Lipid and lipoprotein concentrations in pregnancies complicated by intrauterine growth restriction

Previous studies have shown that in preeclampsia, plasma lipids climb substantially above levels seen in normal pregnancies. Such lipid changes may play a role in the endothelial damage characteristic of preeclampsia. Pregnancies complicated by intrauterine growth restriction (IUGR), without preeclampsia, have similar placental pathology to preeclampsia despite the absence of the maternal systemic manifestations of hypertension and proteinuria. The aim of this study was to perform a cross-sectional study of lipid and lipoprotein concentrations in the third trimester, from normal pregnancies, and those complicated by IUGR without preeclampsia. Our hypothesis was that, in contrast to the exaggerated lipid changes seen in preeclampsia, lipid and lipoprotein concentrations in IUGR would be similar to those of matched healthy pregnant controls. Fasting blood samples for lipids and lipoprotein fractions were taken in the third trimester, from eight women with IUGR; and eight women with uncomplicated pregnancies, matched as a group for age, booking weight, parity, and gestational age at sampling. There were no significant differences (P > 0.05) in the median concentrations of triglyceride, high-density lipoprotein, and very-low-density lipoprotein 1 (VLDL1), between cases and controls. However, women with IUGR pregnancies had significantly lower cholesterol [4.95 mmol/L (3.35-7.10) vs. 7.47 (5.75-8.45); median (range) for IUGR patients and controls, respectively; P < 0.01], low-density lipoprotein (LDL)-cholesterol [2.45 mmol/L (0.95-3.60) vs. 4.25 (3.35-5.60); P < 0.01], VLDL2 mass [59.0 mg/dL (37-87) vs. 103.0 (64-168); P < 0.01], intermediate-density lipoprotein mass [56.0 mg/dL (31-110) vs. 125.6 (91-157); P < 0.01], and total LDL mass [221.0 mg/dL (104-237) vs. 380.3 (267-534); P < 0.01]. In addition, it was noteworthy that, with respect to LDL-cholesterol and total LDL mass, there was little or no overlap in the ranges of concentrations measured between cases and controls. Because VLDL2 and intermediate-density lipoprotein are the synthetic precursors to LDL in the circulation, their significantly lower median concentrations imply a failure of appropriate LDL synthesis in IUGR pregnancies. Whatever the mechanism, if our results are confirmed in larger studies and longitudinal investigations, then LDL-cholesterol measurements (when LDL-cholesterol fails to rise appropriately or is low in the third trimester) may be of use in identifying mothers with, or at risk of, a pregnancy complicated by IUGR.     

Responses of pre-implantation mouse embryos to thalidomide exposure in utero

On Day 1 of pregnancy, a thalidomide suspension (.05 ml) in saline at concentrations of 5 and 10 mcg/ml was infused into the uterine horns via the cervical route of 2 1/2-3 month old Swiss albino mice. Another group was infused on Day 0 at the doses mentioned. Parallel experiments were conducted after intrauterine infusions of saline. Following infusion, the mice were sacrificed on Days 2, 3, and 4 of gestation. Zygote and 4- and 8-cell stages of embryogenesis were most sensitive to the teratogen in terms of the induction of morphological anomalies and cell death. Drug effect was also observed in the postmorula embryos as abnormalities of varying degrees. There was an overall increase in the incidence of mitotic cells.     

11Beta-hydroxysteroid dehydrogenase type 2 in human pregnancy and reduced expression in intrauterine growth restriction

The evolutionary theory of aging predicts that the equilibrium gene frequency for deleterious mutations should increase with age at onset of mutation action because of weaker (postponed) selection against later-acting mutations. According to this mutation accumulation hypothesis, one would expect the genetic variability for survival (additive genetic variance) to increase with age. The ratio of additive genetic variance to the observed phenotypic variance (the heritability of longevity) can be estimated most reliably as the doubled slope of the regression line for offspring life span on paternal age at death. Thus, if longevity is indeed determined by late-acting deleterious mutations, one would expect this slope to become steeper at higher paternal ages. To test this prediction of evolutionary theory of aging, we computerized and analyzed the most reliable and accurate genealogical data on longevity in European royal and noble families. Offspring longevity for each sex (8409 records for males and 3741 records for females) was considered as a dependent variable in the multiple regression model and as a function of three independent predictors: paternal age at death (for estimation of heritability of life span), paternal age at reproduction (control for parental age effects), and cohort life expectancy (control for cohort and secular trends and fluctuations). We found that the regression slope for offspring longevity as a function of paternal longevity increases with paternal longevity, as predicted by the evolutionary theory of aging and by the mutation accumulation hypothesis in particular.     

Failure of nocturnal changes in growth hormone to alter carbohydrate tolerance the following morning

To determine whether the increases in growth hormone that occur during sleep alter carbohydrate tolerance the following morning, two groups of volunteers were studied on two occasions. In one group saline alone was injected and infused (i.e. no octreotide) on one occasion and on the other octreotide was injected at 23.00 hours to inhibit endogenous growth hormone secretion followed by saline infusion to create a state of relative nocturnal growth hormone deficiency. In the other group the octreotide injection was followed on one occasion by a constant growth hormone infusion designed to maintain growth hormone concentrations at "basal" levels throughout the night whereas on the other it was followed by a constant infusion plus two supplemental growth hormone infusions given at midnight and 02.30 hours to mimic the normal nocturnal rise in growth hormone. The next morning, subjects were fed a radiolabelled mixed meal. The differences in the nocturnal growth hormone concentrations had no effect on the glucose, insulin, C-peptide and glucagon concentrations following breakfast ingestion nor did they alter postprandial rates of glucose production, disappearance or substrate oxidation. Thus, the normal nocturnal rise in growth hormone does not appear to be an important regulator of carbohydrate tolerance the following morning.     

Failure to detect the presence of Chlamydia pneumoniae in sarcoid pathology specimens

The pathogenesis of sarcoidosis is not yet known. On the basis of seroepidemiological data, an association between Chlamydia pneumoniae infection and sarcoidosis has been suggested, but so far no study has addressed the direct detection of this agent in the affected tissues. The aim of the present study was to detect C. pneumoniae deoxyribonucleic acid (DNA) within sarcoid tissue specimens by means of a two-step polymerase chain reaction. Lung biopsy specimens of 33 patients with histologically confirmed pulmonary sarcoidosis and 21 control lung biopsies or pathology specimens of patients with pulmonary carcinoma or emphysema were retrospectively analysed. A nested polymerase chain reaction was applied using two sets of primers designed to detect a fragment of the 16 strand ribosomal ribonucleic acid (rRNA) gene of C. pneumoniae. The results of the study failed to demonstrate the presence of C. pneumoniae in biopsy specimens of sarcoid tissue and in the control lung biopsies or pathology specimens. Our results, therefore, tend to rule out the possibility of a direct involvement of Chlamydia pneumoniae in the pathogenesis of sarcoidosis.     

Reproductive sequelae in female rats after in utero and neonatal exposure to the phytoestrogen genistein

OBJECTIVE: To determine reproductive sequelae in female rats after in utero and lactational dietary exposure to genistein. DESIGN: Experimental animal study. SETTING: University laboratory. ANIMAL(S): Sprague Dawley rats. INTERVENTION(S): Pregnant rats were fed control rat chow or rat chow incorporated with genistein (approximately 50 microg/d) beginning on day 17 of gestation and continuing until the end of lactation (postpartum day 21). Genistein-exposed female pups were divided into two groups on day 21. One group continued to receive a genistein-added diet (G70); the other group was changed to a control diet (Ex-G). At necropsy (days 21 and 70), blood and reproductive tissues were collected. MAIN OUTCOME MEASURE(S): Serum levels of gonadotropins and gonadal steroids and histopathologic examination of the ovaries. RESULT(S): The weight of the ovaries and uterus and serum levels of E2 and progesterone in genistein-exposed rats on day 21 (G21) were significantly reduced compared with control rats. On day 70, serum levels of E2, progesterone, LH, and FSH were similar in all groups. Atretic follicles and secondary interstitial glands were more common in G70 and Ex-G rats compared with control rats. Cystic rete ovarii was observed in some G70 and Ex-G rats. CONCLUSION(S): Our data indicate that in utero and lactational exposure to dietary genistein adversely affects reproductive processes in the adult female rat.     

Failure to detect moderating effects: Is multicollinearity the problem?

We show that Morris, Sherman, and Mansfield's (1986) contention that multicollinearity causes ordinary least squares–moderated multiple regression (OLS–MMR) to underestimate the importance of moderator effects is incorrect for their own data. Multicollinearity was reduced to the point that it was negligible by transforming predictor variables and moderator variables to standard scores prior to computing cross-product terms. We show the resulting cross-product terms both mathematically and empirically to have near-zero correlations with standardized predictors and moderators. Yet, as Arnold and Evans (1979) showed, the results of OLS–MMR are unchanged by this linear transformation of scale. Morris et al's (1986) finding of significant moderator effects when using principal-components regression (PCR) is probably a result of some artifact of PCR. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Exencephaly in fetal hamsters following exposure to hyperthermia

This paper reports a rare malformation syndrome which is observed in two sibs (brother and sister) of a family. It consists of nearly symmetric reductive defects of the limbs, flexon contractures of various joints, cleft lip and cleft palate, multiple minor abnormalities including capillary hemangioma of the forehead, hypoplastic cartilages of ears and nose, micrognathia, intrauterine growth retardation, and possibly mental retardation. Chromosomes of both parents and propositi are normal. Genetic data suggest autosomal recessive inheritance.     

Failure to detect a general reduction of surgical wound infections in Danish hospitals

The aim of this study was to see if introduction of continuous monitoring of the incidence of surgical wound infections would result in a reduction in the cumulated infection rates. Data from a Danish sentinel system, including more than 65,000 operations, are shown to be sufficiently representative to be used as the basis of a national surveillance system for surgical wound infections. The overall infection rates increased with age and with contamination of the wound. Antibiotic prophylaxis was used in 36% of the operations, with a higher fraction among elderly patients, and in contaminated or major operations. The length of stay was significantly and equally extended for patients with superficial or deep infections, compared to patients without wound infections. The results from 13 departments could be followed at least two years from the beginning of the registration. No general preventive effects of the continuous monitoring were found in these surgical units.     

Failure to detect binding of LcrH to the V antigen of Yersinia pestis

V antigen of Yersinia pestis has been reported to bind the chaperone LcrH. We were unable to demonstrate this interaction. Despite methodological differences between our study and an earlier study, we believe that the previous findings were artifactual. One likely confounding element was the tendency of LcrH to adhere on its own to metal chelation chromatographic resin.     

In utero exposure to terbutaline: effects on infant behavior and maternal self-esteem

OBJECTIVE: Little is known about correlates of infant behavior after tocolytic intervention. This study investigated three related questions: (a) Are there any behavioral differences in infants exposed in utero to terbutaline and infants not exposed? (b) Is the mother's perception of her infant influenced by group status? (c) Is maternal self-esteem influenced by group status? DESIGN: Group comparison over time of infants exposed in utero to terbutaline and infants not exposed. Group mean cluster scores and recovery curves were compared. Mothers' responses to a series of questionnaires were compared according to group status. The first author remained blind to group status until all measures were completed on all participants. SETTING: Recruitment and first administration of the Brazelton Neonatal Behavioral Assessment Scale occurred in two regional hospitals, at Minneapolis and St. Paul. Subsequent administrations took place in the infants' homes. PARTICIPANTS: Forty-eight healthy, full-term (> or = 37 weeks gestational age) neonates and their mothers, 16 of whom had been given terbutaline, and 32 control subjects. MAIN OUTCOME MEASURES: Brazelton Neonatal Behavioral Assessment Scale was administered three times to each neonate. Mothers completed the Infant Characteristics Questionnaires, the Neonatal Perception Inventories, and the Maternal Self-Report Inventory. RESULTS: Significant differences were found between the two groups of infants on the habituation cluster at Time 1 and the autonomic stability cluster at Time 1 and Time 2. No significant group differences were found in the mothers' responses to the questionnaires. CONCLUSIONS: Nurses can assure parents that neonates exposed to terbutaline, although they may exhibit initial difficulties with behavioral organization, recover well over the course of the neonatal period. In addition, nurses can help mothers discover methods that will help calm their newborns.     

Further consideration of the power to detect nonzero validity coefficients under range restriction.

Extended the research of F. L. Schmidt et al (see record 1976-29035-001) and P. R. Sackett and B. E. Wade (see record 1983-31752-001), who examined the n-size requirements for validity studies to reach a specified level of power under 2 forms of restriction of range to include 2 different types of range restriction (bidimensional direct truncation and combined indirect and direct truncation). Results indicate that sample size requirements are more stringent under these 2 paradigms than under unidimensional direct truncation as applied by Schmidt et al or unidimensional indirect truncation as applied by Sackett and Wade. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

In utero and lactational exposure of the male rat to 2,3,7,8-tetrachlorodibenzo-p-dioxin: impaired prostate growth and development without inhibited androgen production

To determine whether in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure decreases male rat accessory sex organ weights during postnatal development secondary to decreases in testicular androgen production or changes in peripheral androgen metabolism, pregnant Holtzman rats were administered a single dose of TCDD (1.0 microgram/kg, po) or vehicle on Gestation Day 15 and offspring were exposed via placental and subsequent lactational transfer until weaning on Postnatal Day (PND) 21. Between PNDs 21 and 63, circulating androgen concentrations and intratesticular androgen content tended to be decreased by in utero and lactational TCDD exposure, but in most cases decreases were not statistically significant. In vitro human chorionic gonadotropin-stimulated testosterone production by decapsulated testes from TCDD-exposed animals was not different from control, although 5 alpha-androstane-3 alpha,17 beta-diol production was decreased on PNDs 32 and 49 and increased on PND 63. Taken together, these results imply that in utero and lactational TCDD exposure can cause subtle decreases in testicular androgen production. However, the biological relevance of these reductions is equivocal because they do not correlate temporally with one another or with decreases in androgen-dependent male accessory sex organ weights. Of the male accessory sex organs, ventral prostate (VP) and dorsolateral prostate (DLP) were the most severely affected. Between PNDs 21 and 63, relative VP and DLP weights were decreased to 65-84% and 57-80% of control, respectively, and the magnitude of observed decreases was greatest at early times. In contrast, relative weights of the seminal vesicle and coagulating gland ranged from 80 to 104% of control, and the magnitude of observed decreases was greatest at later times. The sensitivity of the prostate to TCDD could not be explained by tissue-specific decreases in dihydrotestosterone (DHT) concentrations. Although VP DHT concentration was decreased to 63% of control on PND 21, DHT concentration was not decreased in the VP between PNDs 32 and 63 or in the DLP at any time. We conclude that in utero and lactational TCDD exposure selectively impairs rat prostate growth and development without inhibiting testicular androgen production or consistently decreasing prostate DHT concentration.     

Tumours in experimental animals following exposure to asbestos dust

The author summarises his research into experimental asbestos-related tumours. He notes in particular the inequality in carcinogenic power of different types of asbestos and the variations in the types of malignant tumour seen (carcinomas or mesotheliomas), according to the variety of asbestos used.     

In utero and lactational exposure of the male rat to 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs prostate development. 2. Effects on growth and cytodifferentiation

In the male Holtzman rat, in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure decreases prostate weight without inhibiting testicular androgen production or decreasing circulating androgen concentrations. Therefore, the present study sought to characterize effects of TCDD exposure on prostate development, from very early outgrowth from the urogenital sinus (Gestation Day [GD] 20) until rapid growth and differentiation are essentially complete (Postnatal Day [PND] 32). Pregnant Holtzman rats were administered a single dose of TCDD (1.0 microgram/kg po) or vehicle on GD 15 and offspring were exposed via placental transfer (GD 20 euthanasia) or placental and subsequent lactational transfer until euthanasia (if before PND 21) or weaning. Results show that the prostatic epithelial budding process was impaired by in utero TCDD exposure, as evidence by significant decreases in the number of buds emerging from dorsal, lateral, and ventral aspects of the GD 20 urogenital sinus. Ventral prostate cell proliferation index was significantly decreased on PND 1 but was similar to or higher than control at later times, whereas apoptosis was an extremely rare event in ventral prostates from both control and TCDD-exposed animals. Delays were noted in the differentiation of pericordal smooth muscle cells and luminal epithelial cells. In addition, ventral prostates from approximately 40% of TCDD-exposed animals examined on PNDs 21 and 32 exhibited alterations in the histological arrangement of cell types that could not be explained by a developmental delay. Compared to controls, these ventral prostates exhibited a disorganized, hyperplastic epithelium containing fewer luminal epithelial cells and an increased density or continuous layer of basal epithelial cells, as well as thicker periductal smooth muscle sheaths. In addition, in ventral prostates from TCDD-exposed animals, the intensity of androgen receptor staining was relatively low in the central and distal epithelium, and the number of androgen receptor-positive cells was relatively high in the periductal stroma. These data suggest that in utero and lactational TCDD exposure interferes with prostate development by decreasing very early epithelial growth, delaying cytodifferentiation, and, in the most severely affected animals, producing alterations in epithelial and stromal cell histological arrangement and the spatial distribution of androgen receptor expression that may be of permanent consequence.     

IgE antibody suppression following aerosol exposure to antigens

Exposure of mice to aerosolized antigens induced a low level IgG1 response but not detectable IgE antibodies. Subsequent intraperitoneal immunization of these mice demonstrated immunoglobulin class-specific IgE suppression. Low concentrations of nebulized antigen induced IgE suppression which was antigen specific and persisted on subsequent secondary and tertiary injections. Although a single aerosolized antigen exposure significantly decreased the IgE response, maximal suppression was observed when the mice were exposed to nebulized antigen once weekly for at least 6 weeks. The suppression was not observed until 3 weeks following nebulizer exposure. Mice exposed once weekly to nebulized antigen for 6 weeks and then rested for 2 months before intraperitoneal immunization still demonstrated suppression. However, animals first immunized intraperitoneally and then exposed to nebulized antigen produced normal secondary IgE and IgG1 responses. These results suggest that antigen exposure by aerosol may profoundly alter the IgE response.