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Biomedical subjects

E M Wallace

Publications and source records attributed to E M Wallace.

At least 73 records · Page 4Linked to original sources
PubMed1997

Amniotic fluid inhibin-A in chromosomally normal and Down's syndrome pregnancies.

Recently, inhibin-A has been shown to be a useful new prenatal marker of Down's syndrome, significantly increasing detection rates. While the placenta is believed to be the major source of inhibin in pregnancy, there are actually very limited data available on specific inhibin dimers in pregnancy. Using a sensitive and specific ELISA we have measured the inhibin-A content of amniotic fluid (AF) to investigate further the biology of inhibin-A in chromosomally normal and abnormal pregnancies. AF from 51 Down's syndrome and 161 chromosomally normal pregnancies between 16 and 19 weeks of gestation were analysed, blinded as to whether the sample was from a Down's syndrome or normal pregnancy. There were no sex differences in inhibin-A content in either the control or Down's syndrome pregnancies. The median (10-90th percentiles) inhibin-A level in the control pregnancies increased from 339.6 (175.2-649.1) pg/ml at 16 weeks to 592.9 (256.4-1027.3) pg/ml at 19 weeks of gestation. The median (95% confidence interval) inhibin-A in the Down's syndrome pregnancies, expressed as multiples of the median (MoM) to correct for gestation, was 0.77 (0.68-0.89) MoM, significantly lower than the controls (P < 0.001, Mann-Whitney U test). We believe that these data are compatible with more than one source of inhibin-A in pregnancy and suggest that the fetal membranes may be contributing significantly to AF inhibin-A content. Further, our data would suggest that the endocrine function of the placenta and the other inhibin source(s) are differentially regulated.

Amniotic Fluid↗
PubMed1997

Degradation of C1-inhibitor by plasmin: implications for the control of inflammatory processes.

BACKGROUND: A correct balance between protease and inhibitor activity is critical in the maintenance of homoeostasis; excessive activation of enzyme pathways is frequently associated with inflammatory disorders. Plasmin is an enzyme ubiquitously activated in inflammatory disorder, and C1-inhibitor (C1-Inh) is a pivotal inhibitor of protease activity, which is particularly important in the regulation of enzyme cascades generated in plasma. The nature of the interaction between plasmin and C1-Inh is poorly understood. MATERIALS AND METHODS: C1-Inh was immunoadsorbed from the plasma of normal individuals (n = 21), from that of patients with systemic lupus erythematosus (n = 18) or adult respiratory distress syndrome (n = 9), and from the plasma and synovial fluid of patients with rheumatoid arthritis (n = 18). As plasmin is a putative enzyme responsible for C1-Inh was examined using SDS-PAGE. In addition, peptides cleaved from C1-Inh by plasmin were isolated and sequenced and the precise cleavage sites determined from the known primary sequence of C1-Inh. Homology models of C1-Inh were then constructed. RESULTS: Increased levels of cleaved and inactivated C1-Inh were found in each of the inflammatory disorders examined. Through SDS-PAGE analysis it was shown that plasmin rapidly degraded C1-Inh in vitro. The pattern of C1-Inh cleavage seen in vivo in patients with inflammatory disorders and that produced in vitro following incubation with plasmin were very similar. Homology models of C1-Inh indicate that the majority of the plasmin cleavage sites are adjacent to the reactive site of the inhibitor. CONCLUSIONS: This study suggests that local C1-Inh degradation by plasmin may be a central and critical event in the loss of protease inhibition during inflammation. These findings have important implications for our understanding of pathogenic mechanisms in inflammation and for the development of more effectively targeted therapeutic regimes. These findings may also explain the efficacy of anti-plasmin agents in the treatment of C1-Inh deficiency states, as they may diminish plasmin-mediated C1-Inh degradation.

Adult↗
PubMed1997

Certified occupational health nursing. Job analysis in the United States.

Specialty nursing certification programs, such as that administered by the American Board for Occupational Health Nurses, Inc. (ABOHN), must be firmly based on current practice to maintain validity. To determine this, ABOHN performed its most recent job analysis and role delineation study between 1992 and 1994. A comprehensive survey tool was developed by ABOHN Board members, and administered to all 3,805 certified occupational health nurses in practice at the time of the study. With a final return rate of 42.7%, the results were believed to be representative of the knowledge, skills, and abilities needed to practice occupational health nursing in the United States at the proficient level of practice. The results of the study formed the basis for the ABOHN test blueprints and the creation of two credentials for occupational health nurses: the Certified Occupational Health Nurse (COHN) and the Certified Occupational Health Nurse Specialist (COHN-S).

Adult↗
PubMed1996

Dimeric inhibin A as a marker for Down's syndrome in early pregnancy.

BACKGROUND: In screening for Down's syndrome in the second trimester of pregnancy, the concentrations of alpha-fetoprotein, the beta subunit of human chorionic gonadotropin, and intact human chorionic gonadotropin in material serum are widely used markers. We investigated a new marker, dimeric inhibin A, and compared its predictive value with that of the established markers. METHODS: Serum samples were obtained at 7 to 18 weeks of gestation from 58 women whose fetuses were known to be affected by Down's syndrome, 32 whose fetuses were affected by trisomy 18, and 438 whose fetuses were normal, and the samples were analyzed for each marker. Individual serum concentrations of each marker were converted to multiples of the median value at the appropriate length of gestation in the women with normal pregnancies, and rates of detection of Down's syndrome by screening for inhibin A in various combinations with the other markers were estimated by multivariate analysis. RESULTS: In the women with fetuses affected by Down's syndrome, the serum inhibin A concentrations were 2.06 times the median value in the women with normal pregnancies (P < 0.001). This compared with 2.00 times the median for the beta subunit of human chorionic gonadotropin, 1.82 times the median for intact human chorionic gonadotropin, and 0.72 for alpha-fetoprotein. The serum concentrations of inhibin A in the women with fetuses affected by Down's syndrome did not appear to be significantly elevated above normal until the end of the first trimester and were not significantly different from normal in the women with fetuses affected by trisomy 18 (P = 0.17). The rate of detection of Down's syndrome was 53 percent and the false positive rate was 5 percent when alpha-fetoprotein, the beta subunit of human chorionic gonadotropin, the maternal age were used together as predictors. The detection rate increased to 75 percent when inhibin A was added (P = 0.002). CONCLUSIONS: In the second trimester of pregnancy, measuring inhibin A in maternal serum, in combination with measurements of alpha-fetoprotein and beta subunit of human chorionic gonadotropin, significantly improved the rate of detection of Down's syndrome.

Biomarkers↗
PubMed1996

Combining inhibin A with existing second-trimester markers in maternal serum screening for Down's syndrome.

To assess the value of inhibin A as an additional second-trimester maternal serum marker of Down's syndrome we studied 56 affected and 280 unaffected pregnancies matched for gestational age. The median level in the cases was 1.62 multiples of the gestation-specific median (MOM) in the controls, with 95 per cent confidence limits of 1.34-1.96. The distribution of inhibin levels in affected and unaffected pregnancies was approximately log Gaussian, with means about 1 standard deviation apart. This degree of separation was similar to that for human chorionic gonadotropin (hCG), free beta-hCG, and unconjugated oestriol (uE3), but about double that of alpha-fetoprotein (AFP) measured in the same samples. Inhibin was largely uncorrelated with AFP and uE3, whereas the log correlation coefficient with hCG was 0.29 (P = 0.19) for Down's syndrome and 0.41 (P < 0.0001) for unaffected pregnancies; with free beta-hCG, it was 0.18 (P = 0.38) and 0.38 (P < 0.0001), respectively. On the basis of these results and other published studies, we estimate that measuring inhibin A in addition to AFP and hCG or free beta-hCG (with or without uE3) will increase the detection rate for a fixed 5 per cent false-positive rate by about 7 per cent.

Biomarkers↗
PubMed1996

Second-trimester dimeric inhibin-A in Down's syndrome screening.

Initial studies of immunoreactive inhibin using a commercial assay have shown levels to be increased in three second-trimester series of maternal samples from Down's syndrome-affected pregnancies. This assay detected non-specifically all forms of circulating inhibin, dimeric and free alpha subunits, whether fully or partially processed. More recently, a new specific assay for dimeric inhibin-A has shown elevated results in both a first-trimester and a second-trimester series of cases. In order to assess the value of dimeric inhibin-A as a potential marker in the second trimester, we have analysed 157 Down's syndrome cases and used 367 unaffected cases across the gestational range 14-20 weeks to establish control medians and population parameters. In our series, the median MOM in Down's cases was 1.77, significantly higher than in the controls. At a 5 per cent false-positive rate, dimeric inhibin-A alone identified 37 per cent of cases. When used in conjunction with maternal age and other marker combinations, mathematical modelling showed detection rates rising from 48 per cent (inhibin-A plus age) to 61 per cent (inhibin-A, free beta hCG, age) and 68 per cent (inhibin-A, AFP, free beta hCG, age). Our data suggest that dimeric inhibin-A may have greater potential earlier in gestation when median levels at 14-16 weeks are 1.92 compared with 1.46 at 17-23 weeks. Dimeric inhibin-A may be a valuable addition to screening protocols, particularly in early gestations.

Biomarkers↗
PubMed1996

Second trimester screening for Down's syndrome using maternal serum dimeric inhibin A.

BACKGROUND AND OBJECTIVE: Prenatal maternal serum screening for Down's syndrome has become an important and established part of modern antenatal care. Previously it has been reported that non-specific immunoreactive inhibin may be useful in this context. Using a novel assay we have evaluated dimeric inhibin A as a possible second trimester marker of Down's syndrome. METHODS: From 1992-1993 records, stored sera from women with Down's affected pregnancies and chromosomally normal control pregnancies were identified and retrieved for analysis. These sera had been prospectively collected at 15, 16 and 17 weeks gestation. SUBJECTS: Records revealed 21 women who had had a Down's syndrome pregnancy and who also had serum available for analysis. Sera from 150 chromosomally normal controls, matched for gestation and duration of storage, were also retrieved. MEASUREMENTS: Dimeric inhibin A was measured using a recently developed two-site enzyme-linked immunoassay. This employs a capture anti inhibin beta A-subunit monoclonal antibody, covalently bound to a microtitre plate and a second anti inhibin alpha-subunit antibody conjugated to alkaline phosphatase, allowing detection. RESULTS: The mean (95% CI) maternal serum dimeric inhibin A in the samples from control pregnancies was 237 (201.5-273.4) ng/l, 266.9 (235.4-298.5) ng/l and 207.2 (178.5-235.9) ng/l at 15, 16 and 17 weeks gestation respectively. Expressing the results from the Down's samples as multiples of the normal median (MoM), the median (95% CI) MoM was 2.6 (2.25-3.57), significantly higher than the controls (P < 0.0001, Mann-Whitney U-test). In the sample set tested, for a given false positive rate of 5.3% inhibin A alone afforded a detection rate of 62%, detecting cases previously undetected by routine screening. CONCLUSIONS: Dimeric inhibin A appears to be a promising new marker for the prenatal detection of Down's syndrome. Further prospective evaluation and assessment with other established markers would now be merited.

Adult↗
PubMed1996

Inhibin in extra-embryonic coelomic and amniotic fluids and maternal serum in early pregnancy.

Inhibins are present in maternal serum during pregnancy. However, the presence of inhibins in the compartments surrounding the fetus in early pregnancy is not well defined. Using novel specific enzyme-linked immunosorbent assays we have demonstrated that the bioactive dimeric inhibin forms, inhibin-A and inhibin-B, and the immunoreactive inhibin forms containing pro- and alpha C sequences are present in different amounts in the extra-embryonic coelomic and amniotic fluids and maternal serum between 8-11 weeks gestation. Of the bioactive dimeric inhibins, both inhibin. A (mean +/- SEM 236.0 +/- 24.8 pg/ml) and inhibin-B (62.0 +/- 8.6 pg/ml) are present in extra-embryonic coelom whereas no dimeric inhibin is present in the amniotic fluid and only inhibin-A (360.2 +/- 32.9 pg/ml) is present in maternal serum. Furthermore, pro-alpha C-related immunoreactivity is present at high concentrations in the extra-embryonic coelom (591.7 +/- 60.5 pg/ml), amniotic fluid (452.4 +/- 76.8 pg/ml) and maternal serum (539.4 +/- 39.5 pg/ml). These findings would indicate that at this stage of gestation inhibin-A, inhibin-B and immunoreactive pro- alpha C-containing inhibin production are likely to arise from different sources including the fetus, placenta and fetal membranes and maternal sources including the ovary. Inhibins may be important regulators of fetal and placental development and involved in the establishment of pregnancy.

Amniotic Fluid↗
PubMed1996

Pregnancies complicated by placenta praevia: what is appropriate management?

OBJECTIVE: To review the outcome of pregnancies complicated by placenta praevia over a three-year period (1991-1993) and to describe in detail the antenatal course and the events leading to delivery, assessing retrospectively whether there are clinical features predictive of outcome and whether outpatient management would be reasonable. DESIGN: A retrospective review of the case records of women with a pregnancy complicated by placenta praevia. SETTING: A tertiary referral teaching hospital in Edinburgh. RESULTS: There were 15,930 deliveries in the study period. Fifty-eight women (0.4%) had a placenta praevia in the third trimester, 42 of whom (72%) had at least one episode of bleeding. Overall, 62% of the women had a major praevia with no differences in the grade of praevia between those women who did or did not have bleeding. Both diagnosis and delivery occurred significantly earlier in women with antepartum bleeding than in those without (median gestation at diagnosis 28.6 weeks versus 33.3 weeks (P < 0.01) and at delivery 36.0 weeks versus 37.1 weeks (P = 0.04), respectively). Delivery by emergency caesarean section was more common in women with bleeding (62% versus 38%). An increasing number of bleeding episodes experienced by individuals was not associated with significant differences in outcomes. Rapid emergency delivery for bleeding was necessary for three women, in none of whom could the bleeding have been predicted. CONCLUSIONS: The clinical outcomes of placenta praevia are highly variable and cannot be predicted confidently from antenatal events. Nonetheless, in the majority of cases with or without bleeding and irrespective of the degree of praevia, outpatient management would appear safe and appropriate.

Ambulatory Care↗
PubMed1996

The pharmacokinetics of oral and intramuscular administration of dexamethasone in late pregnancy.

BACKGROUND: To compare the pharmacokinetics of orally administered dexamethasone with intramuscular administration in antenatal patients at risk of preterm delivery. METHOD: Ten antenatal patients at risk for preterm delivery were given two intramuscular and then one oral dose of dexamethasone. Plasma which was collected at set intervals following the first intramuscular dose and the oral dose was assayed for dexamenthasone. The results were analyzed using pharmacokinetic data-fitting software and pharMacokinetic parameters calculated. RESULTS: After oral adminIstration of dexamethasone the mean maximum plasma concentration obtained was 65% that of the intramuscular dose and the bioavailability of the oral route was calculated as 72% of the intramuscular route. The terminal half-lives of dexamethasone were similar for both routes. CONCLUSIONS: These limited data would suggest that if dexamethasone is to be administered orally, which would be both preferable to patients and more economic, then a proportionately increased dose of oral dexamethasone would be required to provide similar maternal plasma pharmacokinetics to the intramuscular dose in current use. Further, larger studies are now required to confirm this.

Administration, Oral↗
PubMed1996

A solid-phase antibody capture assay for the measurement of C1-inhibitor consumption in vivo.

C1-inhibitor (C1-Inh) is a serine esterase proteinase inhibitor (serpin) which plays an important role in regulating serine proteinases of the early inflammatory response. In this study, we describe a novel and versatile polyclonal antibody capture assay to examine C1-Inh consumption in vivo. This assay has advantages over previously described methods of measuring C1-Inh consumption as it allows the assessment of the relative amounts of native, complexed and cleaved inhibitor circulating in plasma. By using polyclonal antibodies specific for other complement proteins, the C1-Inh capture assay was adapted to measure in vivo activation of C3, C4 and factor B. C1-Inh consumption and complement activation were examined in the plasma of 21 normal individuals, 24 individuals with systemic lupus erythematosus (SLE), nine individuals with adult respiratory distress syndrome (ARDS) and in the paired plasma and synovial fluid from 18 patients with rheumatoid arthritis (RA). The C1-Inh capture assay revealed native, cleaved and complexed C1-Inh migrating at 115 kDa, 96 kDa and 209-225 kDa respectively, in normal plasma. C1-Inh consumption was increased in the plasma of all the inflammatory disorders examined, in comparison to normal plasma. It is proposed that this serpin capture assay could be adapted to the study of serpin involvement in a wide variety of inflammatory disorders.

Arthritis, Rheumatoid↗
PubMed1995

Evaluation of maternal serum dimeric inhibin A as a first-trimester marker of Down's syndrome.

While second-trimester prenatal screening programmes for Down's syndrome have become established in prenatal care, it would be advantageous to be able to offer screening in earlier pregnancy. To this end, we have evaluated a new potential maternal serum marker, dimeric inhibin A, as a possible first-trimester marker. Dimeric inhibin A was measured in prospectively collected maternal serum from 23 cases of Down's syndrome and matched chromosomally normal controls, at 11-13 weeks' gestation. Levels of this protein were significantly elevated in the Down's pregnancies compared with the control pregnancies. The median multiple of the normal median (MOM) for the Down's samples was 2.46 (95 per cent confidence interval: 2.11-3.26, P < 0.0001 vs. controls). These results suggest that dimeric inhibin A is a useful discriminator of Down's-affected pregnancies from normal pregnancies in the first trimester and that sensitive screening in combination with maternal age and other possible markers may be practicable in the first trimester.

Adult↗
PubMed1995

Effect of testosterone enanthate on serum lipoproteins in man.

Sixty-three normal Caucasian men were administered intramuscular testosterone enanthate (TE) 200 mg i.m. weekly for 12 months as part of a male contraceptive trial. This dose of TE caused a 2.5-fold increase in trough serum testosterone concentrations. High density lipoprotein cholesterol (HDL-C) was significantly depressed from pretreatment concentration of 1.19 +/- 0.04 nmol/l to 1.03 +/- 0.04 mmol/l after 12 weeks of treatment, and remained suppressed for the duration of treatment (p < 0.001). There were no changes in serum concentration of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) or triglycerides (TG) during treatment, but the concentrations of TC and LDL-C were depressed at three months post-treatment. There was a sustained elevation in LDL-C:HDL-C ratio during TE treatment (p < 0.005), from 3.41 +/- 0.15 pretreatment to 3.88 +/- 0.19 after 12 weeks of TE treatment. Sex hormone binding globulin (SHBG), but not testosterone (T) or estradiol (E2), was significantly associated with HDL-C (r = 0.83, p = 0.001). Lipoprotein (a) (Lp(a)) was measured in a subgroup of 33 men: serum concentration fell from 187 +/- 45 mg/l pretreatment to 140 +/- 35 mg/l after 16 weeks of TE treatment (p < 0.01).

Adult↗
PubMed1995

Successful excision of a giant acoustic neuroma in the third trimester of pregnancy.

Intracranial neoplasms presenting during pregnancy are uncommon. We report the case of a woman with a giant acoustic neuroma, presenting with hyperemesis gravidarum, and detail the surgical excision of the tumour during the third trimester. The case illustrates the unusual presentation and that such surgery can be performed safely without detriment to mother or fetus.

Adult↗