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Effects of low intermittent concentrations of nitrous oxide on the developing rat fetus.

Five groups of 12 gravid female rats were exposed, during their entire gestation, intermittently for 6 h a day, 5 days per week, to 0.5% (5000 p.p.m.), 0.1% (1000 p.p.m.), 0.05% (500 p.p.m.) and 0.025% (250 p.p.m.) nitrous oxide-air mixtures (v/v), respectively. After killing the gravid rats on the 19th day of their pregnancies the numbers of corpora lutea of pregnancy were counted. Each uterus was examined for placentation sites and embryonic remnants and a detailed examination of the fetuses was undertaken. A significant reduction in mean litter size occurred only in the group exposed to 0.5% nitrous oxide in air (v/v). The mean litter sizes of the control and other exposed groups were comparable. No signs of fetal resorption or skeletal malformation were found in any group. The threshold of pollution for reduction in litter size has been shown in this study to lie between 0.1% and 0.5% nitrous oxide in air (v/v). A previous study on continuous exposure reported the threshold pollution to lie between 0.05% and 0.1% nitrous oxide in air (v/v). This investigation confirms that intermittent exposure to nitrous oxide-air mixtures increases the threshold for reproductive effects in rats.

Abnormalities, Drug-Induced↗

Risk factors associated with prevalent HIV-1 infection among pregnant women in Rwanda. National University of Rwanda-Johns Hopkins University AIDS Research Team.

This study evaluated risk factors associated with prevalent HIV-1 infection among pregnant women in a semi-rural but densely populated area surrounding the town of Butare in Rwanda. Overall seroprevalence was 9.3% in 5690 pregnant women who sought antenatal care at one of five health centres. Factors associated with higher seroprevalence of HIV-1 included history of multiple sexual partners, history of at least one sexually transmitted disease (STD), relatively high socioeconomic status (SES), being unmarried, young age at first pregnancy, and low gravidity. Women who had used oral contraceptives, smoked more than one cigarette per day, whose partners were circumcised, and had had sex to support themselves were also at higher risk of being infected. A history of blood transfusion in the past 5 years was not associated with HIV-1 infection. History of multiple sexual partners, history of STD, high household income, partner circumcision, and past oral contraceptive use remained strongly associated with HIV-1 infection even when simultaneously controlling for other covariates. Among legally married women who lacked sexual behaviour risk factors, history of STD, high SES, young age at first pregnancy, and low gravidity were significantly associated with HIV-1 seroprevalence.

Adolescent↗

Induced abortion and low birthweight in the following pregnancy.

BACKGROUND: To examine whether induced abortion increases the risk of low birthweight in subsequent singleton live births. METHODS: Cohort study using the Danish Medical Birth Registry (MBR), the Hospital Discharge Registry (HDR), and the Induced Abortion Registry (IAR). All women who had their first pregnancy during 1980-1982 were identified in the MBR, the HDR, and the IAR. We included all 15,727 women whose pregnancy was terminated by a first trimester induced abortion in the induced abortion cohort and 46,026 women whose pregnancy was not terminated by an induced abortion were selected for the control cohort. All subsequent pregnancies until 1994 were identified by register record linkage. RESULTS: Low birthweight (<2500 g) in singleton term live births occurred more frequently in women with one, two, three or more previous induced abortions, compared with women without any previous induced abortion of similar gravidity, 2.2% versus 1.5%, 2.4% versus 1.7%, and 1.8% versus 1.6%, respectively. Adjusting for maternal age and residence at time of pregnancy, interpregnancy interval, gender of newborn, number of previous spontaneous abortions and number of previous low birthweight infants (control cohort only), the odds ratios (OR) of low birthweight in singleton term live births in women with one, two or more previous first trimester induced abortions were 1.9 (95% CI: 1.6, 2.3), and 1.9 (95% CI: 1.3, 2.7), respectively, compared with the control cohort of similar gravidity. High risks were mainly seen in women with an interpregnancy interval of more than 6 months. CONCLUSIONS: The findings suggest a positive association between one or more first trimester induced abortions and the risk of low birthweight in subsequent singleton term live births when the interpregnancy interval is longer than 6 months. This result was unexpected and confounding cannot be ruled out.

Abortion, Induced↗

Maternal-fetal pharmacological activity of amikacin.

Thirty healthy gravid patients of six to 20 weeks' gestation each received a single dose of 7.5 mg of amikacin/kg within 24 hr prior to elective hysterectomy. The half-life (t1/2) of amikacin in maternal serum was 2.07 hr. The mean peak concentration of amikacin in the sera of these patients was slightly lower than that in nonpregnant adults. Two-thirds of the placental samples had amikacin concentrations of greater than or equal to 8 microng/g during the 20-hr interval between drug injection and delivery time. In fetal kidney the concentration of amikacin peaked at a level of 22.4 microng/g at 12 hr after administration. The peak concentration of amikacin in fetal urine was 24 microng/ml, and the t1/2 was 3.2 hr. High levels of the drug in fetal urine and low levels in fetal serum (less than 4 microng/ml) and amniotic fluid (less than 3 microng/ml) were unrelated to high levels found in fetal kidney. Levels of amikacin in fetal lung were 1.4-8.0 microng/g during intervals of 1-16 hr between administration of the drug and time of delivery. With the increasing number of drugs available for use, both potential benefits and risks for the fetus must be considered when prescribing an antibiotic to treat the infected gravid patient, and it should be kept in mind that low levels in body fluid may not be equated with safety.

Amikacin↗

Leishmaniasis in the Jordan Valley: differential attraction of dispersing and breeding site populations of Phlebotomus papatasi (Diptera: Psychodidae) to manure and water.

The response of Phlebotomus papatasi Scopoli to traps baited with manure or water was used to compare the behavior of flies near rodent burrows (breeding sites) and dispersing flies in fallow fields. The degree of response in each biotype was defined for each bait by the difference between catches in baited and unbaited traps. Manure bait attracted twice as many flies near the burrows and 2.7 times more flies in the field compared with unbaited traps. In both locations, the manure bait increased the capture of males and nongravid females, whereas gravid females were attracted only near burrows and not in the fields. The catch in the fields with water bait was similar to the unbaited control. However, near burrows, water bait captured more males and gravid females, but not nongravid females. These results demonstrate specific behavioral patterns of the dispersing P. papatasi population.

Animals↗

Persistence of hepatitis B antigen in Culex quinquefasciatus (Diptera: Culicidae).

Groups of wild-caught Culex quinquefaciatus Say, previously tested for the presence of hepatitis B surface antigen (HBsAg), were tested for the presence of hepatitis B e antigen (HBeAg). This antigen was detected at low levels in blood-fed, half-gravid, and gravid groups. A colony of Cx. quinquefasciatus was established in the laboratory and tested for the persistence of HBsAg and HBeAg. Five days after feeding on blood infected with HBsAg and HBeAg, 9 of 20 (45%) pools of Cx. quinquefasciatus were HBeAg-positive and 5 of 20 (25%) pools were HBeAg-positive; low levels of HBsAg and HBeAg were still detectable 28 d after the infective meal in 2 of 20 (10%) and 1 of 20 (5%) pools, respectively. A crude protease extract was prepared from colony mosquitoes, and the effect of this extract on HBsAg and HBeAg present in human serum was tested in vitro. After 20 h, tests for both antigens were still strongly positive. Low levels of HBsAg were detected in ovaries 7 d after infection. Salivary glands were HBsAg- and HBeAg-negative.

Animals↗

Effect of topically treating cattle with permethrin on blood feeding of Psorophora columbiae (Diptera: Culicidae) in a southwestern Louisiana rice-pasture ecosystem.

The percentage of resting mosquitoes that had fed on blood or were gravid-parous was determined in two pastures associated with the riceland agroecosystem in southwestern Louisiana. In one pasture, all of the cattle were treated with permethrin every 14 d over a 22-wk period, whereas cattle in the other pasture were untreated. The percentage of blood-engorged Psorophora columbiae (Dyar & Knab) was significantly lower in the vicinity of the treated herd. The effectiveness of the permethrin treatment in reducing blood feeding decreased over the interval between applications and as a result of increased rainfall. The proportion of Ps. columbiae that was gravid or parous was not significantly affected by the treatment. Anopheles quadrimaculatus Say engorgement rates also were significantly reduced by the treatment; however, Anopheles crucians Wiedemann and Culex salinarius Coquillett engorgement rates did not differ between the two areas. The results indicate that host management by permethrin treatment has potential for controlling Ps. columbia and An. quadrimaculatus populations in the Louisiana riceland-pasture agroecosystem.

Administration, Topical↗

Laboratory demonstration of oviposition by Aedes aegypti (Diptera: Culicidae) in covered water jars.

In Thailand, ceramic jars (135-200 liters) covered by aluminum lids commonly are used to store water for household use. In laboratory cages, gravid female Aedes aegypti (L.) were able to enter and oviposit in a covered water jar. Although the aluminum lid was not a complete barrier to gravid females, it reduced the number of eggs oviposited by 77%. A vertically oriented foam rubber ring which was compressed between the lip of the jar and the flange of the lid effectively sealed the jar against ovipositing mosquitoes.

Aedes↗

Adult German cockroach (Dictyoptera: Blattellidae) movement patterns and resource consumption in a laboratory arena.

Computerized moving-image analysis was used to determine movement behavior of adult German cockroaches among food, water, and harborage resource sites. Adults at different stages in the female reproductive cycle (nonmated females, mated nongravid females, and gravid females) and males were examined continually for 5 d under a photoperiod of 12:12 (L:D) h. Corresponding food and water consumption rates for these adult classes were also determined. Differences were evident among the female reproductive classes and males. Mated nongravid females were the most active overall, and consumed the most resources. Nonmated females were second to the mated nongravid females in consumption and were less active. Gravid females were the most inactive, spending the greatest time in the harborage and consuming the fewest resources. Males were second to females in the mated nongravid class regarding activity, but consumed significantly fewer resources than females in both the mated nongravid and nongravid females. Implications of these findings relating to the biology of these adult classes are discussed.

Animals↗

Bioassays for Culex (Diptera: Culicidae) mosquito oviposition attractants and stimulants.

Bioassay methods for mosquito oviposition attractants and stimulants were developed and compared, using Culex tarsalis Coq. gravid females as test insects, and distilled water, dyed water, or Bermuda grass infusions as the test stimuli. Bioassays with sticky screens covering jars containing volatile test stimuli or with colorless and odorless Triton X100 surfactant in the aqueous oviposition medium demonstrated that gravid mosquitoes were attracted to distilled water, with the attraction increased by the addition of dye, grass infusion, or the steam distillate of grass infusion to the water. A variation of the sticky screen bioassay was used to demonstrate that the grass infusion also contained oviposition stimulants. A forced oviposition bioassay was minimally useful, because it failed to discriminate between a solution known to contain oviposition stimulants and a distilled-water control. Overall, the bioassays developed can be used to distinguish between oviposition attractants and stimulants, a distinction that cannot be made by simply counting egg rafts.

Animals↗

Characteristics that predict risk of breast cancer before and after the menopause.

In a case-control study of 1868 breast cancer patients and 3391 control patients we searched for characteristics that predicted risk of breast cancer diagnosed before and after menopause. Common to increased risk of this disease in both periods of womanhood were: early menarche and late menopause; delayed marriage and first childbirth; more nulliparity or reduced gravidity and parity; reduced frequency of abortions; shorter overall child-bearing interval; more advanced education, higher socioeconomic status, and more contraceptive usage; and familial tendencies toward the disease. Breast cancer patients diagnosed before menopause were leaner than controls at age 20 and at time of diagnosis, but breast cancer risk in the postmenopausal period was related to increased weight-for-height at diagnosis and greater weight-for-height at diagnosis and greater weight gain since age 20. Postmenopausal breast cancer patients had a longer interval between first and second childbirths. Frequency and duration of the gravid state, inversely related to breast cancer risk, were largely dependent on contraceptive practices rather than unexplained infertility per se. Whether the breast cancer reaches diagnosis before or after menopause, the bulk of evidence examined here supports the view that it has a common cause and is subject to modifying influences over the long period of cancer latency.

Abortion, Spontaneous↗

An epidemiologic case-control study of ovarian cancer and reproductive factors.

A population-based case-control study was conducted with 403 white, ovarian cancer patients, 20-79 years of age, who were diagnosed from October 1977 through February 1980 in 11 New York State counties. The study also included 806 controls who were matched to the cases by age, race, and county of residence. The contraceptive and reproductive patterns observed in this study suggest that infertility plays an important role in determining the relationship between reduced parity and gravidity and increased ovarian cancer risk. Ovarian cancer patients were less likely than controls to have ever used nonpermanent birth control methods (relative risk = 0.63, 95% confidence interval = 0.45-0.89), and they tended to practice contraception less often. A direct graded-response relationship was observed between ovarian cancer risk and the number of contraceptive-free years of marriage (chi 2 Linear trend = 5.911, p = 0.02). An inverse graded-response relationship was observed between gravidity and risk. This relationship persisted even after contraception was taken into account (chi 2 Linear trend = 13.002, p = 0.0003). Ovarian cancer risk was not found to be associated with an excess in reported fetal loss.

Adult↗

Entomologic studies after a St. Louis encephalitis epidemic in Grand Junction, Colorado.

In 1986, after a St. Louis encephalitis epidemic in Grand Junction, Colorado, in 1985, vector mosquitoes in the city were surveyed to correlate their bionomics and infection rates with the occurrence of human disease. No human cases were reported, but mosquito surveillance disclosed St. Louis encephalitis virus in Culex tarsalis and Culex pipiens pipiens. Mosquitoes were collected with gravid traps designed to attract Cx. p. pipiens and with Centers for Disease Control light traps. Culex p. pipiens was the predominant vector mosquito collected and was captured chiefly in gravid traps. The Culex tarsalis population emerged and expanded approximately one month earlier than did the Cx. p. pipiens population. Consequently, Cx. p. pipiens was the predominant vector species after August. Infection rates throughout the surveillance period (June to September) were severalfold higher in Cx. tarsalis than in Cx. p. pipiens; however, in late summer, diminished numbers of Cx. tarsalis and a persistent population of Cx. p. pipiens resulted in relatively larger numbers of infected Cx. p. pipiens. Thus, the participation of Cx. p. pipiens as a St. Louis encephalitis vector would have been underestimated in previous studies employing light traps alone. These studies provide further evidence that Cx. p. pipiens-associated urban St. Louis encephalitis and rural Cx. tarsalis-associated St. Louis encephalitis cycles may coexist in the West.

Animals↗

Risk factors for spontaneous abortion and its recurrence.

Pregnancy histories of women interviewed as normal population controls during 1974-1981 in four case-control studies in the US and Canada were examined to identify risk factors for the occurrence of miscarriage. In total, 2,068 ever-gravid women aged 20-79 years at interview (mean age, 50.3 years) described 6,282 pregnancies, including 805 miscarriages. The roles of previous pregnancy history, age at pregnancy, and other factors were evaluated using relative risk binomial regression methods (similar to logistic regression). Risk of miscarriage during a given pregnancy was found to increase directly with the number of previous miscarriages (the risk was closely approximated by (1 + number of prior miscarriages)1.01), but appeared to be unrelated to the order of miscarriages within all previous pregnancies. Maternal age was also highly related to risk after controlling for gravidity and previous miscarriages, with doubled risk (compared with age 20 years) seen for pregnancies in women older than age 40 years. Risk of miscarriage did not appear to be associated with years since previous pregnancy, height, weight or obesity, use of oral contraceptives within one year before pregnancy, or duration of oral contraceptive use. A slight increase in risk was seen for women who had ever regularly smoked cigarettes (relative risk = 1.14, 95 per cent confidence limits = 1.00, 1.30). Thus, the levels of risk of miscarriage found in this analysis are similar to those of previous studies, and the analytic methods suggest how age, obstetric history, and other factors can be simultaneously examined for associations with such risk.

Abortion, Spontaneous↗

Prenatal toxicity of inhaled polymeric methylenediphenyl diisocyanate (MDI) aerosols in pregnant wistar rats.

Mated Wistar rats, 25/group, were exposed to polymeric methylenediphenyl diisocyanate (MDI) aerosol of respirable size for 6 h/day, on gestational days (gd) 6 through 15, at 0, 1, 4, and 12 mg/m3. Maternal clinical signs, body weights, and feed and water consumption were measured throughout gestation. At scheduled sacrifice on gd 20, maternal body, gravid uterine, liver, and paired lung weights were documented. Corpora lutea were counted, implantation sites were identified: resorptions, dead and live fetuses, and placentas were weighed. All live fetuses were counted, sexed, weighed, and examined for external alterations; approximately 50% of the live fetuses/litter were preserved in Bouin's fixative and examined for visceral alterations, and the remaining live fetuses/ litter were cleared and stained with alizarin red S and examined for ossified skeletal alterations. Maternal toxicity was observed at 12 mg/m3, including mortality (2 of 24 pregnant), damage to the respiratory tract, reduced body weights and weight gain, reduced liver and increased lung weights, and reduced gravid uterine weight (the last not statistically significantly different from the control value). Developmental toxicity was also observed at 12 mg/m3, including reduced placental and fetal body weights and an increased incidence of fetal skeletal variations and skeletal retardations. There was no evidence of maternal or developmental toxicity at 1 or 4 mg/m3. The no observed adverse effect concentration for maternal and developmental toxicity was therefore 4 mg/m3. There were no treatment-related teratogenic effects at any concentrations evaluated.

Abnormalities, Drug-Induced↗

Evaluation of the developmental toxicity of formamide in Sprague-Dawley (CD) rats.

Timed-pregnant CD(R) outbred albino Sprague-Dawley rats received formamide (50, 100, or 200 mg/kg/day) or vehicle (5 ml/kg deionized/distilled water, po) on gestational days (gd) 6 through 19. Maternal food and water consumption (absolute and relative), body weight, and clinical signs were monitored at regular intervals throughout gestation. At termination (gd 20), confirmed-pregnant females (21-23 per group) were evaluated for clinical status and gestational outcome; live fetuses were examined for external, visceral, and skeletal malformations and variations. There were no maternal deaths and no dose-related clinical signs. At 200 mg/kg/day, maternal body weight on gd 20, weight gain, and gravid uterine weight were significantly decreased. Maternal weight gain, corrected for gravid uterine weight, liver weight (absolute or relative), and food and water consumption (absolute or relative), were not affected. Formamide did not affect prenatal viability or incidences of fetal malformations or variations. Average fetal body weight/litter was decreased at 100 and 200 mg/kg/day. Fetal body weight was affected at lower daily doses than in previously published studies, possibly due to the longer total exposure period and/or lack of a recovery period between cessation of exposure and termination. In summary, the maternal toxicity no-observed-adverse-effect level (NOAEL) was 100 mg/kg/day and the low observed adverse effect level (LOAEL) was 200 mg/kg/day under the conditions of this study. Similarly, the developmental toxicity NOAEL was 50 mg/kg/day and the LOAEL was 100 mg/kg/day.

Abnormalities, Drug-Induced↗

Evaluation of the developmental toxicity of formamide in New Zealand white rabbits.

Naturally mated female New Zealand White (NZW) rabbits (24/group) received formamide (35, 70, or 140 mg/kg/day) or vehicle (1 ml/kg deionized/distilled water) by gavage on gestational days (GD) 6 through 29. The study was conducted using a 2-replicate design. Maternal food consumption (absolute and relative), body weight, and clinical signs were monitored at regular intervals throughout gestation. One and four maternal deaths occurred at the low and high doses, respectively. Abortions or early deliveries were noted in 0, 2, 2, and 8 females in the 0, 35, 70, and 140-mg/kg/day dose groups, respectively. Other clinical signs associated with formamide exposure were minimal: primarily reduced or absent fecal output at the high dose (2-13 animals/day). Also at the high dose, maternal body weight was significantly depressed on GD 21, 24, and 27 (87-90% of the control value); maternal body weight gain was significantly reduced for GD 12 to 15, 18 to 21, and 21 to 24 (treated animals gained less than 1 g, or lost up to 100 g). In addition, maternal body weight gain was reduced at the middle dose for GD 18 to 21. Maternal body weight gain, corrected for gravid uterine weight, was unaffected. Relative maternal food consumption in the high-dose group was 34-59% of control intake from GD 12 through GD 24, but was comparable to controls thereafter. At termination (GD 30), confirmed-pregnant females (9-20 per group) were evaluated for clinical status, liver weights, and gestational outcome; live fetuses were examined for external, visceral, and skeletal malformations and variations. Maternal liver weight (absolute or relative to body weight) was unaffected by treatment, but gravid uterine weight at the high dose was 71% of the control value. A significantly increasing trend was noted for the percent non-live implants per litter. In addition, although not statistically significant from the control group, the values for the percent late fetal deaths per litter and percent non-live implants per litter in the 140-mg/kg/day group were higher than maximum historical values, suggesting an increase in late gestational deaths in the surviving high-dose animals. Formamide decreased the mean number of live fetuses per litter at the high dose to 66% of the control value. Mean fetal body weight per litter for males and the sexes combined was significantly decreased at the high dose; mean female fetal body weight was also decreased, although the difference did not reach statistical significance. There was no effect of treatment on the incidence of external, visceral, or skeletal malformations or variations in animals surviving to scheduled necropsy. In summary, the no-observed-adverse-effect level (NOAEL) for maternal toxicity was 70 mg/kg/day and the lowest-observed-adverse-effect level (LOAEL) was 140 mg/kg/day under the conditions of this study. Similarly, the NOAEL for developmental toxicity was 70 mg/kg/day and the LOAEL was 140 mg/kg/day.

Animals↗

Expression and localization of alpha-smooth muscle and gamma-actins in the pregnant rat myometrium.

The myometrium undergoes dramatic changes as pregnancy progresses through phases of proliferation, hypertrophy, contractile state and labor. In this study, we showed that the composition of the muscle actin isoforms, a major component of the myometrial contractile apparatus and cytoskeleton, was modified during pregnancy. The expression of smooth muscle alpha-actin (Acta2, which we abbreviate as alpha-SM-actin) and gamma-actin mRNAs and proteins was examined by real-time polymerase chain reaction and Western immunoblot, and was localized with immunohistochemistry, in the nonpregnant, pregnant, and postpartum rat uterus. Both alpha-SM-actin (vascular specific actin isoform) and gamma-actin (predominant in visceral smooth muscle) were detected in the rat myometrium. Myometrial expression of alpha-SM-actin mRNA and protein was high throughout pregnancy. The transcript and protein levels of gamma-actin were increased significantly in the second part of gestation (31.8-fold increase for mRNA and 16.7-fold increase for protein relative to nonpregnant). The localization of gamma-actin was markedly altered during pregnancy. In early gestation, myometria from empty and gravid uterine horns of the unilaterally pregnant rats showed abundant gamma-actin immunostaining in the longitudinal layer but weak staining in the circular layer. Gamma-actin immunostaining increased in only the circular layer of the gravid horn after midgestation and remained low in the empty one. Gamma-actin protein translocated to the membranous region of uterine myocytes at late gestation. The temporal alteration in gamma-actin expression and localization at late gestation suggested that this change in myometrial composition of contractile proteins is important to adequately prepare the myometrium for the development of optimal contractions during labor.

Actins↗