Maternal asthma and idiopathic preterm labor

Previous studies suggest that women with asthma are at increased risk of preterm birth. Moreover, drugs (especially beta-agonists) used to treat asthma are also used to treat preterm labor. The authors carried out a case-control study of 555 women from three hospital centers with idiopathic preterm labor (< 37 weeks), including two overlapping (i.e., non-mutually exclusive) subsamples: cases with early idiopathic preterm labor (< 34 weeks) and cases with idiopathic recurrent preterm labor (< 37 weeks plus a previous history of preterm delivery or second-trimester miscarriage). Controls were matched to cases according to race and smoking history prior to and during pregnancy. All subjects responded in person to questions about atopic, respiratory, obstetric, and sociodemographic histories. Subjects in the early and recurrent preterm labor subsamples were also asked to undergo spirometric testing with methacholine challenge 6-12 weeks after delivery. Cases were significantly more likely to report histories of asthma symptoms and physician-diagnosed asthma (matched odds ratios of 2-3) than controls, particularly those cases with recurrent preterm labor. No significant associations were observed, however, with methacholine responsiveness. These results could not be explained by residual confounding by smoking or other variables, nor by selective recall of asthma symptoms and histories by cases. Women with asthma are at increased risk of idiopathic preterm labor. The fact that no such association was seen with methacholine responsiveness suggests that nonatopic, noncholinergic mechanisms may link bronchial and uterine smooth muscle lability.     

The preterm labor experience: a balancing act

The purpose of the study was to identify how women described, interpreted, and managed their preterm labor experience. Ten married, middle-class women participated in an in-depth, tape-recorded interview in the hospital after preterm labor was stabilized; periodically over the telephone after discharge from the hospital; and in the hospital, home, or via telephone after birth, for a total of 31 interviews. Using qualitative data analysis techniques, the findings were conceptualized as five recursive stages: becoming aware that something was wrong and feeling unbalanced, making sense of the experience as they sought to understand why preterm labor occurred, trying different strategies to re-create a balance in their lives, addressing other life stressors that threatened restoring balance, and emerging from the preterm labor experience with added growth. An increased understanding of the preterm labor experience from the women's perspective can be helpful to health care professionals and others who support women during pregnancy.     

Molecular aspects of preterm labor

Preterm birth is a major problem in clinical obstetrics, occurring in approximately 10% of all pregnancies, and leading to 75% of early neonatal mortality and morbidity. Studies in our laboratory have examined the neuroendocrine mechanisms by which the fetus, through activation of the hypothalamic-pituitary adrenal axis, provides the stimulus to the onset of parturition. Maturation of this axis occurs prematurely in response to stimuli such as stress. Stress induced activation of HPA function in human pregnancy, may lead to increased output of corticotropin-releasing hormone (CRH) from placenta and fetal membranes. CRH is one of the agonists that acts in concert with increased prostaglandin biosynthesis to provide the stimulus to myometrial contractility in late gestation. Recent studies have also recognized that approximately 15% of patients in idiopathic preterm labor present, with deficiency of the major prostaglandin metabolizing enzyme in the fetal membranes, particularly chorionic trophoblast. Understanding these processes may lead to new methods of managing the patient presenting in preterm labor.     

Neonatal consequences of preterm PROM

Preterm premature rupture of the fetal membranes is associated with 30-40% of premature births and is an important cause of perinatal morbidity and mortality. Although the major causes of neonatal death associated with PPROM include prematurity complications, infection, and pulmonary hypoplasia, rupture in a preterm gestation also is associated with an increase in morbidity, including cerebral palsy, other developmental delays, as well as chronic lung disease. When PPROM occurs, antibiotic prophylaxis has been shown to reduce the potential for complications and should be considered. Neonates treated intrapartum with antibiotics should have fewer complications, a longer latency period, and an improved long-term outlook compared with those without antepartum or intrapartum prophylaxis.     

Neutrophil priming: pathophysiological consequences and underlying mechanisms

1. Neutrophil priming by agents such as tumour necrosis factor-alpha, granulocyte/macrophage colony-stimulating factor and lipopolysaccharide causes a dramatic increase in the response of these cells to an activating agent; this process has been shown to be critical for neutrophil-mediated tissue injury both in vitro and in vivo. 2. The principle consequence of priming, aside from a direct effect on cell polarization, deformability and integrin/selectin expression, is to permit secretagogue-induced superoxide anion generation, degranulation and lipid mediator (e.g. leukotriene B4 and arachidonic acid) release. It is now recognized that most priming agents also serve an additional function of delaying apoptosis and hence increasing the functional longevity of these cells at the inflamed site. 3. The potential mechanisms underlying priming are discussed; current data suggest a dissociation between priming and changes in receptor number and/or affinity, G-protein expression, phospholipase C and phospholipase A2 activation and changes in intracellular Ca2+ concentration. However, more recent studies support a key role for protein tyrosine phosphorylation and enhanced phospholipase D and phosphoinositide 3-kinase activity in neutrophil priming. 4. Recent work has also revealed the potential for neutrophils to spontaneously and fully 'de-prime' after an initial challenge with platelet-activating factor. This ability of neutrophils to undergo a complete cycle of priming-de-priming (and re-priming) reveals a previously unrecognized flexibility in the control of neutrophil behaviour at an inflamed site.     

Aeromedical transfer of preterm labor patients

Obstetric patients are transported by air quite frequently. We evaluated transport times, obstetric outcomes, air-versus-ground transport costs, and related data on 22 helicopter aeromedical transports of pregnant patients with preterm labor. We found no significant differences between patients who delivered and those who did not when comparing transport time (167.1 +/- 41.9 minutes versus 177.1 +/- 56.2 minutes), air distance of transport (122.9 +/- 44.8 miles versus 143.6 +/- 23.8 miles), and other outcome measures. No deliveries occurred in flight. Air transport costs were significantly greater than estimated ground transfer ($4613.64 +/- $581.12 versus $604.02 +/- $306.38; P < .01). Two-way air transfer of preterm labor patients over moderate distances is more costly than contracted ground transfer costs at our institution.     

Intraamniotic infection in patients with preterm labor and twin pregnancies

BACKGROUND: Microbial invasion of the amniotic cavity plays a major role in the pathogenesis of preterm labor and delivery in singleton pregnancy. Nevertheless, this association is not well established among patients with multiple gestations. The purpose of our study was to explore the role of intraamniotic infection in the setting of twin pregnancies. METHODS: Consecutive women with twin gestations, intact membranes and preterm labor who underwent transabdominal amniocentesis under sonographic guidance. Amniotic fluid (AF) was retrieved from both sacs and cultured for aerobic and anaerobic microorganisms as well as for Mycoplasma species. Intraamniotic infection was defined as a positive AF culture for microorganisms. Mann Whitney U test or Student t-test or Fisher's exact test were utilized for analysis. RESULTS: Amniotic fluid was obtained from 74 patients. Sixty-eight women delivered prematurely (91.9%). Amniotic fluid culture results were positive for microorganisms in nine cases and all women with intraamniotic infection delivered prematurely as well as 59 (90.7%) patients with negative culture. Among the nine patients with intraamniotic infection, microorganisms were isolated from the presenting sac in five cases (55.6%), from both sacs in three patients (33.3%) and from the upper sac in the remaining case (11.1%). Patients with a positive AF culture had a more advanced cervical dilatation, a shorter interval amniocentesis-to-delivery and a higher incidence of clinical chorioamnionitis than those with a negative AF culture. CONCLUSIONS: The prevalence of intraamniotic infection and clinical and histological chorioamnionitis in twin pregnancies and preterm labor is similar to singleton pregnancies and preterm labor. Therefore, women with multiple gestations and preterm labor should be managed as singleton pregnancies.     

Maternal placental vasculopathy and infection: two distinct subgroups among patients with preterm labor and preterm ruptured membranes

OBJECTIVE: Our aim was to find out whether patients delivered preterm because of preterm labor or preterm premature rupture of membranes can be categorized according to clinical characteristics and placental pathologic findings. STUDY DESIGN: We performed a case-control study of 105 patients who were delivered preterm, 42 because of preterm labor and 63 because of premature rupture of membranes, and 105 patients who were delivered at term after uncomplicated pregnancies. RESULTS: Maternal placental vascular lesions were present in 14 (34.1%) patients with preterm labor, 19 (35.1%) patients with premature rupture of membranes, and 9 (11.8%) control patients (odds ratios 3.8 and 4.0, 95% confidence intervals 1.3 to 11.1 and 1.5 to 10.8, p = 0.0065 and 0.0022, respectively). Infection of the products of conception was found in 16 patients (38%) with preterm labor, 23 patients (36.5%) with premature rupture of membranes, and 19 control patients (18%) (odds ratios 2.7 and 2.6, 95% confidence intervals 1.1 to 6.6 and 1.2 to 5.6, p = 0.017 and 0.01, respectively). Patients with maternal placental vasculopathy had significantly different characteristics compared with those of infected patients. CONCLUSIONS: It is possible to identify two subgroups of patients among those who are delivered preterm because of preterm labor or premature rupture of membranes, one with infection of the products of conception and another with maternal placental vasculopathy.     

Adolescents'' description and management of pregnancy and preterm labor

Xenopus laevis larvae with an elevated expression of c-src were generated by mating a transgenic X. laevis male frog carrying proviral Rous sarcoma virus (RSV) long terminal repeat (LTR) and most of the pol gene sequences in its sperm DNA and a normal X. laevis female frog. Offspring (15-20%) with a higher dosage of c-Src, detected in disorganized myotomal musculature and in cerebral and spinal neuronal cells by immunohistochemical analysis, developed abnormally, with edemas (in most cases), head deformities, and eye and axial system defects. In the remaining embryos, a small increase in c-src expression seemed to be compatible with normal embryogenesis. The dosage of c-Src correlated with the dosage of RSV LTR integrated in frog DNA as revealed by Southern and polymerase chain reaction (PCR) analyses. Authenticity of the integrated RSV LTR including enhancer sequence was proved by sequencing. Probing of total RNA from aberrant larvae demonstrated several times higher dosage of c-src mRNA in their tissues than in control tadpoles. We hypothesize that the integrated RSV regulatory sequences can stimulate the expression of c-src proto-oncogene of X. laevis above a threshold that interferes with the early developmental program of frog embryos.     

Monitoring women at risk for preterm labor

Candida arthritis is infrequent in patients who are not intravenous drug users. We describe a patient who was not an intravenous drug user and without other predisposing factors who developed knee arthritis caused by Candida albicans. We believe that this is the first report of such a case.     

Induction of preterm labor in the rabbit by antiprogesterone

On the 25th day of pregnancy, 14 New Zealand white rabbits were treated orally with 500 mg of the progesterone (P)-synthesis inhibitor: Isoxazol. This treatment was repeated 12 hours (n = 6) or 24 hours (n = 8) later. An additional group of 6 rabbits received at the same time the solvent, without Isoxazol, to serve as vehicle controls. From day 26 onward all these 20 animals were induced every day with a single i.v. injection of 100 mU oxytocin until they delivered. The 14 Isoxazol rabbits responded to oxytocin on day 27.7 plus or minus 0.2 (Mean plus or minus S.E.), while the vehicle controls failed to respond until day 30.3 plus or minus 0.4 of pregnancy (p smaller than 0.001). Progesterone assays in the uterine vein plasma showed that, in comparison with 14 untreated controls of similar gestational age, plasma P of the 14 Isoxazol rabbits was significantly reduced (p smaller than 0.01). The vehicle controls became inducable when their P was endogenously lowered to the level at which oxytocin readily provokes parturition near term. Neither Isoxazol, nor oxytocin altered the normally low prostaglandin F levels of the uterine vein plasma, indicating that Isoxazol provokes premature inducability in the rabbit through P-withdrawal, rather than through an elevation of PG-levels.     

Physiopathologic mechanisms in acute progressive neuronal death: pharmaco-therapeutic consequences]

Although surgical intervention for advanced lung cancer invading the aortic wall is challenging, we successfully carried out such radical surgery under cardiopulmonary bypass as previously reported in this journal. One patient has now been followed for more than 5 years after the operation, so that we conclude if there is no evidence of metastatic cancer in selected patients then complete resection should be attempted using circulatory support, with the hope of an occasional cure.     

Adjustment of magnesium sulfate infusion rate in patients with preterm labor

OBJECTIVE: Our purpose was to investigate factors that might influence serum magnesium levels during intravenous magnesium sulfate tocolytic therapy. STUDY DESIGN: Thirty-three women receiving magnesium sulfate for preterm labor participated in this prospective, observational study. Gestational ages were 24 to 34 weeks. Four groups of women were identified according to the maintenance magnesium infusion rate required for arresting preterm labor after 5 g of therapy induction: 1.5, 2, 2.5, and 3 g/h. Serum magnesium samples were drawn after a predefined period of at least 18 hours of arrested preterm labor, at a minimum of every 6 hours. Variables examined included serum albumin; serum protein; serum ionized calcium; serum creatinine; creatinine clearance; 24-hour urine output; maternal height, weight, body surface area; and body mass index. RESULTS: By use of a multivariate stepwise regression model we identified four variables that independently and significantly contributed to the model: magnesium infusion rate (P < .001); total serum protein level (P < .001); serum creatinine level (P = .009); and maternal weight squared (P = .026). Seventy-two percent of the variance was accounted for by use of these parameters. A predictive linear model, developed to relate these factors, produced the following formula: Suggested magnesium infusion rate = 0.89 x Serum magnesium concentration (mg/dL) - 3.16 x Serum creatinine (mg/dL) - 0.66 x Serum total proteins (g/dL) + 0.0001 x (maternal weight)2 (kg) + 2.30. CONCLUSIONS: Serum creatinine, serum protein, and maternal weight can be used to adjust the dose of magnesium sulfate in patients with premature labor to achieve therapeutic serum levels of magnesium more rapidly and safely.     

Ceramide accumulation during oxidant renal tubular injury: mechanisms and potential consequences

Ceramide is an important signaling molecule that is typically generated via sphingomyelinase (SMase)-mediated sphingomyelin (SM) hydrolysis. Although diverse forms of renal injury elicit ceramide accumulation, the molecular determinants of this change and its contribution to tissue damage are poorly defined. The present study uses iron (Fe/hydroxyquinoline)-mediated injury of cultured human proximal tubular (HK-2) cells to gain additional insights into these issues. A 4-h Fe exposure doubled ceramide levels in the absence of cell death. This was independent of de novo synthesis, since ceramide synthase inhibition (with fumonisin B1) had no effect. Oxidant stress directly suppressed, rather than stimulated, SMase activity by: (1) decreasing SMase levels; (2) depleting SMase-stimulating glutathione; and (3) increasing SM resistance to SMase attack. Fe suppressed cell sphingosine levels (3 to 4 times ceramide/sphingosine ratio increments), suggesting a possible ceramidase block. Fe did not directly affect HK-2 ceramidase levels. However, arachidonic acid (C20:4) accumulation, a consequence of oxidant-induced phospholipase A2 (PLA2) activation, markedly suppressed ceramidase and stimulated SMase activity. Exogenous C20:4, as well as PLA2 (in doses simulating Fe-induced deacylation) recapitulated Fe's ceramide-generating effect. Because C20:4 is directly cytotoxic, it was hypothesized that ceramide might offset some of C20:4's adverse effects. Supporting this possibility were the following: (1) C20:4 exacerbated Fe toxicity; (2) this was abrogated by ceramide treatment; and (3) ceramide blunted Fe-mediated cell death. Conclusions: (1) ceramide accumulation during acute cell injury can be an adaptive response to PLA2 activation/C20:4 generation; (2) C20:4-induced ceramidase inhibition, coupled with SMase stimulation, may trigger this result; and (3) these ceramide increments may exert a "biostat" function, helping to offset C20:4/PLA2- and "catalytic" iron-mediated tubular cell death.