Inspiratory flow limitation during sleep in pre-eclampsia: comparison with normal pregnant and nonpregnant women.

Self-reported snoring is common in pregnancy, particularly in females with pre-eclampsia. The prevalence of inspiratory flow limitation during sleep in preeclamptic females was objectively assessed and compared with normal pregnant and nonpregnant females. Fifteen females with pre-eclampsia were compared to 15 females from each of the three trimesters of pregnancy, as well as to 15 matched nonpregnant control females (total study population, 75 subjects). All subjects had overnight monitoring of respiration, oxygen saturation, and blood pressure (BP). No group had evidence of a clinically significant sleep apnoea syndrome, but patients with pre-eclampsia spent substantially more time (31+/-8.4% of sleep period time, mean+/-SD) with evidence of inspiratory flow limitation compared to 15.5+/-2.3% in third trimester subjects and <5% in the other three groups (p=0.001). In the majority of preeclamptics, the pattern of flow limitation was of prolonged episodes lasting several minutes without associated oxygen desaturation. As expected, systolic and diastolic BPs were significantly higher in the pre-eclamptic group (p<0.001), but all groups showed a significant fall (p< or =0.05) in BP during sleep. Inspiratory flow limitation is common during sleep in patients with pre-eclampsia, which may have implications for the pathophysiology and treatment of this disorder.     

Cytokines, pregnancy, and bacterial vaginosis: comparison of levels of cervical cytokines in pregnant and nonpregnant women with bacterial vaginosis

BACKGROUND: Pregnancy has been considered to be a time of relative immune compromise. Lower-genital-tract immune response appears to be influenced by pregnancy. The objective of this study was to compare, in pregnant versus nonpregnant women, endocervical proinflammatory-cytokine expression in response to bacterial vaginosis. METHODS: Endocervical levels of interleukin (IL)-1 beta , IL-6, and IL-8 in 99 pregnant and 99 nonpregnant women, all with bacterial vaginosis and without concurrent sexually transmitted infections, were assessed by ELISA. Vaginal flora was characterized on the basis of quantitative vaginal cultures. RESULTS: Women in the 2 groups differed with respect to smoking status and microbiological constituents responsible for bacterial vaginosis. When the data were stratified by these potential confounders, the levels of all 3 proinflammatory endocervical cytokines were significantly higher in pregnant women than in nonpregnant women. CONCLUSIONS: The proinflammatory cytokine milieu in the cervix is enhanced in pregnant women with bacterial vaginosis, compared with that in nonpregnant women. The notion of pregnancy as an immune-compromised state may be anatomically compartment specific.     

Expression of microsomal prostaglandin E synthase in bovine endometrium: coexpression with cyclooxygenase type 2 and regulation by interferon-tau

Prostaglandins (PGs) are important regulators of reproductive functions. In ruminants, interferon (IFN)-tau is the embryonic signal responsible for recognition of pregnancy. This is effected by a reduction of the production of PGF(2alpha) relative to PGE(2.) This may be accomplished by a decrease in PGF(2alpha) production, but a stimulation of PGE(2) via the PGE synthase might also be involved. The purpose of the present study was to confirm the presence of PGE synthase (PGES) in the bovine endometrium, identify the factors affecting its expression, and compare it with that of cyclooxygenase-2 (COX-2). This was done by Northern blot analysis using primary cultures of bovine epithelial and stromal cells of the endometrium and bovine endometrial cell line. PGES mRNA expression was increased in the presence of lipopolysaccharides, TNF-alpha, and IFN-tau in stromal cells and IFN-tau in epithelial cells. In stromal cells, IFN-tau induced a rapid increase of PGES and COX-2 mRNA expression. In bovine endometrial cells, phorbol 12-myristate 13-actetate increased PGES mRNA, COX-2 mRNA and PGE(2) production. These results suggest that in endometrial cells, the expression of PGE synthase is correlated with that of COX-2 and is an important enzyme for the production of PGE(2). Increasing this production will modulate the PGE(2)/PGF(2alpha) ratio and contribute to establishment of pregnancy.     

Progesterone attenuates the inhibition of adrenocorticotropin responses by cortisol in nonpregnant ewes

This study was designed to test whether increases in plasma progesterone (P) reduce the efficacy of plasma cortisol (F) in inhibition of ACTH responses to stimuli. Five nonpregnant ewes were each infused with ethanol-saline vehicle, F (4 micrograms/kg.min), P (0.5 or 2.0 microgram/kg.min), or P and F for 60 min. One hour after the end of the vehicle or steroid infusions, nitroprusside (20 micrograms/kg.min) was infused for 10 min to induce hypotension-stimulated ACTH secretion. Nitroprusside produced similar decreases in arterial blood pressure in all groups. Infusion of F alone inhibited plasma ACTH responses to hypotension. Whereas infusion of P without F did not significantly change plasma ACTH responses to hypotension, infusion of P with F caused greater ACTH responses to hypotension than did infusion of F alone. The results indicate that P can interfere with the delayed feedback effect of F in vivo.     

Increase of maternal plasma leptin concentrations during pregnancy: comparison with nonpregnant women

To investigate the physiological changes of leptin levels and whether placenta is linked to its production during pregnancy, plasma of 65 pregnant women at various gestational weeks were compared with those of 34 age- and body mass index (BMI)-matched nonpregnant women in the study. The leptin levels showed a gradual increase from 7-13 gestational week, then continuously elevated during weeks 14-20, 21-27, 28-34, virtually reaching a peak at 35-41 weeks' gestation. When they were compared to those of age- and BMI-matched nonpregnant women, a significant (P < 0.0001) increase was found with every gestational week. There were positive correlations between maternal leptin and BMI of first (7-13th week), second (14-27th week) and third (28-41st week) trimesters, with the correlation coefficients of 0.40 (P < 0.05), 0.54 (P < 0.001), and 0.49 (P < 0.001), respectively. No correlation (r = -0.17, P > 0.05, n = 31) was found between maternal leptin level and the neonatal birth weight. These data suggest that placental production of leptin is one major source of higher levels in maternal circulating leptin other than maternal gain of fat mass and that maternal leptin level is not related to fetal birth weight during pregnancy.     

Effect of subcutaneous and intranasal administration of ovine corticotropin-releasing hormone in man: comparison with intravenous administration

Long term use of ovine corticotropin-releasing hormone (oCRH) requires a convenient route of administration. The effects of 0.3, 3, and 30 micrograms/kg BW synthetic oCRH given as a sc injection and of 10 and 30 micrograms/kg given as an intranasal spray were studied in 10 normal men in the late afternoon. Basal plasma immunoreactive ACTH (IR-ACTH) and IR-cortisol levels were 14 +/- 1.9 pg/ml and 4.3 +/- 0.4 microgram/dl (mean +/- SEM). Peak IR-ACTH levels (mean +/- SEM) were 43 +/- 5.5, 53 +/- 8.1, and 64 +/- 8.9 pg/ml after the 0.3, 3, and 30 micrograms/kg doses of oCRH given sc, respectively, and 23 +/- 4.3 and 36 +/- 4.8 pg/ml after the 10 and 30 micrograms/kg doses of oCRH given intranasally, respectively. The lowest sc dose and both intranasal doses caused only single IR-ACTH peaks. After 3 and 30 micrograms/kg sc oCRH, IR-ACTH rose by 15 min, reached an initial peak at 45-60 min, fell rapidly until 90-120 min, and rose to a second peak at 3-5 h. This biphasic response is similar to that previously found after iv administration. IR-ACTH levels remained elevated for 4, 10, and at least 16 h after 0.3, 3, and 30 micrograms/kg sc oCRH, respectively, and for 1.5 and 3 h after 10 and 30 micrograms/kg intranasal oCRH respectively. The effect on IR-cortisol was similar, but more prolonged. Compared to the iv route, sc oCRH produced similar mean peak IR-ACTH and IR-cortisol levels and had a slightly longer duration of action. Intranasal oCRH was only about 1% as effective. Peak plasma IR-oCRH levels in 2 subjects receiving 3 micrograms/kg sc oCRH were 13 and 17 ng/ml at 90 min. These peaks were lower than those after iv administration of the same dose, but the levels remained elevated longer, probably accounting for the longer duration of action of sc oCRH. Peak plasma IR-oCRH levels in 4 subjects given 10 microgram/kg intranasal oCRH were only 64-122 pg/ml, presumably reflecting poor absorption through the nasal mucosa. These results demonstrate that sc injection of oCRH is at least as effective as the iv route with respect to plasma IR-ACTH and IR-cortisol responses. The convenience of this route of administration and the prolonged duration of action of oCRH suggest the feasibility of long term oCRH use.     

Cervical cytomegalovirus excretion in pregnant and nonpregnant women: suppression in early gestation.

Comparison of 659 pregnant and 202 nonpregnant women with similar demographic characteristics showed overall rates of cervical cytomegalovirus excretion that were identical (9.5% vs. 9.4%) and were surprisingly high, especially since 89% of the pregnant group possessed antibody to cytomegalovirus when admitted to the study. Prevalence of cytomegalovirus among gravidas was significantly lower during the first (1.6%) than during the third (11.3%) trimester. Thus, early pregnancy appeared to exert a suppressive effect on viral excretion that waned with advancing gestation. A similar but less significant occurrence was observed in the two groups with respect to viuria. Increasing age also appeared to suppress the virologic expression of cervical and urinary tract infection, whereas multiparity seemingly produced such an effect only in the cervix. Among both cervical and urinary excreters, a few shed virus thoughout pregnancy, and others shed virus intermittently; however, viral shedding most commonly began in late gestation and frequently continued into the postpartum period. Primary infection was not documented, and antibody status remained unchanged with the advent of viral excretion in most cases. Thus, reactivation of endogenous virus seems the most likely explanation for viral shedding in our population. Similar rates of isolation of Neisseria gonorrhoeae in excreters and nonexcreters further argue against the other major possibility, venereal reinfection.     

Immunohistochemical demonstration of relaxin in the genital tract of pregnant and nonpregnant women

The biotin-avidin immunoperoxidase staining method and antisera against highly purified porcine relaxin were used to localize relaxin in the genital tract of pregnant and nonpregnant women. Formalin-fixed tissue specimens from normal placenta, decidua, myometrium, vagina, corpus luteum, and Fallopian tubes were studied. In pregnant women, relaxin was found in the placental syncytiotrophoblast, decidua, and corpus luteum. In nonpregnant women, relaxin was identified in the corpus luteum and endometrium in the secretory, but not in the proliferative, phase. Myometrium, cervix, vagina, and Fallopian tubes were negative for relaxin. This is the first report describing relaxin in the nonpregnant corpus luteum, and we also confirm results of an early disputed study claiming that endometrium in the secretory phase contains relaxin. The origin and biological role of human endometrial relaxin remain to be studied.     

Intraosseous administration of antibiotics: same-dose comparison with intravenous administration in the weanling pig

STUDY OBJECTIVES: To assess the reliability of the intraosseous route of administration for delivery of a loading dose of broad-spectrum antibiotics in a pediatric animal model. DESIGN: Serum levels achieved within 90 minutes of equivalent intraosseous (IO) and IV bolus dosing of ceftriaxone, cefotaxime, and a combination of ampicillin and gentamicin were compared in the weanling pig. SUBJECTS: Twelve female weanling pigs were studied in the Animal Facilities Laboratory at the University of Mississippi Medical Center. INTERVENTIONS: Through a proximal tibial IO catheter, each anesthetized animal received one of the following: 50 mg/kg ceftriaxone, 50 mg/kg cefotaxime, or 300 mg/kg ampicillin followed immediately by 2.5 mg/kg gentamicin. Venous blood was obtained for antibiotic assay at 15, 30, 45, 60, and 90 minutes after IO injection. The animals were allowed to recover, and, after a one-week washout period, each received the same antibiotic and dose as before through a peripheral IV. Levels were assayed at the same intervals and IO versus IV were compared. MEASUREMENTS AND MAIN RESULTS: Comparable serum levels of all four antibiotics were achieved by the two routes. Gentamicin levels were statistically indistinguishable IO versus IV at all assay intervals. Ampicillin and cefotaxime levels achieved by the two routes were equivalent within one hour of dosing. Serum levels of ceftriaxone after IO administration paralleled those after IV dosing but remained significantly lower at all time intervals. CONCLUSIONS: In the weanling pig model, the IO route was used to deliver serum levels of broad-spectrum antibiotics comparable to those attained after IV administration. The data support the use of standard parenteral doses for IO administration. To overcome potential avid protein binding of ceftriaxone in the bone marrow, we recommend using ceftriaxone at its highest recommended IO loading dose. Consistent with many other medications that have been similarly tested, these data indicate that initial or empiric antibiotic coverage in hypodynamic and shock states in infants and young children need not await the establishment of traditional IV access.     

The secretory patterns of growth hormone in pregnant and hysterectomized ewes.

This work was undertaken to determine the secretory patterns of GH during pregnancy, and to evaluate the effect, if any, of hysterectomy during early pregnancy on subsequent secretion of GH in ewes. The concentrations of GH were determined in the plasma of jugular blood samples collected at 15-min intervals during a 6-h period on days 20, 40, 60, 80, 100 and 120 post-mating, and three times per week between days 29 and 120 post-mating from 5 pregnant ewes and from 5 ewes from which the gravid uterus was removed on day 30 post-mating. A pulse analysis program (Pulsar) was used to analyse the secretory patterns of GH in individual profiles of the serial sampling period. In the two groups of ewes, peripheral concentrations of GH fluctuated in an episodic manner during the frequent blood sampling of any stage of the post-mating period examined. The overall GH concentrations, the basal GH concentrations, the frequency and the amplitude of GH pulses remained fairly stable between days 20 and 120 post-mating in the two groups of ewes. The parameters of GH secretion were not different between the two groups of ewes. The secretory patterns of GH, as determined in plasma of blood collected three times per week between days 29 and 120 post-mating were also not different between the two groups of ewes. In conclusion, results of this study show that (i) the pulsatile secretion of GH does not change as pregnancy advances, and (ii) hysterectomy performed during early pregnancy does not subsequently affect the secretory patterns of GH. These findings suggest that the gravid uterus and/or the feto-placental unit secretory products are unlikely to be involved in the control of GH secretion during pregnancy in the ewe.     

Intratracheal administration of perfluorochemical-gentamicin suspension: a comparison to intravenous administration in normal and injured lungs

Respiratory infections can lead to acute lung injury and perfusion abnormalities. We hypothesized that intratracheal (IT) administration of a perfluorochemical (PFC) gentamicin (G) suspension as compared to intravenous (IV) administration of gentamicin will result in higher lung tissue levels of gentamicin, while maintaining safe serum levels. To test this hypothesis, 21 lambs with normal and acid injured lungs were studied for 4 hr, using 2 different drug delivery methods, IT and IV. Lungs were injured with warm HCl acid in saline lavage, followed by partial liquid ventilation with perflubron (bolus FRC = 20 mL/kg). G at a dose of 5 mg/kg was delivered either IT (G-PFC; 20 mL/kg) or IV (aqueous injection with IT 20 mL/kg PFC alone). Throughout the study, serum G levels, arterial blood gases, respiratory system compliance, and mean arterial blood pressure were measured. Lung tissue G levels were measured at 4 hr and averaged across lobes. Physiologic gas exchange and pulmonary function were maintained throughout the protocol for both the normal and injured lungs. Intravenously administered G resulted in an initial 5-min serum concentration of 43 +/- 2.5 mcg/mL, followed by an exponential decline over the 4-hr protocol to a level of 2.1 +/- 0.23 mcg/mL at hr 4. The intratracheally administered G suspension resulted in a 5-min serum concentration of 1.8 +/- 0.98 mcg/mL and remained relatively constant throughout the protocol, with a 4-hr level of 1.6 +/- 0.29 mcg/mL. With respect to lung tissue G levels, IT administration was significantly more effective in delivering the drug to the normal lungs than IV (31.4 +/- 3.3 mcg/g vs. 4.0 +/- 0.7 mcg/g) 4 hr after administration. In the lung injury group, there was a small but significant difference in lung tissue G levels, with the IT-administered perfluorochemical-G suspension achieving greater levels than the IV-administered G (11.9 +/- 0.52 mcg/g vs. 10.1 +/- 0.8 mcg/g). Additionally, the drug delivered IV and IT in both the normal and injured lung models was homogeneously distributed throughout the lung. These data show that G lung tissue levels in both normal and injured lungs were higher in the IT group when compared to IV administration. The results of this study demonstrate that in normal and injured lungs, homogeneous G lung tissue levels can be more effectively achieved at lower serum levels when delivered IT in a G-PFC suspension as compared to IV administration.