Electrochemical monitoring of anticancer compounds on the human ovarian carcinoma cell line A2780 and its adriamycin- and Cisplatin-resistant variants.

A novel electrochemical technique which detects and monitors real-time changes in cell behavior in vitro has been used to examine the effects of recognized anticancer drugs on the human ovarian carcinoma cell line A2780 and its adriamycin (A2780adr)- and cisplatin (A2780cispt)-resistant variants. These cells, adherent to gold electrodes or sensors, modify the extracellular microenvironment at the cell:sensor interface, producing an electrochemical potential that is different from that of the bulk culture medium. Confluent, adherent A2780 cells produced an electrochemical signal, measured as an open circuit potential (OCP), of approximately -100 mV compared to a cell-free value of approximately -15 mV. Exposure of A2780 cells to cisplatin (range 10(-4) to 10(-6) M), adriamycin (range 10(-5) to 10(-7) M), and vinblastine (10(-6) M) all produced positive shifts in the OCP signal relative to untreated control cells during 24 h of culture, but Taxotere (range 10(-5) to 10(-7) M) had no effect. These positive shifts in OCP signal were evident well before observations of reduced cellular adhesion and viability after 24 h, as judged in parallel cultures with a plastic substratum and by scanning electron microscopy. By contrast, the same treatments applied to the A2780adr and A2780cispt variants showed that each demonstrated different sensitivities to the same drugs applied to the parental A2780 cells. The effects of the same four anticancer drugs on ovarian carcinoma (A2780) and breast carcinoma (8701-BC) cell lines showed that the former was far more responsive to adriamycin and cisplatin. Such differences in drug sensitivities between the two cell lines were subsequently confirmed using the conventional MTT assay over 5 days. Although this electrochemical technology readily detects changes in cell adhesion and viability, the modified OCP signals recorded within a few hours of anticancer drug treatments are evident well before microscopic morphological changes become apparent. It is proposed that these early changes in OCP signals, relative to control untreated cells, reflect modifications of physiological/behavioral processes manifested at the cell surface.

Electrochemical monitoring of cell behaviour in vitro: a new technology.

This article describes a novel electrochemical technique for the real-time monitoring of changes in the behaviour of adherent human cells in vitro: i.e., a biosensor that combines a biological recognition mechanism with a physical transduction technique, described collectively as Oncoprobe. Confluent viable cells adherent to gold electrodes (sensors) modify the extracellular microenvironment at the cell:sensor interface to produce a change in the electrochemical potential compared to that measured in the absence of cells. The potential was measured as an open circuit potential (OCP) with respect to a saturated calomel reference in the bulk culture medium. Typical OCP values for confluent cultures of human breast carcinoma cells, 8701-BC, approximated -100 mV compared with cell-free values of approximately -15 mV. The OCP for 8701-BC cells was modified in response to temperature changes over the range 32 to 40 degrees C and also to treatments with phytohemagglutinin (PHA, 25 microg/mL), cycloheximide (30 microM) and interleukin-1 beta (IL-1, 0.5 ng/mL) over 24 h. Cultures of synovial fibroblasts also responded to the same treatments with similar responses, producing negative shifts in the OCP signal with PHA and IL-I, but a positive shift in OCP signal with cycloheximide, all relative to the untreated control cultures. From experimental data and theoretical considerations it is proposed that the cell-derived signals are mixed electrode potentials reflecting a "conditioned," more reducing environment at the cell:sensor interface. Only viable cells caused a negative shift in the OCP signal, this being lost when cells were rendered nonviable by formalin exposure. This technology appears unique in its ability to passively "listen in" on cell surface activities, suggesting numerous applications in the fields of drug discovery, chemotherapy, and cell behaviour.

Comparison of intrapartum fetal monitor tracings of karyotypically abnormal and control infants.

To determine if there are any specific monitoring patterns associated with chromosomal abnormalities the intrapartum tracings of 17 postnatally diagnosed karyotypically abnormal infants were obtained. Controls were randomly selected from infants born on the same day at the same gestational age. The tracings from these two groups were independently evaluated. Comparison of the monitor interpretations showed: (1) the karyotypically abnormal group was more likely to have decreased or absent short- (p < 0.001) and long-term (p < 0.01) variability; (2) accelerations were more likely to be represented in the control group (p < 0.001); (3) no significant differences were found in the baseline heart rates or in the presence or frequency of mild, moderate, or severe variable or late decelerations. These findings may reflect underlying central nervous system abnormalities as opposed to uteroplacental insufficiency, but are not specific to karyotypically abnormal infants.

Predicting prematurity: the mammary stimulation test.

The MST appears to have theoretical rationale, predictive utility, simplicity, safety, and low cost that suggests that its routine use in prematurity prevention may ultimately save significant health care dollars. Presently, the MST should be used as an adjunct to prenatal care until further and more definitive investigation has been conducted; however, it seems promising that the MST will provide some reassurance in patients with negative tests and signify patients that are at significant risk for premature delivery (positive MST). It is hoped that further investigation will validate the MST's use in prematurity prevention in order to help decrease the incidence of preterm delivery.

The mammary stimulation test--a predictor of preterm delivery?

Clinical risk identification for preterm delivery, the major cause of perinatal morbidity and mortality, remains problematic. To test the hypothesis that a provocative test for uterine contractility at the beginning of the third trimester would reliably identify patients destined to be delivered before and at term, we designed the mammary stimulation test. Uterine contractions in response to nipple stimulation at a mean of 28.6 weeks' gestation, were evaluated in 94 gravid patients at risk for preterm delivery. The mammary stimulation test, the results of which were not used for clinical management, was positive in 50% of patients tested and had a sensitivity of 84% and a positive predictive value of 34% (chi 2 = 11.15, p less than 0.01). Ninety-four percent of patients predicted to be delivered at term actually were delivered at term (negative predictive value). Furthermore, no patients with a negative mammary stimulation test were delivered within 1 month of testing or were delivered of infants weighing less than 2000 gm. Discriminant analysis indicated that the mammary stimulation test provided information beyond that available from clinical risk factors alone. A cost analysis suggested that the use of the mammary stimulation test could reduce the cost of ambulatory uterine activity monitoring by nearly 50%. If these findings can be validated in additional samples, the mammary stimulation test may be useful in prematurity prevention programs.

Report of the Council on Scientific Affairs of the American Medical Association: ultrasound evaluation of the fetus.

Ultrasound evaluation of the fetus has become a vital part of prenatal care not only to detect abnormalities of fetal growth, but to diagnose congenital anomalies, hydatidiform mole and ectopic pregnancy, to assess fetal well-being, and finally to provide ultrasound guidance for invasive procedures. This article will discuss the role of fetal ultrasonography as we head into the 1990s, the changing concepts of indications for ultrasound scanning, the increasing sophistication of the technique, and the types of anomalies detected by this imaging method.

Undergraduate medical education in obstetrics and gynaecology in the USA and Canada, 1985.

Many factors have led to a movement from the emphasis of the 1960s and 1970s on departmental expansion towards an emphasis on cost-effective undergraduate medical education emphasizing the 'art' as well as the 'science' of medicine. In January 1985 a questionnaire was sent under the auspices of the Undergraduate Education Committee of the Association of Professors of Obstetrics and Gynecology to all chairmen of departments of obstetrics and gynecology in the USA and Canada seeking their opinions about these trends and information about the educational programmes in their departments. The information from this study indicates that the chairmen are aware of and responding to this new direction in medical education. A stabilization of teaching staff and clerkship sizes and the emphasis on clinical as well as cognitive evaluation, despite recognition of the cost of the former, shows active interventions towards these ends. An emphasis on education in 'basic' as compared to 'subspecialty' areas which is independent of the subspecialty of the academic chairman also supports this trend.

Student evaluation in obstetrics and gynecology clerkships in the United States and Canada, 1985.

Chairmen of departments of obstetrics and gynecology in the United States and Canada were surveyed to determine how students were evaluated in obstetric-gynecologic clerkships. Internally developed written and oral examinations and subject examinations from the National Board of Medical Examiners were used in more than one-half the departments. Written, oral and practical examinations were considered ideal evaluation methods.

A modified biophysical profile for antenatal fetal surveillance.

Three hundred thirty-seven high-risk pregnancies were screened using a modified biophysical profile consisting of nonstress testing (NST) and ultrasound evaluation of amniotic fluid volume. Ultrasound assessment of fetal breathing and body movements was performed only to evaluate the nonreactive NST. Decreased amniotic fluid volume and spontaneous fetal heart rate (FHR) decelerations were considered abnormal findings during antenatal testing, and served as indications for delivery regardless of FHR reactivity. Despite intervention, decreased amniotic fluid volume and spontaneous decelerations were associated with an increased incidence of meconium staining, decelerations during labor, cesarean section for fetal distress, and small for gestational age infants. Perinatal morbidity also occurred in patients with spontaneous decelerations and normal amniotic fluid volume. The search for spontaneous FHR decelerations by electronic fetal monitoring should continue during antepartum testing because FHR decelerations cannot be identified by conventional ultrasound assessment. The modified profile seems practical for routine assessment of fetal well-being in high-risk pregnancy, and affords insights unavailable with ultrasound surveillance alone.

Maternal risk status and postdate pregnancy outcome.

Using a 1982-1985 regional perinatal network data base of 69,746 infants, a retrospective study was conducted to compare the perinatal outcome of 7,729 postdate infants (greater than or equal to 42 weeks' gestation) by maternal risk status. Due to additional antenatal complications, of which 8.0% were hypertension and/or diabetes, 48.4% of the postdate pregnancies were classified as at risk. As expected, high-risk women experienced a higher incidence of adverse perinatal outcomes than did low-risk women. The incidence of meconium staining, low five-minute Apgar scores and perinatal mortality increased beyond term and was found most commonly in infants from high-risk pregnancies, especially those involving hypertension and diabetes mellitus. These results suggest that high-risk pregnancies probably should not enter the postdate period since their doing so places the infant at serious risk.

Postdate pregnancies: a review of 46 perinatal deaths.

A review of 46 perinatal deaths was conducted using a 1982 to 1985 regional perinatal network database of 6701 delivered postdate (greater than or equal to 42 weeks gestation) infants. Perinatal mortality (6.9 per 1000 births) increased as gestational age advanced beyond 42 weeks, and was higher in young teenagers or mothers with some additional antenatal complications, such as hypertension. Meconium staining of the amniotic fluid, low Apgar scores, low birthweight, congenital malformations, and neonatal complications, including pneumothorax, meconium aspiration, and seizures, were associated with perinatal death.

Perinatal morbidity and mortality in a regional perinatal network.

A study of pregnancy outcome was performed using a 1982-1985 regional network database of 60,456 infants. The perinatal mortality rate was 15.6 deaths per 1,000 births (total, 942), while the antepartum, intrapartum and neonatal mortality rates were 5.3, 1.6 and 8.7, respectively. Seven hundred forty-three multiple gestation pregnancies (1.2%) and 1,632 major congenital anomalies (2.7%) were identified. The corrected perinatal mortality rate was 13.8 deaths per 1,000 births. This study revealed that prematurity, postdatism, congenital anomalies, low Apgar scores and neonatal complications, including respiratory distress syndrome, pneumothorax, persistent fetal circulation, intracerebral hemorrhage and seizure activity, were major factors contributing to mortality. This analysis suggests that a further reduction in mortality should follow a reduction in preterm deliveries and their sequelae and the early identification and management of maternal and fetal antenatal complications.

Effect of gestational age on baseline fetal heart rate during the third trimester of pregnancy.

Analysis of the fetal heart rate in 3,127 reactive nonstress tests revealed that the baseline rate decreased significantly between 28 and 41 weeks' gestation (6.4 beats per minute [4.5%]). Analysis of 235 women with two tests at least four weeks apart revealed that while the majority (51.1%) demonstrated a decrease, 26.8% experienced a rise in the baseline rate during the testing interval.

Perinatal characteristics of uncomplicated postdate pregnancies.

Using a regional perinatal network database of 60,456 births, a study compared 3457 postdate (42 weeks or longer) infants to a control group of 8135 infants born at 40 weeks' gestation from 1982 through 1985. Both patient groups included only uncomplicated pregnancies. Although the differences were small, women who delivered postdate infants had a lower parity, higher weight at delivery, and higher blood pressure during pregnancy than controls. The postdate infants were heavier, more likely to be delivered by forceps or cesarean section, and more likely to experience shoulder dystocia. They also had lower Apgar scores and more meconium aspiration and congenital malformations. Although the overall perinatal mortality was not statistically different, the higher perinatal morbidity in postdate infants suggests that careful attention should be paid to this high-risk problem.

Family history of diabetes mellitus and oral glucose tolerance testing criteria.

A review of 185 obstetrical patients, having a family history of diabetes mellitus without medical history of glucose intolerance in the non-pregnant state was conducted. A 3-hour 100-g oral glucose tolerance test was performed on all patients between 20 and 34 weeks of gestation. According to O'Sullivan's criteria for glucose tolerance testing, normal glucose tolerance occurred in 89.7%, while Class A diabetes was identified in 10.3% of patients tested. 3.8% of the study population fulfilled the O'Sullivan criteria for abnormal glucose intolerance and required insulin treatment during pregnancy. The Division of Perinatal Medicine at Duke University has traditionally defined the abnormal glucose tolerance test at glucose values lower than O'Sullivan's internationally accepted criteria. An intermediate group, having abnormal glucose values according to the Duke criteria, was classified as "Carbohydrate Intolerance", comprised 32.4% of the patients tested and were managed identically to O'Sullivan Class A Diabetes. Analysis or perinatal outcome, including macrosomia, birth trauma and neonatal morbidity, revealed that Carbohydrate Intolerance patients fulfilling O'Sullivan criteria, being similar to patients with 'normal' GTT test results. Patients having a family history of diabetes mellitus, appeared as a group to be at increased risk for macrosomia, fetal distress and cesarean delivery, compared with the general population.

Rupture of the pregnant uterus: a 53-year review.

A 53-year (1931-1983) review of 48 patients who experienced uterine rupture and were cared for at Duke University Medical Center was conducted. The observed incidence was one uterine rupture per 1424 deliveries. From January 1, 1963, through December 31, 1983, 24 cases of ruptured uterus were identified; a detailed review of these patients is presented.

Pregnancy-induced hypertension and postpartum maternal morbidity.

Prospective evaluation of 80 patients experiencing preeclampsia/eclampsia was conducted. Traditional antepartum clinical presentation, classification, and laboratory evaluation were found to be imprecise for the prediction of postpartum maternal morbidity. Serial urine samples were collected from all patients during the antepartum, intrapartum, and postpartum period. Urine albumin and immunoglobulin G (IgG) concentrations were measured by rate nephelometry. The degree of albumin and IgG excretion before and after standard treatment modalities correlates with the occurrence of postpartum morbidity. The nephelometric urinalysis appears to be of assistance in the evaluation of disease severity, the effectiveness of treatment modalities on renal function, and the identification of patients destined to develop postpartum morbidity. In addition, rapid nephelometric urinalysis makes the collection of 24-hour urine samples unnecessary for evaluation of renal function in pregnancy-induced hypertension.

Peripartum hysterectomy: a review of cesarean and postpartum hysterectomy.

A retrospective review of 117 women who underwent peripartum hysterectomy at Duke University Medical Center during the past 21 years was conducted. Seventy-three cesarean hysterectomies were performed electively; 44 cesarean or postpartum hysterectomies were performed as emergencies. Statistically significant differences were noted between these groups in surgical technique, operative time, estimated blood loss, intraoperative hypotension, and intraoperative and total blood replacement. Additional significant differences were noted in postoperative febrile morbidity, use of therapeutic antibiotics, incidence of thromboembolic phenomena, and length of postoperative hospital stay. Separate analysis of elective cesarean hysterectomy patients revealed statistically significant decreases in operative time, estimated blood loss, intraoperative and total blood replacement, and postoperative hospital stay in the group having an experienced surgeon when compared with the group with less experienced surgeons.