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Biomedical subjects

M J Whittle

Publications and source records attributed to M J Whittle.

At least 19 recordsLinked to original sources
PubMed1992

Maternal and fetal atrial natriuretic peptide levels at delivery from normal and growth retarded pregnancies.

OBJECTIVE: To determine whether circulating fetal levels of the vasodilator atrial natriuretic peptide (ANP) are reduced in pregnancies complicated by intrauterine growth retardation (IUGR). DESIGN: Prospective observational study. SETTING: University teaching hospital and research laboratory. SUBJECTS: 25 normal singleton pregnancies delivered at term by spontaneous vertex delivery (n = 16) or by elective caesarean section (n = 9), and a series of 14 singleton pregnancies complicated by IUGR. INTERVENTION: Measurement of ANP by radio-immunoassay in maternal venous, umbilical artery, and umbilical vein plasma from a series of normal, and IUGR pregnancies. MAIN OUTCOME MEASURES: Comparison of plasma ANP levels between the three groups; relation between fetal ANP, PO2 and pH. RESULTS: Mode of delivery did not influence either maternal, umbilical artery or umbilical vein plasma ANP levels in normal term singleton pregnancies. Umbilical vein ANP levels were significantly higher in the IUGR group when compared with normal pregnancies at term (mean 66 95%, CI 36-122 vs mean 37, 95% CI 29-47 pg/ml, P = 0.03) and were inversely related to umbilical artery pH (R2 = 65%; P = 0.003). CONCLUSIONS: These data suggest that umbilical vein ANP levels are elevated in pregnancies complicated by IUGR, and rise appropriately in response to the stress of acidosis. In the absence of any receptor or second messenger defect within feto-placental vascular smooth muscle, these data suggest that ANP is not directly implicated in the vascular pathophysiology of IUGR.

Atrial Natriuretic Factor↗
PubMed1992

Prepregnancy counselling: experience from 1,075 cases.

OBJECTIVE: To assess the activity of a prepregnancy counselling clinic in terms of investigations, counselling, treatment and subsequent pregnancy outcome. DESIGN: Review of 1,075 couples attending over a nine year period. SETTING: University Hospital offering a tertiary referral service for fetal medicine. SUBJECTS: Couples referred to the clinic from a variety of sources. MAIN OUTCOME MEASURES: Categories of referral, value of diagnostic tests, and subsequent pregnancy outcome. RESULTS: The main categories of referral were: previous miscarriage (44.4%); previous fetal abnormality (19.6%); chronic maternal disease (22.3%); and others (13.7%). Routine investigations produced a low yield of abnormality (1%), in contrast to investigations selected for specific reasons (12%). Subsequent pregnancy outcome, which was unaltered in either the previous miscarriage or fetal abnormality groups, did improve in the chronic maternal disease group. CONCLUSIONS: This study does not prove the value of prepregnancy counselling. However, it does illustrate the importance of making an accurate assessment of previous problems and current health as a means of determining both maternal and fetal risks in a subsequent pregnancy, a process which seems to lead to an improved outcome within selected groups. The importance of continuity of care in all couples, especially when there has been a previous adverse pregnancy outcome is emphasized.

Abortion, Spontaneous↗
PubMed1991

Atrial natriuretic peptide: a vasodilator of the fetoplacental circulation?

Paired maternal and fetal atrial natriuretic peptide concentrations were measured in 62 percutaneous umbilical blood samplings performed principally for the assessment and treatment of rhesus isoimmunization. Pretransfusion fetal atrial natriuretic peptide levels were significantly higher than maternal atrial natriuretic peptide levels (median 117 pg/ml vs median 32 pg/ml; p less than 0.001); paired pretransfusion fetal and maternal atrial natriuretic peptide samples showed a weak correlation with each other (R2 = 17%; p = 0.002). Fetal atrial natriuretic peptide levels correlated inversely with hematocrit (R2 = 14%; p = 0.003), but not with albumin or gestational age. Paired pretransfusion and posttransfusion (median = 134 pg/ml) fetal atrial natriuretic peptide levels (n = 38) showed a significant rise after transfusion (p less than 0.001); this rise was related to the percentage of fetoplacental blood volume transfused (R2 = 33%; p = 0.035). In a subgroup of 26 procedures, change in fetal atrial natriuretic peptide levels was weakly correlated with transient reductions in the Doppler systolic/diastolic ratio of the umbilical artery (R2 = 14%; p = 0.07). These data support work in animals that indicate a role for atrial natriuretic peptide in the human fetus, but these data do not confirm that atrial natriuretic peptide modulates fetoplacental vascular impedance in the human fetus.

Atrial Natriuretic Factor↗
PubMed1991

The role of endogenous thromboxane in contractions to U46619, oxygen, 5-HT and 5-CT in the human isolated umbilical artery.

1. The effects of selective thromboxane antagonists and a thromboxane synthase inhibitor on the contraction to 9,11-dideoxy-11 alpha,9 alpha-epoxymethano-prostaglandin F2 alpha (U46619) and oxygen in the human umbilical artery (HUA) were examined. The effect of the antagonists on contractions to both 5-hydroxytryptamine (5-HT) and 5-carboxamidotryptamine (5-CT) were also examined. 2. U46619 (0.3 nM-10 microM) contracted the HUA. This contraction was antagonized by two selective thromboxane receptor antagonists EP092 (10 nM-1 microM) and GR32191B (10 nM-1 microM). The contraction was not affected by the selective thromboxane synthase inhibitor, dazoxiben (10 nM-1 microM). 3. When the oxygen tension was increased from 16 mmHg to 120 mmHg, the HUA transiently contracted. Both thromboxane antagonists inhibited this contraction in a concentration-dependent manner with 1 microM almost completely abolishing the response (the oxygen-induced contraction of the control preparation normally increases with a second exposure to 120 mmHg oxygen). 4. In low (16 mmHg) oxygen, responses to both 5-HT and 5-CT were unaffected by both thromboxane receptor antagonists at concentrations up to 1 microM. In high oxygen (120 mmHg) responses to both 5-HT and 5-CT were biphasic in nature, with an additional initial high sensitivity phase, which was abolished by a cyclo-oxygenase inhibitor. In high oxygen, EP092 and GR32191B blocked this initial phase in a concentration-dependent manner, returning sensitivity to 5-HT and 5-CT to that seen in low oxygen. 5. The thromboxane synthase inhibitor, dazoxiben, at concentrations greater than 10 nm inhibited the contraction to 120 mmHg oxygen and at 1 microM, dazoxiben almost abolished the response. In low oxygen, the response to 5-HT was unaffected by dazoxiben at concentrations up to 10 microM. In high oxygen, the initial phase of the contraction to 5-HT was inhibited by concentrations greater than 10 nm, with no effect on the maximum response. 6. The results show that thromboxane receptor antagonism or blockade of thromboxane synthesis selectively attenuates oxygen-induced contractions and those responses to 5-HT and 5-CT which are dependent on high oxygen for their expression. This suggests that the contractions caused by high oxygen tension, and the enhancement of the contractile effects of low concentrations of 5-HT and 5-CT in the presence of high oxygen tension are mediated by endogenously released thromboxane A2.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1991

Ultrasound detection of neural tube defects in patients with elevated maternal serum alpha-fetoprotein.

We conducted this study to determine the accuracy of ultrasound in the prenatal diagnosis of neural tube defects in women with elevated maternal serum alpha-fetoprotein (MSAFP). Among 905 pregnancies, 49 neural tube defects were correctly diagnosed by ultrasound alone; one was not. Ultrasound scanning had 98% sensitivity and 100% specificity for the detection of neural tube defects. The predictive value of a positive ultrasound diagnosis was 100% and of a negative ultrasound 99.9% for neural tube defects. Forty-three other structural abnormalities were also detected in patients with elevated MSAFP, including 19 abdominal wall defects, seven chromosomal abnormalities, five urinary tract abnormalities, one cardiac abnormality, and 11 others. Two chromosomal abnormalities were not detected. We suggest that ultrasound can be used reliably to detect neural tube defects, thereby avoiding the risks of amniocentesis.

Female↗
PubMed1991

Antenatal assessment of intrauterine growth retardation.

Intrauterine growth retardation is associated with considerable fetal mortality and morbidity. The condition often appears unexpectedly and the various clinical and ultrasound strategies used to screen for it in pregnancy have given disappointing results. Once intrauterine growth retardation is suspected, methods to evaluate the fetus are generally satisfactory provided they are applied systematically.

Algorithms↗
PubMed1990

Prenatal diagnosis of an intra-abdominal sacrococcygeal teratoma.

The prenatal diagnosis of a presacral (type IV) sacrococcygeal teratoma (SCT) is described. The initial ultrasound appearance was suggestive of a lower urinary tract obstruction, but further ultrasonic examination and radiological imaging using contrast medium led to the diagnosis of SCT. This is the first prenatal diagnosis of a totally intra-abdominal SCT.

Adult↗
PubMed1990

Umbilical artery blood velocity waveform analysis in predicting the small-for-dates fetus.

Doppler umbilical artery blood velocity waveforms were recorded longitudinally in 78 randomly selected pregnancies. The waveform maximal (A) to minimal (B) Doppler shift frequency ratios were determined to provide a semi-quantitative measure of impedance to blood flow in the fetoplacental circulation. Fifty-eight of these pregnancies and their outcomes were normal. The A/B ratios from this normal group were used to derive a normal range of this index throughout the second half of pregnancy. A further 45 pregnancies, also randomly selected, were studied once within 2 weeks of delivery. Using those measurements, plus those from the longitudinal groups sampled within 2 weeks of delivery, the predictive values of the A/B ratio in detecting the small for gestational age fetus have been derived. The sensitivity of the umbilical artery A/B ratio in predicting a small for gestational age infant within 2 weeks of delivery was 58% with a specificity of 94%. The positive test predictive value was 69% with a negative test predictive value of 90%. These predictive values are lower than those previously published, probably because high-risk pregnancies were over-represented in earlier studies. Waveform analysis within 2 weeks of delivery did, however, appear to identify fetuses destined to develop a range of perinatal problems. Large prospective studies are needed before the predictive value of Doppler waveform analysis is clarified.

Blood Flow Velocity↗
PubMed1990

Imaging problems in obstetrics.

Ultrasound has become a vitally important contributor to obstetric management. If undertaken at an appropriate time and by well trained staff, it can provide accurate knowledge about gestational age, fetal growth and condition, and also fetal normality. This information allows the obstetrician to give optimal care and ensure the best possible outcome of the pregnancy.

Female↗
PubMed1990

Interaction of angiotensin II and atrial natriuretic peptide in the human fetoplacental unit.

We have identified two classes of membrane receptor for atrial natriuretic peptide (KD (dissociation constant) 0.2, 70.1 nmol/L) and angiotensin II (KD 1.7 nmol/L, 15.2 nmol/L) in human fetoplacental vasculature. In addition, in the isolated perfused placenta atrial natriuretic peptide inhibited the vasoconstrictor action of angiotensin II. These findings suggest that atrial natriuretic factor may regulate fetoplacental blood flow.

Angiotensin II↗
PubMed1990

Rh haemolytic disease: continuing problem of management.

Eighteen patients with severe Rh haemolytic disease, all of whom underwent fetal blood sampling and intrauterine transfusion, were studied. Twelve babies survived (67%) all of whom were delivered by lower segment caesarean section. There were three intrauterine deaths resulting in late abortion, one stillbirth with trisomy 21, and two neonatal deaths (both from severe prematurity). The traditional prognostic indicators were all inaccurate, and fetal blood sampling and measurement of the fetal packed cell volume were the most direct methods of assessing haemolysis. The progression of severe Rh disease is unpredictable, and we believe that all cases should be referred to specialist centres for advice or treatment.

Autoantibodies↗
PubMed1990

Vascular angiotensin II and atrial natriuretic peptide receptors in normal and growth-retarded human placentae.

Receptors for angiotensin II (AII) and atrial natriuretic peptide (ANP) were characterized in a membrane fraction from resistance-type artery from human placentae. Placentae from normal pregnancies and pregnancies complicated by intrauterine growth retardation (IUGR) were studied. High- and low-affinity receptors for AII (dissociation equilibrium constant (Kd) 1.7 and 15.7 nmol/l respectively) and ANP (Kd 0.2 and 55.5 nmol/l respectively) were identified; these parameters were unchanged in IUGR, but there was a reduction in high-affinity receptor number by approximately 50% for AII and 80% for ANP in this condition. Both peptides may have a role in the regulation of fetoplacental blood flow. The alterations in IUGR are consistent with sustained activation of the fetal renin-angiotensin system and suggest altered vascular responsiveness to ANP.

Angiotensin II↗
PubMed1989

Value of antenatal diagnosis of abnormalities of the urinary tract.

OBJECTIVE: To assess the value of antenatal diagnosis of abnormalities of the urinary tract on ultrasonography. DESIGN: Retrospective study. SETTING: Two obstetric units in Glasgow. SUBJECTS: 62 Fetuses in which renal abnormalities were diagnosed on antenatal ultrasonography. INTERVENTIONS: Six fetuses had their bladders aspirated to determine renal function. Fifteen pregnancies were terminated on the basis of the findings on antenatal ultrasonography, and if possible necropsy was performed on the fetuses. In babies who were born alive the final diagnosis was made by postnatal ultrasonography, intravenous urography, radionuclide scanning, cystography, and, in those who died in the early neonatal period, necropsy. Neonates who were referred with a known obstructed kidney had nephrostomy or pyeloplasty. END POINT: Assessment of the value of antenatal diagnosis of renal abnormalities on ultrasonography for babies who had no clinical evidence of disease postnatally. MAIN RESULTS: Eighteen fetuses did not survive birth; the antenatal diagnosis was accurate in all 18. Of the 44 babies born alive, five had normal urinary tracts, in two of whom antenatal ultrasonography had probably indicated a false positive diagnosis. Fourteen babies died during the early neonatal period. Twenty five babies with renal abnormalities were followed up; the antenatal diagnosis was inaccurate for 10 of them, the commonest misdiagnosis being hydronephrosis for multicystic kidney and vice versa, and there was one false positive diagnosis. The initial clinical findings in 14 babies would have led to the early detection of a urological abnormality. In the 30 babies with no clinical evidence of disease the antenatal diagnosis was of definite value in eight, probable value in 15, and marginal value in seven. Overall, an accurate antenatal diagnosis was made in 46 of the 62 cases (74%); in 12 cases renal disease was detected but its specific nature was not determined; and in four cases the diagnosis was misleading. CONCLUSIONS: The overall value of antenatal diagnosis is that it indicates early termination of fetuses with fatal renal disease, prepares parents and medical staff for the likelihood of serious neonatal problems, and shows abnormalities of the urinary tract that may not be detected postnatally.

Abortion, Induced↗