Choosing a computer system.
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Computer Systems↗
Biomedical subjects
T Chard
Publications and source records attributed to T Chard.
Expert systems in obstetrics and gynaecology.
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Algorithms↗
Expression of beta human chorionic gonadotrophin by non-trophoblastic non-endocrine 'normal' and malignant epithelial cells.
Expression of hCG and its free subunits by non-trophoblastic tumours is well recognised. Previously we reported hCG secretion by normal and malignant bladder epithelial cells in vitro. Here we examined culture medium from 83 different cell lines derived mainly from common epithelial tumours. Thirty-two of the cell lines were found to secrete hCG-like material into their culture media. Partial immunochemical characterisation showed that of these only choriocarcinoma and fetal tissue cell lines produced intact hCG and alpha subunit. The remaining 28 hCG-expressing epithelial cell lines, which are of mucosal origin, only secreted free beta subunit. Expression of free beta hCG by non-trophoblastic nonendocrine cells would appear to be especially characteristic of mucosal epithelia from the genitourinary and oral/respiratory tracts. Furthermore, this phenomenon may be characteristic of epithelium with transitional and/or squamous cell-like properties.
Carcinoma↗
Serum PP14 levels in a patient with Turner's syndrome pregnant after frozen embryo transfer.
Data are presented on serum levels of the pregnancy-associated placental protein (PP14) in an XO mother, pregnant after frozen embryo transfer. Steroid replacement before and during early pregnancy was provided with transdermal oestradiol and vaginal micronized progesterone. Characterization of a pre-treatment cycle indicated a physiological response by the endometrium. The pregnancy was associated with normal maternal blood levels of all hormones considered responsible for maintenance of early gestation but with consistently subnormal serum levels of PP14. Hitherto, PP14 has been believed to be an endometrial protein arising from the decidua during pregnancy, under the influence of ovarian steroids. The findings in this case suggest that other factors are involved in its production, possibly under the control of, or originating from, the maternal ovary.
Adult↗
Insulin-like growth factor binding proteins in follicular fluid from normal dominant and cohort follicles, polycystic and multicystic ovaries.
There is now considerable evidence that the insulin-like growth factors (IGFs) play an important role in the human ovary. It has also recently become apparent that the physiological activity of the IGFs is modulated by a number of specific binding proteins (IGFBPs). In order to understand the role of the IGFs in ovarian physiology, the presence and functions of these IGFBPs will need to be characterized. As an initial step towards this we have investigated the presence of the various binding proteins by Western ligand blotting and have measured the levels of one of them, IGFBP-1, in follicular fluid (FF) obtained from unstimulated dominant and cohort follicles in 19 normal women and in eight patients with polycystic and one with multicystic ovaries. In normal women, IGFBP-1 levels in dominant follicles were similar to matched serum levels but were significantly lower in cohort follicles. IGFBP-1 levels correlated with FF-volume (r = 0.58, P less than 0.001) and with paired serum levels (r = 0.63, P less than 0.001). In post-LH surge dominant follicles this relationship with serum levels no longer held and in three out of nine subjects FF levels were higher than in serum. Thus IGFBP-1 in normal human FF appears to be partly derived from the circulation but with additional local production in the larger developing dominant follicles. Western ligand blotting revealed five IGF-binding proteins in FF running parallel with those identified in serum, suggesting that the IGFBP species previously identified in serum may also be present in FF. The two bands in positions corresponding to the components of the large (150kDa) binding complex were, as in serum, the predominant forms and in most FF samples these were even more prominent than in the accompanying serum sample. This contrasts with previous studies in lymph which suggested that the 150kDa complex was largely retained in the circulation. All three small IGFBPs varied considerably between FF samples even within an individual; each IGFBP varied independently of the other IGFBPs. Our results demonstrate that at least four discrete IGFBPs are present in FF and suggest that each may be produced independently within the ovary.
Adult↗
Composition of intact hormone and free subunits in the human chorionic gonadotrophin-like material found in serum and urine of patients with carcinoma of the bladder.
Ectopic-hCG production occurs in approximately 30% of urothelial cancers. However, the clinical features which might be expected to result from elevated hCG levels are rare. We now show that in six of seven metastatic and 20 of 21 localized (Ta-T4) positive hCG bladder cancer patients, only the free beta-subunit of hCG and its respective urinary breakdown product, beta-core, could be detected in clinical samples. Since only intact hCG is biologically active, this explains the discrepancy between biochemical and clinical findings.
Aged↗
Insulin-like growth factor binding protein-1 levels in diabetic adolescents and their relationship to metabolic control.
Circulating levels of the low molecular weight insulin-like growth factor binding protein-1 (IGFBP-1) are insulin dependent and vary markedly throughout the day. IGFBP-1 levels are abnormally high in diabetes but the relationship between this and the metabolic status of the patient has not been defined. We have therefore measured fasting IGFBP-1 levels at 0800 h in 32 diabetic adolescents. IGFBP-1 was measured in 19 of these patients after a normal night and in 27 after a night of euglycaemia, maintained with a glucose clamp. In 13 patients both studies were performed and could be compared. Puberty-matched control data were obtained from 69 normal children. In normal prepubertal children IGFBP-1 levels were high; lower levels were found with advancing pubertal development. This fall in IGFBP-1 correlated with pubertal stage (r= 0.68, p less than 0.001) and with fasting insulin levels (r = 0.60, p less than 0.001) which rose with pubertal advancement. In the diabetic children IGFBP-1 levels also correlated inversely with the 0800 h free insulin level but there was no clear relationship with pubertal development. However, when measured after overnight euglycaemia IGFBP-1 levels correlated inversely with pubertal development (r = 0.67, p less than 0.001) as in the normal children. In the patients studied on two comparable occasions the IGFBP-1 level measured after a normal night relative to that measured under standardized euglycaemic conditions was found to correlate closely with the glycosylated haemoglobin level (r = 0.71, p less than 0.005).
Adolescent↗
Changes in circulating alphafetoprotein following administration of mifepristone in first trimester pregnancy.
The occurrence of fetomaternal haemorrhage was investigated in 30 women by measuring maternal serum alphafetoprotein (AFP) levels before and after the administration of mifepristone (RU 486) for termination of first trimester pregnancy. A significant rise in AFP levels was seen in 21 women (70%), the increase ranging from 6 to 660% of baseline levels. The apparent frequency of fetomaternal haemorrhage was similar to that reported previously for surgical termination of first trimester pregnancies.
Abortifacient Agents, Nonsteroidal↗
Transvaginal ultrasound for diagnosis of uterine malformations.
Uterine malformations were detected in 8 of 300 patients (3%) referred for transvaginal ultrasound scan (TVS) for different indications. Six of them had a partially septate uterus and two had a uterus didelphys. As uterine malformations can be associated with both sterility and reproductive failure, we suggest that the study of uterine morphology and structure could be a part of routine TVS examination.
Adult↗
A comparison of different methods for calculating overall risk scores from risk factors ascertained in a computerized obstetric information system.
Current obstetric risk-scoring systems depend upon simple addition of weighted or unweighted risk factors. In this study a population of 994 pregnant women (470 primiparae; 524 multiparae) has been examined in order to compare the use of weighted and unweighted risk scores, together with Bayes theorem, in estimating an overall risk score from the presence of individual risk factors. The findings have been related to fetal outcome in these pregnancies and expressed as receiver-operating characteristic (ROC) curves for different cutoff levels between normal and abnormal. In primiparae, the use of weighted risk factors, with or without Bayes theorem, was clearly superior to the use of unweighted factors. In multiparae there was only a marginal difference between the three approaches. The increasing use of computerised information system in antenatal care should make calculation of risk scores for every pregnant woman a practical option.
Adolescent↗
Circulating levels of GH-releasing hormone and GH during human pregnancy.
To study the potential role of GH-releasing hormone (GHRH) in maintaining circulating levels of GH during pregnancy, 302 maternal plasma samples were collected from non-fasted subjects at various stages of pregnancy and assayed for GHRH using a 'two-site' immunoradiometric assay. The GH and placental lactogen levels were also determined. In addition, maternal plasma samples taken during labour, amniotic fluid and cord blood were also assayed for these hormones. Maternal plasma GHRH levels were similar to non-pregnant levels throughout gestation despite fluctuations in GH values which were always higher than non-pregnant levels. There was no significant difference between GHRH levels in maternal plasma and cord blood although high GH levels were observed in the latter. These findings suggest that peripheral GHRH levels do not play an important role in maintaining circulating GH levels during pregnancy.
Amniotic Fluid↗
Expert systems for the prediction of ovulation: comparison of an expert system shell (Expertech Xi Plus) with a program written in a traditional language (BASIC).
The use of an expert system shell (EXPERTECH Xi Plus) in the construction of an expert system for the diagnosis of infertility has been evaluated. A module was devised for predicting ovulation from the medical history alone. Two versions of this system were constructed, one using the expert system shell, and the other using QuickBASIC. The two systems have been compared with respect to: (1) ease of construction; (2) ease of knowledge base update; (3) help and explanation facilities; (4) diagnostic accuracy; (5) acceptability to patients and clinicians; (6) user-friendliness and ease of use; (7) use of memory space; and (8) run time. The responses of patients and clinicians were evaluated by questionnaires. The predictions made by the computer systems were compared to the conclusions reached by clinicians and to the "gold standard" of day 21 progesterone. The conclusions of this pilot study are: (1) the construction of this expert system was NOT facilitated by the use of this expert system shell; (2) update of the knowledge base was not facilitated either; (3) the expert system shell offered built-in help and explanation facilities, but as the system increased in complexity these became less useful; (4) after initial adjustment of decision thresholds the diagnostic accuracy of the system equalled that of the clinician; (5) the patient response to computer history-taking was very favorable but much less favorable to computer diagnosis; (6) the clinicians took a positive attitude to computer diagnosis; (7) the systems were easy to use; (8) the expert systems shell required much more memory space and had a much slower response time than the system written in BASIC.
Diagnosis, Computer-Assisted↗
Circulating levels of placental protein 12 in complications of first trimester pregnancy.
Serum placental protein 12 (PP12) levels were determined in 34 women with threatened miscarriage in whom a diagnosis of anembryonic pregnancy (n = 19), missed abortion (n = 4), complete or incomplete abortion (n = 5), hydatidiform mole (n = 1) and subsequent abortion of a live fetus (n = 5), was made ultrasonically and confirmed by histological examination. Twenty-four of the 34 patients had one or more levels between the 10th and 90th centiles of the reference range. In 7 of the 19 patients (37%) with anembryonic pregnancy and in 3 of the 4 patients (75%) with a missed abortion, PP12 levels were markedly elevated. However, in cases where serial measurements were available (n = 6), PP12 levels were seen to fall in all cases. It is concluded that pregnancies that have failed or will subsequently fail in the first or second trimester are not associated with depressed maternal PP12 levels, suggesting that the decidual synthesis of this protein is independent of the presence or viability of the fetus.
Abortion, Spontaneous↗
A model-based system to determine the relative value of different variables in a diagnostic system using Bayes theorem.
A model system is described which simulates the presenting features of cases of vaginal discharge. This system was used to examine the effects of removing individual clinical features on the overall efficiency of diagnosis by Bayes theorem. The diagnostic efficiency was significantly reduced by elimination of inflammation, of a frothy discharge, or of a curdy discharge. Elimination of more than one significant factor further reduced the number of correct diagnoses, but elimination of more than one non-significant factor made no obvious difference. The most significant clinical feature was presence of inflammation; elimination of this feature had a substantial effect on the diagnosis of gardnerella, viral, gonorrhoea and foreign body. Elimination of two of the variables (bloodstaining and odour) which did not influence overall diagnostic efficiency nevertheless had a substantial effect on the diagnosis of neoplasms and foreign bodies. It is proposed that a simulation of this type is of potential practical value in determining a minimum subset of clinical features for diagnostic systems involving Bayes theorem.
Bayes Theorem↗
Maternal serum AFP levels in the first trimester of pregnancy.
Maternal serum alphafetoprotein was assayed in 436 women presenting for termination of pregnancy at 6 to 12 weeks. The normal range for each week is presented. There was a progressive rise of AFP levels from week 7 onwards, but a clear separation from non-pregnant values was only apparent after 8 weeks. The definition of a 'low normal' range for the identification of cases at risk of Down's syndrome will probably only be possible at 11 weeks or later.
Down Syndrome↗
The effect of dependence on the performance of Bayes' theorem: an evaluation using a computer simulation.
A computer simulation is described which generates 'cases' of vaginal discharge. This simulation was used to evaluate the potential effects of dependence between clinical features on the diagnostic performance of Bayes' theorem. The following observations were made: (1) dependence between some but not all pairs of features reduced the overall diagnostic efficiency (judged by the number of true positive diagnoses); (2) the overall reduction in efficiency was never substantial; (3) the largest effects on the diagnosis of individual conditions was observed with rarer diseases, and with combinations of features which were inherently unlikely to be dependent. It is concluded that the diagnostic efficiency of Bayes' theorem will not be greatly influenced by dependence if a reasonable amount of commonsense is applied to the selection of the knowledge base.
Bayes Theorem↗
Circulating levels of placental protein 14 and progesterone following Mifepristone (RU38486) and Gemeprost for termination of first trimester pregnancy.
Ten patients underwent successful termination of first trimester pregnancies with RU38486 (Mifepristone, Roussel Laboratories Ltd., Broadwater Park, Uxbridge, Middlesex, United Kingdom) followed 2 days later by a prostaglandin (Gemeprost, May and Baker Ltd., Dagenham, Essex, United Kingdom) pessary. Four hours after administration of RU38486, the levels of progesterone (P) started to fall and continued to show a gradual decline until the abortion was completed, when a steep fall to follicular phase values was observed. Levels of placental protein 14 remained unaltered until 2 days after RU38486 administration, when levels were increased. The rise in placental protein 14 in association with falling P concentrations suggests that the decidual secretion of placental protein 14 might be independent of P. Fertil Steril 52:66, 1989.
Abortifacient Agents↗
Fetal and maternal oxytocin in human parturition.
Measurements of oxytocin in maternal and fetal circulation during human labor are reviewed and related to known changes in uterine oxytocin sensitivity during pregnancy and labor. It is concluded that oxytocin is secreted in short-lasting spurts; therefore levels measured with infrequent intervals do not give adequate information on the amounts of oxytocin secreted during labor. Presently, there is little evidence for an increased maternal secretion rate of oxytocin at the onset of labor, but during labor a progressive increase occurs, with a maximum at the expulsive phase. Fetal secretion rate also increases markedly during labor, but the timing of this increase is still unknown. The dramatic increase in human uterine oxytocin receptors at term makes the uterus responsive to very small amounts of oxytocin. Hence, an increased oxytocin secretion rate is not a necessary prerequisite for oxytocin-stimulated contractions during labor. Evidence from oxytocin receptor blockade and suppression of oxytocin secretion supports the concept that oxytocin is an important stimulus for uterine contractions in early human labor.
Female↗