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Biomedical subjects

R M Patterson

Publications and source records attributed to R M Patterson.

At least 73 records · Page 4Linked to original sources

Activated oncogenes in B6C3F1 mouse liver tumors: implications for risk assessment.

The validity of mouse liver tumor end points in assessing the potential hazards of chemical exposure to humans is a controversial but important issue, since liver neoplasia in mice is the most frequent tumor target tissue end point in 2-year carcinogenicity studies. The ability to distinguish between promotion of background tumors versus a genotoxic mechanism of tumor initiation by chemical treatment would aid in the interpretation of rodent carcinogenesis data. Activated oncogenes in chemically induced and spontaneously occurring mouse liver tumors were examined and compared as one approach to determine the mechanism by which chemical treatment caused an increased incidence of mouse liver tumors. Data suggest that furan and furfural caused an increased incidence in mouse liver tumors at least in part by induction of novel weakly activating point mutations in ras genes even though both chemicals did not induce mutations in Salmonella assays. In addition to ras oncogenes, two activated raf genes and four non-ras transforming genes were detected. The B6C3F1 mouse liver may thus provide a sensitive assay system to detect various classes of proto-oncogenes that are susceptible to activation by carcinogenic insult. As illustrated with mouse liver tumors, analysis of activated oncogenes in spontaneously occurring and chemically induced rodent tumors will provide information at a molecular level to aid in the use of rodent carcinogenesis data for risk assessment.

Animals↗

Neonatal morphometrics and perinatal outcome: who is growth retarded?

To evaluate the relationship between neonatal morphometrics and poor neonatal outcome resulting from fetal malnutrition, we prospectively examined 355 sequential live-born, singleton neonates greater than 35 weeks' gestational age. Birth weight, neonatal ponderal index, and midarm circumference to head circumference ratio were measured. A birth weight, ponderal index, or midarm circumference to head circumference ratio less than or equal to tenth or greater than or equal to ninetieth percentiles for gestational age was considered abnormal. Poor outcome was defined as operative delivery for fetal distress, 5-minute Apgar score less than 7, meconium aspiration, polycythemia, or hypoglycemia. Thirty-three (9.3%) neonates had perinatal morbidity. Although morbidity was not increased among neonates that were large by any of the criteria, five (25%) of 20 with low birth weight had poor outcome and 18 (26%) of 70 with low ponderal index or midarm circumference to head circumference ratio suffered morbidity. Of the 33 neonates with morbidity, 18 (54.5%) had low ponderal index or midarm circumference to head circumference ratio, but only five (15.2%) had low birth weight. Therefore, low ponderal index and midarm circumference to head circumference ratio are more sensitive predictors of outcome than is birth weight. As such, ponderal index and midarm circumference to head circumference ratio are more appropriate end points for antenatal diagnostic studies than is birth weight.

Birth Weight↗

Sonographic amniotic fluid measurement and fetal growth retardation: a reappraisal.

Sonographic estimation of amniotic fluid volume is commonly used as a diagnostic test for oligohydramnios associated with fetal malnutrition. However, methods of measurement and diagnostic criteria are controversial. We prospectively evaluated the reproducibility of amniotic fluid diameter measurement and studied various threshold definitions of oligohydramnios as predictors of small for gestational age fetuses or fetuses with low ponderal index values. An average of the vertical and two perpendicular horizontal diameters of the largest pocket of amniotic fluid was more reproducible than the maximum vertical pocket and better enabled a single observer to differentiate between patients. An average diameter of 10 mm was highly diagnostic of small for gestational age fetuses but was insufficiently sensitive (27%) to serve as a screening test. Although also of limited sensitivity (40%), an average diameter of approximately 30 mm was probably the best screening threshold. Reduced average diameter was significantly related to the occurrence of a ponderal index less than or equal to the tenth percentile for dates. Three of seven (43%) neonates with a ponderal index less than or equal to the tenth percentile and a birth weight greater than the tenth percentile for dates had a low average diameter, suggesting that reduced average amniotic fluid diameter may help to identify the malnourished fetus with birth weight greater than the tenth percentile for dates.

Amniotic Fluid↗

A comparison of fetal biometric ratios to neonatal morphometrics.

Ratios of fetal abdominal circumference to femur length (AC/FL) and thigh circumference to femur length (TC/FL) have been suggested as indices of fetal nutrition. Birthweight, skin-fold thickness, and ponderal index are accepted neonatal indices of nutrition. The purpose of this study was to compare fetal to neonatal indices of nutrition. In 52 patients in term labor, fetal abdominal circumference, thigh circumference, and femur length were measured ultrasonographically. Neonatal skin-fold thickness was calculated as the average of tricipital, subscapular, abdominal, and anterior thigh measurements determined with Harpenden skin-fold calipers. Linear correlation analysis demonstrated a significant relationship between AC/FL and ponderal index (r = 0.340, P = 0.028) and between TC/FL and ponderal index (r = 0.368, P = 0.007). Neither AC/FL nor TC/FL were significantly related to birthweight or skin-fold thickness. These data suggest that the diagnostic reliability of antenatal studies of fetal biometric ratios may be enhanced by using the ponderal index as a neonatal endpoint rather than birthweight or skin-fold thickness.

Abdomen↗

Modulation of lectin-stimulated lymphocyte agglutination and mitogenesis by estrogen metabolites: effects on early events of lymphocyte activation.

Pharmacological doses of estrogens such as 17-beta estradiol (17-beta E) and diethylstilbestrol (DES) suppress cell-mediated immunity in vivo. In this report, we investigated the direct in vitro effects of 17-beta E and its major metabolites on lymphocyte proliferation in response to the T cell lectin phytohemagglutinin (PHA). PHA-induced lymphocyte agglutination, an early event indicative of active, cytoskeletal-dependent membrane alterations, was monitored in conjunction with blastogenesis. Without exception, the effects of individual estrogen metabolites on the PHA-induced agglutination occurring within minutes were accompanied, at every concentration of compound, by equivalent effects on the blastogenic response of activated cells measured after several days. This observation suggested a role for estrogens in modulating lymphocyte activation at the cell surface rather than through cytosolic receptor-mediated events. As suggested by previous studies with quinone metabolites of benzene, the catechol estrogen metabolite 2-OH estrone (2-OH E) was significantly more potent than the parent compound at suppressing lymphocyte proliferation in vitro and in vivo.

Agglutination↗

The in vivo effect of amniotic fluid on endocervical microflora.

To test the in vivo effect of amniotic fluid on endocervical microflora, we performed endocervical cultures before and after rupture of the membranes in 20 patients in term labor. There were no significant qualitative or quantitative differences in aerobic or anaerobic isolates for up to 4 hours after membrane rupture. Group B streptococci, isolated in two patients (10%), persisted after rupture of the membranes. These data suggest that endocervical cultures are minimally influenced by rupture of the chorioamnion for at least 4 hours.

Amniotic Fluid↗

Rupture pressure of elastic and muscular aortic segments from hypertensive and hypotensive turkeys.

Blood pressures and heart rates were recorded from two groups of turkeys in two trials. In trial one 20 turkeys, 36 weeks of age and in trial two 24 turkeys, 14 weeks of age, were used. Immediately after blood pressures and heart rates had been determined, the turkeys were killed and vascular tissues were excised. Equal numbers from hypertensive and hypotensive lines of turkeys were used in each trial to determine the rupture pressure of both the elastic and muscular segments of the aorta. When values for the two trials were combined, mean hydrostatic pressures of 1478, 1804, and 794 mm Hg respectively were required to rupture the most caudal abdominal aortic segment, the adjacent cranial abdominal segment, and the thoracic aortic segment. There was a significant difference between the two lines for blood pressure in both trials and for heart rate in trial 2. There were no statistically significant correlations between blood pressure, atherosclerotic plaque score and rupture pressure. Birds fed on a diet containing added fat and cholesterol had significantly lower blood pressures than the birds fed on the other two diets. Birds receiving added dietary cholesterol and fat had lower heart rates than birds fed on the diet with added fat only. Lower plaques scores were evident in the caudal abdominal aorta of the birds fed on the control diet compared to birds fed on the other two diets.

Animals↗

Analysis of birth weight percentile as a predictor of perinatal outcome.

Birth weight-gestational age tables are convenient methods for the neonatal evaluation of intrauterine growth, however, the limits of acceptable birth weight for gestational age are controversial. The purpose of this study was to identify the birth weight percentiles that accurately predicted poor perinatal outcome from 28 through 41 weeks' gestational age. In a homogeneous population of 44,811 patients, the birth weight percentile that predicted poor perinatal outcome varied with gestational age. The birth weight percentile that predicted normal outcome in 80% of normal patients declined from the 55th percentile at 28 to 29 weeks to the 24th percentile at 34 to 35 weeks. From 28 through 35 weeks' gestational age, possibly owing to the confounding effects of prematurity, patients classified as normal by birth weight criteria still had a significant risk of poor outcome. After 36 weeks' gestational age, poor perinatal outcome occurred in 3.9% of patients and tended to occur at the extremes of birth weight. Classification by birth weights approximating the tenth and 90th percentiles identified a population in which the majority of the poor perinatal outcome occurred. However, poor outcome occurred in only 10% of patients with birth weights below the tenth or above the 90th percentiles. Among those with birth weights between the tenth and 90th percentiles, outcome was normal in 98%. Therefore, from 36 through 41 weeks' gestational age, the prevalence of poor perinatal outcome was low, and birth weight percentile was a weak predictor of outcome in the individual patient.

Birth Weight↗

Birth weight percentile and perinatal outcome: recurrence of intrauterine growth retardation.

In 9596 patients followed throughout two pregnancies, recurrence of intrauterine growth retardation (IUGR) was evaluated as a function of previous birth weight percentile and attendant complications of pregnancy. Among 4623 patients with two uncomplicated pregnancies, the prevalence of recurrent IUGR was significantly related to the severity of growth retardation in the first pregnancy (P less than .0001). Those patients with both medical complications and IUGR in the first pregnancy remained at significantly increased risk for recurrent IUGR, even when the second pregnancy was uncomplicated. In second pregnancies, the combination of a previous history of an IUGR neonate and an additional current complication of pregnancy acted synergistically to increase the risk of recurrent IUGR to a level higher than that attributable to either risk factor alone.

Birth Weight↗

Modulation of nonspecific cell-mediated growth inhibition by estrogen metabolites.

Chronic exposure of mice to estrogens such as 17-beta estradiol and diethylstilbestrol inhibits natural killer cell-mediated cytotoxicity in vivo. In this report, we investigated the direct in vitro effects of 17-beta estradiol and its major metabolites on nonspecific effector cell function measured as the ability of naive lymphocytes to inhibit the growth of the YAC-1 lymphoma, a classical natural killer-sensitive target cell. Without exception, the effects of individual estrogen metabolites on the growth inhibitory properties of these cells were accompanied, at every concentration of compound, by identical effects on the blastogenic response of lymphocytes to the T cell lectin phytohemagglutinin. These observations suggested membrane-mediated immunomodulation of lymphocyte function by estrogen metabolites. As suggested by previous studies with quinone metabolites of benzene, the catechol estrogen metabolite 2-OH estrone was significantly more potent than the parent compound at suppressing lymphocyte functions in vitro; however, dosing regimens of 2-OH estrone that suppressed blastogenic response in vivo failed to inhibit nonspecific cell-mediated growth inhibition.

Animals↗

Modulation of lymphokine-induced macrophage activation by estrogen metabolites.

Pharmacological doses of estrogens such as 17-beta estradiol (17- beta E) and diethylstilbestrol (DES) activate macrophages in a thymic-dependent manner in vivo. In this report, we investigated the direct in vitro effects of 17- beta E and its major metabolites on macrophage activation in response to lectin-stimulated lymphocyte supernatants containing macrophage-activating factor (MAF), a T cell lymphokine (LK). Activation was measured in terms of macrophage cytostasis against cultured tumor cells. As suggested by previous studies with quinone metabolites of benzene, the catechol estrogen metabolite 2-OH estrone (2-OH E) was the most potent metabolite at suppressing LK-induced macrophage activation. However, if macrophages were first LK-induced, and then exposed to estrogens before addition of tumor cells, then all the estrogens, including 2-OH E, enhanced cytostasis. These observations suggested membrane-mediated immunomodulation of macrophage function by estrogen metabolites and, indirectly, a role for the thymus in these effects via the maintenance of a mature, LK-producing T cell population necessary for macrophage activation.

Animals↗

Estimation of fetal weight during labor.

Fetal weight was estimated clinically and by two ultrasonographic methods in 62 patients in labor at term. Maternal obesity precluded clinical estimation of fetal weight in eight patients (12.9%) and a combination of maternal obesity, anterior placentation, and oligohydramnios prevented ultrasonographic fetal measurement in four patients (6.5%). In 43 patients, in whom all three methods of estimate were obtainable, a regression equation using ultrasonically measured fetal abdominal circumference provided the greatest accuracy. However, significant interpatient variability affecting the accuracy of all three methods of estimating fetal weight may limit the clinical application of these measurement techniques.

Amniotic Fluid↗

Trauma in pregnancy.

In summary, salient points are as follows: The obstetrician must be aware of the normal physiology of pregnancy and the unique response of the pregnant patient to stress and trauma. Maternal stabilization is paramount in the initial management of trauma. With regard to motor vehicle trauma, the three-point restraint system is superior to lap-belt restraint and should be worn by all pregnant women. In the case of maternal survival, placental abruption is the most common cause of fetal death. This may be managed expectantly in many cases. In abdominal trauma requiring laparotomy, the gravid uterus must not compromise maternal care. Management will depend on maternal condition at the time of laparotomy and along a projected course of convalescence. Fetal gestational age and clinical status also must be considered. Vaginal delivery is not contraindicated following exploratory laparotomy. Fetal demise is not an indication for hysterotomy. Postmortem cesarean section is well supported medicolegally. Elapsed time from maternal death and the gestational age of the fetus are the critical factors affecting perinatal outcome.

Abdominal Injuries↗

Ultrasonographically observed early placental maturation and perinatal outcome.

Perinatal outcome in 398 patients who had Grade II or Grade III placentas was analyzed in a cross-sectional study. Early placental maturation was identified in 51 patients. A trend toward lower mean birth weights was identified in the group with early placental maturation as compared to controls; however, statistical significance was achieved only in the Grade II population. In the Grade III population, early placental maturation identified a group of patients with a 16.7% incidence of growth retardation as compared to 4.1% in control patients (p less than 0.01). Early placental maturation was an insensitive predictor of poor perinatal outcome with respect to maternal hypertension, antepartum or intrapartum fetal distress, and perinatal asphyxia.

Adolescent↗