Reduced maternal dexamethasone dosage for the prenatal treatment of congenital adrenal hyperplasia.
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Adrenal Hyperplasia, Congenital↗
Biomedical subjects
M A Coleman
Publications and source records attributed to M A Coleman.
Gene expression changes in mouse brain after exposure to low-dose ionizing radiation.
PURPOSE: To characterize the cellular functions associated with the altered transcript profiles of mouse brain exposed to low-dose in vivo gamma-irradiation. MATERIALS AND METHODS: Cerebral RNA was isolated at 30 min and 4 h after whole-body irradiation at 0.1 or 2 Gy, hybridized to random oligonucleotide arrays, and evaluated for time and dose-response patterns by multifactorial analyses. RESULTS: Brain irradiation modulated the expression patterns of 1574 genes, of which 855 showed more than 1.5-fold variation. about 30% of genes showed dose-dependent variations, including genes exclusively affected by 0.1 Gy. About 60% of genes showed time-dependent variation with more genes affected at 30 min than at 4 h. Early changes involved signal transduction, ion regulation and synaptic signalling. Later changes involved metabolic functions including myelin and protein synthesis. Low-dose radiation also modulated the expression of genes involved in stress response, cell-cycle control and DNA synthesis/repair. CONCLUSIONS: Doses of 0.1 Gy induced changes in gene expression that were qualitatively different from those at 2 Gy. The findings suggest that low-dose irradiation of the brain induces the expression of genes involved in protective and reparative functions, while down-modulating genes involved in neural signalling activity.
Animals↗
Predicting preterm delivery: comparison of cervicovaginal interleukin (IL)-1beta, IL-6 and IL-8 with fetal fibronectin and cervical dilatation.
OBJECTIVE: To compare the cervicovaginal cytokines IL-1beta, IL-6 and IL-8 with fetal fibronectin (fFN) and cervical dilatation in the prediction of preterm delivery. STUDY DESIGN: Cervicovaginal cytokine concentration and fFN status were measured in 104 women with symptoms of preterm labour and intact membranes between 24(0) and 33(6) weeks and related to delivery within 2 and 7 days. RESULTS: A group of 18% had cervical dilatation > or = 1cm and 18% were positive for fFN. Preterm delivery within 2 and 7 days occurred in 5 and 12%, respectively. Only IL-6 demonstrated any ability to predict delivery within 2 and 7 days (area under the ROC curve = 0.63 and 0.75, respectively). Using 35pg/ml (75th centile) as a cut-off, IL-6 had a sensitivity and specificity of 60 and 77% for predicting delivery within 2 days, and 62 and 80% for predicting delivery within 7 days. This is similar to the performance of cervical dilatation or fFN status. CONCLUSIONS: Measurement of cervicovaginal cytokines has limited ability to predict imminent delivery apart from cervicovaginal IL-6 concentrations, which, in this population, is equivalent to that of fFN status and cervical dilatation > or = 1cm.
Adult↗
Functional characterization of Ape1 variants identified in the human population.
Apurinic/apyrimidinic (AP) sites are common mutagenic and cytotoxic DNA lesions. Ape1 is the major human repair enzyme for abasic sites and incises the phosphodiester backbone 5' to the lesion to initiate a cascade of events aimed at removing the AP moiety and maintaining genetic integrity. Through resequencing of genomic DNA from 128 unrelated individuals, and searching published reports and sequence databases, seven amino acid substitution variants were identified in the repair domain of human Ape1. Functional characterization revealed that three of the variants, L104R, E126D and R237A, exhibited approximately 40-60% reductions in specific incision activity. A fourth variant, D283G, is similar to the previously characterized mutant D283A found to exhibit approximately 10% repair capacity. The most common substitution (D148E; observed at an allele frequency of 0.38) had no impact on endonuclease and DNA binding activities, nor did a G306A substitution. A G241R variant showed slightly enhanced endonuclease activity relative to wild-type. In total, four of seven substitutions in the repair domain of Ape1 imparted reduced function. These reduced function variants may represent low penetrance human polymorphisms that associate with increased disease susceptibility.
Amino Acid Substitution↗
Cloning and characterization of HARP/SMARCAL1: a prokaryotic HepA-related SNF2 helicase protein from human and mouse.
The SNF2 gene family consists of a large group of proteins involved in transcriptional regulation, maintenance of chromosome integrity, and various aspects of DNA repair. We cloned a novel SNF2 family human cDNA, with sequence identity to the Escherichia coli RNA polymerase-binding protein HepA and named the human hepA-related protein (HHARP/SMARCAL1). In addition, the mouse ortholog (Mharp/Smarcal1) was cloned, and the Caenorhabditis elegans ortholog (CEHARP) was identified in the GenBank database. Phylogenetic analysis indicates that the HARP proteins share a high level of sequence similarity to the seven motif helicase core region (SNF2 domain) with identifiable orthologs in other eukaryotic species, except for yeast. Purified His-tagged HARP/SMARCAL1 protein exhibits single-stranded DNA-dependent ATPase activity, consistent with it being a member of the SNF2 family of proteins. Both the human and the mouse genes consist of 17 exons and 16 introns. The human gene maps to chromosome 2q34-q36, and the mouse gene is localized to the syntenic region of chromosome 1 (between markers Gls and Acrg). HARP/SMARCAL1 transcripts are ubiquitously expressed in human and mouse tissues, with testis presenting the highest levels of mRNA expression in humans.
ATP-Binding Cassette Transporters↗
Mid-trimester uterine artery Doppler screening as a predictor of adverse pregnancy outcome in high-risk women.
OBJECTIVE: To assess the value of uterine artery Doppler ultrasound screening, when performed in a clinical setting, to predict complications of impaired uteroplacental blood flow in high-risk women. DESIGN: A prospective audit. SUBJECTS: A total of 116 pregnancies in 114 women at high risk of pre-eclampsia and/or small-for-gestational-age (SGA) babies attending a maternal-fetal medicine clinic at National Women's Hospital, a tertiary referral hospital, Auckland, New Zealand. METHODS: Uterine artery Doppler screening was performed as part of clinical practice between 22 and 24 weeks' gestation. A resistance index (RI) was calculated from each uterine artery and the presence or absence of a notch was determined. An RI of > 0.58 was defined as abnormal and an RI of > or = 0.7 was defined as very abnormal. The main outcome measures were: pre-eclampsia, SGA baby (birth weight < 10th centile), placental abruption, intrauterine death, 'all' and 'severe' outcomes. RESULTS: Thirty-two (27.5%) women developed pre-eclampsia, 31 (26.7%) had SGA babies, 23 (20%) were delivered at < 34 weeks because of pregnancy complications, and there were three (2.6%) placental abruptions and three (2.6%) perinatal deaths. The sensitivity of any RI of > 0.58 for pre-eclampsia, SGA, 'all' outcomes and 'severe' outcome was 91%, 84%, 83% and 90%, respectively. The specificity of any RI of > 0.58 for these outcomes was 42%, 39%, 47% and 38%, respectively. The positive predictive value of any RI of > 0.58 for the same outcomes was 37%, 33%, 58% and 24%, respectively. Among women with both RI values of > or = 0.7, 58%, 67%, 85% and 58% developed pre-eclampsia, SGA, 'all' and 'severe' outcomes, respectively. In women with bilateral notches, 47%, 53%, 76% and 65% developed the respective outcomes. Women with both RI values of > or = 0.7 and women with bilateral notches had relative risks of 11.1 (95% CI 2.6-46.4) and 12.7 (95% CI 4.0-40.4) for developing severe outcome, respectively. Only 5% of women with both RI values of < 0.58 developed a severe outcome. CONCLUSION: In high-risk women, uterine artery Doppler waveform analysis performed best in the prediction of severe adverse outcome and was better than clinical risk assessment in the prediction of pre-eclampsia and SGA babies. Further studies are necessary to determine how information from uterine artery Doppler studies should modify current practice in high-risk women.
Adult↗
Enhanced expression of intercellular adhesion molecule-1 (ICAM-1) in amnion with term and preterm labour.
To evaluate the association between intercellular adhesion molecule-1 (ICAM-1) in the amnion and preterm labour and delivery, we have assessed ICAM-1 mRNA abundance by Northern analysis and protein levels by enzyme-linked immunosorbent assay (ELISA), in samples of this tissue after term and preterm delivery. The median ICAM-1 mRNA expression following preterm delivery (PTD, n=30) was 24 times greater (P< 0.05) than following elective caesarean section prior to labour at term (CST, n=14). ICAM-1 expression following vaginal delivery after spontaneous labour at term (SLT, n=11) was seven times greater than in the CST group (P< 0.05). The concentration of ICAM-1 protein in the PTD samples (n=31) was four-fold greater than (P< 0.05) in CST (n=14). It was also three-fold greater than in the SLT (n=15) samples (P< 0.05). The results were substantially the same when a preterm spontaneous labour group (PTL) (n=26), exclusive of deliveries complicated by pre-eclampsia (n=1) or intrauterine growth restriction (n=3), was compared to the CST and SLT groups. The ICAM-1 mRNA expression did not differ significantly (P=0.93) between PTL with (n=12) or without (n=14) indicators of intrauterine infection. The results were similar when ICAM-1 protein concentrations were compared (P=0.43) between these two groups. These findings indicate that ICAM-1 is expressed by the human amnion and that this expression is elevated with preterm labour and delivery.
Amnion↗
Corticotropin-releasing hormone, corticotropin-releasing hormone-binding protein, and activin A in maternal serum: prediction of preterm delivery and response to glucocorticoids in women with symptoms of preterm labor.
OBJECTIVE: The aim of this study was to determine prospectively whether serum concentrations of corticotropin-releasing hormone, corticotropin-releasing hormone-binding protein, and activin A (1) predict preterm birth within 10 days of hospital admission or at <37 weeks' gestation among women with symptoms of preterm labor and (2) are affected by glucocorticoid therapy. STUDY DESIGN: Serum concentrations of corticotropin-releasing hormone and activin A were measured in 94 women with symptoms of preterm labor between 24 and 34 weeks' gestation, and delivery outcomes were monitored. Corticotropin-releasing hormone-binding protein concentrations were measured in 71 of these women. In a subgroup of 15 women the serum analytes were assayed in conjunction with estriol before and 12 to 24 hours after administration of dexamethasone. RESULTS: Forty-six percent (6/13) of the women who were delivered within 10 days of hospital admission had a raised serum corticotropin-releasing hormone level, but the predictive relationship was not significant (chi(2) = 1.7; P =.2). Among the 31 women (including the 6 previously mentioned) who were delivered at <37 weeks' gestation, 39% (12/31) had a raised corticotropin-releasing hormone level. Although a raised corticotropin-releasing hormone concentration was positively associated with delivery at <37 weeks' gestation (chi(2) = 9; P =.003), the predictive diagnostic value was poor, with sensitivity, specificity, and positive and negative predictive values of 39%, 90%, 67%, and 75%, respectively. The serum concentrations of corticotropin-releasing hormone-binding protein and activin A were unrelated to gestational age at delivery. Dexamethasone markedly lowered the serum estriol level (P <.001) but had no effect on concentrations of corticotropinreleasing hormone, corticotropin-releasing hormone-binding protein, and activin A. CONCLUSION: Serum concentrations of corticotropin-releasing hormone, corticotropin-releasing hormone-binding protein, and activin A are not clinically useful for the prediction of preterm delivery among women with symptoms of preterm labor and are not affected by administration of glucocorticoids.
Activins↗
Intercellular adhesion molecule-1 (ICAM-1) in cervicovaginal fluid of women presenting with preterm labor: predictive value for preterm delivery.
PROBLEM: Clinically useful tests for the prediction and diagnosis of preterm labor and delivery remain to be established. We have hypothesized that soluble intercellular adhesion molecule-1 (sICAM-1) in the cervicovaginal fluid of women with preterm labor may be a useful diagnostic tool. METHOD OF STUDY: The cervicovaginal fluid of 103 women between 24(0) and 33(6) weeks gestation with preterm contractions and intact membranes was assayed for sICAM-1. RESULTS: Elevated sICAM-1 concentrations predicted short intervals to delivery (area under receiver operator characteristic (ROC) curves, 0.70-0.72 for delivery within 3, 7 and 10 days), with high specificity. Characteristics for delivery within 3 days at a 3 ng/mL threshold for a positive test were sensitivity 33.3%, specificity 98.9%, and positive and negative predictive values of 75.0% and 93.9%, respectively. Predictive ability was independent of and complementary to that of fetal fibronectin (fFN). CONCLUSIONS: Measurement of sICAM-1 in cervicovaginal fluid has potential as a predictor of preterm delivery in women with symptoms of preterm labor, particularly in conjunction with fFN testing.
Adult↗
Expression of intercellular adhesion molecule-1 (ICAM-1) in choriodecidua with labour and delivery at term and preterm.
To evaluate the association between intercellular adhesion molecule-1 (ICAM-1) in the choriodecidua and preterm labour and delivery, ICAM-1 mRNA abundance was assessed by northern analysis, and protein levels by ELISA, in samples of this tissue after term and preterm delivery. The median ICAM-1 mRNA expression following preterm delivery (PTD) was 4.8 and 3.8 times (P<0.05), respectively, those following elective Caesarean section prior to labour at term (CST) and following vaginal delivery after spontaneous labour at term (SLT). The concentration of ICAM-1 protein in the PTD samples was 2.2 and 3.0 times (P<0.05) those in CST and SLT samples, respectively. The differences between the term groups were not significant. The results were substantially the same when a preterm spontaneous labour (PTL) subgroup, exclusive of deliveries complicated by pre-eclampsia or intrauterine growth restriction, was compared with the term groups. Choriodecidual ICAM-1 mRNA expression, but not ICAM-1 protein concentration, significantly correlated to the degree of leukocyte infiltration of the PTD gestational membranes. Neither correlated significantly to clinical indications of intrauterine or neonatal infection. These findings indicate that ICAM-1 is expressed by the human choriodecidua and that this expression is elevated with preterm labour and delivery, particularly with increased leukocyte infiltration.
Albuterol↗
Hex1: a new human Rad2 nuclease family member with homology to yeast exonuclease 1.
Nucleolytic processing of chromosomal DNA is required in operations such as DNA repair, recombination and replication. We have identified a human gene, named HEX1 forhumanexonuclease 1, by searching the EST database for cDNAs that encode a homolog to the Saccharomyces cerevisiae EXO1 gene product. Based on its homology to this and other DNA repair proteins of the Rad2 family, most notably Schizosaccharomyces pombe exonuclease 1 (Exo1), Hex1 presumably functions as a nuclease in aspects of recombination or mismatch repair. Similar to the yeast proteins, recombinant Hex1 exhibits a 5'-->3' exonuclease activity. Northern blot analysis revealed that HEX1 expression is highest in fetal liver and adult bone marrow, suggesting that the encoded protein may operate prominently in processes specific to hemopoietic stem cell development. HEX1 gene equivalents were found in all vertebrates examined. The human gene includes 14 exons and 13 introns that span approximately 42 kb of genomic DNA and maps to the chromosomal position 1q42-43, a region lost in some cases of acute leukemia and in several solid tumors.
Amino Acid Sequence↗
Fetal fibronectin detection in preterm labor: evaluation of a prototype bedside dipstick technique and cervical assessment.
OBJECTIVE: The aims of this study were to evaluate a prototype bedside test for fetal fibronectin detection in women with symptoms of preterm labor, to compare the efficacy of obtaining fetal fibronectin swabs with and without a speculum, and to assess the value of combining the fetal fibronectin test with cervical dilatation for predicting delivery within 10 days. STUDY DESIGN: This investigation prospectively studied a cohort of women with symptoms of preterm labor (n = 121), gestational age between 24 and 33 6/7 weeks, and cervical dilatation </=3 cm. Vaginal swabs for fibronectin testing with the bedside dipstick Fetal Fibronectin Membrane Immunoassay test (Adeza Biomedical, Sunnyvale, Calif) were obtained with and without a speculum. Results were not available to the clinicians. RESULTS: Twenty-two percent of the fetal fibronectin samples collected with a speculum (27/121) yielded positive results. The incidence of delivery within 10 days of testing was 14% (17/121). Fetal fibronectin detection predicted delivery within 10 days with sensitivity, specificity, and positive and negative predictive values of 65%, 85%, 41%, and 94%, respectively. The positive and negative likelihood ratios were 4.3 and 0.41, respectively. There was substantial association between samples obtained with and without a speculum (Cohen kappa statistic 0.65, 95% confidence interval 0.44-0.87). Cervical dilatation >/=1 cm predicted delivery within 10 days with sensitivity, specificity, and positive and negative predictive values of 71%, 87%, 46%, and 95%, respectively, with positive and negative likelihood ratios of 5.5 and 0.33, respectively. Combination of fetal fibronectin testing with cervical dilatation >/=1 cm did not significantly improve the fetal fibronectin test characteristics. After exclusion of women with slight vaginal bleeding, cervical dilatation >/=1 cm and fetal fibronectin status remained the only independent variables associated with delivery within 10 days. CONCLUSION: Fetal fibronectin testing according to this prototype may have a limited role in clinical decision analysis. In this study a cervical dilatation >/=1 cm had predictive values equivalent to those of the fetal fibronectin test, and it should be evaluated further in a clinical setting.
Adult↗
Glucocorticoid response to forced exercise in laboratory house mice (Mus domesticus).
We examined the time course and sex differences of the glucocorticoid response to forced, moderate-intensity treadmill exercise in outbred laboratory house mice. Mice (n = 64 total) were divided into eight groups, each of four males and four females, which were run on a motorized treadmill at 1.0 km/h for either 0, 2, 5, 10, 15, 25, 40, or 60 min. Serum samples were taken immediately after exercise and corticosterone (CORT) concentration was determined by radioimmunoassay. Resting CORT levels ranged between 11.6 and 29.5 ng/mL for both sexes. CORT levels increased with length of exercise and then exhibited a plateau by 25 min in females and by 40 min in males. Females displayed a significantly more rapid increase in serum CORT levels and attained higher maximal CORT levels than males. Females also had significantly larger adrenal glands, both in absolute terms and relative to body mass.
Adrenal Glands↗
Traveling for care: factors influencing health care access for rural dwellers.
This study explored 19 rural dwellers' perceptions of health care issues through semi-structured interviews. Sample selection, data collection, and analysis adhered to the grounded theory method in that an interactive design was maintained. The strategy of traveling for care describes how rural dwellers deal with the problem of varying access to health care. This study uncovers the influencing factors that impact on rural dwellers' decisions when traveling for care. Most rural dwellers choose to wait before seeking health care; those factors that contributed to the decision to wait includes limited financial resources to pay for health care, prior experiences within the system, and the prevalent belief that they can provide self-care effectively. When self-care was not successful they evaluated their resources to assist in their decision making. The last phase of this strategy was choosing the distance they would go to receive health care. Choosing the distance varied greatly among the participants. A few choose to go without health care whereas others would go to any lengths to resolve their health problem.
Data Collection↗
Prevention of atmospheric contamination during isoflurane sedation.
With a view to minimising staff exposure to exhaled isoflurane which had been used for sedation, we assessed the efficacy of either activated charcoal adsorption or active or passive mechanical scavenging systems in intensive care units (ICUs). Personal monitoring revealed minimal exposure of staff to the sedating agent. Infra-red analyses of ambient air rarely showed isoflurane levels greater than 26 ppm, with mean concentrations of around 1 ppm. Small spillages during vaporiser filling were of no polluting significance. The activated charcoal adsorbers functioned highly efficiently for at least 12-hour periods. With simple scavenging techniques, atmospheric isoflurane contamination during sedation with the agent remains well within an acceptable range and is unlikely to pose a health risk to nursing and medical staff.
Adsorption↗
Clinical assessment--a computer-based aid to assessing the clinical problem solving ability of medical students.
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Clinical Clerkship↗
The chronically mentally ill: issues of individual freedom versus societal neglect.
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Chronic Disease↗
Undergraduate preparation for occupational health nursing.
Seven baccalaureate nursing programs in Arkansas were surveyed to ascertain what content pertinent to occupational health nursing was included in the curriculum. Programs were examined for clinical experiences in occupational health settings. All programs failed to include some of the needed content. None of the programs covered the Occupational Health and Safety Act and its importance in occupational health nursing. Only four of the seven programs offered clinical experiences ranging from a one day observation to a six week preceptorship in an occupational health setting.
Arkansas↗