Biomedical subjects

David F Lewis

Publications and source records attributed to David F Lewis.

At least 19 recordsLinked to original sources

PubMed2007

Endothelial barrier function in preeclampsia.

Impaired endothelial barrier function resulting in increased vascular permeability is a characteristic vascular response in preeclampsia, a hypertensive and multiple systemic disorder of human pregnancy. During the last two decades, endothelial function in preeclampsia has been intensively studied and significant progress has been made in understanding the cellular and molecular bases of the altered endothelial cell response. In this review, we address the nature and mechanisms that are proposed to underlie the disturbed endothelial barrier function in preeclampsia and discuss the potential relevance of the endothelial cell responses to the initiation and/or progression of this vascular syndrome. Insights gained from the characterization of the endothelial cell phenotype assumed by the preeclamptic microvasculature may lead to novel therapeutic strategies for the management of this syndrome.

Capillary Permeability↗

PubMed2006

Reduced cellular glutathione reductase activity and increased adhesion molecule expression in endothelial cells cultured with maternal plasma from women with preeclampsia.

OBJECTIVE: The purpose of the current study was to determine whether maternal circulating components could regulate oxidative status of glutathione redox cycle and adhesion molecule expression in endothelial cells (ECs). METHODS: Maternal plasma was extracted from venous blood obtained from normal term pregnant women and from women with preeclampsia (PE). Normal and PE pregnancies were defined as American College of Obstetricians and Gynecologists criteria. Confluent ECs were incubated with EC growth medium (EGM) containing 20% plasma from women with normal (n = 8) and PE (n = 8) pregnancies for 4 hours. ECs incubated with EGM only were used as control. EC oxidative status was assessed by measuring cellular glutathione reductase (GR) and glutathione peroxidase (GPx) activities. Adhesion molecule expressions for intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), P-selectin, and E-selectin were determined by colorimetric assays detected on EC surface by UV spectrophotometer at OD 450 nm. Data are presented as mean +/- SE and analyzed by analysis of variance (ANOVA). A P value < .05 was set as statistically significant. RESULTS: Cellular GR activity was reduced approximately 35% in ECs treated with normal plasma and 70% in ECs treated with PE plasma compared to that in untreated control cells: 0.072 +/- 0.014 (P < .05), 0.039 +/- 0.006 (P < .01), versus 0.117 +/- 0.010 U/mg cellular protein, respectively. In contrast, GPx activity was slightly increased in ECs treated with normal plasma and significantly increased in ECs treated with PE plasma compared to that in untreated control cells: 0.059 +/- 0.005, 0.075 +/- 0.012 (P < .05) versus 0.044 +/- 0.002 U/mg cellular protein, respectively. P-selectin, E-selectin, and VCAM expressions were elevated in cells treated with normal plasma but significantly increased in cells treated with PE plasma compared to those of untreated controls: P-selectin--0.18 +/- 0.03, 0.35 +/- 0.04 versus 0.04 +/- 0.01 OD 450 nm, P < .01; E--selectin-0.06 +/- 0.02, 0.10 +/- 0.02 (P < .05) versus 0.03 +/- 0.01 OD 450 nm; VCAM--0.12 +/- 0.02, 0.16 +/- 0.03 (P < .01) versus 0.08 +/- 0.02 OD 450 nm, respectively. There was no difference for ICAM expression in cells treated with normal or PE plasma compared to controls. CONCLUSIONS: These data suggest that endothelial pro- and anti-oxidative status could be directly affected by circulating components during pregnancy. Reduced cellular GR activity and increased GPx activity accompany increased inflammatory reactions in ECs responding to circulating "toxic" factors in preeclampsia.

Antibodies, Monoclonal↗

PubMed2006

Increased superoxide generation and decreased stress protein Hsp90 expression in human umbilical cord vein endothelial cells (HUVECs) from pregnancies complicated by preeclampsia.

OBJECTIVE: Endothelial dysfunction is associated with increased oxidative stress in the vascular system in women with preeclampsia (PE), a hypertensive disorder occurring during human pregnancy. However, due to the nature of the disease, direct evidence of increased endothelial oxidative stress in the maternal vascular system at an in vivo situation is still lacking. We previously reported that primary cultured endothelial cells (ECs) from umbilical cords (HUVECs) from pregnancies complicated by PE exhibit phenotypic changes compared to those from normal pregnancies such as reduced eNOs expression associated with disorganized endothelial junction protein distribution and increased endothelial permeability. In this study, we sought to determine whether increased oxidative stress was also present in primary cultured HUVECs from women with PE. METHODS: HUVECs were isolated from normal and PE pregnancies and EC oxidative stress was examined by superoxide generation using positive nuclear dihydroethidium (DHE) staining as an indicator. Since Hsp90 is believed to have protective effects on endothelial function, we also determined mRNA and protein expression for Hsp90. Using Hsp90 inhibitor geldanamycin (GA), we further determined the potential role of Hsp90 in superoxide generation, eNOs expression, and prostacyclin production of altered EC function associated with PE pregnancies. RESULTS: We found that primary cultured ECs from PE pregnancies showed an increase in DHE positive cells, p < 0.01. Hsp90 protein expression was significantly decreased in ECs from PE compared with that from normal pregnancies, p < 0.05. Inhibition of Hsp90 by GA resulted in an increase in superoxide generation and a decrease in eNOs protein expression. Decreased prostacyclin production was also found in ECs treated with GA. CONCLUSION: These in vitro HUVEC data suggest that increased endothelial oxidative stress may also occur in the fetal compartment during preeclampsia.

Benzoquinones↗

PubMed2006

Expression of lymphatic vascular endothelial hyaluronan receptor-1 (LYVE-1) in the human placenta.

BACKGROUND: Lymphatic vascular endothelial hyaluronan receptor-1 (LYVE-1) is a selective marker for lymphatic endothelium and a homolog of CD44, the hyaluronan (HA) receptor. HA in the extracellular matrix plays roles in tissue remodeling, development, and homeostasis, and as an HA receptor, LYVE-1 mediated HA metabolism might regulate these events. Currently, little is known about the lymphatic character within the human placenta. This study therefore determined LYVE-1 and other lymphatic markers in human placentas. METHODS AND RESULTS: Placentas and villous tissue were fixed and immunostained for human LYVE-1 and CD44 and examined by RT-PCR. LYVE-1 was expressed at both protein and mRNA levels in trophoblast cells (TC) and in villous core endothelium (VCE). Predominant protein expression for LYVE-1 was observed in syncytiotrophoblast cells (TCs) of preterm placentas. Neither mRNA or protein for CD44 was expressed. Other blood and lymphatic-lineage molecules (VEGF-A, -C, and -D, Flt-1, KDR, Flt-4, and Prox-1) were examined by RT-PCR. VEGF-A, VEGF-D, and Flt-1 mRNA were observed in TCs and VCEs, while mRNA for VEGF-C, KDR, and Flt-4 was mainly observed in VCEs. Prox-1 was found at the mRNA, but not protein level in TCs and VCEs. Our findings indicate (1) the importance of LYVE-1, but not CD44, in regulation of HA metabolism in the maternal-fetal interface and fetal circulation, and (2) possible dual blood and lymphatic phenotypic characteristics in fetal endothelium. These results provide new insights into HA metabolism and lymphatic-lineage molecule expression in the human placenta.

Endothelium, Vascular↗

PubMed2006

Urolithiasis in pregnancy: Current diagnosis, treatment, and pregnancy complications.

UNLABELLED: Urolithiasis complicates up to one in every 200 pregnancies; consequently, the practicing obstetrician should be aware of the symptoms of urolithiasis, the diagnostic procedures available for its diagnosis, and their associated risks. These include ultrasound, urography, and magnetic resonance imaging. Diagnosis of urolithiasis during pregnancy can be a challenge as a result of the normal physiological changes of pregnancy. Conservative management is the first-line treatment for noncomplicated urolithiasis in pregnancy. If spontaneous passage of the stone does not occur or if complications develop, urologic consultation should be obtained. Several obstetric complications have been associated with urolithiasis, including preterm labor and preterm premature rupture of membranes, although the reported rates of these complications in association with urolithiasis vary widely and overlap normal background rates. Given that urolithiasis will be encountered by most obstetricians, and that obstetricians are often on the front line of management for this condition, an appreciation of current diagnostic modalities, treatment protocols, and associated potential obstetric complications is warranted. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall that urolithiasis is common in pregnancy, state that there are a variety of diagnostic procedures, summarize that conservative treatment is usually successful, and explain that complications of pregnancy usually occur when there is failure of conservative treatment.

Diagnosis, Differential↗

PubMed2005

A prospective randomized trial of magnesium sulfate in severe preeclampsia: use of diuresis as a clinical parameter to determine the duration of postpartum therapy.

OBJECTIVE: The purpose of this study was to assess the use of the onset of diuresis in the determination of the duration of postpartum magnesium sulfate therapy among patients with severe preeclampsia. STUDY DESIGN: A prospective randomized trial of postpartum therapy with magnesium sulfate was conducted. The control group received 24 hours of therapy, and the study group received therapy until the onset of diuresis (urine output >100 mL/hr for 2 consecutive hours). The Student t test, chi 2 test, and Fisher's exact test were used for analysis of data; a probability value of <.05 was considered statistically significant. RESULTS: There were 50 patients in the control group and 48 patients in the study group. There was no difference in maternal demographic data, severe disease criteria, blood pressure, 24-hour postpartum urine output, or need for antihypertensive therapy. The study group had a significantly shorter duration of therapy, and no patient had eclampsia or required the re-initiation of therapy. CONCLUSION: The use of the onset of diuresis in the postpartum period as the determinant clinical parameter for the discontinuation of magnesium sulfate in patients with severe preeclampsia was associated with no untoward outcomes or need for the re-initiation of treatment.

Adult↗

PubMed2005

Hypoxia promotes interleukin-6 and -8 but reduces interleukin-10 production by placental trophoblast cells from preeclamptic pregnancies.

OBJECTIVE: Placental hypoxia and altered placental cytokine productions have been considered to play a significant role in the pathophysiology of preeclampsia. The objective of this study was to determine whether hypoxia could modify interleukin (IL)-6, IL-8, and IL-10 production by placental trophoblast cells (TCs) from normal and preeclamptic (PE) pregnancies. METHODS: Placentas were obtained from nine normal and nine PE pregnancies immediately after delivery. Placental TCs were isolated and cultured under normoxic (21% O(2)/air) and hypoxic (2% O(2)/5% CO(2)/92% N(2)) conditions for 48 hours. TC productions of IL-6, IL-8, and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). Unpaired t tests or paired t test was used for the statistical analysis and data are expressed as means +/- SE (pg/mug cellular protein). A P value less than .05 was considered statistically significant. RESULTS: PE-TCs produced significantly more IL-6, IL-8, and IL-10 than those of normal-TCs when they were cultured under normoxic condition, P < .05. Both normal-TCs and PE-TCs produced more IL-6 and IL-8 when they were cultured under hypoxic conditions. Hypoxia reduced IL-10 production by PE-TCs, but had no effect on IL-10 production by normal-TCs. CONCLUSIONS: Hypoxia promotes both IL-6 and IL-8 but reduces IL-10 production by placental TCs from PE pregnancies.

Adult↗

PubMed2005

Effects of peroxynitrite and superoxide radicals on endothelial monolayer permeability: potential role of peroxynitrite in preeclampsia.

OBJECTIVE: Increased endothelial permeability is associated with increased oxidative stress in the maternal vasculature in women with preeclampsia. This study was to determine if oxidative stress elicited by peroxynitrite could lead to an increase in endothelial permeability. METHODS: Endothelial oxidative stress was produced by adding 3-morpholinosydnonimine (SIN-1, a peroxynitrite generator) to the cell culture. Confluent endothelial cells (ECs) grown in cell culture inserts were treated with SIN-1 at a concentration of 0.5 mM alone or in combination with MnTMPyP (a peroxynitrite scavenger) or superoxide dismutase (SOD). EC permeability was determined by measuring EC electrical resistance (ER) and horseradish peroxide (HRP) leakage. Data are presented as means +/- SE and analyzed by analysis of variance (ANOVA). Junctional protein expression and distribution for vascular endothelial (VE)-cadherin, occludin, and phosphorylated focal adhesion kinase (FAK) at tyrosine 397 [pY397] were examined by fluorescent staining of ECs. RESULTS: First, ER was significantly reduced and HRP leakage was significantly increased in ECs treated with SIN-1 compared to those in control cells, ER: 26.97 +/- 1.41 versus 42.27 +/- 0.40 Omega.cm2, P <.01; HRP: 0.26 +/- 0.07 versus 0.02 +/- 0.01 OD 470 nm, P <.01, respectively. Second, cells treated with SIN-1 showed formation of gaps and disorganized VE-cadherin and occludin distribution at cell contact regions. FAK[pY397] expression was completely lost in cells treated with SIN-1. Finally, these functional and morphologic changes in ECs induced by SIN-1 were blocked in cells pretreated with MnTMPyP and SOD. CONCLUSIONS: Disorganization of junctional proteins and dephosphorylation of FAK[pY397] may account for the increased endothelial permeability induced by oxidative stress associated with preeclampsia.

Cell Membrane Permeability↗

PubMed2005

Magnesium sulfate: the first-line tocolytic.

Magnesium sulfate has become the first-line tocolytic for short-term use to arrest idiopathic preterm labor. The reasons for its acceptance include familiarity of the drug, ease of use, and the virtual absence of serious maternal side effects. Sufficient data exist showing its efficacy if used in higher doses. Attention to treating preterm labor has shifted to seeking answers about the fundamental causes. Gathering information about the specific causes and designing tailor-made treatment protocols for each of the numerous potential causes is essential. Scientifically sound research is needed to obtain answers about the important clinical questions surrounding magnesium sulfate.

Drug Therapy, Combination↗

PubMed2005

Increased phospholipase A2 and thromboxane but not prostacyclin production by placental trophoblast cells from normal and preeclamptic pregnancies cultured under hypoxia condition.

In this study we determined whether hypoxia could promote vasoactivator thromboxane (TX) and prostacyclin (PGI2) as well as phospholipase A2 (PLA2) production by placental trophoblast cells (TCs) from normal and preeclamptic (PE) pregnancies. Placentas were obtained immediately after delivery from normal (n=9) and preeclamptic (n=9) pregnancies. TCs were isolated by dispase digestion of villous tissue and purified by Percoll gradient centrifugation. TCs (5x10(6) cells/well) were cultured with Dulbecco's Modified Eagles Medium (DMEM) under hypoxia condition (2% O2/5% CO2/93% N2) for 48 h. TCs cultured under normoxia condition (5% CO2/air) were used as control. Culture medium was collected at the end of incubation. Productions for TX, PGI2 and PLA2 were measured by ACE competitive enzyme immunoassay (EIA). Comparisons were made using the Mann-Whitney U test or paired t-test and the data are expressed as mean+/-SE (pg/microg cellular protein). Significance was set at a p-value of <0.05. We found: (1) PE-TCs produced more TXB2 and PLA2 than normal-TCs under normoxia conditions, TXB2: 4.33+/-1.03 vs. 1.84+/-0.29 pg/microg protein, p<0.05; PLA2: 0.38+/-0.08 vs. 0.21+/-0.03 pg/microg protein, p<0.05, respectively. (2) Hypoxia promoted both PE- and normal-TCs to generate more TXB2 and PLA2, TXB2: 6.36+/-1.72 vs. 3.05+/-0.45 pg/microg; PLA2: 0.52+/-0.10 vs. 0.30+/-0.04 pg/microg, respectively. (3) No change in 6-keto PGF1alpha production was observed for normal-TCs or PE-TCs when compared under normoxia vs. hypoxia condition, normal-TCs: 0.20+/-0.05 vs. 0.21+/-0.05 pg/microg; PE-TCs: 0.38+/-0.05 vs. 0.36+/-0.04 pg/microg, respectively. We concluded that hypoxia promotes both PLA2 and TX, but not PGI2, production by placental trophoblast cells cultured under hypoxia condition. These results suggest that increased PLA2 release may alter the arachidonic acid cascade and promote TX synthesis. Relative hypoxia could contribute to the increase in TX production and result in vasoconstriction in placental vasculature in preeclampsia.

6-Ketoprostaglandin F1 alpha↗

PubMed2005

Abruptio placentae associated with misoprostol use in women with preeclampsia.

OBJECTIVE: To evaluate complications associated with cervical ripening with vaginal administration of misoprostol and dinoprostone vaginal inserts in women with preeclampsia. preeclampsia. STUDY DESIGN: Retrospective study of patients with preeclampsia undergoing cervical ripening with vaginal misoprostol and dinoprostone vaginal inserts prior to labor induction. RESULTS: Among 203 patients with preeclampsia undergoing cervical ripening prior to induction, 95 received vaginal misoprostol, and 108 received dinoprostone. The incidence of uterine hyperstimulation requiring medical therapy and the need for emergency cesarean section due tofetal heart rate abnormalities were significantly higher among patients receiving misoprostol (22.1% versus 12.0%, p = 0.04, and 17.9% versus 8.3%, p = 0.03, respectively). The overall incidence of abruptio placentae was 7.4%, with a significantly higher incidence among those receiving misoprostol as compared to dinoprostone (13.7% versus 1.9%, p = 0.001). CONCLUSION: Among patients with preeclampsia undergoing cervical ripening prior to labor induction, there is a higher incidence of acute intrapartum complications (uterine hyperstimulation, cesarean section for fetal heart rate abnormalities and abruptio placentae) with vaginal misoprostol, as compared to dinoprostone, vaginal insert.

Abruptio Placentae↗

PubMed2004

Evidence of endothelial dysfunction in preeclampsia: decreased endothelial nitric oxide synthase expression is associated with increased cell permeability in endothelial cells from preeclampsia.

OBJECTIVE: The purposes of this study were to examine endothelial nitric oxide synthase expression in endothelial cells and to determine whether the inhibition of endothelial nitric oxide synthase could impair endothelial barrier function in preeclampsia. STUDY DESIGN: Messenger RNA and protein expression for endothelial nitric oxide synthase were examined in endothelial cells that were isolated from normal and preeclamptic pregnancies. Endothelial monolayer permeable response to interleukin-8 stimulation was determined. Normal endothelial cells that were treated with nitric oxide inhibitor were used to test the association of endothelial nitric oxide synthase and endothelial barrier function. Messenger RNA expression for endothelial nitric oxide synthase was determined by reverse transcription-polymerase chain reaction, and protein expression was determined by Western blot analysis. Endothelial permeability was measured by horseradish peroxidase leakage through endothelial cell filters. Interleukin-8 production was measured by enzyme-linked immunosorbent assay. Data were presented as mean+/-SE and analyzed by analysis of variance or nonparametric Mann-Whitney test. RESULTS: Relative messenger RNA expression and protein expression for endothelial nitric oxide synthase were decreased significantly in endothelial cells from preeclampsia compared with cells from normal pregnancies (messenger RNA expression, 0.191+/-0.057 vs 0.508+/-0.061 [P <.01]; protein expression, 0.225+/-0.08 vs 0.786+/-0.098 [P<.01], respectively). Horseradish peroxidase leakage in normal endothelial cells was 0.30+/-0.26 micromol/L (interleukin-8, 1 pg/mL), 3.14+/-2.45 micromol/L (interleukin-8, 5 pg/ml), and 9.08+/-2.69 micromol/L (interleukin-8, 25 pg/mL; P<.01; compared with 0.77+/-0.47 micromol/L [control endothelial cells]). Horseradish peroxidase leakage in preeclamptic endothelial cells was 6.20+/-2.19 micromol/L, 8.44+/-85 micromol/L, and 15.79+/-2.06 micromol/L (P<.05) compared with 5.23+/-1.28 micromol/L, respectively. The ratio of horseradish peroxidase leakage was >7-fold increase in normal endothelial cells, but only a 4-fold increase in preeclamptic endothelial cells in response to interleukin-8 stimulation at 25 pg/mL. The inhibition of endothelial nitric oxide synthase with N(G)-Monomethyl-L-arginine resulted in an increase in interleukin-8-induced endothelial cell permeability. No difference for interleukin-8 production was observed between normal and preeclamptic endothelial cells (1.15+/-0.21 ng/mg protein vs 1.29+/-0.23 ng/mg protein, P>.5). CONCLUSION: Increased endothelial permeability may be associated with decreased endothelial nitric oxide synthase expression and activity in endothelial cells from preeclampsia.

Case-Control Studies↗

PubMed2004

Heme oxygenase-1 mediates up-regulation of adhesion molecule expression induced by peroxynitrite in endothelial cells.

OBJECTIVE: Endothelial cell (EC) activation with up-regulation of cellular adhesion molecule (CAM) expression is a pathophysiologic feature in preeclampsia (PE). Enhanced peroxynitrite formation in the vasculature of women with PE was also reported. This study was to test whether EC oxidative stress induced by peroxynitrite could up-regulate EC CAM expression, and whether heme oxygenase-1 (HO-1) has protective effects on this peroxynitrite-induced cellular response. METHODS: Confluent ECs were stimulated with 3-morpholinosydnonimine-HCl (SIN-1, a peroxynitrite generator) alone or combined with Mn(III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP, a peroxynitrite scavenger) up to 4 hours. EC surface protein expressions for ICAM, VCAM, P-selectin, and E-selectin were measured by colorimetric assay. ECs were also treated with Sn(IV) mesophorphyrin IX dichloride (SnMP, a HO-1 inhibitor) to determine if HO-1 was involved in the increased CAM expression in stressed cells. Protein and mRNA expressions for HO-1 were determined by Western blot analysis and reverse-transcriptase polymerase chain reaction (RT-PCR). Data are presented as the mean +/- SE and analyzed by analysis of variance (ANOVA). RESULTS: Endothelial CAM expressions for VCAM, P-selectin, and E-selectin, but not ICAM, were significantly increased in SIN-1-treated ECs. Protein and mRNA expressions for HO-1 were also up-regulated in cells treated with SIN-1. MnTMPyP blocked both mRNA and protein expressions for HO-1, whereas SnMP only blocked HO-1 protein expression. Both MnTMPyP and SnMP abolished SIN-1-induced up-regulation of VCAM, P-selectin, and E-selectin expression in ECs. CONCLUSIONS: Peroxynitrite-induced EC oxidative stress produces differential effects on CAM expression, which may be mediated by HO-1 regulation. Our results suggest that increased peroxynitrite formation in the maternal vasculature may contribute to the increased CAM expression and enhanced neutrophil-endothelial interaction associated with PE.

Cell Adhesion Molecules↗

PubMed2004

Placental trophoblast-derived factors diminish endothelial barrier function.

Although increased vascular permeability is an important event in the pathogenesis of preeclampsia, the origin of the circulating factor(s) that elicits this endothelial barrier dysfunction is not known. In this study, we use coculture of endothelial cells and placental trophoblast cells to determine whether placental trophoblasts are a potential source of the factor(s) that mediate the increased vascular permeability of preeclampsia. Human umbilical vein endothelial cells grown in Transwell inserts or on coverslips were cocultured with trophoblast cells isolated from normal and preeclamptic placentas or placenta conditioned media. Endothelial cell barrier function was determined by: 1). measurements of electrical resistance and leakage of horseradish peroxidase, and 2). immunofluorescent staining of vascular endothelial-cadherin, pan-cadherin, and occludin. Uterine myometrium endothelial cells were also studied for comparison. We observed the following: 1). electrical resistance was significantly (P < 0.01) decreased (compared with control endothelial cells) in endothelial cell monolayers cocultured with normal trophoblast cells and further reduced in endothelial cells cocultured with preeclamptic trophoblast cells; 2). an increased horseradish peroxidase leakage that was correlated with the decreased electrical resistance in cocultured cells; and 3). disorganized tight junction proteins and an altered distribution of vascular endothelial-cadherin and occludin in monolayers of endothelial cells cocultured with preeclamptic trophoblast cells. Similar responses were noted in uterine myometrium endothelial cells. We conclude that: 1). placental trophoblast cells produce factors that diminish the barrier function of endothelial cells; 2). endothelial tight junctions are more susceptible to factors released from preeclamptic trophoblast cells than from normal trophoblast cells; and 3). these results implicate trophoblast-derived factors in the increased vascular permeability associated with preeclampsia.

Adherens Junctions↗

PubMed2003

Antibiotic therapy in preterm premature rupture of membranes: Are seven days necessary? A preliminary, randomized clinical trial.

OBJECTIVE: The purpose of this study was to determine whether 3 days of broad-spectrum antibiotic therapy, which is intended to prolong latency in patients with preterm premature rupture of membranes, is comparable to 7 days of therapy. STUDY DESIGN: Patients with preterm premature rupture of membranes at three separate study sites were asked to participate in this intent-to-treat, prospective, randomized trial. They were assigned randomly to either 3 or 7 days of ampicillin-sulbactam (3 g intravenously every 6 hours). The primary outcome of interest was the latency period from membrane rupture to delivery. RESULTS: Forty-two individuals were enrolled in each group. No difference was noted in the latency interval between the two groups (3 days, 214 +/- 225 hours, vs 7 days, 229 +/- 218 hours). A significantly higher number of patients in the 3-day group completed therapy (80.1% vs 47.6%, P =.003). No other parameters were significantly different between the two groups. No adverse events or trends were noted in either group. CONCLUSION: There appears to be no difference in the latency period between 3 and 7 days of ampicillin-sulbactam antibiotic therapy. More patients are needed to exclude a type II error.

Adult↗

PubMed2003

Expectant management of preterm premature rupture of membranes complicated by active recurrent genital herpes.

OBJECTIVE: The study objective was to examine the neonatal outcome in pregnancies with early preterm premature rupture of the membranes (PPROM) who were managed expectantly despite the development of recurrent active genital herpes. STUDY DESIGN: Pregnancies complicated by PPROM at < or =14;31 weeks' gestation that developed an active recurrent genital herpes lesion were collected. The latency time from herpes lesion development to delivery and the neonatal outcome were analyzed. A control group of patients with PPROM at < or =14;31 weeks' gestation with no herpes infection was also obtained. RESULTS: A total of 29 patients were identified during the study period. The mean gestational age at herpes lesion development after PPROM was 28.7 weeks (range 24.6-31.0 weeks). The mean latency period from herpes development to delivery was 13.2 days (range 1-35 days). No cases of neonatal herpes developed in the delivered newborn infants and all neonatal cultures were negative (0 of 29 cases, 95% CI 0%-10.4%). Twelve newborn infants (41%) had major morbidity caused by prematurity and 3 of these (10.3%) died. There were no differences seen between the study cases and the control group. In the study, 15 of the 29 pregnancies were delivered beyond 30 weeks' gestation. If delivery had occurred on the day the herpes lesion developed, only 5 pregnancies would have been delivered beyond 30 weeks' gestation. CONCLUSION: On the basis of the 95% CI of these data, the maximum risk for development of a neonatal herpes infection in the face of PPROM and active recurrent genital herpes was 10.4%. This was equal to the mortality rate and was 75% lower than the major morbidity rate caused by prematurity. If delivery had occurred on the day the herpes lesions developed, on average, the neonates would have been nearly 2 weeks more premature, thereby potentially increasing the morbidity and mortality related to prematurity. These data concur with the American College of Obstetricians and Gynecologists consensus and expert opinion and would suggest that expectant management of PPROM at </=14;31 weeks' gestation with active recurrent genital herpes is warranted.

Adult↗

PubMed2003

Perinatal outcomes in preeclampsia that is complicated by massive proteinuria.

OBJECTIVE: Current treatment of preeclampsia no longer mandates delivery for proteinuria of >5 g per 24 hours. We sought to determine whether delayed delivery of preeclampsia with massive proteinuria (>10 g/24 h) increased maternal or neonatal morbidity. STUDY DESIGN: Records of all women with preeclampsia who were delivered at <37 weeks of gestation between January 1, 1997, and June 30, 2001, were reviewed. Patients with underlying renal disease or multiple gestation were excluded. Patients were characterized as having mild (<5 g/24 h), severe (5-9.9 g/24 h), or massive (>10 g/24 h) proteinuria. Outcomes were compared using the chi(2) test, one-way analysis of variance, or Fisher exact test. RESULTS: Two hundred nine patients met the inclusion criteria: 125 patients had mild proteinuria, 43 patients had severe proteinuria, and 41 patients had massive proteinuria. No significant differences in maternal morbidity were seen. Massive proteinuria was associated with earlier onset of preeclampsia, earlier gestational age at delivery, and higher rates of prematurity complications. After correction for prematurity, massive proteinuria has no significant effect on neonatal outcomes. CONCLUSION: Women with preeclampsia and massive proteinuria did not have increased maternal morbidity compared with women with severe or mild proteinuria. Massive proteinuria appears to be a marker for early-onset disease and progression to severe preeclampsia. Neonatal morbidity appears to be a function of prematurity rather than of massive proteinuria itself.

Abruptio Placentae↗

PubMed2003

Urolithiasis in pregnancy. Diagnosis, management and pregnancy outcome.

OBJECTIVE: To review our experiences with ureterolithiasis and nephrolithiasis in pregnancy and compare their outcomes with those in the rest of the obstetric population. STUDY DESIGN: A database of obstetric deliveries was used to identify patients with (cases) and without (controls) urolithiasis and to compare demographics and pregnancy complications between the groups. Furthermore, retrospective chart review of the cases group was utilized to obtain additional pertinent information. RESULTS: Over a 3-year period, there were 21,010 deliveries, 86 of which had symptomatic urolithiasis, for an incidence of 1 in 244 pregnancies. Renal calculi occurred more commonly in Caucasians than African Americans. Patients were more likely to become symptomatic in the second or third trimester, and most stones passed spontaneously. Pregnancy complications were similar between the groups; however, there was a higher percentage of preterm premature rupture of membranes in the nephrolithiasis cases (7.0% vs. 2.9%, P < .05). CONCLUSION: Nephrolithiasis and ureterolithiasis occurred more commonly in Caucasians during pregnancy. The majority of patients became symptomatic in the last two-thirds of pregnancy and usually passed the calculus spontaneously. A higher incidence of preterm premature rupture of membranes was noted in pregnancies complicated by urolithiasis.

Adult↗