.2%, p = 0.04), but there was no difference at 36 hours (76.2% vs 75.0%). Uterine hyperstimulation and fetal distress during ripening occurred only in the prostaglandin E2 group, at a rate of 4.8%. CONCLUSIONS: After cervical ripening with prostaglandin E2 gel or low-dose oxytocin vaginal delivery can be expected in three fourths of patients within 24 to 36 hours. We recommend that patients with an unfavorable cervix who require delivery undergo cervical ripening and induction of labor rather than automatic delivery by cesarean section.

Adult↗
PubMed1994

Clinical value of amniotic fluid interleukin-6 determinations in the management of preterm labour.

OBJECTIVE: To ascertain whether the determination of amniotic fluid interleukin-6 (IL-6) concentrations would be a useful clinical test in the management of women with preterm contractions. SETTING: The labour and delivery unit and the Fetal Diagnostic Centre at the University of Utah. SUBJECTS: Pregnant women at various stages of gestation in the third trimester. DESIGN: Amniotic fluid samples were collected from women experiencing one of four clinical scenarios: 1. term pregnancy, not in labour with no evidence of intrauterine infection; 2. normal term labour with no evidence of infection; 3. preterm labour with no evidence of infection and undelivered within one week of sampling; and 4. preterm labour and delivered within seven days of sample collection. Amniotic fluid was obtained by amniocentesis or at the time of amniotomy or hysterotomy. IL-6 in each specimen was determined by a specific rapid ELISA. RESULTS: Amniotic fluid IL-6 levels, given as mean (SEM) in the four groups of women listed were: 1. term pregnancy, not in labour: 20.9 (7.2) pg/ml (n = 60); 2. normal term labour with no infection: 554 (90.7) pg/ml (n = 46); 3. preterm labour with no evidence of infection, undelivered: 47.0 (17.2) pg/ml (n = 35); and 4. preterm labour, delivered: 456.7 (101.7) pg/ml (n = 40). There was no significant difference in the means of amniotic fluid IL-6 for the term labour and preterm labour delivered groups. In general, amniotic fluid IL-6 levels during term labour increased with advancing cervical dilation. There was no correlation of cervical dilation and amniotic fluid IL-6 levels in women having preterm delivery. Receiver-operator curves revealed optimal IL-6 levels for discrimination of labour at term to be 50 pg/ml and for preterm delivery to be 200 pg/ml. CONCLUSIONS: IL-6 can readily be detected in the amniotic fluid of most women who are in active labour, regardless of gestational age. Our data suggest that amniotic fluid IL-6 determinations may be clinically useful in the management of preterm labour.

Adult↗
PubMed1994

Prenatal substance use in a Western urban community.

To assess the extent of prenatal substance use in a predominantly white population in an urban area of the western United States and to develop a risk profile for this population, a cross-sectional prevalence study was done. Prenatal clinics (10 public and 10 private) anonymously recorded demographic information about and collected aliquots of routinely obtained urine specimens from women during prenatal visits. Urine specimens were screened by enzyme immunoassay for amphetamines, marijuana, cocaine, opiates, and ethanol. Of the 935 women screened, 92 (9.8%) had urine specimens positive for one or more of these substances. Urine screens were positive in 56 (10.0%) of 562 women attending private clinics and 36 (9.6%) of 373 women attending public clinics. Only 7 of the 935 women (0.7%) had screens positive for cocaine. Ethanol was the most frequently detected substance in the private clinic group (6.4%), whereas marijuana was most common among women attending public clinics (5.1%). Although substance use in this group of pregnant women occurs at a lower rate and a different pattern from those found in other more densely populated areas, the rate is high enough to be of concern to all prenatal care professionals, who should incorporate substance use history taking and selective urine drug screening into their routine prenatal practices.

Adult↗
PubMed1994

Recurrent pregnancy loss.

Recurrent pregnancy loss is a frustrating clinical dilemma for both patients and physicians because, in most cases, causes are nebulous and few treatments with proven benefit can be offered. Involved, expensive tests have frequently been proposed and their use has often filtered into clinical practice before their utility has been firmly demonstrated. Proposed causes of recurrent pregnancy loss include genetic and environmental etiologies, infectious agents, maternal congenital and acquired anatomic abnormalities, and immunologic and endocrinologic dysfunction. Appropriate management relies upon a realistic understanding of the often substantial limitations of currently available therapies.

Abortion, Habitual↗
PubMed1993

Cranial magnetic resonance imaging in severe preeclampsia vs eclampsia.

OBJECTIVE: This study was undertaken to evaluate the hypothesis that severe preeclampsia and eclampsia are associated with unique cranial magnetic resonance images. DESIGN: Case series of women with severe preeclampsia and eclampsia. SETTING: Referral center. PATIENTS: Sixteen women with severe preeclampsia and 10 women with eclampsia. RESULTS: Half of the women with severe preeclampsia had abnormal scans with nonspecific foci of increased signal in the deep cerebral white matter on T2-weighted images. However, women with eclampsia had either a multifocal area of increased signal at the gray-white matter junction on T2-weighted images or cortical edema and hemorrhage. These findings are consistent with necropsy descriptions of cortical edema and petechial hemorrhage. Basal ganglion lesions were also common. CONCLUSIONS: These findings appear to be unique to eclamptic women and should be considered of diagnostic significance in contrast to the nonspecific changes in patients with severe preeclampsia. Cranial magnetic resonance imaging may, thus, be of value in cases with diagnostic uncertainty, atypical presentation, or focal neurologic deficit.

Adult↗
PubMed1993

Regulation of fetal fibronectin production in human chorion cells.

OBJECTIVE: Our purpose was to evaluate the role of human chorion in production of fetal fibronectin and to assess the regulation of fetal fibronectin production by inflammatory products and cytokines. STUDY DESIGN: Human chorion cells were grown in culture, and at confluence cells were incubated with and without lipopolysaccharide, interleukin-1 beta, tumor necrosis factor-alpha, and acetylsalicylic acid. Fetal fibronectin production was measured in the supernatants by means of enzyme-linked immunosorbent assay. RESULTS: Production of fetal fibronectin was increased by lipopolysaccharide, interleukin-1 beta, and tumor necrosis factor-alpha. Acetylsalicylic acid had no effect on fetal fibronectin biosynthesis. CONCLUSIONS: Fetal fibronectin production by human chorion cells in vitro is stimulated by inflammatory products and mediators, which are considered to be important in the initiation of some cases of preterm labor.

Cells, Cultured↗
PubMed1993

Severe pulmonary hypertension in pregnancy following successful repair of ventricular septal defect in childhood.

BACKGROUND: Because of advances in surgical repair, an increasing number of women born with structural cardiac disease now live to reproductive age. Patients treated successfully in childhood are followed for varying periods of time, then may be lost to follow-up or told that no follow-up is necessary because their condition is stable. However, the hemodynamic changes that accompany pregnancy may result in cardiovascular decompensation, even after years of apparently good health. CASES: We have recently cared for two women who had undergone repair of congenital heart disease in childhood. Although they thought that their repair was complete and they had been asymptomatic until the pregnancy, both presented with symptoms and signs of severe pulmonary hypertension, subsequently confirmed on cardiac catheterization. One patient elected to terminate her pregnancy, and the other died in the immediate puerperium. CONCLUSION: Despite normal physical function and an absence of abnormal physical findings, a thorough cardiac evaluation including echocardiography should be considered for pregnant patients with a history of repaired congenital heart disease, especially if the original defect is known to lead to pulmonary hypertension.

Adult↗
PubMed1993

The prevalence of substance abuse among pregnant women in Utah.

OBJECTIVE: To determine the rate of substance use among Utah's pregnant women, who are primarily white and middle class, for comparison to rates reported in studies of inner-city populations. METHODS: Urine specimens and demographic data were obtained anonymously from women who delivered infants at ten hospitals in urban and suburban Utah. Urine samples were screened by enzyme immunoassay for amphetamines, marijuana, cocaine, methadone, opiates, benzodiazepines, and ethanol. RESULTS: Among 792 women screened, the mean age was 26.2 years, 86.1% were white, 62.9% were multigravidas, and 66.3% had private insurance. Cocaine was detected in nine samples (1.1%), illicit amphetamines in five (0.6%), marijuana in 23 (2.9%), ethanol in 32 (4.0%), over-the-counter amphetamines in 51 (6.4%), and benzodiazepines in seven (0.9%). The prevalence rate for women positive for illicit drugs and alcohol combined was 7.8%. Cocaine-positive and marijuana-positive women were more likely to be non-white or Hispanic and to have Medicaid or no insurance than were women negative for either substance. Women with Medicaid or no insurance were four times more likely to be positive for illicit substances (10.7%) than were those with private insurance (2.3%) (P = .0001). CONCLUSION: The rates and patterns of substance use differ between Utah's pregnant women and inner-city populations. The patterns in Utah may be more representative of many communities in the United States that have a predominantly middle-class, white population.

Adult↗
PubMed1992

Pseudomyxoma peritonei associated with secondary infertility.

In summary, we report a case of secondary infertility attributed to pseudomyxoma peritonei caused by ruptured appendiceal mucocele. Resection of the tumor and visible mucinous ascites resulted in spontaneous conception. We hypothesize secondary infertility was caused by significant peritoneal inflammation and inhibition of sperm-oocyte interaction from the ascites.

Adult↗
PubMed1991

Controlled prospective study of postpartum mood disorders: psychological, environmental, and hormonal variables.

Demographic, psychiatric, social, cognitive, and life stress variables were used to determine the etiology of depression in childbearing (CB; n = 182) and nonchildbearing (NCB; n = 179) women. Hormonal variables in postpartum depression were also evaluated. In the CB group predictors of depression diagnosis were previous depression, depression during pregnancy, and a Vulnerability (V) x Life Stress (LS) interaction; predictors of depressive symptomatology were previous depression, depressive symptoms during pregnancy, life events, and V x LS. Only estradiol was associated with postpartum depression diagnosis. In the NCB group V X LS was the only predictor of depression diagnosis; depressive symptoms during pregnancy and life events were predictors of depressive symptomatology. Previous findings about depression vulnerability were replicated. The significant V x LS interactions support the vulnerability-stress model of postpartum depression.

Adult↗
PubMed1991

The outcome of pregnancies complicated by bleeding during the second trimester.

Vaginal bleeding during the second trimester has historically been associated with high perinatal mortality rates (33 to 82 per cent). Because this topic has not been specifically studied since the advent of obstetric ultrasound and electronic fetal heart rate monitoring, we reviewed the experience at the University of Utah with second trimester vaginal bleeding from 1 January 1983 through 15 June 1989. The cause of the bleeding was found to fit into four general categories. These are placenta previa, abruption, both previa and abruption, and other or unknown. Midtrimester bleeding is still associated with a high perinatal mortality rate (22.3 per cent), being highest when associated with placental abruption (36.6 per cent) and lowest with placenta previa (7.4 per cent). For the entire series, pregnancies maintained into the third trimester were associated with a much lower perinatal mortality rate than those in which delivery occurred during the second trimester (7.1 versus 54.5 per cent). These relatively improved outcomes suggest that aggressive obstetric management is warranted in most instances.

Abruptio Placentae↗