Pharmacokinetics and expert systems as aids for risk assessment in reproductive toxicology.

A minimal approach to risk assessment in reproductive toxicology involves four components: hazard identification, hazard characterization, exposure characterization, and risk characterization. In practice, risk assessment in reproductive toxicology has been reduced to arbitrary safety factors or mathematical models of the dose-response relationship. These approaches obscure biological differences across species rather than using this important and frequently accessible information. Two approaches that are formally capable of using biologically relevant information (pharmacokinetics and expert system shells) are explored as aids to risk assessment in reproductive toxicology.

Alterations of occlusive cuff impedance plethysmography results in the obstetric patient.

Impedance plethysmography (IPG) is an attractive diagnostic method for evaluating deep vein thrombosis in the pregnant patient because it is noninvasive and it avoids x-ray or radionuclide exposure. However, the accurate diagnosis of deep venous thrombosis by IPG in pregnant patients might be altered by the normal physiologic and anatomic changes that occur during pregnancy. We evaluated 50 healthy women by IPG throughout their pregnancies and during their nonpregnant state. We found that venous capacitance during pregnancy increases 50% over venous capacitance during the non pregnant state. Most of this change occurs during early pregnancy because of a decrease in venous tone caused by rising levels of progesterone and estradiol. During the third trimester of pregnancy venous outflow is diminished compared to outflow during early pregnancy. Venous obstruction by the gravid uterus and fetal head engaging in the pelvis are factors that contribute to this finding. The IPG results in four patients with ileofemoral thrombosis and in three with postpartum pulmonary emboli are also reported. IPG may be utilized as an accurate diagnostic technique in the pregnant woman if the physiologic and anatomic alterations of pregnancy, which are reflected as significant changes in venous capacitance and outflow on IPG testing, are considered.

Sexual behavior during pregnancy.

This descriptive study of sexual behavior and response in 1500 obstetric patients registering for prenatal care demonstrates complex interactions of various sociodemographic factors. Variables most predictive of coital frequency during pregnancy include marital status, gestational age, parity, and race, as well as some unique combinations of statistics. Orgasmic response increases with patient age but lack of understanding of the terminology makes further interpretation unreliable. Dyspareunia is experienced infrequently during pregnancy. When it occurs, it decreases coital frequency in single women more than in married women. Studies examining differences or changes in sexual behavior during pregnancy versus fetal outcome must take into account that factors known to affect fetal outcome are also associated with changes in sexual behavior.

Information management needs of the obstetrician-gynecologist--a survey.

A random sample survey of members of The American College of Obstetricians and Gynecologists (ACOG) was conducted to ascertain the extent to which computer technology was being used by the members, and what further computer services and applications were needed. Computers were used by 38% of the members, with an additional 13% planning on getting a computer within the year. An average of 48% of the members had no plans for computerization, although this number was lower (29%) for physicians 36-45 years of age. There was no significant variation of use by physician sex or type of practice (office- versus non-office-based). Word processing and financial management were the most frequently used computer applications; clinical patient care tasks were used much less frequently and were presumably less available, because software for these tasks was also highly desirable. The most desired information services were uniform coding and terminology, high-risk patient management, electronic access to full-text obstetric and gynecologic data bases, and online clinical management protocols. Prescription writing, patient recall by drug, and drug inventory computer applications were among the least requested. Several educational, project development, communication, and member service strategies have been formulated to integrate medical information management activities for ACOG members.

Thromboembolism complicating surgery for cervical and uterine malignancy: incidence, risk factors, and prophylaxis.

Venous thromboembolism is a leading cause of death and morbidity after extended surgery for early malignancies of the cervix and uterus. Two hundred eighty-one patients who underwent such surgery were retrospectively evaluated for associated risk factors, the incidence of clinically significant thromboembolic complications, and prophylactic value of low-dose heparin and antiembolism stockings. Significant thromboemboli were encountered in 7.8% of patients postoperatively and accounted for the only 4 postoperative deaths. Forty-five percent of patients who developed thromboemboli did so after discharge from the hospital. The preoperative risk factors found to be associated with thromboembolism, in order of statistical significance, were weight in excess of 85.5 kg, advanced clinical stage of malignancy, and radiation therapy within 6 weeks of the operative procedure. Low-dose heparin therapy and the use of antiembolism stockings as preventative measures did not appear to reduce the incidence of thromboembolic complications. A prospective study will be necessary to evaluate definitely the effectiveness of various therapeutic modalities on thromboembolism in gynecologic oncology patients.

Prediction of risk for human developmental toxicity: how important are animal studies for hazard identification?

To determine how developmental toxicity studies in animals can be used in human risk assessment, a data base was assembled from the literature. It included probable, suspected, unknown, and probably negative teratogenic or embryotoxic drugs and chemical compounds. For each of 175 substances, we recorded the results of any developmental toxicity testing in up to 14 animal species and any reports of mutagenicity or carcinogenicity. Logistic regression and discriminant analysis were used to predict a compound's effect in humans. A measure of the number of positive animal studies and bacterial mutagenicity were important predictors in both models, as were the specific results in hamsters and subhuman primates. The fact that a compound had been tested at all in subhuman primates was more important in predicting human risk than was the result itself. The methods used correctly classified the study compounds 63-91% of the time, depending upon how the suspicious and unknown compounds were treated. The models had a sensitivity of 62-75%, a positive predictive value of 75-100%, and a negative predictive value of 64-91%. These findings imply that studies in laboratory animals carry weight in predicting human developmental toxicity. The more animal species in which a compound is positive, the more likely it is to have a human effect, albeit not the same effect as in the animals. Clinicians should not ignore developmental toxicity tests in animals "because laboratory rats are not like humans."

The effects of prophylactic management and therapeutics on hypertensive disease in pregnancy: preliminary studies.

A controlled prospective evaluation of pregnancy complicated by chronic hypertension is proposed and preliminary data on population selection and pregnancy outcome are presented. Sixty-three women with evidence of underlying hypertensive disease were followed prospectively throughout pregnancy. Twenty-three patients were followed in a protocol of intensified prenatal care and randomized assignment of antihypertensive agents: placebo, hydralazine, or methyldopa. Forty patients were followed in the high-risk pregnancy clinics at Duke University. The incidence of preeclampsia in the randomized prophylactic antihypertensive group was statistically lower than that in the nonrandomized group (8.7 versus 32.5%; P less than .01). There were no other statistically significant differences between the groups. The 63 hypertensive women had a high incidence of diabetes mellitus diagnosed during pregnancy (49.2%) as compared to the authors' general obstetric population (8.1%).

A computerized obstetric medical record.

Duke University has utilized computerized obstetric medical records since 1971. System evolution is described. Deficiencies in the current system appear to evolve from the computer/human interface rather than from basic system design. Critical elements in system success are physician acceptance of the appearance of data collection sheets and printed notes and continual rapid response in programing modification to allow for physician individuality and changes in medical practice. The limiting factor in the potential usefulness of such a system is the rate of incomplete data collection. It is suggested that if the physician were to enter data directly into the computer through a terminal, data collection would be more accurate and complete.

Effect of oocyte number and rate of atresia on the age of menopause.

Menopause occurs when oocyte number falls below the threshold required for ovarian function. The age of menopause is decreased by some drugs, some occupational exposures, and cigarette smoke (both active and passive). Using data collected by Block (Acta Anat (Basel) 1954; 14:208), we have constructed four, two parameter models to explore the effect of oocyte number and rate of atresia on age at menopause. The models used are: linear [O(A) = OB + R * A]; natural log [O(A) = R * In (A)]; exponential [O(A) = OB * exp(R * A)], and power [O(A) = OB * Age(R)]. OB = oocyte number at birth, ATR = rate of atresia, and O(A) = number of oocytes at age A. The parameters for the four models are: (formula; see text) Each model has different behavior with respect to alterations in oocyte number and rate of atresia on age at menopause. Animal studies suggest that ovarian failure is only weakly dependent on oocyte number, consistent with the power and exponential models. These suggest that the decrease in age at menopause following xenobiotic exposures results from an increase in the rate of atresia.

Developmental toxicity risk assessment: a rough sets approach.

A rough-sets approach was applied to a data set consisting of animal study results and other compound characteristics to generate local and global (certain/possible) sets of rules for prediction of developmental toxicity in human subjects. A modified version of the rough-sets approach is proposed to allow the construction of an approximate set of rules to use for prediction in a manner similar to that of discriminant analysis. The modified rough-sets approach is superior in predictability to the original form of rough-sets methodology. In comparison to discriminant analysis, modified rough sets (approximate rules) appear to be better in overall classification, sensitivity, positive and negative predictive values. The findings were supported by applying the modified rough sets and discriminant analysis on a test data set generated from the original data set by using a resampling plan.

Teaching basic principles of surgical technique using a placental model.

Surgical technique was taught to third-year medical students using the placenta as tissue for practice and to illustrate the proper use of surgical tools, using principles that promote accuracy, security and efficiency of manual control.

Premature rupture of the membranes: maternal and neonatal infectious morbidity related to betamethasone and antibiotic therapy.

A retrospective study of patients delivering in 1976-77 at Duke University Medical Center was performed to assess the impact of betamethasone and prophylactic antibiotics on infectious morbidity in mothers with premature rupture of the membranes (PROM) at 26 to 34 weeks' gestation and in their neonates. Ninety-five records were reviewed for evidence of maternal and neonatal infection and perinatal mortality. Betamethasone had no impact on maternal or neonatal infection. Antibiotics given concurrently with betamethasone significantly reduced the incidence of maternal and/or neonatal infection (18.0% vs. 0). Perinatal mortality increased when the duration of the latent period was 72 hours and greater because of factors other than infection.

Microcomputer-aided instruction for ob-gyn education.

PC-CAI is a computer program that presents text characters from a word-processed file. The software was created to allow rapid authoring of computer-aided-instruction modules or multiple choice tests that give explanation and feedback to the student about their choice of responses. The program is IBM-PC/XT/AT compatible under MS-DOS. It is used in the Department of Obstetrics and Gynecology for medical students to supplement faculty lectures and also to administer pre- and post-tests to those students. The program is additionally used to create practice tests for our residents to prepare for their in-training exams. The software's main forte is to create multiple choice question modules, with feedback and explanations, that serve as learning tools rather than just as testing tools. Its use has enabled our department to create a comprehensive set of teaching modules in a relatively short period of time. These modules are easily modifiable as medical concepts or teacher emphasis changes.

Learning resources for medical computing.

For medical professionals to acquire computer literacy can be an arduous task. Resources for learning medical computing fall into four major categories: learning technical microcomputer use, computerizing an office practice, tracking patient care experience and integrating medical information systems. Both microcomputer use and tracking patient care experience are technical skills similar to learning any medical procedure with which physicians are already familiar. These skills can be acquired by consulting general, commercial resources such as computer stores, popular computer magazines or software manuals. Computerizing an office practice involves diagnosing office information problems by thoroughly analyzing how data flow during outpatient care. Medical information system design and management is a cognitive specialty in which principles of computer science and medical information management are applied to patient care experience.

Application of computer technology to reproductive endocrinology.

Data manipulation and information management activities are as central to physicians as writing is to the literary profession. It is not surprising that the computer, as an information tool, has become important and accepted in many aspects of our professional lives. Computer applications can significantly help in daily patient care activities as well as serve as instruments for advancing and managing medical knowledge. Even if the rate of computer technology change slows down from its exponential increase in the last decade, useful software applications will continue at the same or faster rate since they do not now, fully utilize existing hardware features. This presents an exciting future for all information management, decision-rich professions.

Computer applications in obstetrics.

The potential impact of the computer on the practice of obstetrics has long been recognized and is slowly being realized. Computers are already essential in many administrative aspects of obstetrics and indispensable in data storage and analysis for clinical research. Emerging applications include computer systems for taking the perinatal history, storage and on-line interpretation of fetal monitor tracings, information retrieval for case management and research purposes, and computer-assisted instruction. Future applications offer possibilities of computerized consulting for support of obstetric decisions and sophisticated case simulations for continuing education.