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Biomedical subjects

J W Ritchie

Publications and source records attributed to J W Ritchie.

At least 19 recordsLinked to original sources
PubMed1998

Umbilical artery blood flow velocity in pregnancies complicated by systemic lupus erythematosus.

PURPOSE: We evaluated the role of umbilical artery Doppler velocimetry in the surveillance of pregnancies complicated by systemic lupus erythematosus (SLE). METHODS: We retrospectively studied 56 women with SLE whose pregnancies were managed at our perinatal center between 1988 and 1995. RESULTS: Absent or reversed end-diastolic flow velocity was detected in 6 (11%) of 56 patients. This sub-group of patients had an increased risk of pre-eclampsia, intrauterine growth restriction, cesarean section, and preterm delivery. CONCLUSIONS: A high incidence (11%) of abnormal umbilical artery waveforms was detected. This finding was associated with an increased risk of maternal and fetal complications.

Adult↗
PubMed1998

Elevated high-density lipoprotein cholesterol and dietary fat intake in women with cyclic mastopathy.

OBJECTIVE: This study was designed to examine the contribution of plasma lipids to the pathophysiology of cyclic mastopathy, before and after consideration of diet and sex hormones. STUDY DESIGN: Thirty-four women with severe cyclic mastopathy (case patients) and 29 women without cyclic mastopathy (control subjects) recorded their breast symptoms daily during 1 menstrual cycle. During each menstrual phase (follicular, early luteal, late luteal, and menstrual) they prospectively completed 2 24-hour dietary diaries, provided blood for lipid and hormone assays, and underwent anthropometric measurements. RESULTS: Mean age was 34 years. Premenstrual breast swelling and tenderness were significantly more severe in case patients (P < .0001). Cyclic change (late luteal vs follicular) of high-density lipoprotein cholesterol differed between case patients and control subjects, with case patients having a relative excess of high-density lipoprotein cholesterol in the premenstrual phase (P = .01). Dietary fat intake was greater throughout the cycle in case patients (37.5 vs 33.7% of calories, P = .02), and case patients reported increased appetite in the premenstrual phase (P = .01). In multivariate analyses the contributions of mean dietary fat intake and of cyclic change in high-density lipoprotein cholesterol were independently significant, with odds ratios for upper versus lower quintiles being slightly >5. CONCLUSIONS: Women with cyclic mastopathy had a relative excess of high-density lipoprotein cholesterol during the symptomatic late luteal phase of the menstrual cycle and a higher fat intake throughout the cycle than did control subjects. These observations support the hypothesis that lipids (notably high-density lipoprotein cholesterol) and a high-fat diet play a role in the pathophysiologic characteristics of cyclic mastopathy.

Adult↗
PubMed1998

The Toronto Tri-Hospital Gestational Diabetes Project. A preliminary review.

In this study, we assessed maternal-fetal outcomes in untreated patients with increasing carbohydrate intolerance not meeting the current criteria for the diagnosis of gestational diabetes mellitus (GDM), examined the relationship between birth weight and mode of delivery among women with untreated borderline GDM, treated overt GDM, and normoglycemia, and established more efficient screening strategies for detection of GDM. This was a prospective analytic cohort study in which nondiabetic women aged > or = 24 years were eligible for enrollment. A 50-g glucose challenge test (GCT) and a 100-g oral glucose tolerance test (OGTT) were administered at 26 and 28 weeks gestational age, respectively. Risk factors for unfavorable maternal-fetal outcomes were recorded. Time since the last meal prior to the screening test was recorded, as well. Caregivers and patients were blinded to glucose values except when test results met the National Diabetes Data Group criteria for GDM. Maternal and fetal outcomes, including the mode of the delivery, were recorded in the postpartum period. Of 4,274 patients screened, 3,836 (90%) continued to the diagnostic oral glucose tolerance test. GDM was seen in 145 women. Increasing carbohydrate intolerance in women without overt gestational diabetes was associated with a significantly increased incidence of cesarean section, preeclampsia, macrosomia, and need for phototherapy, as well as an increased length of maternal and neonatal hospital stay. Multivariate analysis showed that increasing carbohydrate intolerance remained an independent predictor for various unfavorable outcomes, but the strength of the associations was diminished. Compared with normoglycemic control subjects, the untreated borderline GDM group had increased rates of macrosomia (28.7 vs. 13.7%, P < 0.001) and cesarean delivery (29.6 vs. 20.2%, P = 0.03). Usual care of known GDM patients normalized birth weights, but the cesarean delivery rate was about 33%, whether macrosomia was present or absent. An increased risk of cesarean delivery among treated patients compared with normoglycemic control subjects persisted after adjustment for multiple maternal risk factors. As for the screening tests, time since the last meal had a marked effect on mean plasma glucose. Receiver operating characteristic curve analysis allowed the selection of the most efficient cut points for the GCT based on the time since the last meal. These cut points were 8.2, 7.9, and 8.3 mmol/l (1 mmol/l = 18.015 mg/dl) for elapsed postprandial time of < 2, 2-3, and > 3 h, respectively. With this change from the current threshold of 7.8 mmol/l, the number of patients with a positive screening test dropped from 18.5 to 13.7%. There was an increase in positive predictive value from 14.4 to 18.7%. The overall rate of patient misclassification fell from 18.0 to 13.1%. In conclusion, increasing maternal carbohydrate intolerance in pregnant women without GDM is associated with a graded increase in adverse maternal and fetal outcomes. Infant macrosomia is an important factor in high cesarean delivery rates for women with untreated borderline GDM. Although detection and treatment of GDM normalizes birth weights, rates of cesarean delivery remain inexplicably high. Recognition of GDM may lead to a lower threshold for surgical delivery. The efficiency of screening for GDM can be enhanced by adjusting the current GCT threshold of 7.8 mmol/l to new values related to time since the last meal before screening. Further analyses are underway to elucidate whether maternal risk factors can be used to achieve additional efficiency gains in screening.

Birth Weight↗
PubMed1997

Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss.

BACKGROUND: Recurrent fetal loss has been well described in women with antiphospholipid antibodies. Such women also often have other autoantibodies commonly found in patients with systemic lupus erythematosus. Treating them with prednisone and aspirin may reduce the risk of fetal loss. METHODS: We screened 773 nonpregnant women who had the unexplained loss of at least two fetuses for antinuclear, anti-DNA, antilymphocyte, and anticardiolipin antibodies and for the lupus anticoagulant. Of 385 women with at least one autoantibody, 202 who later became pregnant were randomly assigned in equal numbers to receive either prednisone (0.5 to 0.8 mg per kilogram of body weight per day) and aspirin (100 mg per day) or placebo for the duration of the pregnancy. The women were stratified according to age (18 to 34 years or 35 to 39 years) and the week of gestation at which the previous fetal losses had occurred (< or = 12 or > 12 weeks). The primary outcome measure was a successful pregnancy. RESULTS: Live infants were born to 66 women in the treatment group (65 percent) and 57 women in the placebo group (56 percent, P=0.19). More infants were born prematurely in the treatment group than in the placebo group (62 percent vs. 12 percent, P<0.001). The major side effects of therapy in the mothers were hypertension (treatment group, 13 percent; placebo group, 5 percent; P=0.05) and diabetes mellitus (15 percent and 5 percent, P=0.02). CONCLUSIONS: Treating women who have autoantibodies and recurrent fetal loss with prednisone and aspirin is not effective in promoting live birth, and it increases the risk of prematurity.

Abortion, Habitual↗
PubMed1997

Endoglin regulates trophoblast differentiation along the invasive pathway in human placental villous explants.

Successful invasion of the maternal vascular system by trophoblast cells is a prerequisite for the establishment of a normal hemochorial placenta. Transforming growth factor-beta (TGFbeta) has been implicated in the regulation of trophoblast invasiveness into the uterus. Endoglin is a component of the TGFbeta receptor complex that binds beta1 and beta3 isoforms and is expressed at high levels on syncytiotrophoblast throughout pregnancy and is also transiently up-regulated on extravillous trophoblasts differentiating along the invasive pathway. We investigated the role of endoglin in a serum-free human villous explant culture system that allows the study of trophoblast outgrowth, migration, and invasion and mimics events occurring in anchoring villi during the first trimester of gestation. Addition to explant cultures from 5-8 weeks gestation of a monoclonal antibody to endoglin or of antisense endoglin oligonucleotides significantly stimulated trophoblast outgrowth and migration. These responses were specific, as incubation of explants with nonimmune IgG or sense and scrambled oligonucleotides had no effect. Antisense endoglin-induced trophoblast outgrowth and migration were accompanied by cell division of villous-associated trophoblasts within the proximal region of the forming column and by the characteristic switch in integrins observed in anchoring villi in situ. Treatment of villous explants with antibody and antisense oligonucleotides to endoglin also resulted in an increased fibronectin release into the culture medium. The stimulatory effect of antisense endoglin on fibronectin production was overcome by the addition of exogenous TGFbeta2, but not TGFbeta1 and -beta3. These findings suggest that endoglin expression in the transition from polarized to nonpolarized trophoblasts in anchoring villi is necessary for mediation of the inhibitory effect of TGFbeta1 and/or TGFbeta3 on trophoblast differentiation along the invasive pathway.

Antibodies↗
PubMed1995

Impact of increasing carbohydrate intolerance on maternal-fetal outcomes in 3637 women without gestational diabetes. The Toronto Tri-Hospital Gestational Diabetes Project.

OBJECTIVE: Our purpose was to assess maternal-fetal outcomes in patients with increasing carbohydrate intolerance not meeting the current criteria for the diagnosis of gestational diabetes. STUDY DESIGN: We conducted a prospective analytic cohort study in which nondiabetic women aged > or = 24 years, receiving prenatal care in three Toronto teaching hospitals, were eligible for enrollment. A glucose challenge test and an oral glucose tolerance test were administered at 26 and 28 weeks' gestation, respectively; risk factors for unfavorable maternal-fetal outcomes were recorded. Caregivers and patients were blinded to glucose values except when test results met the current criteria for gestational diabetes. RESULTS: Of 4274 patients screened, 3836 (90%) continued to the diagnostic oral glucose tolerance test. The study cohort was formed by the 3637 (95%) patients without gestational diabetes, carrying singleton fetuses. Increasing carbohydrate intolerance in women without overt gestational diabetes was associated with a significantly increased incidence of cesarean sections, preeclampsia, macrosomia, and need for phototherapy, as well as an increased length of maternal and neonatal hospital stay. Multivariate analysis showed that increasing carbohydrate intolerance is an independent predictor for various unfavorable outcomes. CONCLUSION: Increasing maternal carbohydrate intolerance in pregnant women without gestational diabetes is associated with a graded increase in adverse maternal-fetal outcomes.

Adult↗
PubMed1995

Reduced placental villous tree elaboration in small-for-gestational-age pregnancies: relationship with umbilical artery Doppler waveforms.

OBJECTIVE: Our purpose was to investigate the three-dimensional architecture of placental villi from normal and growth-restricted fetuses and relate findings to umbilical artery blood flow velocity waveforms. STUDY DESIGN: Placentas from term (n = 15) and preterm (n = 5) appropriately grown and term (n = 9) and preterm (n = 7) growth-restricted fetuses (birth weight < 10th percentile) were examined to determine the number of arteries per stem villus and the three-dimensional configuration of the villous trees and their vessels. Umbilical blood flow before delivery was assessed by Doppler ultrasonography. The effects of age and growth restriction were determined by two-way analyses of variance. RESULTS: Growth restriction was associated with reduced large vessel wall thickness (p < or = 0.05) but no reduction in the number of these vessels per stem villus. The volumes and surface areas of intermediate and terminal villi were reduced (p < or = 0.001), especially in preterm growth-restricted cases, where a marked reduction in diastolic blood flow velocity was observed in the umbilical artery. CONCLUSIONS: Reduced villous development may contribute to abnormal umbilical artery blood flood flow, as assessed by Doppler ultrasonography, in some cases of intrauterine growth restriction.

Blood Flow Velocity↗
PubMed1995

The effects of maternal aerobic exercise on human placental development: placental volumetric composition and surface areas.

The histomorphometry of term placentae from women who exercised regularly throughout either the first half or all of pregnancy was compared to that of placentae from matched controls to determine if regular exercise during pregnancy produced histomorphometric evidence of altered development and transport capacity. Conventional stereological techniques were used to estimate placental volumetric composition, surface areas, and villous and vascular configurations in the three groups. Exercise confined to early pregnancy increased the parenchymal component of the placenta, total vascular volume and site-specific capillary volume and surface area. Exercise throughout pregnancy increased these and multiple other histomorphometric parameters associated with the rate of placental perfusion and transfer function. However, significant changes were confined to villi > 80 microns in diameter. The localization of both the timing of the stimulus and the anatomical sites affected indicates that regular, sustained exercise modifies placental development primarily in early and mid-pregnancy. We speculate that the lack of significant changes in the structure and configuration of the smaller villi indicates that other adaptive mechanisms, such as increased rates of placental blood flow, must be well developed by the latter portion of the mid-trimester and adequately maintain fetal oxygenation and substrate delivery throughout the third trimester.

Adult↗
PubMed1994

Impact of time since last meal on the gestational glucose challenge test. The Toronto Tri-Hospital Gestational Diabetes Project.

OBJECTIVE: The purpose of the study was to evaluate the impact of time since the last meal on the glucose challenge test and to find cut points that are most likely to predict the outcome of the oral glucose tolerance test in patients screened for gestational diabetes. STUDY DESIGN: This prospective analytic cohort study was carried out at the University of Toronto Perinatal Complex. A 50 gm glucose load was given at 26 weeks' gestation and the time since previous meal ingestion was recorded. At 28 weeks' gestation a 100 gm oral glucose tolerance test was administered. A total of 4274 eligible patients were screened. RESULTS: Time since the last meal had a marked effect on mean plasma glucose. Receiver-operator characteristic curve analysis with National Diabetes Data Group criteria to interpret the oral glucose tolerance allowed the selection of the most efficient cut points for the glucose challenge test on the basis of time since the last meal. These cut points were 8.2, 7.9, and 8.3 mmol/L for elapsed postprandial times of < 2, 2 to 3, and > 3 hours, respectively. With this change from the current threshold of 7.8 mmol/L the number of patients with a positive screening test dropped from 18.5% to 13.7%. There was an increase in positive predictive value from 14.4% to 18.7%. The rate of patient misclassification fell from 18.0% to 13.1%. CONCLUSION: We suggest that screening strategies for detection of gestational diabetes be reconsidered, to account for the impact of variable postprandial status on the test results.

Adult↗
PubMed1994

Localization of two angiogenic growth factors (PDECGF and VEGF) in human placentae throughout gestation.

The spatiotemporal distribution of two angiogenic growth factors, platelet-derived endothelial cell growth factor (PDECGF) and vascular endothelial growth factor (VEGF) were determined using immunohistochemistry on sections of human placentae from each trimester of pregnancy. In the first trimester PDECGF was detected in trophoblast and in a band in the centre of the villous core. During gestation staining spread throughout the stroma but began to weaken in trophoblast until, by term, it was found only in stroma and in some endothelial cells. VEGF was detected exclusively in cytotrophoblast during the first trimester and then in syncytiotrophoblast throughout the remainder of pregnancy. Western blot analysis revealed that PDECGF antisera bound to three bands approximately 27, 47 and 94 kDa. The lowest band was not detected in platelet lysate and may represent an alternatively processed form of this peptide in placenta. VEGF antisera bound strongly to bands approximately 36, 46, 54, 56 and 64 kDa. The intensity of most bands increased between the first and second trimesters, consistent with an increased level of angiogenesis as the placenta develops. The presence of both factors in trophoblast in early pregnancy may be indicative of the trophoblast playing an active role in influencing the development of the villous vascular network.

Blotting, Western↗
PubMed1994

Determinants of increased left ventricular output during in utero ventilation in fetal sheep.

A model of in utero ventilation was used to elucidate the mechanisms by which left ventricular (LV) output increases with the transition from a fetal to a neonatal circulation. Using a conductance catheter, LV volumes were measured in seven anesthetized, near-term fetal sheep. Pressure-volume data was recorded before and with oxygen ventilation and again after occlusion of the umbilical cord. Ventilation caused increases in LV end-diastolic volume measured in seven anesthetized, near-term fetal sheep. Pressure-volume data was recorded before and with oxygen ventilation and again after occlusion of the umbilical cord. Ventilation caused increases in LV end-diastolic volume (2.3 +/- 0.9 to 2.9 +/- 0.6 mL/kg; p < 0.05), stroke volume (1.2 +/- 0.3 to 1.9 +2- 0.2 mL/kg; p < 0.001), and ejection fraction (52.8 +/- 11.1 to 66.4 +/- 8.8%; p < 0.001). Contractile state, as assessed by end-systolic elastance, did not change during the transition. Heart rate also remained constant. Afterload, as assessed by effective arterial elastance, decreased from 1.80 +/- 0.37 to 1.04 +/- 0.33 kPa/mL (p < 0.01). Occlusion of the umbilical cord did not result in any further change in hemodynamic parameters. Pressure-volume analysis revealed that a decrease in effective LV afterload and an increased LV end-diastolic volume are the major determinants of, and contribute comparably to, the profound increase in LV output with in utero ventilation. Enhanced contractility is not required for the increase in LV output to occur.

Animals↗
PubMed1993

Absent end-diastolic flow velocity waveforms in the umbilical artery--the subsequent pregnancy.

OBJECTIVE: Our purpose was to assess the recurrence risk, course, and outcome of subsequent pregnancies in women with absent umbilical end-diastolic velocity. STUDY DESIGN: Absent umbilical end-diastolic velocity was detected in 88 women. Sixteen of them were prospectively followed up in their 19 subsequent pregnancies. These pregnancies were compared with their index pregnancies. RESULTS: The index pregnancy was invariably complicated with a perinatal mortality of 56%, growth restriction in 94% (15/16), and prematurity in 100% (75% < 32 weeks' gestation). In contrast, the outcome of the subsequent pregnancies was much better, and 74% (14/19) were uncomplicated. No perinatal deaths occurred, and none were delivered before 32 weeks' gestation. Absent umbilical end-diastolic velocity recurred in only two pregnancies, both of which were complicated. Six women had autoantibodies; these accounted for 80% (4/5) of subsequent complicated pregnancies. CONCLUSION: After an index pregnancy with absent umbilical end-diastolic velocity, subsequent pregnancies had favorable outcomes. Recurrence of absent umbilical end-diastolic velocity was low. The absence of autoantibodies and normal Doppler studies were associated with improved outcome.

Adult↗
PubMed1993

The effects of hypoxic acidemia on left ventricular end-systolic elastance in fetal sheep.

Using the conductance catheter technique, we measured the effects of hypoxic acidemia on left ventricular end-systolic elastance in anesthetized, 133-d gestation, in utero fetal sheep (n = 7). Conductance and Millar catheters were introduced into the left ventricle through a carotid artery cutdown. Fetuses were rendered progressively hypoxic and acidemic by placental embolization with repeated injections of 5 x 10(5) 50-microns plastic spheres every 15 min via a catheter placed in the fetal abdominal aorta. We recorded pressure-volume data and arterial blood gases at 15-min intervals. End-systolic elastance was computed using a single-beat method of extrapolating maximum isovolumic pressure. A mean of five boluses was required to cause fetal death. Placental embolization caused progressive fetal acidemia. Mean baseline fetal arterial pH was 7.32 +/- 0.06 (mean +/- SD) and gradually decreased with embolization (p < 0.0001). A linear relationship was found to exist between elastance and pH with a mean decrease of 0.46 kPa/mL per 0.1-unit drop in pH (r = 0.96; p < 0.0001). Despite the decrease in end-systolic elastance, stroke volume and left-ventricular output were maintained due to a parallel decrease in afterload. The decrease in end-systolic elastance was gradual and extended over the entire clinically important range of pH, rather than being a terminal event. This study, which, to our knowledge, is the first to use the conductance catheter to measure fetal left ventricular function demonstrates that hypoxic acidemia adversely affects myocardial contractility assessed by end-systolic elastance.

Acidosis↗
PubMed1992

Cardiac electromechanical dissociation in the hypoxic fetal sheep may have clinical implications.

OBJECTIVES: Our purpose was to determine the sequence of fetal cardiac electrical and mechanical events associated with acute hypoxic acidemia and to correlate those events with terminal fetal heart rate patterns preceding fetal death. STUDY DESIGN: Eight acutely catheterized fetal sheep were rendered hypoxic by placental embolization with microspheres until fetal death occurred. The fetal electrocardiogram, Doppler cardiogram, left ventricular and aortic pressures, and fetal heart rate were continuously recorded. RESULTS: All eight fetuses showed a terminal bradycardia consisting of two phases: an initial phase of falling ventricular pressures, culminating in mechanical asystole, and a subsequent phase after asystole during which the electrocardiographic signal persisted for an average duration of 15.2 +/- 8.7 minutes (range 3.1 to 32.4) and triggered a Hewlett-Packard 8040A monitor to show a heart rate pattern. CONCLUSIONS: The phenomenon of cardiac electromechanical dissociation may be occurring during similar terminal bradycardias that are observed in human labor and explains the delivery of a fresh stillbirth in spite of the recording of an electrocardiographic signal from a scalp electrode.

Animals↗
PubMed1991

What is a low-lying placenta?

Transvaginal ultrasonography was performed in 127 women thought to have placenta previa. In all cases of complete previa, placental location was confirmed at cesarean section. Where the placenta was situated in the lower segment of the uterus but did not cover the cervical os the distance from the placental edge to the internal cervical os was measured. This distance was analyzed in relation to the route of delivery. No patient with a placental edge greater than 2 cm from the internal cervical os required cesarean section for the indication of placenta previa, whereas seven of eight patients with a distance of less than or equal to 2 cm underwent cesarean section because of bleeding characteristic of a placenta previa. These preliminary results suggest that transvaginal ultrasonography measurement may indicate the optimal delivery route and make the traditional classification of placenta previa obsolete.

Cesarean Section↗
PubMed1991

Use of Doppler technology in assessing fetal health.

Doppler technology has provided new information about the fetus during intrauterine life. Changes in red cell velocity in the umbilical artery relate well to changes in downstream resistance in the placenta. Resistance (or more correctly impedance) appears to be closely linked to the number of small fetal arterioles in the tertiary stem villus. Placental pathology leading to a reduction in these arterioles is often associated with severe intrauterine growth restriction and poor perinatal outcome. Whilst there is no good evidence that screening women with low risk pregnancies is clinically useful, umbilical artery Doppler information would appear to be useful in the management of pregnancies already identified as at risk. Here abnormal Doppler findings suggest the need for maternal rest, increased fetal surveillance and early delivery when indicated.

Female↗