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Biomedical subjects

K Belanger

Publications and source records attributed to K Belanger.

36 records · Page 2Linked to original sources
PubMed1992

Fetal humeral length to detect Down syndrome.

OBJECTIVE: Our aim was to evaluate the utility of ultrasonographic humeral length measurements for detection of fetuses with Down syndrome in the midtrimester of gestation. STUDY DESIGN: Ultrasonographic biometry data obtained before genetic amniocenteses on 43 fetuses with Down syndrome and 204 randomly chosen normal fetuses were analyzed. Regression equations relating biparietal diameter to humeral length and femoral length were used to calculate ratios of observed-to-expected length and sensitivity and specificity at various cutoff points. RESULTS: Humeral length in Down syndrome fetuses was significantly shorter than in normal controls (p less than 0.001). A ratio of 0.90 for observed/expected humeral length yielded a sensitivity of 28%, a specificity of 91%, and positive predictive values of 1.23% and 0.41% in populations at risk for Down syndrome of 1 in 250 and 1 in 750, respectively. The equivalent ratio for femoral length yielded a sensitivity of 19%, a specificity of 91%, and positive predictive values of 0.87% and 0.28% for baseline risks of 1 in 250 and 1 in 750, respectively. CONCLUSIONS: The sensitivity of fetal humeral length measurements for Down syndrome detection in our hands was remarkably lower than previously reported. Independence of this parameter from currently used serum screening markers has not been established; therefore implementation in screening programs is not advisable at this point.

Down Syndrome↗
PubMed1990

Does the umbilical artery systolic/diastolic ratio reflect flow or acidosis? An umbilical artery Doppler study of fetal sheep.

We studied four fetal sheep at 114 to 139 days' gestation to evaluate the effect of acute placental embolization on placental perfusion, fetal oxygenation and acid-base status, and the umbilical artery systolic/diastolic ratio. Studies were performed after maternal anesthesia was induced in an acute model, with serial umbilical artery embolizations performed at 20 to 30 minute intervals. Fetal umbilical flow, systolic/diastolic ratio, and arterial blood gas levels were followed up. One animal maintained a normal systolic/diastolic ratio despite a 50% drop in flow after the first injection and pH of 6.91, and died after the second injection. The remaining three animals showed significantly decreased flow after the third injection (p less than 0.02), with no change in the systolic/diastolic ratio. The systolic/diastolic ratio increased significantly after the fourth injection (p less than 0.05) when flow had dropped even further. Corresponding decreases in PO2 and pH did not achieve statistical significance. The magnitude of all changes increased with subsequent embolizations. We conclude that in this model significant reductions in flow result in small increases in the systolic/diastolic ratio and that greater magnitude changes in the systolic/diastolic ratio appear only with severely diminished flow and PO2, when acidosis develops.

Acidosis↗
PubMed1989

Pulsed Doppler flow-velocity waveforms in the prediction of fetal hematocrit of the severely isoimmunized pregnancy.

We previously reported a significant relationship between the hematocrit levels of anemic fetuses and information derived from ultrasonographic and Doppler flow-velocity waveforms. In this study we prospectively tested two formulas for the prediction of hematocrit values, by use of gestational age, presence or absence of hydrops, and Doppler indices. Although one of the two formulas predicted hematocrit values significantly, the only component of the formula that made a significant contribution was fetal hydrops. We conclude that currently available fetal Doppler measurements are unable to be applied in the prospective prediction of hematocrit values in anemic fetuses of isoimmunized pregnancies.

Blood Flow Velocity↗
PubMed1989

Fetal cardiac output in the isoimmunized pregnancy: a pulsed Doppler-echocardiographic study of patients undergoing intravascular intrauterine transfusion.

The mechanism of development of hydrops fetalis in severe isoimmunization has been subject to speculation. We performed pulsed Doppler assessment of cardiac output in 13 severely isoimmunized fetuses before and after intravascular transfusion and compared the results with 37 control fetuses between 20 and 34 weeks' gestation. The cardiac index of the anemic fetuses was significantly greater than that of the control group. A significant (right ventricle, p less than 0.01; left ventricle, p less than 0.02) increase in indexed output was noted from both ventricles and in the combined ventricular output (mean +/- SEM 644 +/- 35.3 ml/kg/min in control fetuses versus 879 +/- 86.0 ml/kg/min in anemic fetuses, p less than 0.006). An increase in cardiac output was also noted when anemic fetuses were compared with gestational age-specific norms. We conclude that severely anemic fetuses of isoimmunized pregnancies tend to have significantly higher cardiac output than do unaffected fetuses and that this high output state may play a part in the development of hydrops fetalis.

Blood Transfusion, Intrauterine↗
PubMed1989

Iododeoxyuridine (IdUrd) incorporation into DNA of human hematopoietic cells, normal liver and hepatic metastases in man: as a radiosensitizer and as a marker for cell kinetic studies.

Iododeoxyuridine (IdUrd) was administered as a continuous infusion for 14 days to patients with glioblastoma and sarcoma, and for 3 days to patients with metastatic colorectal carcinoma. In the first group, the maximum incorporation of IdUrd into DNA was determined, taking granulocytes as parameter. In the second group, selective incorporation into DNA of normal liver and hepatic metastases of colorectal cancer was investigated. The highest dose of 675 mg/sq.m./day for 14 days produced IdUrd plasma concentrations of 1.8 +/- 0.3 microM, and a substitution of dThd by IdUrd in the range of 7.1-11.7%. Coadministration of fluorodeoxyuridine did not show significant enhancement of IdUrd-incorporation in granulocytes. Three-day intravenous infusions of IdUrd 1000 mg/sq.m./day produced 1.7-4.5% IdUrd-incorporation in hepatic metastases. Three-day intraarterial infusions (hepatic artery) produced 3.8-10.5% dThd-replacement, whereas, in 9/10 patients this was less than 1% in normal liver. In tumor tissue there was a trend towards FdUrd-modulated enhancement of IdUrd-incorporation, although there was considerable scatter. Cell kinetic studies revealed that IdUrd-incorporation in monocytes and granulocytes was very similar. In lymphocytes, a much lower fraction incorporated IdUrd. Liver tumor contained a considerably higher fraction of IdUrd-labeled cells, compared with normal liver. Potential doubling times for the tumors were estimated to be 10 days.

Cell Cycle↗
PubMed1988

Fluorodeoxyuridine modulation of the incorporation of iododeoxyuridine into DNA of granulocytes: a phase I and clinical pharmacological study.

The amount of iododeoxyuridine (IdUrd) incorporated into DNA determines the degree of radiosensitization. Fluorodeoxyuridine (FdUrd) has been shown to biochemically modulate IdUrd incorporation into DNA in vitro and in vivo. In this Phase I study, these drugs were coadministered to patients during 14-day continuous i.v. infusion periods in order to investigate whether the incorporation of IdUrd into DNA in vivo could be increased without increasing the dose of IdUrd. IdUrd plasma concentrations and incorporation of IdUrd into DNA of granulocytes were measured by high-performance liquid chromatography. Up to 8.8% substitution of thymidine by IdUrd was observed. Even at 3.5 mg/m2/day FdUrd for 14 days (78% of the maximum-tolerated dose as a single agent), no clinically relevant enhancement of incorporation of IdUrd into DNA of granulocytes was observed. Also, no changes in plasma levels of IdUrd were observed with escalating doses of FdUrd. Toxicity patterns (stomatitis, diarrhea, and bone marrow depression) and isobologram analysis suggested that IdUrd and FdUrd had additive, rather than synergistic, effects.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Pulsed Doppler flow-velocity waveforms before and after intrauterine intravascular transfusion for severe erythroblastosis fetalis.

Pulsed Doppler studies of the fetal and maternal circulations were carried out before and after 64 intrauterine transfusions performed on 24 fetuses. A model was derived for the prediction of hematocrit before the first transfusion: Hematocrit = 7.778 - (0.088 x peak velocity in descending aorta) + (0.968 x gestational age [weeks]) - (10.911 if hydrops present) (r = 0.876, p less than 0.0001). An alternative formula, excluding hydrops, was slightly less predictive: Hematocrit = 45.312 - (56.261 x umbilical cord Pourcelot index) - (0.128 x peak velocity in descending aorta) + (1.042 x gestational age) r = 0.822, p less than 0.001). Neither model was accurate in the prediction of hematocrit before second or subsequent transfusions. A third model was derived from second-transfusion data: Hematocrit = 40.524 - (0.045 x peak velocity in descending aorta) - (10.693 x pulsatility index of maternal uterine artery) (r = 0.81, p less than 0.003). However, this model was unable to predict hematocrit before third or later transfusions. No changes in Doppler parameters before and after transfusion were found. We conclude that pulsed Doppler ultrasound may be helpful in the evaluation of isoimmunized pregnancies, in differentiating anemic from normal fetuses. It does not appear to be useful in determining the timing of later transfusions. The lack of change before and after transfusions suggests that these vessels will not provide significant information concerning the effect of rapid volume and hematocrit changes in the fetus.

Blood Transfusion, Intrauterine↗
PubMed1988

Amniotic fluid alpha-fetoprotein concentrations in twin gestations: dependence on placental membrane anatomy.

Placental membrane anatomy was evaluated after delivery in 65 twin pregnancies undergoing genetic amniocentesis with amniotic fluid alpha-fetoprotein and acetylcholinesterase determinations when indicated. Each twin member in the 57 uncomplicated twin pregnancies was found to have an amniotic fluid alpha-fetoprotein concentration similar to that of singleton pregnancies of an equivalent gestational age. Eight twin pregnancies were found to be discordant for fetal anomalies associated with an elevated amniotic fluid alpha-fetoprotein and acetylcholinesterase level. The amniotic fluid alpha-fetoprotein concentration in the unaffected fetus in these eight cases was found to be dependent on placental membrane structure. Of the five discordant twin pregnancies with diamnionic-dichorionic placentas, all unaffected twins demonstrated an amniotic fluid alpha-fetoprotein concentration within the normal range for gestational age with a normal acetylcholinesterase level. In three twin pairs with diamnionic-monochorionic placentas, the unaffected twin member had significantly elevated amniotic fluid alpha-fetoprotein and acetylcholinesterase levels, which suggested diffusion of alpha-fetoprotein and acetylcholinesterase through the amnion-amnion interface.

Acetylcholinesterase↗
PubMed1988

Ultrasonographic assessment of gestational age with the distal femoral and proximal tibial ossification centers in the third trimester.

A prospective sonographic evaluation of the distal femoral and proximal tibial epiphyseal ossification centers in 228 normal pregnant women was carried out from 28 to 40 weeks' gestation. The mean gestational age at which the distal femoral epiphysis and proximal tibial epiphysis were imaged was 34 and 38 weeks, respectively. The distal femoral epiphysis was not identifiable before 28 weeks but was observed in 72% of fetuses at 33 weeks and in 94% of fetuses at 34 weeks' gestation. The presence of a distal femoral epiphysis measuring 1 or 2 mm was associated with a gestational age of greater than 33 weeks in 87.0% of fetuses, whereas a distal femoral epiphysis measuring greater than or equal to 3 mm was associated with a gestational age greater than 37 weeks in 85% of fetuses. The proximal tibial epiphysis, which was absent before 34 weeks' gestation, was observed in 56% of fetuses at 36 weeks, in 80% of fetuses at 37 weeks, and in 100% of fetuses at 39 weeks of gestation. The presence of a proximal tibial epiphysis of 1 or 2 mm was associated with a gestational age of greater than 36 weeks in 88% of fetuses, whereas a proximal tibial epiphysis greater than or equal to 3 mm was associated with a gestational age of greater than 38 weeks in 94% of fetuses. The sonographic evaluation of distal femoral epiphysis/proximal tibial epiphysis can be used as independent markers for estimation of gestational age during the third trimester, a period in which standard fetal biometric estimates of gestational age are least accurate.

Epiphyses↗
PubMed1988

Selective incorporation of iododeoxyuridine into DNA of hepatic metastases versus normal human liver.

Fourteen patients received 5-iodo-2(1)-deoxyuridine (IdUrd) before surgery for placement of a hepatic arterial catheter. Biopsy specimens were obtained at the time of surgery and incorporation of IdUrd into deoxyribonucleic acid (DNA) in tumor and normal hepatic tissue was measured by HPLC and used as an index of drug selectivity. Over a 3-day intravenous infusion of IdUrd at 1000 mg/m2/day, substitution for thymidine in tumor DNA averaged 3.1%. Normal hepatic DNA contained less than 1% substitution by IdUrd. Arterial delivery of IdUrd increased levels in DNA, whereas modulation with fluorodeoxyuridine produced mixed results. In six patients, flow cytometric analysis showed that the tumor contained a median of 32% of tumor cells that had incorporated IdUrd in 3 days, corresponding to a potential doubling time of only 10 days. Thymidylate synthetase activity in tumors was 20-fold greater than in normal liver tissue, whereas thymidine kinase activity was twofold greater in tumors. These pharmacologic studies encourage further clinical trials of IdUrd as a cytotoxic agent or radiosensitizer.

Adult↗
PubMed1987

Technique for detection of DNA nucleobases by reversed-phase high-performance liquid chromatography optimized for quantitative determination of thymidine substitution by iododeoxyuridine.

A reversed-phase high-performance liquid chromatographic (HPLC) method for quantification of iododeoxyuridine (IdUrd) substitution for thymidine in DNA was developed. IdUrd substitution was determined by HPLC with ultraviolet absorbance in two cell lines (L1210 and HT-29) after incubation in vitro with IdUrd alone or with IdUrd and fluorodeoxyuridine. In addition, radiolabeled IdUrd was used concomitantly with HPLC to evaluate the degree of dehalogenation. This HPLC technique has also been applied to the measurement of IdUrd incorporation in vivo into DNA from peripheral granulocytes of patients receiving IdUrd. This method provides an interesting tool for the quantification of drug substitution into DNA and can be applied to multiple sampling sites in animal and human studies.

Animals↗
PubMed1987

A sonographic screening method for Down syndrome.

We describe a potential screening method for the second trimester detection of the fetus with Down syndrome by the use of standard sonographic biometry. Retrospective assessment of the biparietal diameter, femur length, and biparietal diameter/femur length ratio in 55 fetuses with Down syndrome and 544 control fetuses was performed at two medical centers. Adequate numbers of cases and controls were available to permit statistically significant comparisons between the groups at 15 to 23 weeks' gestation. Fetuses with Down syndrome displayed no statistically significant differences in the cephalic index or the biparietal diameter compared with controls at a given gestational age. Significant femur length shortening was observed, but the greatest statistical difference was noted for the biparietal diameter/femur length ratio. This ratio was found to decrease with gestational age in the normal population and was consistently elevated in the Down syndrome population (compared with control) throughout the second trimester. With a cutoff value of 1.5 SD above the normal population mean for the biparietal diameter/femur length ratio, 50% to 70% of fetuses with Down syndrome could be identified in 6% of the total population (p less than 0.0001). This preliminary study suggests that the biparietal diameter/femur length ratio may prove superior to current Down syndrome screening methods and, as a third independent variable, may significantly enhance the sensitivity and specificity of combined maternal age/maternal serum alpha-fetoprotein screening modalities.

Down Syndrome↗
PubMed1986

Incorporation of iododeoxyuridine into DNA of granulocytes in patients.

Iododeoxyuridine (IdUrd) competes with thymidine for incorporation into DNA. In order to measure the incorporation of the drug in vivo, granulocytes were isolated from peripheral blood of patients at various times during and after 9- to 14-day IdUrd i.v. continuous infusions. DNA was extracted and enzymatically hydrolyzed. Both thymidine and IdUrd were separated and measured by high-performance liquid chromatography. Thymidine substitution by IdUrd was less than 1% prior to the fifth day of infusion and then increased rapidly to achieve a maximal value between 7 and 17% at the end of the infusion. In our protocol, thrombocytopenia was the most frequent dose-limiting systemic toxicity. For our group of patients, there was a clear overall relationship between the extent of substitution by IdUrd and the hematological toxicity. To our knowledge, these data provide the first direct quantitative determination of substitution by a drug into DNA in vivo without the use of radiolabeled compounds. The ability to directly monitor drug incorporation into DNA may provide the basis for monitoring and improving the selectivity of therapy.

DNA↗
PubMedDate not supplied

Metabolism of polynuclear aromatic hydrocarbon in human term placenta influenced by cigarette smoke exposure.

The relative contributions of biologic and environmental factors on embryo-fetal development were elucidated in a population of pregnant women who were exposed to varying amounts of active cigarette smoke and women who were not exposed to cigarette smoke. The neonatal weight at birth, placental weight at delivery, duration of pregnancy, and placental xenobiotic (polynuclear aromatic hydrocarbon, PAH) metabolism potential were assessed in this population. The overall metabolic capability in exposed and unexposed placental tissue was measured by in vitro assays using microsomes and a PAH substrate, benzo[a]pyrene (B[a]P). Toxicity potential was determined by B[a]P-metabolite-DNA adduct generation under the same incubation condition. Cigarette smoke exposure increased the overall PAH metabolism potential in placental tissues by approximately 200% (nonsmoker 176.2 +/- 33.6, n = 25; smoker 524.5 +/- 75.5, n = 32 pmol/mg protein) whereas PAH-DNA adduct formation potential did not increase significantly over the basal level (nonsmoker 5002 +/- 830, n = 15; smoker 6172 +/- 1443, n = 22 fmol B[a]P equivalent/mumol DNA/mg protein). Exposure to cigarette smoke during pregnancy is deleterious to fetal development as reflected by reduced neonatal weight at birth. In contrast, placental weight reduction is indistinct, but placentae expressed markedly augmented overall xenobiotic (PAH) metabolism capability in response to cigarette smoke exposure during pregnancy, indicating placental metabolism may be an important mediator of adverse effects induced by such xenobiotic exposure.

Analysis of Variance↗
PubMedDate not supplied

Fetal growth and birthweight in isoimmunized pregnancies after intravenous intrauterine transfusion.

Forty-seven fetuses treated with intravenous intrauterine transfusion for rhesus isoimmunization were studied. At the time of first transfusion the fetuses were below average in size with the fetal femur length being directly related to the degree of fetal anemia. Subsequent to transfusion therapy there was increased growth of all fetal parameters measured. Birthweight was similar to a control group of unaffected fetuses. This contrasts with results after intraperitoneal transfusion where birthweights have been reported as being below average.

Birth Weight↗