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Biomedical subjects

S Campbell

Publications and source records attributed to S Campbell.

At least 19 recordsLinked to original sources

Understanding the pathophysiology of intra-uterine growth retardation: the role of the 'lower limb reflex' in redistribution of blood flow.

Doppler ultrasound was used to investigate the circulatory redistribution and underlying reflex responses of fetal cardiovascular compensation in 30 small-for-gestational age (SGA) fetuses. The utero-placental bed, umbilical artery and vein, thoracic and abdominal aorta, internal and external cerebral arteries were evaluated. The values were compared to reference ranges constructed from 135 normal pregnancies, correlated to fetal blood gases obtained by cordocentesis and compared to the outcomes. In Group I (mortality and morbidity), all fetuses had loss of end-diastolic frequencies (L-EDF) in the abdominal aorta (100%), but only 20 (87%) and 13 (56%) had L-EDF in the thoracic aorta and umbilical artery respectively. High vascular resistance in the placental bed and low impedance in the middle cerebral and common carotid arteries was found in 14 (61%), 12 (52%) and 20 (87%) fetuses, respectively. In Group II (Healthy infants) two fetuses had high utero-placental vascular resistance and one had brain-sparing. Doppler indices did not always reflect fetal hypoxaemia demonstrating that redistribution in SGA fetuses may not be triggered by a fall in pO2, and that hypoxaemia is an associated pathology but may not be the underlying cause. It is postulated that redistribution in SGA fetuses is regulated by reflex mechanisms (the 'lower limb reflex') which result in severe vasoconstriction in the abdominal aorta, mesentery and carcass, favouring the brain and cardiac muscles. This mechanism explains the good predictive value of L-EDF in the abdominal aorta for poor neonatal outcome (sensitivity, specificity and positive predictive value, all 100%).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Circulation

Ultrasonographically detectable markers of fetal chromosomal abnormalities.

Screening for fetal chromosomal abnormalities on the basis of maternal age has not resulted in a substantial fall in the proportion of infants born with an abnormal karyotype. Most fetuses with major chromosomal abnormalities have defects that can be recognised on detailed ultrasonographic examination. Therefore, provided the cardinal signs of each chromosomal syndrome are recognised, it is possible that screening by ultrasound examination could have a greater impact. We karyotyped 2086 fetuses after ultrasonographic examination had revealed fetal malformations, growth retardation, or both. Chromosomal abnormalities were detected in 301 (14%) cases and were more common among fetuses with multisystem malformations (29%) than among those with isolated defects (2%). The commonest chromosomal abnormality was trisomy 18, followed by trisomy 21, triploidy, Turner's syndrome, unbalanced chromosomal rearrangements, and trisomy 13. Trisomy 18 was associated with strawberry-shaped head, choroid plexus cysts, facial cleft, micrognathia, heart defects, exomphalos, malformations of hands and feet, and growth retardation. In trisomy 21, the associated defects were subtle and included nuchal oedema, macroglossia, atrioventricular septal defects, mild hydronephrosis, clinodactyly, and sandal gap. The frequency of autosomal abnormalities increased with maternal age, but if fetal karyotyping had been restricted to mothers older than 35 years, large proportions of chromosomally abnormal fetuses would not have been diagnosed prenatally (64-97%). Our findings provide guidelines as to which defects to search for in screening studies for the detection of chromosomal abnormalities.

Adolescent

Expression of TTK, a novel human protein kinase, is associated with cell proliferation.

We have isolated the full-length sequence for a unique human kinase, designated TTK. TTK was initially identified by screening of a T cell expression library with anti-phosphotyrosine antibodies. The kinases most closely related to TTK are the SPK1 serine, threonine and tyrosine kinase, the Pim1, PBS2, and CDC2 serine/threonine kinases, and the TIK kinase which was also identified through screening of an expression library with anti-phosphotyrosine antibodies. However, the relationships are distant with less than 25% identity. Nevertheless, TTK is highly conserved throughout phylogeny with hybridizing sequences being detected in mammals, fish, and yeast. TTK mRNA is present at relatively high levels in testis and thymus, tissues which contain a large number of proliferating cells, but is not detected in most other benign tissues. Freshly isolated cells from most malignant tumors assessed expressed TTK mRNA. As well, all rapidly proliferating cell lines tested expressed TTK mRNA. Escherichia coli expressing the complete kinase domain of TTK contain markedly elevated levels of phosphoserine and phosphothreonine as well as slightly increased levels of phosphotyrosine. Taken together, these findings suggest that expression of TTK, a previously unidentified member of the family of kinases which can phosphorylate serine, threonine, and tyrosine hydroxyamino acids, is associated with cell proliferation.

Amino Acid Sequence

Intravascular ultrasound imaging combined with coronary angioplasty.

A novel catheter combining ultrasound imaging and coronary balloon angioplasty was used in the treatment of 69 coronary-artery lesions in 51 patients. The ultrasound transducer enables real-time cross-sectional imaging and qualitative and quantitative assessment of the vessel wall before and after angioplasty. The combination catheter successfully dilated 67 lesions. There was a characteristic three-layered appearance, representing intima, media, and adventitia, in 60 cases. Intravascular imaging provided information on the vessel wall unobtainable by standard contrast angiography in 28 cases and influenced our management in 6 cases.

Adult

Cumulative conception and livebirth rates after in-vitro fertilisation.

Cumulative conception and livebirth rates related to age and cause of infertility provide the most useful estimate of success after in-vitro fertilisation (IVF), but limited data are available. It is also uncertain whether the probability of pregnancy, livebirth, and pregnancy failure changes with repeated treatment cycles. To assess the effects of patients' age and cause of infertility on these outcomes, we studied the results of 5055 consecutive IVF cycles (773 clinical pregnancies, 518 livebirths) undertaken on 2735 patients in a single IVF unit. Cumulative conception and livebirth rates were analysed by the life-table approach and differences in rates between age-groups and between causes of infertility were measured by the log-rank test and logistic regression modelling. Both conception and livebirth rates per cycle declined with age (p less than 0.001), and cumulative conception and livebirth rates after five treatment cycles were about 54% and 45%, respectively, at 20-34 years, compared with 38.7% and 28.9% at 35-39 years and 20.2% and 14.4% at greater than or equal to 40 years. The two rates were significantly different between causal groups (p less than 0.001 and p = 0.02, respectively) and were lowest in patients with male infertility or multiple infertility factors. The pregnancy failure rate was higher (p = 0.006) in women over the age of 34 years and there was a significant decline in the chances of pregnancy and livebirth per cycle with successive treatment cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Doppler ultrasonographic features of the developing placental circulation: Correlation with anatomic findings.

Color Doppler was used to study the placental circulations of 28 pregnancies between 10 and 17 weeks' gestation. A histomorphometric investigation was performed on placental tissue samples from those pregnancies, and the results were compared with Doppler features. Important changes were found around 14 weeks' gestation in both uterine and umbilical circulations. The appearance of end-diastolic frequencies in the umbilical arteries was related to an abrupt and significant (p less than 0.005) increase in uterine velocity and to the establishment of a continuous intervillous circulation.

Blood Flow Velocity

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

Characteristics of transient myocardial ischaemia and acute occlusion in the immediate post-angioplasty period.

Holter monitoring was used to assess the incidence and characteristics of myocardial ischaemia immediately after successful coronary angioplasty in 24 patients. In 5 patients a total of 16 episodes of ST depression were recorded. All were asymptomatic but ranged from 4 minutes to over 20 hours in duration. These patients, however, made an uncomplicated recovery, as did 18 patients with no ischaemic episodes. In the remaining patient, initially labile, but then, fixed ST elevation, accompanied by chest pain occurred. Subsequent angiography demonstrated acute vessel occlusion. These labile ischaemic changes indicate that prior to complete occlusion the vessel may be in a dynamic state when antispasmodic and antithrombotic therapies may be of value.

Adult

Obstetric outcome of in vitro fertilization pregnancies compared with normally conceived pregnancies.

OBJECTIVE: To compare the obstetric outcome of in vitro fertilization pregnancies with normally conceived pregnancies. STUDY DESIGN: The obstetric outcome of in vitro fertilization pregnancies achieved in 763 British residents at two in vitro fertilization clinics resulting in the births of 961 babies were compared by means of the relative risk statistic with a control group of naturally conceived primiparous pregnancies matched by maternal age and multiplicity of pregnancy. RESULTS: Twenty-five percent of in vitro fertilization pregnancies were multiple pregnancies. The incidence of singleton term breech presentation was similar to that among controls. As compared with controls there was an increased incidence among in vitro fertilization pregnancies of vaginal bleeding and hypertension requiring hospitalization (p less than 0.001) and cesarean births (p less than 0.001) and, among in vitro fertilization singleton pregnancies, an increased incidence of intrauterine growth retardation (p less than 0.05), placenta previa (p less than 0.05), and preterm delivery (p less than 0.001). The congenital malformation, stillbirth, and perinatal mortality rates were comparable with maternal age-standardized national rates. CONCLUSIONS: Although the majority of in vitro fertilization pregnancies have a satisfactory obstetric outcome, there are a number of increased obstetric risks that may reflect the history of infertility, the relatively high incidence of poor obstetric history, and the lower threshold for obstetric intervention in in vitro fertilization patients.

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

The routine use of gonadotropin-releasing hormone agonists for all patients undergoing in vitro fertilization. Is there any medical advantage? A prospective randomized study.

OBJECTIVE: To determine if the routine use of gonadotropin-releasing hormone agonists (GnRH-a) for all patients undergoing in vitro fertilization (IVF) produces any significant medical advantage. DESIGN: Prospective randomized study. PATIENTS: Three hundred eight patients having their first ever IVF attempt. INTERVENTIONS: Patients were randomly divided into four groups and received either human menopausal gonadotropin (hMG) alone for ovarian simulation (group A, n = 81); clomiphene citrate and hMG (group B, n = 77); a 3-day ultrashort course of GnRH-a and hMG (group C, n = 74); or pituitary desensitization with GnRH-a followed by hMG (group D, n = 76). RESULTS: The indications for IVF and mean age of all four groups of patients were comparable. There was a significant difference in the number of embryos cleaved and transferred among the groups, but there were no significant differences in the cancellation rate, mean number of oocytes collected or fertilized, and number of cases of failed fertilization. There were also no significant differences in the pregnancy and live birth rates per cycle commenced or per embryo transfer. CONCLUSION: The routine use of GnRH-a for all patients undergoing IVF has practical but no significant medical advantages.

Abortion, Spontaneous

The long protocol of administration of gonadotropin-releasing hormone agonist is superior to the short protocol for ovarian stimulation for in vitro fertilization.

OBJECTIVE: To investigate whether pituitary desensitization with the gonadotropin-releasing hormone agonist (GnRH-a), buserelin acetate, before the administration of human menopausal gonadotropin (hMG) for ovarian stimulation in in vitro fertilization (IVF) is superior to the simultaneous administration of both hormones at the beginning of the treatment cycle. DESIGN: Prospective randomized study. PATIENTS: Ninety-one patients having their first attempt at IVF. INTERVENTIONS: Patients in group 1 (long protocol) were administered subcutaneous (SC) buserelin acetate 200 micrograms/d from day 1 of the menstrual cycle, and hMG was started only after pituitary desensitization had been achieved at least 14 days later. Patients in group 2 (short protocol) were administered SC buserelin acetate 200 micrograms/d from day 2 and the same dose of hMG used in the long protocol from day 3 of the menstrual cycle. RESULTS: The median total amount of hMG required in both groups was comparable. There were significantly more follicles (P = 0.0001), oocytes (P = 0.0008), fertilized oocytes (P = 0.0001), and cleaved embryos (P = 0.0001), and a higher fertilization rate (P = 0.0047) in patients in group 1. The pregnancy rates per initiated cycle and per embryo transfer were 19.57% and 25.71% in group 1 compared with 8.89% and 16.67% in group 2. CONCLUSIONS: The long protocol is superior in terms of significantly greater follicular recruitment, oocyte recovery and fertilization rates, and significantly greater number of embryos available for transfer. In general, it is the preferred method when GnRH-a are used for ovarian stimulation in IVF.

Adult

Transvaginal peritoneal oocyte and sperm transfer for the treatment of nontubal infertility.

OBJECTIVE: To investigate if peritoneal oocyte and sperm transfer (POST) performed transvaginally is an effective treatment for nontubal infertility. DESIGN, SETTING, AND PATIENTS: Prospective study of 18 patients (4 with unexplained infertility, 13 with failed donor insemination, and 1 with male factor infertility) having 20 cycles of transvaginal POST in a specialist infertility unit. INTERVENTIONS: Ovarian stimulation was achieved with human menopausal gonadotropin (hMG) alone, hMG and clomiphene citrate, or gonadotropin-releasing hormone agonist with hMG. Oocyte recovery was performed transvaginally under ultrasound guidance, the pouch of Douglas rinsed repeatedly and an embryo transfer catheter used to transfer 4 x 10(6) progressively motile sperm in 1 mL and up to four oocytes into the pouch of Douglas. Luteal support was provided with human chorionic gonadotropin injections given 2 and 5 days later. RESULTS: The mean age of the patients was 32.65 +/- 5.0, and the mean length of infertility 5.07 +/- 2.32 years. The mean number of oocytes transferred was 3.53 +/- 0.87. Three pregnancies were achieved in the failed donor insemination group and 1 each in those with unexplained and male factor infertility, giving overall clinical pregnancy and live birth rates of 25% and 20% per initiated cycle. All pregnancies were achieved in those who had three or four oocytes transferred. CONCLUSION: Transvaginal POST is a useful assisted conception technique for the treatment of nontubal infertility.

Adult

A prospective randomized study of the optimum timing of human chorionic gonadotropin administration after pituitary desensitization in in vitro fertilization.

OBJECTIVE: To determine if there is an optimum time for the administration of human chorionic gonadotropin (hCG) after pituitary desensitization with gonadotropin-releasing hormone agonists (GnRH-a) has been achieved before ovarian stimulation for in vitro fertilization (IVF). DESIGN: Prospective randomized study. PATIENTS: Two hundred forty-seven patients undergoing an IVF treatment cycle who were randomly divided into three groups. INTERVENTIONS: All patients were administered subcutaneously buserelin acetate 500 micrograms/d from day 1 of the menstrual cycle. After pituitary desensitization had been achieved at least 14 days later, ovarian stimulation with human menopausal gonadotropin was commenced. Ovarian stimulation, cycle monitoring, oocyte recovery, and IVF and embryo transfer (ET) techniques were identical in all three groups. Patients in group 1 (n = 79) had hCG administered when the mean diameter of the largest follicle had reached 18 mm, at least two other follicles were greater than 14 mm, and serum estradiol (E2) levels were consistent with the number of follicles observed on ultrasound. Patients in groups 2 (n = 84) and 3 (n = 84) had hCG administered 1 day and 2 days, respectively, after the above criteria had been reached. RESULTS: The mean day of hCG administration (P less than 0.01), maximum serum E2 concentration (P = 0.06), number of days of serum E2 rise (P = 0.03), and mean diameter of the largest follicle (P less than 0.0001) were significantly different. There were, however, no significant differences in the mean number of preovulatory and medium size follicles, number of oocytes recovered or embryos transferred. There were also no significant differences in the oocyte recovery, fertilization and cleavage rates, in the number of embryos frozen, or in the pregnancy rates per initiated cycle and per ET. CONCLUSIONS: There is no significant advantage in the precise timing of hCG administration after pituitary desensitization with GnRH-a.

Adult

The administration of glucocorticoids for the prevention of ovarian hyperstimulation syndrome in in vitro fertilization: a prospective randomized study.

OBJECTIVE: To determine if the administration of glucocorticoids reduced the rate of ovarian hyperstimulation syndrome (OHSS) in high-risk patients after ovarian stimulation for in vitro fertilization (IVF). DESIGN: Prospective randomized study. PATIENTS: Thirty-one patients who were stimulated with human menopausal gonadotropin (hMG) after pituitary desensitization by gonadotropin-releasing hormone agonist and who developed greater than 20 follicles greater than 12 mm and/or had a serum estradiol (E2) level of greater than 10,000 pmol/L on the day of administration of human chorionic gonadotropin (hCG). INTERVENTIONS: Patients were randomly divided into two groups. Those who were randomized to receive glucocorticoids (group A) (n = 17) were administered intravenous hydrocortisone, 100 mg, immediately after ultrasound (US)-directed oocyte recovery. Prednisolone, 10 mg three times per day, was given for 5 days starting on the day of oocyte recovery followed by prednisolone 10 mg two times a day for 3 days and 10 mg/d for 2 days. Those in group B (n = 14) did not receive any glucocorticoid treatment. In both groups, luteal support was provided by intramuscular injections of gestone 100 mg/d. RESULTS: The two groups of patients were comparable in terms of age, duration of infertility, and total dose of hMG used. All had polycystic ovaries on US examination. On the day of hCG administration, the mean number of follicles in the two groups were 26.76 +/- 2.49 and 25.93 +/- 1.44 and the serum E2 concentration 13,404 +/- 710 and 13,915 +/- 901 pmol/L, respectively. There were no significant differences in the number of oocytes collected or in the fertilization, cleavage, and implantation rates in the two groups. The pregnancy rates per initiated cycle were 41.18% and 35.71%, respectively. Seven of the 17 patients (41.2%) who received glucocorticoids developed ovarian hyperstimulation syndrome compared with 6 of the 14 patients (42.9%) who did not receive glucocorticoids. CONCLUSIONS: Administrations of glucocorticoids to high risk patients did not reduce the rate of OHSS after ovarian stimulation for IVF.

Adult

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