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Biomedical subjects

J A Canick

Publications and source records attributed to J A Canick.

At least 73 records · Page 4Linked to original sources
PubMed1993

First trimester bleeding and pregnancy outcome in gravidas with normal and low folate levels.

The purpose of this study was to examine whether women with first trimester uterine bleeding and low serum folate have a higher incidence of spontaneous abortions and adverse perinatal outcome compared with women whose folate levels are normal. Serum folate and vitamin B12 levels were obtained on 225 women who presented with first trimester vaginal bleeding; pregnancy outcomes of those whose folate or vitamin B12 levels were low were compared with those with normal levels using the chi-square test. Of the 151 women included, 52 had low folate levels (less than 4.0 ng/ml). Their spontaneous abortion rate and perinatal outcomes were similar to those whose folate levels were normal. We concluded that in pregnancies complicated by first trimester vaginal bleeding, low folate levels do not appear to be associated with an increased risk of pregnancy loss and adverse outcome.

Abortion, Spontaneous↗
PubMed1993

Cigarette smoking and levels of maternal serum alpha-fetoprotein, unconjugated estriol, and hCG: impact on Down syndrome screening.

OBJECTIVE: To investigate the association between maternal cigarette smoking and serum levels of alpha-fetoprotein (AFP), unconjugated estriol (uE3), and hCG and to determine whether it is appropriate to take smoking status into account when screening for fetal Down syndrome. METHODS: Smoking information was obtained from 23,668 pregnant women at the time of routine screening for fetal Down syndrome. Serum levels of AFP, uE3, and hCG were stratified by smoking status and compared. Individual risks for fetal Down syndrome were analyzed both before and after adjusting the hCG levels for the effect of smoking. The prevalence of Down syndrome in the study population was calculated for both smokers and non-smokers. RESULTS: The average AFP, uE3, and hCG levels in women who smoked cigarettes were 3% greater (95% confidence interval [CI] 2-4%), 3% less (95% CI 2-4%), and 23% less (95% CI 22-24%), respectively, compared with levels in non-smokers. At comparable maternal ages, women who smoked cigarettes were identified as being at high risk for fetal Down syndrome 40% less often than non-smokers (4.0 versus 7.1% at a risk level of 1:250). Adjusting hCG levels for smoking status reduced the overall false-positive rate from 6.4 to 6.1% (using a term risk cutoff level of 1:250). The predicted effect on detection was small (a 0.7% increase). The prevalence of Down syndrome was lower among smokers, but the difference was not statistically significant (odds ratio 0.51, 95% CI 0.15-1.5). CONCLUSIONS: Adjusting the serum markers used for Down syndrome screening for the effect of maternal smoking has a small effect on overall screening performance. Given the uncertainty over whether there is a lower birth prevalence among women who smoke cigarettes, such adjustment is not currently justified.

Adult↗
PubMed1993

Maternal serum screening for aneuploidy and open fetal defects.

The application of population-based maternal serum screening to prenatal diagnosis has been shown to be practical and is now wide-spread. It has been estimated that more than 40% of genetics programs in the United States that offer second trimester maternal serum screening now use at least one analyte in addition to AFP (Dr. George J. Knight, personal communication). The studies described here suggest that additional refinements in maternal serum screening are not only possible but inevitable. The use and interpretation of the analytes AFP, uE3, and hCG continue to be examined and expanded upon (Table 1). In the future, it seems logical that other analytes may be added or may replace one or more of these currently used markers. We have demonstrated that with AFP, uE3, and hCG, a separate protocol will identify a significant portion of trisomy 18 fetuses with a minimal increase in the number of amniocenteses performed. Other significant aneuploidies, including Turner syndrome and triploidy, will be identified in screening for Down syndrome and trisomy 18. Although separate screening protocols for the detection of Turner syndrome and triploidy would not be of practical value, their detection within a screening protocol for Down syndrome is an added benefit and increases the value of the screening markers. The use of first trimester screening is being investigated. Although earlier diagnosis is attractive, routine first trimester screening for aneuploidy would necessitate the creation of an entirely new protocol for the collection of maternal serum samples and their interpretation, as well as a second round of screening for open fetal defects during the early second trimester. In contrast, an advantage of the current protocols is that screening for both types of abnormalities is possible using the same serum sample. Although research may eventually demonstrate that first trimester screening is technically feasible, an evaluation of the logistics of such screening may show it to be impractical. Obstetric implications of elevations and decreases in the new serum markers have not yet been studied carefully. It is logical, however, that just as with abnormal AFP (not explainable on a genetic basis), extreme levels of uE3 and hCG may also be associated with particular obstetric problems. Information on such deviations in analyte levels is just beginning to emerge. Finally, the study of maternal serum markers may contribute to an understanding of placental function in the second trimester, and ultimately advance our understanding of the underlying pathophysiologies of various fetal chromosomal and morphologic defects.(ABSTRACT TRUNCATED AT 400 WORDS)

Aneuploidy↗
PubMed1992

Prenatal screening for Down's syndrome with use of maternal serum markers.

BACKGROUND: Approximately 35 percent of all cases of Down's syndrome in fetuses can be detected by measuring maternal serum alpha-fetoprotein during the second trimester in the general population of pregnant women. Recent case-control studies indicate that this detection rate could be approximately doubled by measuring serum levels of unconjugated estriol and chorionic gonadotropin, which are abnormally low and abnormally high, respectively, in women carrying fetuses affected by Down's syndrome. METHODS: We prospectively screened 25,207 women and adolescents in the second trimester of pregnancy and assigned each a risk of fetal Down's syndrome with an algorithm that took into account measurements of all three serum markers in combination with maternal age. On this basis, 1661 subjects (6.6 percent) were initially assigned a second-trimester risk of fetal Down's syndrome of at least 1 in 190, and 962 (3.8 percent) were offered amniocentesis for chromosomal analysis after verification of gestational age. Gestational age was determined on the basis of the first day of the last menstrual period or, when available, by ultrasonography. RESULTS: Among the 760 women and adolescents who chose amniocentesis, 20 cases of fetal Down's syndrome were detected, along with 7 other chromosomal disorders. There was 1 additional case of fetal Down's syndrome among the 202 women who chose not to have amniocentesis. The rate of detection of Down's syndrome was thus 58 percent (21 of 36 expected cases), and the frequency of identifying a fetus with Down's syndrome in women undergoing amniocentesis was 1 per 38 amniocenteses (95 percent confidence interval, 1 in 25 to 1 in 62). CONCLUSIONS: Measuring serum alpha-fetoprotein, chorionic gonadotropin, and estriol is more effective in screening for fetal Down's syndrome than measuring maternal serum alpha-fetoprotein alone. Such an expanded protocol can readily be incorporated into existing prenatal screening programs.

Adolescent↗
PubMed1992

Prospective intervention trial of a screening protocol to identify fetal trisomy 18 using maternal serum alpha-fetoprotein, unconjugated oestriol, and human chorionic gonadotropin.

Two prenatal centres in New England, routinely using a screening protocol for fetal Down syndrome that included maternal serum alpha-fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotropin (hCG) measurements in combination with maternal age, adopted a separate screening protocol for trisomy 18. That protocol identified a pregnancy as being at high risk when AFP, uE3, and hCG measurements all fell at or below specified cut-offs (0.75, 0.60, and 0.55 multiples of the median, respectively), regardless of maternal age. Among the first 19,491 women screened, 98 (0.5 per cent) were found to have values which placed them in the high-risk category. Four of these women were subsequently found not to be pregnant. In two others, samples from non-pregnant individuals were found to have been incorrectly submitted for analysis in place of the samples from the pregnant women. All of the remaining 92 women were counselled and offered amniocentesis and fetal karyotyping. Eighty-eight (96 per cent) accepted. Karyotypes or birth outcomes were available on all 92 pregnancies. Six cases of trisomy 18 and one case of Turner syndrome were identified by karyotype. One case of trisomy 18 was identified for every 14 unaffected pregnancies offered amniocentesis. In the present prospective study, an estimated 85 per cent of the cases of trisomy 18 were identified. However, given the small number of cases (six), the 95 per cent confidence interval for the detection rate is broad (40-95 per cent).

Adult↗
PubMed1992

Steroid sulfatase in the human ovary and placenta: enzyme kinetics and phosphate inhibition.

In 5 placental homogenates the Km of steroid sulfatase for DHEA sulfate increased from 15.4 in Tris buffer to 26.8 microM in phosphate (both buffers 0.1 M, pH 7.4), P less than 0.05. In 3 pooled ovarian preparations the Km increased from 14.3 microM in Tris to 33.0 microM in phosphate, P less than 0.01. There was no significant difference between the ovarian and placental values for Km in either Tris or phosphate (P greater than 0.5), and the increase in the Km produced by phosphate in ovarian tissue was not significantly different from that in the placenta (P greater than 0.5). In the placentas the Vmax in Tris was 1420 pmol/min/mg protein and this fell to 523 pmol/min/mg protein in phosphate (P less than 0.005). The Vmax was 50-fold higher in the placenta than in the ovary in either Tris or phosphate (both P less than 0.001). In the ovary, the Vmax was 27.6 pmol/min/mg protein in Tris and 11.0 pmol/min/mg protein in phosphate (P less than 0.05). The reduction of Vmax produced by phosphate in the ovary was not significantly different from that in the placenta (P greater than 0.5). The slope of the 1/v vs 1/S plot (Km/Vmax) increased 4.7-fold in the placentas and 5.8-fold in the ovaries in phosphate over that in Tris (both P less than 0.001); the increase in the placentas was not significantly different from that in the ovaries (P greater than 0.5). Phosphate ion acts as a mixed inhibitor of both placental and ovarian steroid sulfatase.

Arylsulfatases↗
PubMed1992

Multiple-marker screening in pregnancies with hydropic and nonhydropic Turner syndrome.

OBJECTIVE: The combination of maternal serum alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin levels and maternal age has been used to increase the sensitivity of screening for fetal Down syndrome and trisomy 18 in early-second-trimester pregnancies. We hypothesized that a unique pattern of these analytes also may be characteristic of fetal Turner syndrome, with or without hydrops. STUDY DESIGN: We studied preamniocentesis, second-trimester maternal serum specimens from seven hydropic and eight nonhydropic cases of fetal Turner syndrome. Clinical and pathologic records were reviewed. Statistical analysis of the data was performed by the rank sum test. RESULTS: In both hydropic and nonhydropic cases, alpha-fetoprotein levels were slightly reduced, and unconjugated estriol levels were markedly reduced. In hydropic pregnancies human chorionic gonadotropin levels were elevated, and nonhydropic pregnancies had low human chorionic gonadotropin levels (p = 0.001). CONCLUSIONS: The results suggest that the morphologic defect of hydrops, rather than the aneuploidy itself, is responsible for the elevation in human chorionic gonadotropin. In conjunction with the low unconjugated estriol levels, the elevation in human chorionic gonadotropin levels will result in the prenatal identification of hydropic fetal Turner syndrome pregnancies as being at increased risk for fetal Down syndrome.

Biomarkers↗
PubMed1990

Second-trimester levels of maternal serum unconjugated oestriol and human chorionic gonadotropin in pregnancies affected by fetal anencephaly and open spina bifida.

Unconjugated oestriol (uE3) and human chorionic gonadotropin (hCG) levels were determined in second-trimester maternal serum (MS) samples from 21 pregnancies associated with fetal anencephaly and 15 pregnancies associated with fetal open spina bifida. Each measurement was expressed as a multiple of the median (MoM) for unaffected pregnancies for each completed week of gestation. In pregnancies associated with anencephaly, the median value for MSuE3 was very low (0.17 MoM, range less than 0.12-0.33 MoM), suggesting a functional defect in the fetal adrenal prior to 20 weeks' gestation; the median value for MShCG was also low (0.73 MoM), although not to the same extent as for MSuE3. A biological explanation for the hCG result is not apparent. In pregnancies associated with open spina bifida, the MSuE3 and MShCG values were unremarkable, consistent with a lack of involvement of these open fetal defects in the synthesis and secretion of uE3 and hCG.

Anencephaly↗
PubMed1990

Steroid sulphatase activity in the human ovarian corpus luteum, stroma, and follicle: comparison to activity in other tissues and the placenta.

Steroid sulfatase activity was measured in 89 human samples, using dehydroepiandrosterone sulfate (DHEAS) as substrate. The lowest activity was that of follicular fluid which was significantly lower than that of other tissues tested (each P less than 0.01). The steroid sulfatase activity of ovarian tissue taken collectively (corpus luteum, stroma, and follicles) was higher than that of other tissues taken collectively (abdominal skin, uterus, and fallopian tube) (P less than 0.001), and the steroid sulfatase activity of either the follicle (P less than 0.01) or the stroma (P less than 0.05) was significantly greater than that of the corpus luteum. The geometric mean steroid sulfatase activity of the placenta was significantly higher than other tissues tested (each P less than 0.01) and was 22-fold higher than that of the follicle, the tissue with the next highest activity. These data indicate that the human ovary (particularly the stroma and follicle) is capable of utilizing DHEAS, an adrenal product, as a substrate for production of other androgens such as dehydroepiandrosterone (DHEA), androstenedione, and testosterone.

Arylsulfatases↗
PubMed1990

Maternal serum screening for aneuploid pregnancy by alpha-fetoprotein, hCG, and unconjugated estriol.

A number of serum screening protocols are either currently in use or proposed to identify pregnant women under 35 years of age who are at increased risk for a Down syndrome fetus. It has been suggested that these same screening methods be applied to gravidas over 35 years of age to identify those women who should be offered amniocentesis. To evaluate the efficacy of screening for detection of aneuploid pregnancy in this age group, the serum samples of 34 women who underwent amniocentesis and who had confirmed fetal aneuploidy were assayed for alpha-fetoprotein (AFP), hCG, and unconjugated estriol (E3). These concentrations were compared with those of 85 women with known euploid pregnancy who underwent amniocentesis for advanced maternal age. The mean multiple of the median (MoM) for each of the three markers was significantly different from control values in cases of trisomy 21 (AFP median MoM = 0.82; unconjugated E3 median MoM = 0.77; and hCG median MoM = 1.89). These differences were not found when other aneuploidies were considered. Likelihood ratios were calculated for cases and controls and examined for their ability to predict the need for amniocentesis, based on currently recommended risk levels. There was a significant difference between the mean likelihood ratio for cases of trisomy 21 compared with that of controls (mean likelihood ratio = 13.48); there was no significant difference for other aneuploidies (mean likelihood ratio = 1.08). Of the 16 cases of trisomy 21 analyzed, four would not have been diagnosed antenatally if recommendation against amniocentesis had been made based on each woman's individual age-specific risk as modified by her likelihood ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1988

Maternal serum screening for Down's syndrome in early pregnancy.

The possibility of improving the effectiveness of antenatal screening for Down's syndrome by measuring human chorionic gonadotrophin concentrations in maternal serum during the second trimester to select women for diagnostic amniocentesis was examined. The median maternal serum human chorionic gonadotrophin concentration in 77 pregnancies associated with Down's syndrome was twice the median concentration in 385 unaffected pregnancies matched for maternal age, gestational age, and duration of storage of the serum sample. Measuring human chorionic gonadotrophin in maternal serum was an effective screening test, giving a lower false positive rate (3%) at a 30% detection rate than that for maternal age (5%) and the two existing serum screening tests, unconjugated oestriol (7%) and alpha fetoprotein (11%). The most effective screening results were obtained with all four variables combined; at the same 30% detection rate the false positive rate declined to 0.5%. The new screening method would detect over 60% of affected pregnancies, more than double that achievable with the same amniocentesis rate in existing programmes (5%), and could reduce the number of children born with Down's syndrome in the United Kingdom from about 900 a year to about 350 a year.

Chorionic Gonadotropin↗
PubMed1988

Low second trimester maternal serum unconjugated oestriol in pregnancies with Down's syndrome.

Second trimester maternal serum unconjugated oestriol levels were measured in the stored serum samples from 22 pregnancies associated with Down's syndrome and 110 unaffected control pregnancies, matched for maternal age, gestational age, duration of storage of the serum sample, smoking habits and maternal weight. The serum unconjugated oestriol level of each affected pregnancy was expressed as a multiple of the median (MoM) of its five matched controls. The unconjugated oestriol levels were significantly lower in the affected pregnancies than in the unaffected pregnancies; the median MoM was 0.79 (P less than 0.05). This association between low serum unconjugated oestriol and fetal Down's syndrome early in pregnancy raises the possibility that serum unconjugated oestriol measurement may be added to maternal age and alpha-fetoprotein measurement in the antenatal screening for Down's syndrome.

Down Syndrome↗
PubMed1988

Maternal serum unconjugated oestriol as an antenatal screening test for Down's syndrome.

The median maternal serum unconjugated oestriol level between 13 and 27 weeks gestation in 77 pregnancies associated with Down's syndrome was lower than the median level in 385 unaffected control pregnancies matched for maternal age, gestational age, and duration of serum sample storage (P less than 0.001). The median level for the affected pregnancies was 73% of that in the controls. Low unconjugated oestriol levels can be used to detect fetal Down's syndrome; at cut-off levels selected to detect at least 35% of affected pregnancies, unconjugated serum oestriol was a better screening test than either maternal age or serum alpha-fetoprotein (AFP). The use of all three variables in combination to select women with a 1:250 or greater risk of a Down's syndrome term pregnancy would yield a 45% detection rate with a false-positive rate of 5.2%. The same detection rate using maternal age alone or using age and serum AFP in combination would yield higher false-positive rates, 15% and 9.8% respectively. The addition of unconjugated oestriol to a Down's syndrome screening programme would therefore be more efficient than the use of age and AFP alone; for a given detection rate fewer women would need an amniocentesis or, for a given percentage of women having an amniocentesis, more pregnancies with Down's syndrome would be detected.

Down Syndrome↗
PubMed1986

Localization of aromatase and 5 alpha-reductase to neuronal and non-neuronal cells in the fetal rat hypothalamus.

Experiments were designed to identify the neural cell type(s) responsible for the aromatization and 5 alpha-reduction of androgens in the rat hypothalamus. Primary cultures of fetal rat hypothalamic cells, which had enhanced neuronal morphology, were treated at various times after plating with kainic acid (KA), a neurotoxic agent which selectively destroys neuronal cells. Neuronal morphology was disrupted in a time (0-6 days)- and dose (10(-4)-10(-2) M)-dependent fashion after KA treatment, with no apparent change in the appearance of the flattened, underlying non-neuronal cells. KA treatment for 4 days decreased aromatization by 94% in a dose-dependent fashion (10(-4)-10(-2) M KA), while 5 alpha-reduction declined by no more than 25%. A 6-day time course with 10(-3) M KA showed a dramatic decline in aromatization and no alteration in 5 alpha-reduction. In control experiments, substance P, a neuronal peptide, declined after KA treatment while the activity of glutamine synthetase, a glial enzyme, did not change. We conclude from these results that aromatase is localized primarily to neuronal cells in the hypothalamus while 5 alpha-reductase is confined primarily to non-neuronal cells.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗