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Biomedical subjects

W P Collins

Publications and source records attributed to W P Collins.

At least 19 recordsLinked to original sources

Association of thymidine phosphorylase concentration with ultrasound-derived indices of blood flow in ovarian masses.

BACKGROUND: The aim of this study was to determine the relationship between the concentration of thymidine phosphorylase (a known angiogenic factor) and indices of blood flow in physiologic ovarian tissues and overt (benign and malignant) tumors. METHODS: The ovaries of all patients were examined by transvaginal ultrasonography, with color Doppler imaging and pulsed Doppler spectral analysis, within the 24 hours preceding laparotomy. Ovaries removed at surgery were dissected into their main components (follicles, corpus luteum, and tumor) and, where possible, into areas of high blood velocity according to the results of color Doppler imaging. The concentration of thymidine phosphorylase was measured by an enzyme-linked immunosorbent assay. RESULTS: Thirty-eight tissue aliquots (16 from normal ovaries and 22 from ovarian tumors) were obtained from 33 patients. Twenty-nine tissue samples (76%) came from areas of measurable (high) blood velocity. The concentration of thymidine phosphorylase was significantly higher in tissue associated with high blood velocity (median 17.9, range 1.8-78.3 units per mg of protein vs. median 6.8, range 1.3-24.7 units per mg of protein, respectively; P < 0.05, Mann-Whitney U test). All of 8 corpora lutea, 12 of 14 benign tumors, and 7 of 7 malignant tumors had measurable blood velocity. There was a significant correlation between the concentration of thymidine phosphorylase and the peak systolic velocity in benign tumors (correlation coefficient [r] = 0.79, P < 0.01) and malignant tumors (r = 0.87, P < 0.05). CONCLUSIONS: High intratumoral peak systolic velocity as determined by transvaginal color Doppler imaging and spectral analysis reflects high production of thymidine phosphorylase. This finding may aid the development of antivascular therapy for patients with ovarian carcinoma.

Adolescent

Sonographic prediction of malignancy in adnexal masses using multivariate logistic regression analysis.

The aim of the study was to assign a probability of malignancy for any patient with an adnexal tumor by the application of multivariate logistic regression analysis to variables recorded at the time of pelvic sonography. Sixty-seven women with known adnexal masses were examined using transvaginal B-mode and color Doppler imaging. For each patient the variables included: (1) age, (2) maximum tumor diameter, (3) tumor volume, (4) unilocularity (presence (0) or absence(1)), (5) papillary projections (presence (1) or absence (0)), (6) random echogenicity (presence (1) or absence (0)), (7) highest peak systolic velocity (PSV), (8) time-averaged maximum velocity (TAMXV), (9) pulsatility index (PI) and (10) resistance index (RI). The TAMXV, PI and RI were those associated with the highest PSV. These ten independent variables and the final histological diagnosis for each patient (the dependent variable) were used for the regression analysis. Approximately 75% of the entire dataset was randomly selected for generating the regression model. The remaining 25% was used as the testing set for cross-validation of the model. In the entire dataset there were 52 women with benign, three with borderline and 12 with invasive ovarian tumors. Regression analysis on the ten variables resulted in the retention of only 'age', 'papillary projection score' and 'TAMXV' as significantly contributing to predicting the presence or absence of malignancy. The probability of malignancy for any patient was given by solving the equation: Probability = 1/(1 + e-z) where e is the base value for natural logarithms and z = (0.1273 x Age) + (0.2794 x TAMXV) + (4.4136 x Papillary projections score) - 14.2046. Cross-validation of the model on the test set of data gave a 100% sensitivity and specificity. However, for the entire dataset the best sensitivity and specificity were 93.3 and 90.4%, respectively, at a cut-off value of 25% probability of malignancy. In conclusion, multivariate logistic regression analysis enables the calculation of probability of malignancy for any patient with a known adnexal mass. The accuracy of this prediction appears to be better than that of morphological or Doppler criteria when the latter are used independently. The value of this model needs to be tested prospectively.

Adult

Volumetric self-sampling of cervicovaginal fluid to determine potential fertility: a multicentre pre-effectiveness study of the Rovumeter.

The aim of this study was to assess how effectively the Rovumeter, designed for the volumetric self-sampling of cervicovaginal fluid (CVF), can be used to locate the minimum period of potential fertility (PPF) during ovulatory cycles. A multicentre, prospective study was undertaken of volunteers (attending natural family planning clinics) over three consecutive, apparently normal, menstrual cycles. All women collected daily samples of early morning urine and CVF and recorded the volumes (to the nearest 1.0 and 0.1 ml respectively). The concentrations of oestrone glucuronide (EG), luteinizing hormone (LH) and pregnanediol glucuronide (PG) were measured in all samples of early morning urine by immunoassay. A preliminary data set was used to optimize an algorithm to detect the start and end of potential fertility from the volumes of CVF. The end-points used were the normality of each menstrual cycle from its length, the length of luteal phase, and concentrations of EG, LH and PG, the start and end days of potential fertility from CVF volumes, and the minimum PPF, which was defined as the day of the LH peak minus 3 to day plus 2 inclusive. Overall, 72 women (median age 30 years, range 24-38) were recruited from three centres (23 from Birmingham, 24 from Milan, 25 from Santiago) and contributed data from 235 menstrual cycles (median length 28 days, range 23-44). The urinary LH peak was identified in 228 cycles (97%; median time, day 15 from day 1 of last menses, with range day 10 to day 35). The use of the Rovumeter gave start and end signals of potential fertility during 138 cycles (59%). The median length of the derived PPF was 8 days (range 4-18). The signals covered the defined, minimum PPF in 113 cycles [i.e. 50% of those with an LH peak; range 28% (Milan) to 62% (Birmingham)]. Overall 16/72 women (22%) had successful tests over three consecutive menstrual cycles [range 2/24 (8%; Milan) to 8/23 (35%; Birmingham)]. We conclude that signals from daily changes in the volume of CVF as determined by the use of the Rovumeter consistently locate the minimum period of potential fertility in only a small proportion of women.

Adult

Spontaneous corneal rupture in Noonan syndrome. A case report.

PURPOSE/METHODS: A variety of ocular and periocular manifestations have been described in Noonan syndrome. Collagen abnormalities have been described; however, to our knowledge spontaneous corneal rupture has not been reported. A forty-three-year-old female who presented with spontaneous corneal rupture was later diagnosed as having Noonan syndrome. RESULTS/CONCLUSIONS: Collagen abnormalities have been described with Noonan syndrome and this is likely the cause of corneal rupture in this patient.

Adult

A comparison of intratumoural indices of blood flow velocity and impedance for the diagnosis of ovarian cancer.

The aim was to assess the value of blood flow velocity indices in an ultrasound-based test to discriminate between malignant and benign adnexal tumours. Fifty-one women (35 premenopausal and 16 postmenopausal) with persistent adnexal masses were scanned prior to surgery using transvaginal sonography with colour Doppler imaging. Intratumoural flow velocity waveforms obtained by pulsed Doppler sonography were used to determine the time averaged maximum velocity (TAMXV), peak systolic velocity (PSV), pulsatility index (PI) and resistance index (RI). The tumours were classified by histologic criteria (42 benign, 1 borderline and 8 malignant tumours). Two of the malignant and the single borderline tumour were stage I, five were stage III and one was stage IV. Detectable blood flow signals were found in all malignant and borderline tumours and in 33 of 42 (78.6%) of the benign tumours. TAMXV was the best parameter for discrimination of benign and malignant adnexal pathology and at a cut-off value of TAMXV > or = 12 cm/s to indicate malignancy, the sensitivity and specificity were 88.9% and 81.0%, respectively. At the same sensitivity level, this gave a better specificity than the PI < or = 0.90 (specificity 61.9%, P = 0.036), RI < or = 0.60 (specificity 54.8%, P = 0.010) and PSV > or = 16 cm/s (specificity 71.4%, P = 0.121). Discrimination between benign and malignant tumours was improved further by using two criteria rather than one. When the two criteria of a TAMXV of > or = 12 cm/s and a PI < or = 1.0 were applied simultaneously, the tumours could be characterised with a sensitivity of 88.9% and a specificity of 88.1%. Therefore, intratumoural PSV and TAMXV could be used to discriminate between benign and malignant adnexal tumours better than values for PI and RI. The best discrimination was achieved by using a combination of cut-off values for velocity and impedance parameters as two criteria to define malignancy.

Adult

Prediction of oocyte recovery rate by transvaginal ultrasonography and color Doppler imaging before human chorionic gonadotropin administration in in vitro fertilization cycles.

OBJECTIVE: To detect and quantify follicular vascularity before hCG administration in women undergoing IVF-ET. To correlate follicular vascularity with the oocyte recovery rate after direct follicle aspiration. DESIGN: A prospective, longitudinal study of consecutive women undergoing IVF-ET at the assisted conception unit of King's College Hospital, London and having at least 20 follicles between the two ovaries on the day of hCG administration. INTERVENTIONS: An Acuson 128XP1O computed sonography system (Acuson Ltd., Uxbridge, United Kingdom) was used to measure follicular diameters, indices of blood flow impedance (pulsatility index), peak systolic velocities (Vmax), and the proportion of follicles demonstrating pulsatile vascularity, i.e., follicular vascularity index. For the purpose of analysis, each woman was classified into one of four groups (I to IV) based on their oocyte recovery rate. RESULTS: The mean age, duration of infertility, Dmax, pulsatility index, and Vmax were similar in the four groups, but the follicular vascularity index was higher in the groups with the highest oocyte recovery rates. Furthermore, there was a positive correlation between the follicular vascularity index and the oocyte recovery rate. CONCLUSION: The follicular vascularity index correlates positively with oocyte recovery rates. Detection and quantification of follicular vascularity with color Doppler imaging can therefore be used to predict oocyte recovery rate and hence may be useful in determining the most appropriate time to administer hCG to optimize oocyte recovery rates.

Adult

Intrafollicular hemodynamics before the administration of human chorionic gonadotropin in women at risk of the ovarian hyperstimulation syndrome.

OBJECTIVE: To test the hypothesis that alteration of intrafollicular hemodynamics precedes the ovarian hyperstimulation syndrome (OHSS). DESIGN: A prospective study. SETTING: The IVF unit and the Doppler imaging laboratory of King's College Hospital, London. PATIENTS: Twenty-four women undergoing IVF and considered to have an exaggerated response to ovarian stimulation and hence at risk of OHSS. INTERVENTIONS: Transvaginal Doppler imaging of the intrafollicular blood flow was performed before hCG administration to determine the indexes of intrafollicular hemodynamics. MAIN OUTCOME MEASURES: Moderate or severe OHSS. RESULTS: There was no statistically significant difference in mean age (32.63 +/- 1.77 versus 31.48 +/- 3.87), duration of infertility (6.00 +/- 2.19 versus 5.29 +/- 2.73), maximum peak systolic velocity (0.25 +/- 0.16 versus 0.26 +/- 0.21 m/s), mean of six maximal peak systolic velocity (0.15 +/- 0.04 versus 0.21 +/- 0.10), minimum pulsatility index (0.76 +/- 0.26 versus 0.59 +/- 0.23), mean of six minimal pulsatility indexes (0.89 +/- 0.30 versus 0.79 +/- 0.14), minimum resistance index (0.47 +/- 0.06 versus 0.41 +/- 0.10), and mean of six minimal resistance indexes (0.56 +/- 0.05 versus 0.53 +/- 0.06) of intrafollicular blood flow between the women who developed moderate or severe OHSS and matched controls. CONCLUSION: Measurement of intrafollicular hemodynamics before hCG administration does not predict the development of the OHSS.

Adult

Ultrasound studies of vascular and morphological changes in the human uterus after a positive self-test for the urinary luteinizing hormone surge.

The aim of the study reported here was to establish complementary data for changes in uterine size, echogenicity and vascularity during the menstrual cycle relative to a positive self-test for urinary luteinizing hormone (LH) and day 1 of next menses. Thirteen volunteers (aged 23-32 years) with apparently regular menstrual cycles were recruited from the nursing staff. The plan was to examine all women by transvaginal ultrasonography with colour Doppler imaging on day 11 of the menstrual cycle. A urinary LH self-test was to be used daily until a positive result was obtained and the women were to be re-scanned daily until the dominant follicle had ruptured. All women were then to be scanned at least every 48 h (within +/- 2 h of the same time of day) until day 6 of the next menstrual cycle. Matched samples of peripheral blood were taken at the time of each scan for hormone analysis. The main outcome measures were the times of follicular rupture, a positive test result for urinary LH and the start of menses, uterine volume, cavity length, endometrial thickness and grade, pulsatility index (PI), and time-averaged and peak systolic maximum velocities in uterine and radial arteries and in subendometrial vessels. Nine women fulfilled the criteria for an ovulatory cycle, and seven provided data over the complete study. The principal changes relative to a positive urinary LH test were (i) a continued rise in endometrial thickness to days 3 and 4 (this index then remained relatively constant, but the layered appearance was lost) and (ii) a gradual decrease in the uterine arterial PI. There was a significant rise in uterine volume, cavity length and uterine arterial PI around the time of the next menses, and a fall in endometrial thickness and blood velocity in the uterine and radial arteries and subendometrial vessels. The data may have implications for the assessment of reproductive status and the design of future studies on disorders of implantation or menstruation.

Adult

Ultrasound derived indices of follicular blood flow before HCG administration and the prediction of oocyte recovery and preimplantation embryo quality.

The principal aim of the study was to relate ultrasound-derived indices of blood flow in individual follicles on the day of, but before, the administration of human chorionic gonadotrophin (HCG) to the subsequent recovery of oocytes and the production of preimplantation embryos. Data were obtained from 21 women (aged 29-43 years) with bilateral tubal occlusion, who were undergoing treatment by in-vitro fertilization (IVF) and embryo transfer. Transvaginal ultrasonography with colour Doppler imaging and pulsed Doppler spectral analysis were used to measure follicular volume and derive indices of blood flow. The end-points for each follicle were the volume, peak systolic velocity (PSV), pulsatility index (PI), and the recovery or non-recovery of an oocyte, the subsequent production or non-production of a preimplantation embryo and the morphological grade of each embryo. A total of 94 follicles were studied; 74 oocytes were recovered (79%) and 40 embryos (33 grade I or II) were produced. There were four clinical pregnancies (pregnancy rate 25.0% per transfer, 19.0% per patient). There was a significant correlation between whether or not follicular blood flow was detected and whether or not an oocyte was recovered (P < 0.05, chi 2 test). The values for volume and PI were not clinically useful. The PSV (cm/s, mean +/- SD) was higher in follicles that were associated with the production of an embryo (12.7 +/- 5.9) compared with those that were not (8.5 +/- 5.0; P < 0.05, Student's t-test). The probability of producing a grade I or grade II embryo was 75% if the PSV was > or = 10 cm/s. The corresponding value was 40% if the PSV was < 10 cm/s and 24% if blood flow was not detected (i.e. PSV < 3 cm/s). There was a significant increase (P < 0.05, Student's t-test) in the PSV before aspiration in those follicles associated with the subsequent production of an embryo. We conclude that the value for PSV, before the administration of HCG, can be used to identify follicles with a high probability of producing an oocyte and a high grade preimplantation embryo. The information may also be used to time the administration of HCG to achieve the optimum number and quality of embryos for patient management.

Adult

Potent inhibitory effects of steroids in an in vitro model of angiogenesis.

The regulation of angiogenesis in the ovarian follicle and corpus luteum is unclear. Steroids are produced at very high concentrations in these tissues and we therefore examined the effect of steroids on angiogenesis in vitro. Explants of rat aorta were embedded in collagen gel and cultured in serum-free medium. Capillary-like microvessels were produced from the explants and microvessel number and length were measured in the presence and absence of steroids. At a concentration of 10 micrograms/ml, cortisol, progesterone, 17 alpha-hydroxyprogesterone and medroxyprogesterone acetate produced degeneration of microvessels after 7 days of steroid treatment (P < 0.01). Androstenedione and tetrahydro-S-(11-deoxytetrahydrocortisol) (tetrahydro S) produced degeneration at a slower rate: androstenedione inhibited microvessel growth after 11 days (P < 0.01) and tetrahydro S after 14 days (P < 0.05). Oestriol had no effect on microvessels; oestrone had a slow degenerative effect with significant inhibition seen after 14 days (P < 0.01). Oestradiol-17 beta at a concentration of 10 micrograms/ml completely inhibited microvessel growth from the explant cultures (P < 0.01) while at 1 microgram/ml it caused degenerative effects on growing microvessels. The effects of oestradiol and cortisol were reversible on removal of steroid-containing medium and replacement with 10% serum. We conclude that oestradiol may modulate angiogenesis in tissues in which the steroid concentration is high.

17-alpha-Hydroxyprogesterone

Ultrasound studies of vascular and morphological changes in the human corpus luteum during the menstrual cycle.

OBJECTIVE: To determine changes in corpus luteum (CL) volume, echogenicity, vascularity, and P production relative to a positive test result for urinary LH and day 1 of next menses. SUBJECTS: Thirteen healthy volunteers (age 23 to 32 years). INTERVENTIONS: All women underwent transvaginal ultrasonography on cycle day 11 and a urinary LH self-test was used daily. The plan was to rescan all women immediately after a positive test result and then at least every 48 hours (until day 6 of the next cycle); samples of peripheral blood were taken for analysis. MAIN OUTCOME MEASURES: The times of follicular rupture, a positive urinary LH test, and the start of menses; CL volume and echogenicity, maximum peak systolic velocity and minimum impedance, the circulating levels of serum P, E2, LH, and FSH. RESULTS: Nine women fulfilled criteria for an ovulatory cycle. There was a good correlation between peak systolic velocity, CL volume, and the concentration of serum P from day 4 to 10 after a positive LH test. Peak systolic velocity reached a maximum value between days 7 and 9 relative to a positive urinary LH test and started to decline from day 1 of menses minus 3, 4 days. CONCLUSION: Changes in peak systolic velocity from the time of a positive urinary LH self-test might be a useful adjunct for monitoring CL function.

Adult

Effects of indomethacin on follicular structure, vascularity, and function over the periovulatory period in women.

OBJECTIVE: To assess the effect of indomethacin (taken at defined times) on follicular rupture, indexes of intrafollicular blood flow, and steroidogenesis. PARTICIPANTS: Six healthy volunteers awaiting treatment for infertility by IVF-ET during subsequent natural cycles. INTERVENTIONS: All women were examined (at least every 8 hours) by transvaginal ultrasonography with color Doppler imaging and had samples of blood taken for hormone analysis. A self-test for urinary LH was performed before each scan. Indomethacin was first taken (50 mg three times per day) according to the maximum follicular diameter (first four women) or when the LH dipstick gave a positive result; the drug was taken for > or = 3 days. RESULTS: Follicular rupture was delayed in five of six cases (by 2 to 12 days). There was a reduction in intrafollicular peak systolic velocity before and after the positive urinary LH test compared with historical controls. Three follicles (50% of women) with the highest peak systolic velocity had an hemorrhagic appearance and persisted longer. There was no significant effect on menstrual cycle length or the levels of circulating FSH, E2, LH, or P. CONCLUSION: Indomethacin administered at the time of a positive self-test for urinary LH can delay follicular rupture with an associated reduction in intrafollicular blood flow but with no apparent effects on hormonal or menstrual status.

Adult

Total ovarian volume before human chorionic gonadotrophin administration for ovulation induction may predict the hyperstimulation syndrome.

Total ovarian volumes were measured before the administration of HCG in 42 women undergoing treatment for infertility by in-vitro fertilization (IVF) and embryo transfer and considered to have an exaggerated response to stimulation ( > 20 follicles). Seven women who subsequently developed moderate or severe ovarian hyperstimulation syndrome (OHSS) (n = 7; group 1) were compared with 35 matched controls (five matched controls per case; n = 35; group 2) of similar age, number of follicles and duration of infertility who underwent follicular stimulation, oocyte recovery, in-vitro fertilization and embryo transfer during the same period but did not develop moderate or severe OHSS. The mean age, duration of infertility and total number of follicles were similar but the mean total ovarian volume was significantly higher in the group of women who developed moderate or severe OHSS compared with controls (271.00 +/- 87.00 versus 157.30 +/- 54.20 ml; P < 0.01). We conclude that total ovarian volume measured before HCG administration is higher in women who develop moderate or severe OHSS compared with controls and may therefore be used as an additional parameter in the preventative strategy for the ovarian hyperstimulation syndrome.

Adult

Association of ovarian malignancy with expression of platelet-derived endothelial cell growth factor.

BACKGROUND: At the present time, the pathogenesis of ovarian cancer remains poorly understood, with invasive diagnosis and ineffective treatment for women with the disease. Despite scientific and medical advances in oncology, the overall 5-year survival rate of 30% for ovarian cancer patients has not changed in 20 years. An understanding of the angiogenic process as it occurs in ovarian cancer would not only increase our knowledge of the pathogenesis of this cancer but also might offer novel opportunities for therapeutic intervention. PURPOSE: Our aim was to study the expression of messenger RNA (mRNA) coding for four putative angiogenic factors in normal ovaries and benign and malignant ovarian tumors: platelet-derived endothelial cell growth factor (thymidine phosphorylase), vascular endothelial growth factor, basic fibroblast growth factor, and transforming growth factor-beta 1. METHODS: Four normal ovaries and 25 tumors (seven benign, one of borderline malignancy, and 17 malignant) were collected from 29 patients during elective oophorectomy. The site of sampling (areas of high-velocity blood flow) was directed by transvaginal color Doppler imaging performed within 24 hours of the surgery. Increased blood flow within the tissues was demonstrated by the presence of color (i.e., the velocity was > 7 cm/s) and, together with a pulsatile index of less than 1.0, constituted a positive scanning result. In scan-positive tissues, the area of maximum blood flow was chosen. In scan-negative tissues, a solid area was chosen in complex lesions, or the cyst wall was chosen in simple lesions. Ovarian RNA was subsequently extracted from areas of high-velocity flow (i.e., tissues with a positive scanning result) or from solid areas or septa in tissues with a negative scanning result. A ribonuclease protection assay was used to assess the expression of mRNA coding for the four angiogenic factors. RESULTS: Two normal ovaries (containing a corpus luteum) and one benign and 17 malignant tumors (plus the borderline) gave a positive scanning result. There was a significant difference between the expression of mRNA for platelet-derived endothelial cell growth factor between scan-positive and scan-negative tissues (P < .001) and between benign and malignant tumors (P < .001). CONCLUSIONS: Areas of high blood velocity in ovarian tumors are associated with increased expression of platelet-derived endothelial cell growth factor. IMPLICATIONS: Drugs that affect the angiogenic activity of platelet-derived endothelial cell growth factor offer a potential route for therapeutic intervention.

Autoradiography

Effects of tamoxifen on uterus and ovaries of postmenopausal women in a randomised breast cancer prevention trial.

Randomised, double-blind controlled trials have been started to determine whether tamoxifen can prevent or delay development of breast cancer in healthy women with a family history of the disease. We recruited a randomised cohort of 111 postmenopausal women (aged 46-71 years) from the Pilot Breast Cancer Prevention Trial at the Royal Marsden Hospital to study the effect of tamoxifen on the uterus and ovaries. The main outcome measures were obtained by transvaginal ultrasonography with colour doppler imaging and microscopic examination of endometrial biopsies removed at the time of the scan. There was no significant difference between tamoxifen (20 mg/day) and placebo groups in the age of the women, or the time of the scan (and sampling) after randomisation. Women taking tamoxifen had a significantly larger uterus and a lower impedance to blood flow in the uterine arteries. 39% of women taking tamoxifen had histological evidence of an abnormal endometrium compared with 10% in the control group. 10 patients in the tamoxifen group (16%) had atypical hyperplasia and another 5 (8%) had a polyp. Women with a histological abnormality had a significantly thicker endometrium and a decreased impedance to blood flow in the uterine arteries. There was no correlation between the presence of uterine abnormalities and the age of the women, or the concentrations of tamoxifen or desmethyl tamoxifen in the peripheral blood. These findings confirm that tamoxifen can cause potentially malignant changes in the endometrium of postmenopausal women. Transvaginal ultrasonography can be used to identify those women who should have endometrial samples removed for microscopic analysis.

Aged

The potential role of serum CA 125 in an ultrasound-based screening program for familial ovarian cancer.

We have assessed the potential role of a test based upon the measurement of serum CA 125 in an ultrasound-based screening program for familial ovarian cancer. A sample of peripheral blood was taken from 1502 self-referred, asymptomatic women whose pedigree showed that at least one close relative had developed the disease. All women in the study underwent one screening by transvaginal ultrasonography (consisting of one or more scans) to detect any persistent lesion and a change in ovarian volume. Women with a positive result were referred for surgery. The concentration of serum CA 125 was measured in all samples at the end of the study. Seven ovarian cancers (4 invasive and 3 of borderline malignancy; 5 FIGO stage Ia, 1 stage IIa, 1 stage III) and 55 benign lesions were detected. We calculated the effect that a prescreening test (based on different threshold values for serum CA 125) would have had on the number of women entering the ultrasound-based screening program, and on the detection rate and false-positive rate of the overall procedure. There was a direct relationship between the number of women referred for ultrasound screening and the detection rate. The use of a threshold value for serum CA 125 > or = 20 U/ml would have meant that 380 women (25.3%) were referred for ultrasonography and 5 out of 7 cancers (71%) would have been detected with a false-positive rate of 1.1%. The odds of a woman with a positive screening result having cancer at surgery would have been about 1:3 (which would improve to about 1:1 if observational indices of color Doppler imaging and a morphological score had been used throughout). We concluded that a prescreening immunochemical test based on the measurement of serum CA 125 (with a threshold value of > or = 20 U/ml) would increase the prior odds for familial ovarian cancer by 2.8, but would lower the overall detection rate by 29% at the prevalence screening.

Adolescent

Investigation of the acid-base balance of coelomic and amniotic fluids in early human pregnancy.

OBJECTIVE: The aim of our study was to analyze and compare the acid-base status of coelomic and amniotic fluids in early human pregnancy. STUDY DESIGN: Coelomic fluid, amniotic fluid, and maternal serum were obtained from 55 normal pregnancies between 7 and 14 weeks of gestation and assayed for pH, PCO2, bicarbonate, chloride, phosphate, total protein, glucose, and lactate concentrations. RESULTS: The coelomic fluid had a significantly lower pH and base excess and contained significantly lower glucose, total protein, and bicarbonate concentrations and higher PCO2, lactate, and phosphate levels than did maternal serum. In the amniotic fluid significantly higher pH, base excess, and lactate and bicarbonate levels and lower concentrations of chloride and phosphate were found compared with the coelomic fluid. Little variation was observed in the coelomic and amniotic fluid composition before 11 weeks of gestation. A significant increase in PCO2, total protein, and chloride levels and a decrease in pH, base excess, and bicarbonate concentrations were observed in the amniotic fluid between 11 and 14 weeks compared with 7 to 10 weeks. CONCLUSIONS: The coelomic fluid composition was indicative of an anaerobic metabolic acidosis probably related to the accumulation of acid compounds from placental metabolism. During the same period of gestation the composition of the amniotic fluid demonstrated a metabolic alkalosis that probably arises from the accumulation of basic substances through the unkeratinized embryonic skin and from the metabolism of organic anions in the embryonic tissues. The changes in the amniotic composition and acid-base balance at the end of the first trimester may correspond to the switch from the mesonephros to the metanephros and result from the excretion in the amniotic fluid of acid metabolic fetal bioproducts through the maturing kidneys.

Acid-Base Equilibrium

The temporal effect of progestogen on uterine artery pulsatility index in postmenopausal women receiving sequential hormone replacement therapy.

OBJECTIVE: To determine the time relationship between the ingestion of progestogen during sequential hormone replacement therapy (HRT) and impedance to blood flow in the uterine arteries. DESIGN: Nine postmenopausal women who had already received HRT for at least 6 months were treated with either transdermal 17 beta-E2, 0.1 mg/d, or conjugated equine estrogens (Es), 1.25 mg/d, to which norethindrone, 0.7 mg/d, was added for 12 days in a single 28-day cycle of therapy. Transvaginal ultrasonography with color flow imaging was used to measure the pulsatility index (PI) in the uterine arteries every 3 to 5 days over one 28-day treatment cycle. RESULTS: The ingestion of norethindrone increased the mean uterine artery PI by 30% (SE 16.4%). The PI fell significantly within 4 days of ceasing norethindrone. CONCLUSION: Progestogen addition in sequential HRT causes changes in the uterine arterial tone, but the effect subsides within 4 days of progestogen withdrawal.

Arteries