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Background: Interferon-β1b (IFN-β1b), an effective treatment for multiple sclerosis (MS), lessens disease severity in MS patients. However, the mechanisms of its immunoregulatory and anti-inflammatory effects in MS remain only partially understood. Matrix metalloproteinases (MMP) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) are involved in blood brain barrier disruption and formation of MS lesions. Th1/Th17 cytokines e.g. interleukins IL-12p40, IL-17, and IL-23, are associated with MS disease activity and are significant players in pathogenesis of MS. Objective: During a 1-year prospective study, we serially measured serum MMP-8, MMP-9, TIMP-1, IL-12p40, IL-17, and IL-23 in 24 patients with relapsing-remitting MS. We compared the results to clinical course and to brain magnetic resonance imaging. IFN-β1b decreased serum MMP-8 and MMP-9 (not TIMP-1). Results: The sustained treatment with IFN-β1b attenuated the pro-inflammatory environment by significantly reducing the serum IL-12p40, IL-23, and showed a trend for decreasing IL-17. Decreased serum MMP-8, MMP-9, IL-12 and IL-23 levels were correlated with a decrease in the number of contrast-enhanced T2-weighted lesions. Conclusion: Early treatment of MS with IFN-β1b may stabilize clinical disease by attenuating levels of inflammatory cytokines and MMPs. Serial measurement of inflammatory mediators may serve as sensitive markers to gauge therapeutic responses to IFN-β1b during the first year of treatment. [ABSTRACT FROM AUTHOR]

Placenta previa percreta with bladder involvement is a rare but devastating complication of pregnancy. Antepartum diagnosis of this serious condition allows the obstetrician to alter his or her management of abdominal delivery and minimize the magnitude of bleeding. We report a case in which magnetic resonance imaging was able to detect placenta percreta in the first trimester. If further research demonstrates usefulness of this diagnostic modality, magnetic resonance imaging may prove to be useful in caring for patients with this condition. [ABSTRACT FROM AUTHOR]

Background: Inflammatory cytokines dysregulate microvascular function, yet how cytokines affect lymphatic endothelial cells (LEC) are unclear., Methods and Results: We examined effects of TNF-α, IL-1 beta, and IFN-gamma on LEC proliferation, endothelial cell adhesion molecule (ECAM) expression, capillary formation, and barrier changes in murine (SV-LEC) and human LECs (HMEC-1a)., Results: All cytokines induced ICAM-1, VCAM-1, MAdCAM-1, and E-selectin in SV-LECs; TNF-α, IL-1 beta; and IFN-gamma induced ECAMs (but not MAdCAM-1) in HMEC-1a. IL-1 beta increased, while IFN-gamma and TNF-α reduced SV-LEC proliferation. While TNF-α induced, IFN-gamma decreased, and IL-1 beta did not show any effect on HMEC-1a proliferation. TNF-α, IL-1 beta, and IFN-gamma each reduced capillary formation in SV-LEC and in HMEC-1a. TNF-α and IL-1 beta reduced barrier in SV-LEC and HMEC-1a; IFN-gamma did not affect SV-LEC barrier, but enhanced HMEC-1a barrier. Inflammatory cytokines alter LEC growth, activation and barrier function in vitro and may disturb lymphatic clearance increasing tissue edema in vivo., Conclusion: Therapies that maintain or restore lymphatic function (including cytokines blockade), may represent important strategies for limiting inflammation.

Background: Interferon-beta1b (IFN-beta1b), an effective treatment for multiple sclerosis (MS), lessens disease severity in MS patients. However, the mechanisms of its immunoregulatory and anti-inflammatory effects in MS remain only partially understood. Matrix metalloproteinases (MMP) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) are involved in blood brain barrier disruption and formation of MS lesions. Th1/Th17 cytokines e.g. interleukins IL-12p40, IL-17, and IL-23, are associated with MS disease activity and are significant players in pathogenesis of MS., Objective: During a 1-year prospective study, we serially measured serum MMP-8, MMP-9, TIMP-1, IL-12p40, IL-17, and IL-23 in 24 patients with relapsing-remitting MS. We compared the results to clinical course and to brain magnetic resonance imaging. IFN-beta1b decreased serum MMP-8 and MMP-9 (not TIMP-1)., Results: The sustained treatment with IFN-beta1b attenuated the pro-inflammatory environment by significantly reducing the serum IL-12p40, IL-23, and showed a trend for decreasing IL-17. Decreased serum MMP-8, MMP-9, IL-12 and IL-23 levels were correlated with a decrease in the number of contrast-enhanced T2-weighted lesions., Conclusion: Early treatment of MS with IFN-beta1b may stabilize clinical disease by attenuating levels of inflammatory cytokines and MMPs. Serial measurement of inflammatory mediators may serve as sensitive markers to gauge therapeutic responses to IFN-beta1b during the first year of treatment.

Objective: To determine whether preeclampsia is associated with an increase in placental apoptosis and differential expression of mediators of apoptosis., Methods: Placental samples from 31 preeclamptic women and 31 normotensive controls were analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining. Expression of Fas, Fas ligand, Bcl-2, and Bax was assessed using immunohistochemistry., Results: The median percent apoptotic nuclei was significantly higher for the study group than for the controls (0.49 versus 0.19; P =.001), as was the median percent apoptotic nuclei in the trophoblast nuclei (0.33 versus 0.09; P <.01). Fas ligand expression was significantly less and Fas expression significantly greater in the villus trophoblast among the study subjects compared with controls. There was no difference in the expression of Bax or Bcl-2 between groups., Conclusion: Placental apoptosis and altered expression of Fas and Fas ligand in trophoblast might influence pathogenesis or sequelae of preeclampsia.

Objective: To determine whether fetal fibronectin (FFN) might serve as a marker to distinguish intrauterine versus extrauterine pregnancy., Design: Prospective cohort study., Setting: Academic research center., Patient(s): Cervicovaginal FFN samples were obtained from 46 women who were at high risk for or presented with signs and/or symptoms of extrauterine pregnancy., Intervention(s): Samples of blood were analyzed for FFN with use of an enzyme-linked immunoabsorbent assay (ELISA)., Main Outcome Measure(s): Fetal fibronectin level., Result(s): The rate of extrauterine pregnancy in our study was 26.1%, with 12 extrauterine and 34 intrauterine pregnancies identified by ultrasonography or at time of surgery. Seventeen samples had FFN levels of > 50 ng/mL and were considered positive (range, 0-1,000 ng/mL). Positive FFN levels were observed in 41.7% (5 of 12) of women with extrauterine pregnancies versus 35.3%) (12 of 34) of women with intrauterine pregnancies. The sensitivity, specificity, and positive and negative predictive values for extrauterine pregnancy were 41.7%, 64.7%, 29.4%, and 75.9%, respectively., Conclusion(s): The use of FFN does not appear to alter significantly the likelihood of identifying extrauterine pregnancy over current laboratory or ultrasonographic methods.

During normal pregnancy, maternal hormones and locally acting cytokines play a key role in regulating the onset of labor, cervical ripening, uterine contraction, and delivery. Maternal infections during pregnancy have been demonstrated to perturb this normal cytokine and hormone-regulated gestation, sometimes resulting in preterm labor, preterm premature rupture of membranes, and preterm low birth weight (PLBW), i.e., < 2,500 g and < 37 weeks of gestation. Our research focus has been to determine whether periodontal infections can provide sufficient challenge to the mother to trigger PLBW. New experiments from 48 case-control subjects have measured gingival crevicular fluid (GCF) levels of PGE(2) and IL-1-beta to determine whether mediator levels were related to current pregnancy outcome. In addition, the levels of 4 periodontal pathogens were measured by using microbe-specific DNA probes. Results indicate that GCF-PGE(2) levels are significantly higher in PLBW mothers, as compared with normal birth weight (NBW) controls (131.4 +/- 21.8 vs. 62.6 +/- 10.3 [mean +/- SE ng/mL], respectively, at P = 0.02). Furthermore, within primiparous PLBW mothers, there was a significant inverse association between birth weight (as well as gestational age) and GCF-PGE(2) levels at P = 0.023. These data suggest a dose-response relationship for increasing GCF-PGE(2) as a marker of current periodontal disease activity and decreasing birth weight. Microbial data indicate that 4 organisms associated with mature plaque and progressing periodontitis--bacteroides forsythus, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, and Treponema denticola--were detected at higher levels in PLBW mothers, as compared to NBW controls. These data suggest that biochemical measures of maternal periodontal status and oral microbial burden are associated with current PLBW.

Objective: To review published data pertaining to safety of psychoactive drugs used to treat psychiatric disorders during pregnancy and lactation., Data Sources: A computerized search of articles published through July 1995 was performed on the MEDLINE data base. Additional sources were identified through cross-referencing., Methods of Study Selection: All identified references were reviewed with particular attention given to study design., Data Extraction and Synthesis: Each reference was reviewed to determine the safety of psychoactive agents to treat depression, bipolar disease, schizophrenia, and anxiety during pregnancy and lactation. Prospective or large retrospective studies were given more importance than case reports., Conclusion: Psychoactive medications may be used during pregnancy. Because data on safety are largely retrospective, treatment decisions must be weighed carefully.

Background: Teratomas of the head and neck are rare and occur almost exclusively in neonates. Prenatal diagnosis of these tumors allows for a carefully planned delivery that maintains an open airway and potentially improves perinatal outcome. We report the perinatal management of a huge intrapharyngeal and intra-oral teratoma that had a broad connection to the base of the tongue., Case: An anterior neck mass (5 x 5 cm) in an otherwise normal-appearing fetus was detected at 19 weeks' gestation. The mass increased in size over the next 10 weeks to 8 x 6.8 x 4.3 cm. Marked fetal head deflexion was noted along with concomitant hydramnios. The mother had spontaneous rupture of membranes with preterm labor at 29 weeks' gestation. A 1860-g male neonate was delivered by classical cesarean delivery. A tracheostomy was performed in the delivery room for ventilation after the upper airway could not be accessed by bronchoscopy. Histologic examination after surgical excision confirmed a congenital teratoma with immature neuroectodermal tissue and alpha-fetoprotein-bearing endodermal sinus tumor components with exclusively polyvesicular vitelline characteristics. The origin of the pharyngeal mass was the base of the tongue., Conclusion: The prenatal diagnosis of a pharyngeal teratoma should prompt a careful delivery plan to optimize perinatal outcome.

After ultrasound diagnosis of a fetus with severe hydrocephalus and Dandy-Walker malformation, amniocentesis revealed chromosomal mosaicism for dup(lq) and del(Xq). The neonate had dysmorphic facial features, vertebral abnormalities, and pulmonary hypoplasia, and expired shortly after birth. This report confirms the poor prognosis reported for partial trisomies involving the long arm of chromosome number 1.

Patients with Goodpasture syndrome have classically had decreased fertility and associated pregnancy wastage. Renal transplantation can increase the likelihood of successful pregnancy. We describe a patient who carried a pregnancy into the third trimester and had a good neonatal outcome. However, she developed superimposed preeclampsia with subsequent graft rejection.

To determine the characteristics of maternal varicella at our institution, we reviewed all cases of primary varicella in pregnancy. Using a perinatal database that summarizes all obstetric admissions, we reviewed the medical records of women with varicella infections during pregnancy. Over a 5 1/2-year period, 31 pregnancies were affected by varicella infection among 11,753 deliveries. The mean age of those patients was 19.6 years, significantly different from our overall population of 25.3 years (P < .05). The racial composition of 35% Hispanic, 35% white, and 29% African American was different from that of our general population of 55% white, 38% African American, and 6% Hispanic (P = .023). The mean gestational age of the eruption of vesicles was 25 weeks. Of the 31 women, 7 had preterm labor within a week of their varicella, 3 delivered prematurely, and 3 infants had a birth weight of less than 2,700 grams. Respiratory symptoms developed in 6 women, and pneumonia developed in 4, 2 of whom required ventilatory support, 1 for 5 days, the other for 49 days. Eight women received acyclovir during gestation, and none suffered sequelae. In all, 6 infants had lesions and anomalies noted at birth, 5 possibly associated with varicella. Varicella infection is associated with a greater-than-expected level of both maternal and fetal morbidity. The fetal disease may occur due to maternal infection at any gestation and is most likely a spectrum of complications. The maternal disease appears to be worse in the latter half of pregnancy. Programs of prevention through vaccination must account for a possibly decreased level of immunity in different populations.

The terminology we employ influences our perceptions. Thus, we believe in reviewing terminology regularly. The term "cesarean section" should be abandoned. A medical procedure is rarely named after a historic figure, and almost never after an ancient Roman law. Cesarean section has recently been amended to cesarean birth; however, the term is still inadequate. The word "hysterotomy" more appropriately describes the procedure we regularly perform. The adjectives used to describe cesarean birth should also be reevaluated. If we are to keep the term "classical" for the original fundal vertical uterine incision, then the other designations of hysterotomy should retain the same architectural context. Contemporary hysterotomy should be used in reference to a low transverse cesarean. Neoclassical hysterotomy might be used to describe the low vertical procedure. Transitional hysterotomy may be an appropriate term for the "hockey stick" or "J" incision. Cesarean delivery best describes a postmortem cesarean. Vaginal birth after cesarean (VBAC) is inappropriate because a vaginal birth after a cesarean section would not occur if cesarean section refers to a perimortem procedure. Vaginal birth after hysterotomy should be substituted for VBAC. Such revision of our terminology will keep obstetrics at the forefront of medical science and bring us most efficiently into the 21st century.