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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

Use of family history in a screening clinic for familial ovarian cancer.

We have estimated the risks of ovarian and other types of cancer in first-degree relatives of women who have developed the disease (the index patients). The number of deaths from each type of cancer was determined from pedigrees taken from 391 self-referred, asymptomatic women attending a screening clinic for familial ovarian cancer. These values were compared with the expected number of deaths for women in the general population (calculated from life tables), and the relative risks were used to estimate lifetime risks. The overall relative risk were 4.5, 1.4, 1.3, and 1.1 for ovarian, stomach, breast, and endometrial cancers, respectively. The risks were invariably higher if the index patient was < 55 years old. Ovarian cancer appeared to have no clear inheritance pattern in 290 pedigrees and there was no increased risk for the first-degree relatives. Eighty-two pedigrees were compatible with a diagnosis of a multiple-site cancer family syndrome and the relative risks were 6.1, 2.8, 3.7, and 2.7 for ovarian, breast, stomach, and colorectal cancer, respectively. There was evidence of site-specific ovarian cancer in 19 families; the relative risk for the first-degree relatives was 39.1 and the lifetime risk 1 in 2. We believe that family history can be used to identify women who are at a high risk of developing ovarian and certain other types of cancer. This information can be used to counsel women attending ovarian cancer screening clinics and to maximize the usefulness of current resources.

Female

Correlation in ages at death from familial ovarian cancer among sisters.

The analysis of pedigrees taken from 97 of 1466 women attending a screening clinic for early familial ovarian cancer showed that there was a strong correlation in the ages at death from the disease among sisters (r = 0.68, confidence limits 0.51-0.82, P < 0.001), but not between mothers and daughters. This information can be used to help counsel women who are considering the appropriate time for more intensive screening or prophylactic oophorectomy.

Adult

The use of transvaginal color flow imaging after in vitro fertilization to identify optimum uterine conditions before embryo transfer.

OBJECTIVE: To assess whether a measure of uterine blood flow impedance (the pulsatility index, PI) as determined by transvaginal ultrasonography with color blood flow imaging, may be used to assess endometrial receptivity immediately before the time of embryo transfer (ET) after assisted conception. DESIGN: A prospective study of infertile women who had undergone treatment to induce multiple follicular development followed by ultrasound-guided oocyte retrieval. The oocytes were fertilized in vitro. SETTING: The Hallam Medical Centre. PATIENTS: Eight-two women (22 to 44 years of age) who all had three or four good quality embryos available for transfer to the uterus. INTERVENTIONS: All women were examined by transvaginal ultrasonography, with color flow imaging and blood flow analysis, immediately before ET. MAIN OUTCOME MEASURES: The mean PI of the left and right uterine arteries, the pregnancy rate (PR) (%), the embryo implantation rate (%), and the multiple PR (%). RESULTS: The patients were grouped according to whether the PI was low (1.00 to 1.99), medium (2.00 to 2.99), or high (3+). There were 27 women in the low PI group, 36 in the medium, and 19 in the high. The PR (%), embryo implantation rate (%), and multiple PR (%) were 41%, 15.3%, and 27.3% for the low PI group and 47%, 22.2%, and 47.1% for the medium PI group. There were no pregnancies in the high PI group. Thus 35% (19/54) of women who failed to become pregnant had a PI value greater than 3.0. CONCLUSIONS: These data suggest that the PI value on the day of ET could be used to: (1) increase the implantation rate by showing which embryos should be cryopreserved until the uterus is more receptive and (2) reduce the multiple PR by indicating that the number of embryos transferred should be limited when the uterus is most receptive.

Embryo Transfer

Differential effects of transdermal estradiol and sequential progestogens on impedance to flow within the uterine arteries of postmenopausal women.

OBJECTIVE: To investigate the relationship between estradiol (E2), progestogen, and impedance to blood flow in the uterine artery. SUBJECTS: Twelve postmenopausal women treated for two cycles with transdermal E2, 0.05 mg/d, with either norethindrone acetate, 0.7 mg, or medroxyprogesterone acetate, 10 mg added sequentially. MEASUREMENTS: Transvaginal ultrasonography and color flow imaging were used to measure the pulsatility index in the uterine arteries before and during the E2-only and combined E2/progestogen phases. RESULTS: The mean pulsatility index fell to 53% of its pretreatment value within 12 days E2 administration (P < or = 0.0001) and was 66% of its pretreatment value in the combined phase (P < 0.005). Similar changes were seen in cycle 2. Time since menopause was correlated with the pretreatment pulsatility index (r = 0.674, P < 0.05) and change in pulsatility index on treatment (r = 0.856, P < 0.001). CONCLUSION: Gonadal hormones have a profound effect on arterial tone in postmenopausal women; this action may help explain some of the beneficial effects of estrogen on arterial disease risk.

Administration, Cutaneous

Transvaginal color Doppler study of blood flow in ectopic pregnancies.

OBJECTIVE: To compare Doppler indices of blood flow in the uterine and spiral arteries and the corpus luteum (CL), in ectopic and intrauterine pregnancies (IUPs). DESIGN: A prospective study of women with an ectopic or singleton IUP at the corresponding stage of gestation. SETTING: The Gynaecological Ultrasound Clinic, King's College Hospital. PATIENTS: Fifty-two women, 19 with an ectopic pregnancy (EP) and 33 with an IUP. INTERVENTIONS: All women were examined by transvaginal ultrasonography with color Doppler immediately before surgery. MAIN OUTCOME MEASURES: The resistance index from the left and right uterine arteries, the spiral arteries, and the CL. The peak blood velocity (cm/sec) from the uterine arteries. The length of gestation. RESULTS: Fetal heart activity was observed in all cases of IUP at 5 weeks' gestation. Three women had an EP with a live embryo, 5 had an embryo with no heart activity, 5 contained only a yolk sac, and 2 had an empty sac. A hematocele was seen in 3 women, and 1 had tubal thickening. The mean uterine and spiral arterial resistance index decreased with the gestational age of IUPs but remained constant during EPs. Peak blood velocity in the uterine arteries increased with the gestational age of IUPs, and the values were significantly higher than in EPs. A CL was seen in 88% of women with an IUP and in 100% of women with an EP. The resistance index was similar in CL associated with both types of pregnancy, and the values did not change with gestational age. CONCLUSION: These data show that: (1) blood flow impedance in the uterine and spiral arteries, and CL, is similar in IUPs and EPs and (2) peak flow velocity in the uterine arteries reflects a decreased blood supply to EPs.

Female

Detection of endometrial cancer by transvaginal ultrasonography with color flow imaging and blood flow analysis: a preliminary report.

A prospective study was undertaken to assess whether changes in uterine blood flow could be used to detect endometrial cancer in 138 selected postmenopausal women (34 had uterine bleeding, 17 with endometrial cancer; 104 did not have uterine bleeding; 1 had endometrial cancer). Thirty-five of the asymptomatic women were receiving estrogen replacement therapy (ERT). The endpoints were endometrial (including tumoral) thickness and a pulsatility index (PI) derived from flow velocity waveforms recorded from both uterine arteries and from within a tumor. We found an overlap in endometrial thickness between those women with endometrial cancer and those without. The mean arterial PI value was invariably lower in women with postmenopausal bleeding and endometrial cancer (mean 0.91, range 0.31-1.49) than in those with other reasons for the blood loss (mean 3.83, range 1.95-6.40). The index was 1.10 in the woman with endometrial cancer but no sign of postmenopausal bleeding. Blood flow impedance was inversely related to stage of cancer. PI values in healthy women tended to increase slightly with age, but decrease during ERT. The detection rate was 100% within the limitations of the study design, and the false-positive rate was 1% for all women not receiving ERT and 11% for patients receiving ERT. Malignant tumors show signs of altered vascularization and a low PI (mean 0.49, range 0.29-0.92). We conclude that transvaginal ultrasonography, with or without color flow imaging, and blood flow analysis can be used to detect endometrial cancer in women with postmenopausal bleeding. A screening procedure for asymptomatic women must allow for changes in uterine blood flow during ERT.

Aged

Ultrasound screening for familial ovarian cancer.

We have used transvaginal ultrasonography to screen 776 asymptomatic women for familial ovarian cancer. Every woman had at least one first- or second-degree relative develop the disease (677, 87%; and 98, 13%, respectively). The mean age of the study population was 51 years (range, 24 to 78 years); 52% were premenopausal, 36% were naturally postmenopausal, and 12% had undergone a hysterectomy. Overall, 43 women (5.5%) were referred for surgical investigation and 39 had a laparatomy. Nineteen/thirty-nine (48%) had bilateral ovarian masses, and 15% of abnormal ovaries had more than one type of histopathology. Twenty-three tumors and thirty-two tumor-like conditions were detected. There were 3 cases of primary ovarian cancer (prevalence, 3.9/1000), all FIGO stage Ia. None of the women has developed ovarian cancer within the first year of the scan (giving a provisional detection rate of 100%). The false positive rate was 40/773 (5.2%), the predictive value of a positive screen result was 7.7%, and the odds in favor of finding any mass at laparotomy were about 19 to 1 or for any tumor, 1 to 1. At surgery the odds against finding primary ovarian cancer were 12 to 1. The positive predictive value of the screening procedure and the prevalence of the disease were significantly higher than the corresponding values from a previous population-based screening program.

Adult

Symptothermal and hormonal markers of potential fertility in climacteric women.

One hundred seventy-seven menstrual cycles in 36 women between 45 and 53 years of age were studied prospectively. All the women were experienced in the symptothermal method of natural family planning. The objective was to determine the symptothermal and hormonal indices of potential fertility by measuring urinary estrone glucuronide and pregnanediol glucuronide. Thirty-three percent had regular cycles consistent with potential fertility, 19% had cycles consistent with infertility, and 47% had a mixture of both types of cycle.

Biomarkers

The evolution of reference methods to monitor ovulation.

Reference methods to predict or detect ovulation have evolved substantially during the past few decades. The potential use and limitations of such methods are reviewed. The use of transvaginal ultrasonography with color flow mapping to monitor periovulatory changes in the intrafollicular morphology and blood flow is described.

Biomarkers

Genetic epidemiology of ovarian cancer: segregation analysis.

The genetic epidemiology of ovarian cancer has been investigated by complex segregation analysis of 462 pedigrees ascertained through a normal consultant. The observed pattern of ovarian cancer is compatible with an autosomal dominant gene. The gene frequency of the abnormal allele is 0.0015-0.0026 with a lifetime penetrance of 0.74-0.79. The gene frequency accounts for a significant proportion of ovarian cancer in young women. By age 70 the majority of affected women are phenocopies. The results from this analysis should enable the risks of ovarian cancer to be more accurately estimated than by empiric methods for relatives of affected women, and can maximize the usefulness of screening programmes and future linkage studies.

Adult

The effect of human chorionic gonadotropin and pregnancy on the circulating level of relaxin.

The effect of hCG and pregnancy on the circulating levels of relaxin was investigated in 48 women undergoing in vitro fertilization and embryo transfer (ET) for the treatment of infertility. Subjects were allocated randomly to receive hCG (Profasi; 2000 IU, im) or placebo on the day of ET (day 0) and on day 3 after ET (day 3). Samples of peripheral blood were taken on days -4, 6, and 10. An additional sample was taken on day 22 from women who became pregnant. The subjects were allocated retrospectively to 1 of 4 groups: no pregnancy, no hCG (NP); pregnancy, no hCG (P); no pregnancy, hCG (NPH); and pregnancy, hCG (PH). Two patients with blighted ova and one with a tubal pregnancy were excluded from the analysis. The concentrations of relaxin were similar and rose significantly in all groups at each time point (P less than 0.05). On day 6 there was no significant difference in the increment between the groups, but by day 10, circulating levels in the P compared to the NP and those in the PH compared to the NPH group were significantly greater (P less than 0.05). By day 22 the difference between the PH and the P groups was significant (P less than 0.05). Relaxin levels correlated with progesterone levels on day 10 in the NP and P groups (r = 0.633; P less than 0.05 and r = 0.697; P less than 0.05, respectively) and with estradiol levels in the P group only on days 6 and 22 (r = 0.659; P less than 0.05 and r = 0.783; P less than 0.05, respectively). These data demonstrate that in women undergoing in vitro fertilization, relaxin levels increase during the luteal phase, and in those women who establish a pregnancy, the values are significantly greater by day 10. The administration of hCG in the early luteal phase, before implantation, to women who subsequently become pregnant significantly increased the level of circulating relaxin on day 22. The positive correlation between relaxin levels and ovarian steroid levels in the groups not receiving exogenous hCG suggests that a common factor may control the release of both.

Chorionic Gonadotropin

Transvaginal colour flow imaging of the uterine arteries during the ovarian and menstrual cycles.

Uterine arterial blood flow was studied at defined times during the ovarian or menstrual cycles. Transvaginal colour pulsed ultrasound was used to identify the vessels in 23 healthy women. Blood flow impedance as reflected by the pulsatility index (PI) was determined for both arteries on 132 occasions. There was no significant difference in the PI values between the right and left arteries. The average PI value was used for subsequent analysis (range 0.5-5.6; mean 2.8). Peak mean PI values occurred on day 1 of menses (4.6), the day of the plasma oestradiol peak (3.7) and the day of the LH peak plus 3 (2.9). The lowest mean PI values (indicating the least impedance to blood flow) occurred on the day of the LH peak minus 6 (2.6), and the day of the LH peak plus 9 (1.9). There are complex temporal relationships between uterine blood flow, ovarian morphology, the concentrations of plasma oestradiol and progesterone and the thickness of the endometrium.

Adult

Novel screening strategies for early ovarian cancer by transabdominal ultrasonography.

Data collected during a prospective study to assess the efficacy of detecting early ovarian cancer by transabdominal ultrasonography have been used to refine and extend the screening procedure. The analysis was based on results from 5479 self-referred asymptomatic women, who were scheduled to undergo three annual screens consisting of one or more ultrasound scans. A positive result (based mainly on the presence of abnormal morphology) was obtained at 338 screens (326 women). Five patients with primary ovarian cancer (four stage 1a, one stage 1b; two at screen 1, three at screen 2) were identified (prevalence 0.09%). The apparent detection rate was 100% and the false-positive rate (FPR) was 3.5% at screen 1 and 2.3% overall. The use of abnormal morphology, or the maximum ovarian volume (MOV) greater than 96th centile as alternative criteria for a positive screen result, together with a defined volume change at rescan (VC) would give a FPR of 3.1% at screen 1 and 2.0% overall. The use of abnormal morphology alone at scan 1 and VC at rescan would give an overall FPR of 1.6%. The odds that a positive screen result would indicate the presence of an ovarian mass, a benign tumour, any ovarian cancer or primary ovarian cancer would be about 4 to 1, 2 to 1, 1 to 26, and 1 to 50 respectively. The results provide a more rational basis for the application and development of screening procedures for early ovarian cancer in both pre- and post-menopausal women.

Adolescent

Transabdominal ultrasound screening for early ovarian cancer.

OBJECTIVE: To assess the value of ultrasonography in a screening procedure for early ovarian cancer. DESIGN: Prospective study of at least 5000 self referred women without symptoms of ovarian cancer. Each woman was scheduled to undergo three annual screenings (consisting of one or more scans) to detect grossly abnormal ovaries or non-regressing masses. SETTING: The ovarian screening clinic at King's College Hospital, London. SUBJECTS: 5479 Self referred women without symptoms (aged 18-78, mean age 52). INTERVENTIONS: Women with a positive result on screening were referred for laparoscopy or laparotomy, or both. MAIN OUTCOME MEASURES: Findings at surgery and from histology of abnormal ovaries. RESULTS: A total of 14,594 screenings (15,977 scans) were performed. A positive result was obtained at 338 screens (2.3%) comprising 326 subjects (5.9%). Five patients with primary ovarian cancer (four stage Ia, one stage Ib; two at first screening three at second) were identified (prevalence 0.09%). An additional four patients had metastatic ovarian cancer (three at first screening, one at second). The apparent detection rate was 100%. It was not possible to differentiate between the ultrasonic appearance of early malignant and benign tumours. The rate of false positive results for primary ovarian cancer was 3.5% at the first screening, 1.8% at the second, and 1.2% at the third. Overall the rate of false positive results was 2.3%; the specificity was 97.7% and the predictive value of a positive result on screening was 1.5%. The odds that a positive result on screening indicated the presence of an ovarian tumour, any ovarian cancer, or primary ovarian cancer were about one to two, one to 37, and one to 67 respectively. CONCLUSION: Ultrasonography can be used to screen women without symptoms for persistent ovarian masses that will include early ovarian cancer.

Adolescent

Transvaginal colour flow imaging: a possible new screening technique for ovarian cancer.

OBJECTIVE: To assess whether changes in the intraovarian vasculature or blood flow impedance can be used to identify potentially malignant masses. DESIGN: Open, non-comparative prospective study. SETTING: Ovarian screening clinics at King's College Hospital and the Hallam Medical Centre. SUBJECTS: 50 Women selected on the basis of their medical history and the result of a previous transvaginal ultrasound scan. Thirty women (10 premenopausal (scan taken on days 1 to 8 of the menstrual cycle) and 20 postmenopausal) had normal ovaries, and 20 had at least one ovary with an abnormal morphology or volume, or both. INTERVENTIONS: Women with a positive result on screening were referred for laparotomy. MAIN OUTCOME MEASURES: Presence or absence of coloured areas (neovascularisation) and the pulsatility index within each ovary. The pulsatility index is a measure of the impedance to blood flow, a low value indicating decreased impedance and a high value increased impedance to blood flow. RESULTS: Two women with a positive result on screening had hydrosalpinges, 10 a benign tumour or a tumour-like condition, and eight primary ovarian cancers. No areas of neovascularisation were seen in the 30 women with morphologically normal ovaries and the two patients with hydrosalpinges; the pulsatility index ranged from 3.1 to 9.4. Similarly, nine patients (10 affected ovaries) with a non-malignant mass had no signs of neovascularisation and the pulsatility index varied from 3.2 to 7.0. One patient with bilateral dermoid cysts containing nests of thyroid-like cells had vascular changes and pulsatility index values of 0.4 and 0.8. Seven patients (eight ovaries) with primary ovarian cancer (one stage IV, four stage II, and two stage Ia) showed clear evidence of neovascularisation and pulsatility index values were from 0.3 to 1.0. One patient with an intraepithelial serous cystadenocarcinoma in a small ovary (less than 5 ml volume) had no signs of any vascular change and the pulsatility index was 5.5. CONCLUSION: Transvaginal colour flow imaging may be used to identify potentially malignant ovarian masses and help elucidate the early stages of tumorigenesis. The routine application of this technique may reduce the rate of false positive results of an ultrasonography based screening procedure.

Adult