Amnioinfusion in very early preterm prelabor rupture of membranes (AMIPROM): pregnancy, neonatal and maternal outcomes in a randomized controlled pilot study.

OBJECTIVE: To assess short- and long-term outcomes of pregnant women with very early rupture of membranes randomized to serial amnioinfusion or expectant management, and to collect data to inform a larger, more definitive clinical trial. METHODS: This was a prospective non-blinded randomized controlled trial with randomization stratified for pregnancies in which the membranes ruptured between 16 + 0 and 19 + 6 weeks' gestation and 20 + 0 and 23 + 6 weeks' gestation to minimize the risk of random imbalance in gestational age distribution between randomized groups. Intention-to-treat analysis was used. The study was conducted in four UK hospital-based fetal medicine units (Liverpool Women's NHS Trust, St Mary's Hospital Manchester, Birmingham Women's NHS Foundation Trust and Wirral University Hospitals Trust). The participants were women with confirmed preterm prelabor rupture of membranes at 16 + 0 to 24 + 0 weeks' gestation. Women with multiple pregnancy, fetal abnormality or obstetric indication for immediate delivery were excluded. Participants were randomly allocated to either serial weekly transabdominal amnioinfusions if the deepest pool of amniotic fluid was < 2 cm or expectant management until 37 weeks' gestation. Short-term maternal, pregnancy and neonatal and long-term outcomes for the child were studied. Long-term respiratory morbidity was assessed using validated respiratory questionnaires at 6, 12 and 18 months of age and infant lung function test at around 12 months of age. Neurodevelopment was assessed using the Bayley Scales of Infant Development, second edition (BSID-II) at corrected age of 2 years. RESULTS: Fifty-eight women were randomized to the study. Two babies were excluded from the analysis because of termination of pregnancy for lethal anomaly, leaving 56 participants (28 assigned to serial amnioinfusion and 28 to expectant management) recruited between 2002 and 2009. There was no significant difference in perinatal mortality (19/28 vs 19/28; relative risk (RR) 1.0 (95% CI, 0.70-1.43)) and maternal or neonatal morbidity. The overall chance of surviving without long-term respiratory or neurodevelopmental disability was 4/56 (7.1%); 4/28 (14.3%) in the amnioinfusion group and 0/28 in the expectant group (RR 9.0 (95% CI, 0.51-159.70)). CONCLUSIONS: This pilot study found no major differences in maternal, perinatal or pregnancy outcomes. The study was not designed to show a difference between the groups and the number of survivors was too small to draw any conclusions about long-term outcomes. It does, however, signal that a larger definitive study to evaluate amnioinfusion for improvement in healthy survival is needed. The pilot suggests that, with appropriate funding, such a study is feasible.

Titrated low-dose vaginal and/or oral misoprostol to induce labour for prelabour membrane rupture: a randomised trial.

OBJECTIVE: To evaluate the clinical effectiveness and safety of titrated low-dose misoprostol for induction of labour (IOL) in the presence of prelabour rupture of membranes (PROM). DESIGN: Randomised controlled trial. SETTING: Maternity units in the UK (9) and Egypt (1). POPULATION: Women >34 weeks of gestation with PROM, singleton viable fetus and no previous caesarean section. METHODS: Subjects randomised to IOL with a titrated low-dose misoprostol regimen (oral except if unfavourable cervix, where initial dose vaginal) or a standard induction method, namely vaginal dinoprostone followed by intravenous oxytocin if the cervix was unfavourable or intravenous oxytocin alone if the cervix was favourable. MAIN OUTCOME MEASURES: Primary outcome measures were caesarean section and failure to achieve vaginal delivery within 24 hours. Analysis was by intention to treat. RESULTS: The trial did not achieve the planned sample size of 1890 due to failure in obtaining external funding. Seven hundred and fifty-eight women were randomised (375 misoprostol and 383 standard). There were less caesarean section (14 versus 18%, relative risk [RR] 0.79; 95% CI 0.57-1.09) and less women who failed to achieve vaginal delivery within 24 hours in the misoprostol group (24 versus 31%, RR 0.79; 95% CI 0.63-1.00), but the differences were not statistically significant. Subgroup analysis showed that with unfavourable cervix, misoprostol may be more effective than vaginal dinoprostone. There was no difference in hyperstimulation syndrome. There were more maternal adverse effects with misoprostol, but no significant differences in maternal and neonatal complications. CONCLUSIONS: Titrated low-dose misoprostol may be a reasonable alternative for IOL in the presence of PROM, particularly in women with an unfavourable cervix. Safety and rare serious adverse events could not be evaluated in a trial of this size.

WITHDRAWN: Routine Doppler ultrasound in pregnancy.

BACKGROUND: Doppler ultrasound study of umbilical artery waveforms helps identify the compromised fetus in 'high risk' pregnancies and, therefore, deserves assessment as a screening test in 'low risk' pregnancies. One of the main aims of routine antenatal care is to identify the 'at risk' fetus in order to apply clinical interventions which could result in reduced perinatal morbidity and mortality. OBJECTIVES: To assess the effects on obstetric practice and pregnancy outcome of routine Doppler ultrasound in unselected and low risk pregnancies. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group Specialised Register of Controlled Trials and the Cochrane Controlled Trials Register were searched. Date of last search: September 1999 SELECTION CRITERIA: Acceptably controlled trials of routine Doppler ultrasound (umbilical circulation and/or uterine circulation) in unselected or low risk pregnancies. DATA COLLECTION AND ANALYSIS: Both reviewers assessed trial quality and extracted data. Authors of two trials were contacted for additional information. MAIN RESULTS: Five trials were included which recruited 14,338 women. The methodological quality of the trials was generally good. Based on existing evidence, routine Doppler ultrasound examination in low risk or unselected populations did not result in increased antenatal, obstetric and neonatal interventions, and no overall differences were detected for substantive short term clinical outcomes such as perinatal mortality. There is no available evidence to assess the effect on substantive long term outcomes such as childhood neurodevelopment. There is no available evidence to assess maternal outcomes, particularly psychological effects. In two studies there were unexpected findings suggesting possible harmful effects, but the explanation for this is not clear, and further evaluation regarding the safety of Doppler ultrasound is required. AUTHORS' CONCLUSIONS: Based on existing evidence, routine Doppler ultrasound in low risk or unselected populations does not confer benefit on mother or baby. Future research should be powerful enough to address small changes in perinatal outcome, and should include evaluation of maternal psychological effects, long term outcomes such as neurodevelopment, and issues of safety.

WITHDRAWN: Routine ultrasound in late pregnancy (after 24 weeks' gestation).

BACKGROUND: Diagnostic ultrasound is used selectively in late pregnancy where there are specific clinical indications. However, the value of routine late pregnancy ultrasound screening in unselected populations is controversial. The rationale for such screening would be the detection of clinical conditions which place the fetus or mother at high risk, which would not necessarily have been detected by other means such as clinical examination, and for which subsequent management would improve perinatal outcome. OBJECTIVES: To assess the effects on obstetric practice and pregnancy outcome of routine late pregnancy ultrasound, defined as greater than 24 weeks gestation, in women with either unselected or low risk pregnancies. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group Specialised Register of Controlled Trials and the Cochrane Controlled Trials Register were searched. SELECTION CRITERIA: All acceptably controlled trials of routine ultrasound in late pregnancy (defined as after 24 weeks). DATA COLLECTION AND ANALYSIS: The principal reviewer assessed trial quality and extracted data, under supervision of the co-reviewer. MAIN RESULTS: Seven trials recruiting 25,036 women were included. The quality of trials overall was satisfactory. There was no difference in antenatal, obstetric and neonatal intervention or morbidity in screened versus control groups. Routine late pregnancy ultrasound was not associated with improvements in overall perinatal mortality. Placental grading as an adjunct to third trimester examination scan was associated with a significant reduction in the stillbirth rate in the one trial that assessed it. There is a lack of data with regard to long term substantive outcomes such as neurodevelopment. There is a lack of data on maternal psychological effects. AUTHORS' CONCLUSIONS: Based on existing evidence, routine late pregnancy ultrasound in low risk or unselected populations does not confer benefit on mother or baby. There is a lack of data about the potential psychological effects of routine ultrasound in late pregnancy, and the effects on both short and long term neonatal and childhood outcome. Placental grading in the third trimester may be valuable, but whether reported results are reproducible remains to be seen, and future research of late pregnancy ultrasound should include evaluation of placental textural assessment.

Poor uterine contractility in obese women.

OBJECTIVE: The aim of the study was to elucidate the reason for the high rate of caesarean section in obese women. We examined the following hypotheses: (1) obese women have a high incidence of complications related to poor uterine contractility--caesarean section for dysfunctional labour and postpartum haemorrhage. 2) The myometrium from obese women has less ability to contract in vitro. DESIGN: First, a clinical retrospective analysis of data from 3913 completed singleton pregnancies was performed. Secondly, in a prospective study the force, frequency and intracellular [Ca(2+)] flux of spontaneously contracting myometrium were related to the maternal body mass index. SETTING: Liverpool Women's Hospital and University of Liverpool. POPULATION: The clinical study involved all women who delivered in one hospital in 2002. The in vitro study myometrial biopsies were obtained from 73 women who had elective caesarean section at term. RESULTS: Maternal obesity carried significant risk of caesarean section in labour that was highest for delay in the first stage of labour (OR 3.54). The increased risk of caesarean section in obese women largely occurred in women with normal- and not with high-birthweight infants. Obese women delivering vaginally had increased risk of prolonged first stage of labour and excessive blood loss. Myometrium from obese women contracted with less force and frequency and had less [Ca(2+)] flux than that from normal-weight women. CONCLUSIONS: We suggest that these findings indicate that obesity may impair the ability of the uterus to contract in labour.

British National Health Service's and women's costs of antenatal ultrasound screening and follow-up tests.

OBJECTIVE: To estimate resource use and costs associated with routine obstetric ultrasound and follow-up tests from both the British National Health Service and women's perspectives. METHODS: Women attending Liverpool Women's Hospital (UK) in 1998 and 1999 were involved in the study. Bottom-up and top-down costings of National Health Service resources using questionnaires and diaries to record staff time associated with procedures were performed. Questionnaires were used to assess women's costs of attending for antenatal ultrasound scans. RESULTS: Routine antenatal ultrasound scans at Liverpool Women's Hospital cost the National Health Service between 14 pounds sterling and 16 pounds sterling per scan. More detailed secondary scans and other follow-up procedures cost substantially more. Costs to women, their families and their employers were estimated at between 9 pounds sterling and 15 pounds sterling per scan, depending on assumptions about the opportunity costs of time when not in paid employment and costs to employers of women who were in paid employment. CONCLUSIONS: Accurate estimates of costs to the National Health Service associated with routine antenatal ultrasound scanning are substantially lower than that cited in much of the literature. Costs to women are very similar to National Health Service costs. Economic evaluations should attempt to include costs to users of the service, particularly when the burden of cost is likely to shift.

Types of pregnancy loss in recurrent miscarriage: implications for research and clinical practice.

BACKGROUND: In recurrent pregnancy loss, there is much debate about cause and association, as exact pathophysiological mechanisms have not been elucidated. The aim of this study was to assess whether recurrent pregnancy loss (RPL) patterns differ according to causal/associated conditions, suggesting differing disease processes. METHODS: Following investigation, 427 women with RPL were classified into the following 'diagnostic' groups: idiopathic, oligomenorrhoea, antiphospholipid syndrome (APS) and 'possible' APS. A total of 323 subsequently conceived, and underwent serial ultrasonography in early pregnancy; of these, 87 (26.9%) miscarried, and the types of pregnancy loss for the four diagnostic groups were allocated to either embryo loss (fetal heart never seen) and fetal loss (fetal heart seen prior to pregnancy loss). RESULTS: Overall, there were 75 embryonic losses and 12 fetal losses. The fetal loss rates in each group were similar: idiopathic 5.1%, oligomenorrhoea 3.4%, 'possible' APS 4.9% and APS 4.8%. CONCLUSIONS: Serial ultrasound helps to discriminate type of pregnancy loss and demonstrates that embryo loss is more common than fetal loss. More importantly, pregnancy loss patterns do not seem to differ between diagnostic groups in a treated population. The fetal loss rate in each of the diagnostic groups is similar to that in other reported populations.

Diabetes in adolescent patients: diagnostic dilemmas.

The classification of diabetes mellitus by types (1 or 2), or by age of onset (juvenile or adult), helps to clarify many aspects of pathophysiology, prognosis, and therapy. However, less-commonly encountered patients, presenting in childhood or adolescence, may not fit neatly into one or the other group. These include teenagers who present with new-onset diabetes with ketoacidosis, but who are later able to be managed permanently as type 2 patients. Other adolescent patients present with only minimal glucose intolerance, then proceed to develop type 1 diabetes, with evidence of autoimmune etiology, after a variable number of years. Four patients are presented to illustrate these diagnostic dilemmas.

Intractable diarrhea in hyperthyroidism: management with beta-adrenergic blockade.

OBJECTIVE: To describe a patient with intractable diarrhea and thyrotoxic Graves' disease, for whom b-adrenergic blockade ultimately proved to be effective therapy for the diarrhea, and to review the types of hyperthyroidism-associated diarrhea. METHODS: We present the clinical course of a young man with a prolonged siege of diarrhea that proved elusive to diagnostic inquiries and resistant to all means of management until its endocrine basis was discovered. Control of such cases with b-adrenergic blockade is discussed, as are the pathophysiologic bases of intestinal hypermotility in hyperthyroidism. RESULTS: A 26-year-old man with Down syndrome, and no prior gastrointestinal disorder, had insidious, chronic, constant diarrhea, which was associated with loss of 14 kg during a 5-month period. Numerous laboratory and imaging studies and endoscopic examinations failed to disclose the cause of the diarrhea. Furthermore, a broad range of antibiotics and other empiric remedies failed to control the problem. No other symptoms of hyperthyroidism were reported, but when the endocrinopathy was suspected and identified, the diarrhea was promptly controlled by treatment with propranolol. In patients with hyperthyroidism, two types of diarrheal disorders have been described-secretory diarrhea and steatorrhea; bile acid malabsorption may have a role in either of these settings. CONCLUSION: In addition to its capacity for blocking the peripheral effects of thyroid hormone on the heart and central nervous system, b-adrenergic blockade is effective in slowing intestinal transit time and ameliorating the uncommon diarrhea associated with hyperthyroidism. Thyroid hormone in excess, among its other possible effects on the gastrointestinal tract, may exert a stimulatory effect by means of intermediary sympathetic activation, as it does with the heart. Thus, sympathetic blockade can mimic the salutary effects on the gastrointestinal tract conventionally brought about by direct antithyroid therapy, and well before the hyperthyroid state per se is eliminated. The current patient illustrates the value of considering hyperthyroidism in the differential diagnosis of diarrhea of unknown cause.

Amniotomy alone for induction of labour.

BACKGROUND: Amniotomy (deliberate rupture of the membranes) is a simple procedure which can be used alone for induction of labour if the membranes are accessible, thus avoiding the need for pharmacological intervention. However, the time interval from amniotomy to established labour may not be acceptable to clinicians and women, and in a number of cases labour may not ensue. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. OBJECTIVES: To determine the effects of amniotomy alone for third trimester labour induction in women with a live fetus. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled trials register and bibliographies of relevant papers. SELECTION CRITERIA: The criteria for inclusion included the following: (1) clinical trials comparing amniotomy alone for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods; (2) random or pseudo-random allocation to the treatment or control group; (3) ideally adequate allocation concealment (4) violations of allocated management not sufficient to materially affect conclusions; (5) clinically meaningful outcome measures reported; (6) data available for analysis according to the random allocation; (7) missing data insufficient to materially affect the conclusions. DATA COLLECTION AND ANALYSIS: This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. The initial data extraction was done centrally, and incorporated into the series of primary reviews arranged by methods of induction of labour. The data from the primary reviews will be incorporated into a series of secondary reviews, arranged by category of woman to reflect clinical scenarios. To avoid duplication of data in the primary reviews, the labour induction methods have been listed in a specific order, from one to 25. Each primary review includes comparisons between one of the methods (from two to 25) with only those methods above it on the list. This review includes comparisons between amniotomy alone (number 5 on the list) with only those methods above it on the list (no treatment / placebo; intravaginal prostaglandins; intracervical prostaglandins; and oxytocin alone). MAIN RESULTS: Two trials comprising 50 and 260 women respectively were eligible for inclusion in this review. No conclusions could be drawn from comparisons of amniotomy alone versus no intervention, and amniotomy alone versus oxytocin alone (small trial, only one pre-specified outcome reported). No trials compared amniotomy alone with intracervical prostaglandins. One trial compared amniotomy alone with a single dose of vaginal prostaglandins for women with a favourable cervix, and found a significant increase in the need for oxytocin augmentation in the amniotomy alone group (44% versus 15%; RR 2.85, 95% CI 1.82-4.46). This should be viewed with caution as this was the result of a single centre trial. Furthermore, secondary intervention occurred 4 hours after amniotomy, and this time interval may not have been appropriate. REVIEWER'S CONCLUSIONS: Data is lacking about the value of amniotomy alone for induction of labour. While there are now other modern methods available for induction of labour (pharmacological agents), there remain clinical scenarios where amniotomy alone may be desirable and appropriate, and this method is worthy of further research. This research should include evaluation of the appropriate time interval from amniotomy to secondary intervention, women and caregivers' satisfaction and economic analysis.

Intravenous prostaglandin for induction of labour.

BACKGROUND: Intravenous prostaglandin E2 and F2 alpha can be used to induce labour. The use of intravenous prostaglandins in this context has been limited by perceived unacceptable maternal side effect profiles. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. OBJECTIVES: To determine the effects of intravenous prostaglandin for third trimester cervical ripening or induction of labour. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register, The Cochrane Controlled Trials Register and bibliographies of relevant papers. SELECTION CRITERIA: The criteria for inclusion included the following: (1) clinical trials comparing intravenous prostaglandin used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods; (2) random allocation to the treatment or control group; (3) adequate allocation concealment; (4) violations of allocated management not sufficient to materially affect conclusions; (5) clinically meaningful outcome measures reported; (6) data available for analysis according to the random allocation; (7) missing data insufficient to materially affect the conclusions. DATA COLLECTION AND ANALYSIS: A strategy has been developed to deal with the large volume and complexity of trial data relating to labour induction. This involves a two-stage method of data extraction. The initial data extraction is done centrally, and incorporated into a series of primary reviews arranged by methods of induction of labour, following a standardised methodology. The data will then be extracted from the primary reviews into a series of secondary reviews, arranged by category of woman. To avoid duplication of data in the primary reviews, the labour induction methods have been listed in a specific order, from one to 25. Each primary review includes comparisons between one of the methods (from two to 25) with only those methods above it on the list. MAIN RESULTS: Thirteen trials were eligible for inclusion in this review. Two trials (comprising 400 women) compared intravenous prostaglandin E2 to intravenous oxytocin, a further seven trials (comprising 590 women) compared intravenous prostaglandin F2 alpha to intravenous oxytocin. Two trials (comprising 115 women) each randomised women to one of three treatment arms namely intravenous oxytocin or intravenous prostaglandin F2 alpha or prostaglandin E2. One trial reported a comparison of combined oxytocin and prostaglandin F2 alpha and oxytocin alone in 20 women and lastly one trial compared extra amniotic prostaglandin E2 versus intravenous prostaglandin E2 (40 women). The use of intravenous prostaglandin was associated with higher rates of uterine hyperstimulation with changes in the fetal heart rate (relative risk (RR) 6.76, 95% confidence interval (CI) 1.23-37.11) and without (RR 4.25, 95%CI 1.48-12.24) compared to oxytocin. Use of prostaglandins was also associated with significantly more maternal side effects (gastrointestinal, thrombophlebitis and pyrexia, RR 3.75, 95% CI 2.46-5.70) than oxytocin. Prostaglandin was no more likely to result in vaginal delivery than oxytocin (RR 0.85, 95% CI 0.61-1.18). No significant differences emerged from subgroup analysis or from the trials comparing combination oxytocin/prostaglandin F2 alpha and oxytocin or extra amniotic versus intravenous prostaglandin E2. REVIEWER'S CONCLUSIONS: Intravenous prostaglandin is no more efficient than intravenous oxytocin for the induction of labour but its use is associated with higher rates of maternal side effects and uterine hyperstimulation than oxytocin. No conclusions can be drawn form the comparisons of combination of prostaglandin F2 alpha and oxytocin compared to oxytocin alone or extra amniotic and intravenous prostaglandin E2.

Routine doppler ultrasound in pregnancy.

BACKGROUND: Doppler ultrasound study of umbilical artery waveforms helps identify the compromised fetus in 'high risk' pregnancies and, therefore, deserves assessment as a screening test in 'low risk' pregnancies. One of the main aims of routine antenatal care is to identify the 'at risk' fetus in order to apply clinical interventions which could result in reduced perinatal morbidity and mortality. OBJECTIVES: To assess the effects on obstetric practice and pregnancy outcome of routine Doppler ultrasound in unselected and low risk pregnancies. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group Specialised Register of Controlled Trials and the Cochrane Controlled Trials Register were searched. Date of last search: September 1999 SELECTION CRITERIA: Acceptably controlled trials of routine Doppler ultrasound (umbilical circulation and/or uterine circulation) in unselected or low risk pregnancies. DATA COLLECTION AND ANALYSIS: Both reviewers assessed trial quality and extracted data. Authors of two trials were contacted for additional information. MAIN RESULTS: Five trials were included which recruited 14,338 women. The methodological quality of the trials was generally good. Based on existing evidence, routine Doppler ultrasound examination in low risk or unselected populations did not result in increased antenatal, obstetric and neonatal interventions, and no overall differences were detected for substantive short term clinical outcomes such as perinatal mortality. There is no available evidence to assess the effect on substantive long term outcomes such as childhood neurodevelopment. There is no available evidence to assess maternal outcomes, particularly psychological effects. In two studies there were unexpected findings suggesting possible harmful effects, but the explanation for this is not clear, and further evaluation regarding the safety of Doppler ultrasound is required. REVIEWER'S CONCLUSIONS: Based on existing evidence, routine Doppler ultrasound in low risk or unselected populations does not confer benefit on mother or baby. Future research should be powerful enough to address small changes in perinatal outcome, and should include evaluation of maternal psychological effects, long term outcomes such as neurodevelopment, and issues of safety.

Routine ultrasound in late pregnancy (after 24 weeks gestation).

BACKGROUND: Diagnostic ultrasound is used selectively in late pregnancy where there are specific clinical indications. However, the value of routine late pregnancy ultrasound screening in unselected populations is controversial. The rationale for such screening would be the detection of clinical conditions which place the fetus or mother at high risk, which would not necessarily have been detected by other means such as clinical examination, and for which subsequent management would improve perinatal outcome. OBJECTIVES: To assess the effects on obstetric practice and pregnancy outcome of routine late pregnancy ultrasound, defined as greater than 24 weeks gestation, in women with either unselected or low risk pregnancies. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group Specialised Register of Controlled Trials and the Cochrane Controlled Trials Register were searched. SELECTION CRITERIA: All acceptably controlled trials of routine ultrasound in late pregnancy (defined as after 24 weeks). DATA COLLECTION AND ANALYSIS: The principal reviewer assessed trial quality and extracted data, under supervision of the co-reviewer. MAIN RESULTS: Seven trials recruiting 25,036 women were included. The quality of trials overall was satisfactory. There was no difference in antenatal, obstetric and neonatal intervention or morbidity in screened versus control groups. Routine late pregnancy ultrasound was not associated with improvements in overall perinatal mortality. Placental grading as an adjunct to third trimester examination scan was associated with a significant reduction in the stillbirth rate in the one trial that assessed it. There is a lack of data with regard to long term substantive outcomes such as neurodevelopment. There is a lack of data on maternal psychological effects. REVIEWER'S CONCLUSIONS: Based on existing evidence, routine late pregnancy ultrasound in low risk or unselected populations does not confer benefit on mother or baby. There is a lack of data about the potential psychological effects of routine ultrasound in late pregnancy, and the effects on both short and long term neonatal and childhood outcome. Placental grading in the third trimester may be valuable, but whether reported results are reproducible remains to be seen, and future research of late pregnancy ultrasound should include evaluation of placental textural assessment.

Tumor control of locally advanced prostate cancer following combined estramustine, vinblastine, and radiation therapy.

PURPOSE: A prospective phase II study was carried out to determine whether estramustine phosphate (EMP) plus vinblastine (VBL) in combination with radiotherapy (RT) would improve the control of locally advanced prostate cancer. The rationale for combining EMP plus VBL with RT was based on the clinical and radiobiological data that EMP plus VBL acted as an excellent radiation sensitizer in cultured human prostatic carcinoma cells with the property of tissue selectivity. The combined EMP and VBL were well tolerated in the phase II clinical study of patients with advanced prostate cancer. MATERIALS AND METHODS: Between January 1991 and July 1996, 65 patients, stage T2 (B2) through stage T4 (D1), were entered into the study. Gleason pattern scores ranged from 4 to 10. Pretreatment prostate-specific antigen (PSA) was as follows: < 20 in 21 patients (32%), 20 to 50 in 23 patients (35%), and > 50 in 21 patients (32%). The median age was 70 years (55-83). All patients were treated with megavoltage beam radiation with a total tumor dose of 65 to 70 Gy. Oral EMP 450 mg/m2 daily and VBL 3 mg/m2 weekly were given concomitantly in 46 patients during the 7- to 7 1/2-week course of radiotherapy. RESULTS: All patients showed prompt and complete tumor regression on digital rectal examination at 6 weeks following the completion of treatment. Median follow-up time is 43 months (3-65). PSA fell to an undetectable level by 6 weeks in 56 of 65 patients (86%). For the whole group at 5 years clinical control was 81%, but biochemical control (PSA < 4 ng/mL) was 48%. The likelihood of being free of biochemical relapse at 5 years was a function of initial PSA value (PSA < 20 in 64% of the cases, 21-50 in 60%, and > 50 in 0%). The biochemical-relapse-free survival at 5 years for each stage was T2, 49%; T3, 38%; and T4, 17%. In particular, a group of patients with pretreatment PSA levels of 20 to 50 ng/mL responded quite favorably to the present combined regimen in that only 40% of the patients showed a biochemical failure at 5 years, considering the high level of initial PSA. CONCLUSIONS: The present combined approach is effective in achieving a high rate of tumor control with no disproportionately enhanced side effects. The rapid regression of the tumor nodules and sustained freedom from biochemical relapse suggest excellent long-term tumor control, especially in the group of patients with pretreatment PSA levels of 20 to 50 ng/mL.

Relative effects of high saturated fatty acid levels in meat, dairy products, and tropical oils on serum lipoprotein and low-density lipoprotein degradation by mononuclear cells in healthy males.

To determine the effects of three saturated fatty acid combinations on lipoprotein metabolism, we fed 18 21- to 32-year-old men three diets in a crossover design for 28-day periods separated by washout periods of 4 to 6 weeks. The men self-selected a prescribed diet at home emphasizing saturated fat as the visible fat for 1 week. Then, they ate experimental diets providing 40%, 15%, 17%, and 7% of food energy, respectively, as total, saturated, monounsaturated, and polyunsaturated fatty acids, levels representing amounts available in the US diet. Different test fatty acid combinations, given at 4 to 6 energy% (en%) each, were incorporated into food products: 12:0 + 14:0, 14:0 + 16:0, and 16:0 + 18:0. Test fatty acids were equalized by giving free myristic acid (14:0) with palm kernel oil or butter and sheanut butter (high in 18:0) with lard. The diet highest in 12:0 + 14:0 also provided 4.2 en% 16:0, the most common saturated fatty acid in the US diet. Mean apparent absorption of all fatty acids was at least 90%. The three diets produced similar concentrations of serum total and low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B-100 regardless of the apo E phenotype of the subjects. Compared with baseline, the experimental diets affected serum high-density lipoprotein (HDL) concentrations (P < .06), with the highest values occurring on diet 12:0 + 14:0. When the change from baseline in receptor-mediated degradation of 125I-LDL in freshly isolated mononuclear cells (MNC) was stratified by apo E phenotype, diet 16:0 + 18:0 produced a 30% increase, compared with a 9% decrease on diet 12:0 + 14:0 and a 6% increase on diet 14:0 + 16:0 in subjects with the apo E3/3 phenotype. These results suggested that different saturated fatty acid combinations, consumed at levels typical of availability in the United States and with diets providing ample unsaturated fat, had similar cholesterolemic properties in healthy males despite some subtly different effects on lipoprotein metabolism.

Selective removal of plasma low density lipoprotein with the HELP system: biweekly versus weekly therapy.

PURPOSE: Biweekly (once every 2 weeks) heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) therapy was evaluated for safety and efficacy in selectively reducing LDL cholesterol levels compared with weekly HELP therapy. PATIENTS AND METHODS: Biweekly treatments were given to high-risk, diet/drug resistant hypercholesterolemic patients (n = 23) after 6 months of weekly HELP therapy. Lipids, lipoprotein cholesterol, apolipoproteins A-I and B, and fibrinogen were measured on plasma samples before and after treatment. RESULTS: Mean plasma volume treated was 2.8 l and mean treatment duration 1.7 h. Therapy complications were minimal. In 98% of 268 biweekly HELP treatments, LDL cholesterol levels were reduced by > 30%. For patients completing 6 months of biweekly therapy following 6 months' weekly therapy (n = 23), mean LDL cholesterol levels were reduced 138.5 mg/dl (111.2 mg/dl weekly) with a time-averaged decrease from mean pre-apheresis levels of 33% for biweekly therapy (39% weekly). Mean total cholesterol (161.2 mg/dl biweekly versus 132.9 weekly) and apolipoprotein B (104.6 mg/dl versus 92.6) levels were also reduced with each treatment. Mean HDL cholesterol was reduced only 6.1 mg/dl (6.3 mg/dl weekly). CONCLUSIONS: Biweekly HELP treatments can safely reduce LDL cholesterol levels as consistently as weekly HELP treatments. However, the higher pre-treatment LDL cholesterol levels with biweekly treatments may produce less therapeutic benefit than with weekly therapy.