Circulating cytokines in patients undergoing tonsillectomy with fibrin glue.

OBJECTIVE: Fibrin glue is used as a haemostatic agent or as a sealant. The aim of this study is to objectively evaluate the efficacy of the use of fibrin glue Quixil - a human surgical sealer - in tonsillectomy, for the reduction of post-operative inflammatory response. STUDY DESIGN: A prospective randomized single-blind study. METHODS: The study was performed on 40 consecutive patients undergoing adenotonsillectomy (T&A). Patients were randomly assigned to one of two sub-groups: a study group and a control group. The tonsillar beds of patients in the study group were coated with fibrin glue (Quixil, OMRIX biopharmaceuticals) at the end of the operation; the patients in the control group were treated for hemostasis without the use of fibrin glue. Complete blood counts and circulating pro-inflammatory cytokines (assayed by specific immunoassay - ELISA) were assessed in samples drawn pre- and 16 h post-tonsillectomy. RESULTS: Forty patients (aged 5.8 ± 2.4 years) were consecutively enrolled; 45% (18) of the patients were treated with fibrin glue, 55% (22) were not. Compared to controls, Quixil-treated patients demonstrated a reduction in post-tonsillectomy circulating leukocytes (29.2% vs. 45.4%, p<0.05), neutrophiles (28.3% vs. 42.1%, p<0.05), IL-6 (+1% vs. +42%, p<0.05), and TNF-alpha (+8% vs. +26%, p<0.05. CONCLUSIONS: Intra-operative fibrin glue therapy is associated with decreased immediate inflammatory response following T&A. Further studies are warranted to assess long-term outcome. LEVEL OF EVIDENCE: 1B.

Perfusion with lipopolysaccharide differently affects the secretion of interleukin-1 beta and interleukin-1 receptor antagonist by term and preterm human placentae.

The aim of the present study was to examine the effect of lipopolysaccharide (LPS) on the secretion of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) and of its natural inhibitor interleukin-1 receptor antagonist (IL-1Ra), by perfused human term and preterm placental tissue. Eight term and eight preterm placentae were collected immediately after delivery; four term and four preterm placentae were perfused with control medium (without LPS) and the other four term and four preterm placentae were perfused with medium containing LPS. The release of IL-1beta into the maternal compartment by term placenta was significantly higher than the release by preterm placenta (p<0.001). However, there were no significant differences between IL-1beta levels released into the fetal compartments of term and preterm placentae. No significant differences were observed in the release of IL-1Ra into the maternal and fetal compartments of term placenta, when compared to preterm placenta. Exposure to LPS significantly decreased the capacity of term placenta to release IL-1beta into the maternal compartment (p<0.001) and increased the capacity of term placenta to release IL-1Ra into the maternal and fetal compartments (p<0.001 and p=0.017, respectively). However, the capacity of preterm placentae to release IL-1beta and IL-Ra into the maternal and fetal compartments was not affected by LPS. IL-1beta was expressed by both term and preterm placentae before and after perfusion (+/- LPS), by epithelial cells of the amnion, chorion, by syncytiotrophoblast and stromal cells of villous tissue and by the decidua. IL-1Ra in term and preterm placentae was expressed before perfusion mainly in epithelial cells of the amnion. After perfusion of term placentae (+/- LPS), additional IL-1Ra expression was seen in epithelial cells of the amnion and in syncytiotrophoblast and stromal cells of villous tissue and by the decidua. However, perfusion of preterm placentae (+/- LPS) did not affect IL-1Ra expression. The localization of IL-1beta and IL-1Ra in both term and preterm human placental tissue suggests a their physiologic role. The data presented indicates that the IL-1 system in term and preterm placentae seems to be differently affected by LPS. Down-regulation in the release of the pro-inflammatory cytokine IL-1beta and the up-regulation of its antagonist (IL-1Ra) may be a part of the inflammatory response to infection in human term, but not preterm, placentae. The IL-1 system in term and preterm placentae seems to be differently affected by LPS.

Method of placental removal during cesarean delivery and postpartum complications.

OBJECTIVE: The study was aimed to determine whether the method of placental removal at the time of the cesarean delivery is associated with postpartum complications such as postpartum fever and wound infection. In addition it was aimed to identify other complications following cesarean delivery. METHODS: A prospective observational study was conducted, including 426 women who underwent cesarean deliveries between January 2004 and March 2005, in a tertiary medical center. A multivariable logistic regression model, with backward elimination, was constructed in order to identify independent risk factors associated with the occurrence of wound infection or fever. A sample size of about 150 subjects in each group was needed to demonstrate a difference of 15% between the two methods of placental removal, with a probability of 95% and power of 80%. RESULTS: Manual removal of the placenta occurred in 269 operations while in 157 women the placenta was removed in a spontaneous method. No statistically significant differences were noted between the two methods of removal of the placenta regarding the risk for fever (7.8% in the group of the manual removal, as compared with 5.1% in the group of the spontaneous method; P=0.284) or for wound infection (3.7% in the group of the manual removal compared with 5.1% in the group of the spontaneous method; P=0.495). Using a multivariable logistic regression model, with backward elimination, the following risk factors were identified for postcesarean fever, or wound infection: unskilled surgeon (OR 3.2, 95% CI 1.4-7.8), number of previous cesarean deliveries (OR 1.8, 95% CI 1.3-2.6) and maternal hypertension (OR 3.3, 95% CI 2.0-38.5). CONCLUSION: The method of placental removal during cesarean delivery is not associated with the risk for either wound infection or postpartum fever.

Risk factors for wound infection following cesarean deliveries.

OBJECTIVE: To identify risk factors for early wound infection (diagnosed prior to discharge) following cesarean delivery. METHODS: A population-based study comparing women who have and have not developed a wound infection prior to discharge from Soroka University Medical Center, Ben Gurion University of the Negev, between 1988 and 2002. RESULTS: Of the 19,416 cesarean deliveries performed during the study period, 726 (3.7%) were followed by wound infection. Using a multivariable logistic regression model, the following risk factors were identified: obesity (odds ratio [OR] = 2.2; 95% confidence interval [CI], 1.6-3.1); hypertensive disorders (OR = 1.7; 95% CI, 1.4-2.1); premature rupture of membranes (OR = 1.5; 95% CI, 1.2-1.9); diabetes mellitus (OR = 1.4; 95% CI, 1.1-1.7); emergency cesarean delivery (OR = 1.3; 95% CI, 1.1-1.5); and twin delivery (OR = 1.6; 95% CI, 1.3-2.0). Combined obesity and diabetes (gestational and pregestational) increased the risk for wound infection 9.3-fold (95% CI, 4.5-19.2; P < .001). CONCLUSION: Independent risk factors for an early wound infection are obesity, diabetes, hypertension, premature rupture of membranes, emergency cesarean delivery, and twin delivery. Information regarding higher rates of wound infection should be provided to obese women undergoing cesarean delivery, especially when diabetes coexists.

Twelve cases of placental chorioangioma. Pregnancy outcome and clinical significance.

INTRODUCTION: To determine perinatal complications and pregnancy outcome in 12 women with chorioangioma of placenta. STUDY DESIGN: During the period between January 1986 and December 1997, 12 women with histologic diagnosis of chorioangioma of placenta who delivered in our institution were studied. Case-control study was designed. Sixty women with histologic examination of the placenta without chorioangioma were randomly identified as control group matched for maternal age and parity. Statistical analyses included t-test, Chi-square test and Fisher's exact test when appropriate. RESULTS: Nine cases (75%) were diagnosed postnatal. The mean gestational age was significantly lower and preterm delivery rate was significantly higher among the chorioangioma group (34 vs. 38.8 weeks P<0.0001; 66% vs. 10%; P<0.001 respectively). CONCLUSIONS: Chorioangioma of the placenta, in a high risk population, although small, is associated with significantly higher risk for preterm delivery. This emphasizes the need for pathologic examination of all placentas of patients with preterm delivery

Gestational diabetes complicated by hydramnios was not associated with increased risk of perinatal morbidity and mortality.

OBJECTIVE: To determine whether gestational diabetes (GDM) complicated with hydramnios is associated with higher rates of perinatal morbidity and mortality than those with normal amniotic fluid (AFI). STUDY DESIGN: A case control study of 368 pregnant women with GDM was conducted between January 1995 and December 1996. The study group consisted of 184 women with hydramnios (AFI>25 cm) that were matched for maternal age, parity, and gestational age to 184 women with gestational diabetes and normal AFI. A Student's t-test, McNemar test and logistic regression test were used to compare the two groups. RESULTS: Both groups were under strict metabolic control; mean glucose levels of 5.2+/-2.4 mmol/l in the study group and 5.5+/-2.4 mmol/l in the controls (P>0.05). There were no significant differences between groups in the rates of severe preeclampsia, premature rupture of membranes (PROM), cesarean section rate, intrauterine growth restriction (IUGR), antepartum fetal death, fetal distress, prolapse of umbilical cord and placenta abruption. Even though the prevalence of large for gestational age (LGA) and birth weight were significantly higher in the study group (31 versus 19% and 3441+/-477 versus 3232+/-554 g, respectively), the prevalence of neonatal trauma was the same in both groups (2.6%). There was no significant difference in the Apgar scores (1 and 5 min), newborn hypoglycemia, metabolic acidosis and hyperbilirubinemia. CONCLUSIONS: Hydramnios in women with GDM was not associated with increased risk of perinatal morbidity and mortality.

Risk factors associated with true knots of the umbilical cord.

OBJECTIVE: To determine obstetrical risk factors and pregnancy outcome of fetuses with true knot of the umbilical cord. METHODS: Study population included 69,139 singleton deliveries occurring between the years 1990-1997. Data were retrieved from the database of the Soroka University Medical Center. Fetuses with malformations were excluded. RESULTS: The incidence of true knots was 1.2% (841/69,139). In a multivariate analysis the following factors were found to be significantly associated with true knot of cord: grandmultiparity, chronic hypertension, hydramnios, patients who undergone genetic amniocentesis, male gender and cord problems (prolapse of cord and cord around the neck). The incidence of fetal distress and meconium stained amniotic fluid was significantly higher among patients with true knots of cord (7% versus 3.6%, P<0.001 and 22% versus 16%, respectively, P<0.0001). Moreover, there was a four-fold higher rate of antepartum fetal death among those fetuses (1.9% versus 0.5%, P<0.0001). In addition, fetuses with true knots of the umbilical cord were more often delivered by a cesarean section (130/841 versus 711/68,298, P<0.0001). The following obstetrical factors were found to be significantly correlated to true knots of the umbilical cord in a multiple logistic regression model: gestational diabetes, hydramnios, patients undergoing genetic amniocentesis, male fetuses. CONCLUSIONS: Patients with hydramnios, who underwent genetic amniocentesis and those carrying male fetuses are at an increased risk for having true knots of the umbilical cord. Thus, careful sonographic and Doppler examinations should be seriously performed in these patients for detection of the complication of the umbilical cord.

Wilson's disease in pregnancy: five successful consecutive pregnancies of the same woman.

Wilson's disease is an autosomal recessive disorder of copper metabolism characterized mainly by liver cirrhosis and neurological disorders. Appropriate treatment with chelating agents allows normal fertility function. We report five consecutive successful pregnancies of the same woman, treated in the high-risk unit at our medical center. The management dilemmas and treatment options are discussed.

Albumin-dependent digoxin transfer in isolated perfused human placenta.

OBJECTIVE: To determine the effects of albumin (BSA) concentration in perfusion medium on digoxin transfer in isolated perfused human placental cotyledon. STUDY DESIGN: Isolated placental cotyledons from 13 normal human placentas were dually perfused after cannulating artery and vein of the chorionic plate and piercing 4 catheters through the corresponding basal plate with M199 medium enriched with BSA and glucose. Flow rates were 12 and 6 ml/min in the maternal and fetal circuits, respectively. Digoxin was added to the maternal reservoir at a final concentration of 5.51 +/- 1.00 ng/ml. BSA in maternal and fetal perfusate was kept at 3 concentrations: 1, 3 and 5 mg/ml (Groups I, II, III). Transplacental passage of digoxin was calculated from repeated fetal and maternal perfusate samples collected over 3 hours in the 3 groups. Digoxin levels were measured by FPIA (TDx, Abbott). RESULTS: There was no transfer of digoxin from the maternal to fetal compartment when the concentration of BSA was 1 mg/ml. Increasing the concentration of BSA led to a substantial increase in the transfer of digoxin to the fetal compartment. Steady state levels of digoxin in the fetal compartment were 0.61 +/- 0.19 ng/ml at 3 mg/ml of BSA. CONCLUSION: Maternal and fetal serum concentration of BSA affect digoxin transfer in isolated perfused human placentas. Three mg/ml are considered to be the optimal albumin concentration.

Indomethacin activity in the fetal vasculature of normal and meconium exposed human placentae.

OBJECTIVE: To study the effect of indomethacin on the vasculature of isolated perfused human placental cotyledon in normal and meconium pretreated placentae. STUDY DESIGN: Isolated placental cotyledons were dually perfused and fetal perfusion pressure was used as an index of vascular resistance. Meconium-stained amniotic fluid (MSAF) was collected from patients after artificial rupture of membranes, diluted 1:2, 1:4, 1:16 and 1:32 and a spectrophotometric determination of meconium concentration in amniotic fluid was performed. Only MSAF with an optical density of 20.0 units per gram was used in this study. In five placentae, the effect of indomethacin (100 microg/ml continuous perfusion from the fetal site) on basal pressure of the fetal-placental vasculature was established. In five more placentae, the effect of indomethacin on MSAF-induced vasoconstriction was established when a bolus injections of 1 ml MSAF was made into the fetal circulation. The statistical significance of response to MSAF injection was determined by paired t-test and ANOVA repeated measurements. RESULTS: A significant vasoconstrictor response to MSAF was achieved in normal placentae. Bolus injections of MSAF into the fetal circulation resulted in a significant increase in perfusion pressure (P=0.0026). Indomethacin was capable of significantly reducing the basal perfusion pressure (P=0.03). Significant attenuation of vasoconstrictor response to MSAF occurred in the presence of indomethacin (P=0.0016). CONCLUSION: Indomethacin causes a significant reduction in basal pressure of fetal placental vasculature in the human placental circulation in vitro and is capable of attenuating the vasoconstrictory activity of MSAF. The mechanism of such activity may be explained partially by the inhibitory effect of indomethacin on the PG-mediated pathways.

Increased production of tumor necrosis factor-alpha TNF-alpha by IUGR human placentae.

OBJECTIVE: To evaluate the effect of pathological placental conditions such as intrauterine growth restriction (IUGR) or exposure to angiotensin II (AII) on TNF-alpha secretion in the vasculature of isolated human placental cotyledons. STUDY DESIGN: Isolated placental cotyledons from 10 normal and four intrauterine growth restricted fetuses were dually perfused. Perfusate samples from the fetal circulation were collected every 30 min during 120 min. TNF-alpha levels in the fetal-placental perfusate were evaluated using specific commercial ELISA kits. In three additional normal placentae, bolus injections of angiotensin II (10(-9)-10(-4) mol/l) were given into the fetal-placental circulation and perfusate samples were collected. Statistical significance of difference TNF-alpha levels between different conditions was determined by analysis of variance (ANOVA) and paired t-test. RESULTS: TNF-alpha levels were significantly higher in the perfusate of IUGR placentae as compared with normal placentae after 120 min of perfusion (mean 410+/-121 vs. 39+/-14 pg/ml, P=0.005). There was a significant dose-dependent increase in TNF-alpha levels in the placental perfusate after a bolus injection of AII 66 pg/ml with AII 10(-9) mol/l vs. 97 pg/ml with AII 10(-5) mol/l (P=0.004), respectively. CONCLUSIONS: Placental pathology related to condition IUGR might induce the secretion of proinflammatory cytokines such as TNF-alpha, which may enhance the vasoconstriction of the fetal placental vascular bed.

[Anaphylactic shock after diclofenac sodium (Voltaren)].

Anaphylaxis due to diclofenac sodium (Voltaren) is rare. We describe a 39-year-old woman who received a suppository of diclofenac for analgesia 6-hours after cesarean section. She developed severe angioedema and profound hemodynamic shock 10 minutes after the diclofenac, to which she had been exposed in the past without any side-effects. There are few reports of such an acute, life-threatening, multisystem reaction to this drug in the English literature.

Maternal serum concentrations of CA-125 in second trimester pregnancy complicated by congenital fetal anomalies.

OBJECTIVE: The purpose of the study was to determine the value of maternal serum CA-125 concentrations in pregnancies complicated by fetal anomalies with or without hydramnios. STUDY DESIGN: The study population (n=40) consisted of the following four groups of patients: (1) 10 women with abnormal maternal serum alpha fetal protein (MSAFP) in whom no fetal anomalies were observed; (2) 10 women in whom fetal anomalies were diagnosed in addition to abnormal MSAFP; (3) 10 women with fetal anomalies accompanied by hydramnios and abnormal MSAF, and (4) 10 women had normal MSAFP and were diagnosed with hydramnios without fetal anomaly. The control group consisted of 10 patients who were matched for gestational age with normal MSAFP and normal ultrasonographic examination. In all 50 cases MSAFP and maternal serum CA-125 levels were assessed. CA-125 was measured using OC 125 monoclonal antibody (IMX CA-125, Abott Lab. IL) and a value of >20 U/ml was defined as abnormal. RESULTS: Maternal serum CA-125 levels were significantly higher in the study group than in the control group, 19.8+/-15.9 U/ml and 9.9+/-4.0 U/ml (P=0.015). The difference was even greater when patients with malformed fetuses and hydramnios were compared to those with fetal anomalies and normal amount of amniotic fluid, 32.4+/-12.7 U/ml and 7.2+/-2.1 U/ml, respectively (P=0.0005). The maternal serum CA-125 levels in patients with hydramnios but without fetal anomalies were significantly lower when compared with those of the malformed fetuses and hydramnios, 9.8+/-2.3 U/ml and 32.4+/-12.7 U/ml, respectively (P=0.002). CONCLUSION: Maternal serum CA-125 is lacking in value for screening fetal structural anomalies as a significant increase in maternal serum CA-125 levels was found only in patients with fetal anomalies accompanied by hydramnios.

Vasoconstrictive activity of meconium stained amniotic fluid in the human placental vasculature.

OBJECTIVE: The purpose of this study was to study was to determine the effect of meconium stained amniotic fluid on the vasculature of isolated perfused human placental cotyledon. STUDY DESIGN: Isolated placental cotyledons were dually perfused. Fetal perfusion pressure was used as an index of vascular resistance. Meconium stained amniotic fluid (MSAF) was collected from patients after artificial rupture of membranes in term gestation. A dilution of meconium (1:2; 1:4; 1:8; 1:16) was performed. Optical density (OD) of MSAF varied between 0 and 35.0 units/g as determined by spectrophotometry. Bolus injections of 1.0 ml of MSAF at different concentrations were injected into the fetal circulation. Heated and dialyzed MSAF after adequate dilution and evaluation of optical density were injected into fetal circulation in separate experiments. RESULTS: Analysis of variance (ANOVA) and paired t-test were used for statistical analysis. Bolus injections of MSAF into the fetal circulation resulted in a concentration-dependent increase in perfusion pressure. MSAF with the highest OD resulted in a greater change in perfusion pressure as compared to more dilute MSAF (P=0.0001). After high OD amniotic fluid injections the provoked contractions lasted longer compared to dilute MSAF (P=0.006). MSAF after dialyzation did not exhibit any vasoconstrictive effect. CONCLUSION: Meconium is a vasoconstrictive agent in the fetal-placental vasculature and has a concentration dependent effect.

Neurofibromatosis in pregnancy. Maternal and perinatal outcome.

OBJECTIVE: The aim of this study was to assess the maternal and perinatal outcome in pregnant patients with neurofibromatosis (NF). STUDY DESIGN: During the period between January 1994 and December 1996 eight women with NF were delivered at the Soroka University Medical Center. Maternal age, parity, gravidy and ethnic origin were matched with a control group that included 65 healthy parturients out of a total of 31,642 deliveries that occurred in our institution during this period. Maternal outcome and perinatal complications were compared between the two groups. RESULTS: The prevalence of NF during the study period was 1:2434 deliveries. The mean gestational age at delivery was significantly lower in the study group as compared to the control group, 36.8+/-3.3 vs. 39.2+/-1.5 weeks, respectively (P=0.029). The rate of intrauterine growth restriction was significantly higher in the study group, (46.2% vs. 8.95%, respectively, P=0.0005), as well as stillbirth rate (23% vs. 1.5%, respectively, P=0.011) and cesarean section rate (38.5% vs. 7.7%, respectively, P=0.01). CONCLUSION: Patients with NF have an increased risk of perinatal complications. Thus, close antenatal observation at high risk tertiary centers is required.

Perinatal vasoconstrictive renal insufficiency associated with maternal nimesulide use.

A full-term newborn developed oliguric renal failure at 24 hr of life, which persisted for several days. Her mother ingested therapeutic doses of nimesulide, a non-steroidal anti-inflammatory (cyclo-oxygenase-2 inhibitor) drug, during the last 2 weeks of pregnancy. She was found at delivery to have developed oligohydramnion, esophagitis, and a bleeding peptic ulcer. The infant's fractional excretion of sodium was very low (0.5%) pointing for a severe vasoconstrictive mechanism involved. Renal sonogram showed hyperechogenic medullary papillae, which resolved during convalescence. This case emphasizes the importance of renal prostagandins in the control of vascular tone and sodium homeostasis. This is the first report of an adverse effect of fetal renal circulation by maternal ingestion of nimesulide.

Pregnancy outcome after repeated blunt abdominal trauma.

During a four-year period, five of 49671 parturients were admitted on a prospective study protocol for repeated direct blunt abdominal trauma due to falls during pregnancy. Preterm contractions were noted in three patients one of which delivered preterm. No delayed abruptio placentae, intrauterine growth restriction or antepartum death were encountered. All patients delivered spontaneously. Repeated blunt abdominal trauma occurs rarely in pregnancy. Routine hospitalised surveillance in the absence of vaginal bleeding or uterine contractions may not be warranted.

The interaction of nitric oxide and superoxide in the human fetal-placental vasculature.

OBJECTIVE: Our purpose was to study the interaction of nitric oxide and superoxide anion on the vasculature of the isolated perfused human placental cotyledon. STUDY DESIGN: Isolated placental cotyledons were preconstricted with the thromboxane mimetic U46619, and fetal perfusion pressure was used as an index of response. The interaction of nitric oxide and O2- was studied by three protocols: (1) with endogenous nitric oxide, (2) with addition of exogenous nitric oxide, and (3) with inhibition of nitric oxide synthesis by the nitric oxide synthase inhibitor N-nitro-L-arginine. O2- was generated by infusion of purine-xanthine oxidase. Statistical significance of response to treatment was determined by paired t test. RESULTS: Infusion of xanthine oxidase with purine in the presence of endogenous nitric oxide resulted in vasodilation (p < 0.05). Vasodilation was more pronounced in the presence of exogenous nitric oxide (p < 0.008). Coinfusion of xanthine oxidase with purine in the presence of N-nitro-L-arginine to inhibit nitric oxide synthesis resulted in vasoconstriction. CONCLUSION: We conclude that, rather than superoxide inactivating nitric oxide, interaction of the two radicals generates in the placental vasculature a vasodilator, which may be peroxynitrite.

Hypoglycemia: the price of intensive insulin therapy for pregnant women with insulin-dependent diabetes mellitus.

OBJECTIVE: To evaluate the risk of hypoglycemia associated with intensive insulin therapy of type I diabetes during pregnancy. METHODS: Eighty-four women with type I diabetes were recruited before 9 weeks' gestation and received intensive insulin therapy throughout pregnancy. Patients monitored glucose concentrations with memory glucometers, and insulin dosages were adjusted weekly accordingly. A detailed history of clinical hypoglycemic events was obtained at each weekly clinic visit. RESULTS: Clinically significant hypoglycemia requiring assistance from another person occurred in 71% of pregnant patients, with a peak incidence between 10-15 weeks. Severe hypoglycemia during the early weeks of embryogenesis was not associated with an increase in embryopathy. Glycemic control was similar in women with or without recurrent hypoglycemia, but glucose fluctuations were significantly greater in hypoglycemic women. CONCLUSION: Severe hypoglycemia is a significant maternal risk associated with intensive insulin therapy of pregnant women with type I diabetes. In women with recurrent episodes of hypoglycemia, the clear benefits of strict glycemic control must be weighed against the hazards of hypoglycemia.