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Hypercoagulability is often associated with a variety of disease states, leading to cardiovascular complications. Polyethylenimine (PEI) prolonged prothrombin time, demonstrating its anticoagulant potential. In vitro, PEI at low concentration (nM) significantly blocked thrombin-catalyzed fibrin formation, accounting for its mode of anticoagulation. The uncompetitive inhibition by PEI of fibrin formation was independent of the concentration of fibrinogen (FBG), thrombin, or NaCl. PEI showed no effect on thrombin amidolytic activity, suggesting that the blockade of thrombin interaction with FBG could account for the inhibition on fibrin formation. PEI drastically depressed rabbit brain thromboplastin procoagulation monitored by a single-stage clotting assay using human plasma. In a THP-1 monocytic hypercoagulation model, a 4-h exposure to bacterial endotoxin or Ca(2+) ionophore A23187, respectively, resulted in a 5- or 10-fold enhancement in monocytic tissue factor (mTF) procoagulation. mTF hypercoagulation was offset by PEI included in the assay mixture. PEI showed the potential to arrest mTF hypercoagulation with IC(50) around 1.2 nM. Using a chromogenic assay to dissect the extrinsic pathway, we further assessed whether PEI has any effect on other clotting factors. PEI was not an inhibitor for either FVIIa or FXa, having no effect on not only the amidolytic but also their corresponding functionally catalytic activities. Although PEI upregulated TF-dependent FVII activation under the low-salt condition, the effective downstream inhibition of fibrin formation readily abolished and overrode the upstream enhancement, demonstrating the overall anticoagulation. PEI could present a new class of anticoagulant.

The enhanced extrinsic blood coagulation following septic shock often manifests cardiovascular complications. The upregulated monocytic tissue factor (mTF) was shown to be a primary contributor to the extrinsic hypercoagulation following acute bacterial endotoxin (LPS) infection. A single-stage clotting assay monitors TF-initiated coagulation. We herein demonstrate a novel anticoagulant activity of antimicrobial peptide Buforin I (BF I) in offsetting LPS-induced mTF hypercoagulation in THP-1 cells, which was confirmed in a cell-free in vitro model, showing that BF I effectively blocked rabbit brain thromboplastin (rbTF) procoagulant activity. Upon inclusion of 25 microM BF I into human plasma, the prolonged prothrombin time (PT) was consistent with the depressed TF-initiated coagulation. In a two-stage chromogenic assay monitoring S-2288 hydrolysis, BF I significantly inhibited not only mTF- but also rbTF-catalyzed FVII activation accompanied by the diminished FVIIa formation. The inhibition by BF I of FVII activation accounted for its novel anticoagulant activity in offsetting mTF-initiated hypercoagulation., (Copyright 2001 Academic Press.)

Objectives: The study's objectives were as follows: (1) to determine the rate of vaginal delivery after labor induction in severe preeclampsia remote from term and (2) to determine potential predictors of success., Study Design: Retrospective chart review was conducted on live-born singleton pregnancies complicated by severe preeclampsia and delivered at 24 to 34 weeks' gestation from January 1, 1992, to December 31, 1996. Exclusion criteria included eclampsia, presence of labor or spontaneous rupture of membranes on admission, and complication of pregnancy by an ultrasonographically detected fetal congenital anomaly. Patients were divided into 3 groups: elective cesarean delivery without labor, cesarean delivery after labor induction, and vaginal delivery after labor induction. Statistical analyses included multiple logistic regression, the Student t test, the chi2 test, and the Mann-Whitney test. P 32 weeks' gestation. The most common indication for cesarean delivery after induction, in 50.7% of the cases, was nonreassuring fetal heart rate. The median Bishop score was significantly higher (3 vs 2, P =.004) and the total hospital stay was significantly shorter in the vaginal delivery after induction group than in the cesarean delivery after induction group. However, there were no significant differences between the 2 groups in use of cervical ripening agents, gestational age at delivery, birth weight, 5-minute Apgar score, or postpartum endometritis. After exclusion of cesarean deliveries performed for malpresentation, there was no statistically significant difference in classic incision rates between the elective cesarean delivery without labor and cesarean delivery after induction groups (13.6% vs 6.8%; P =.137). According to logistic regression analysis, only the Bishop score was significantly associated with a successful induction (odds ratio 1.38, 95% confidence interval 1.11-1.71). Gestational age reached marginal significance (odds ratio 1.30, 95% confidence interval 0.89-1.89)., Conclusions: (1) Labor induction should be considered a reasonable option for patients with severe preeclampsia at

Objective: Our purpose was to determine the degree of fetal pyelectasis predictive of neonatal renal pathologic processes., Study Design: Eighty-four cases of pyelectasis were identified during the study period (1989 through 1993). Fetuses with anteroposterior diameter of the renal pelvis > or = 4 mm before 33 weeks or > or = 7 mm after 33 weeks without caliectasis were included. Fetuses with an anteroposterior diameter of > 10 mm were excluded. Postnatal evaluation included renal sonogram, voiding cystourethrogram, and renal flow and function studies., Results: Sixteen cases were excluded because of incomplete postnatal workup. Renal pathologic processes were found in 30 of 68 (44%) at birth; the most common were ureteropelvic junction obstruction (37%) and vesicoureteral reflux (33%). Only four cases required surgical intervention (13%), and the remaining 87% were managed conservatively. A normal urinary tract was found in 25% of the infants and the remaining 21 of 68 (31%) had regression of pyelectasis before birth. Fetuses with a dilated anteroposterior diameter > or = 8 mm after 28 weeks' gestation were found to have renal pathologic features in two of three of the cases, with sensitivity, specificity, and positive and negative predictive values of 87%, 41%, 66.7% and 70%, respectively., Conclusion: Fetuses with an anteroposterior diameter of the renal pelvis > or = 8 mm after 28 weeks' gestation require appropriate urologic evaluation after birth.

The effects of epidural analgesia, given during the first stage of labor, on the course of labor, mode of delivery, and fetal outcome were evaluated in 43 matched controlled patients. Both stages of labor were prolonged, more forceps were applied, and more patients needed oxytocin augmentation for a longer period in the epidural group. Cesarean section was associated also with the use of epidural analgesia, owing to failure to progress. Fetal outcome was similar in both groups as judged by Apgar scores. Patients who elect this mode of pain relief in labor should be made aware that these side effects can be expected.

Experimentally and clinically, treatment with high-doses of TRH produces a net excitation of spinal lower motor neurons (LMNs) that is subsequently reduced or completely lost through continuous or repeated exposure to the peptide. This is operationally termed "autorefractoriness" (AR). We have performed biochemical and in vivo pharmacologic experiments to investigate the mechanism(s) of AR. Biochemically, we classified TRH and several analogs into three groups based on their binding by spinal-cord TRH-receptors (TRH-Rs): high-affinity, (low nanomolar range; MeTRH, TRH); intermediate-affinity (mid-nanomolar range; MK-771, RX77368) or low-affinity (micromolar range; DN-1417, PNP). When tested in vivo for LMN excitatory activity in cordotomized (T8) rats, TRH and MK-771 produced rapid-onset excitation followed AR. In contrast, sustained excitation with much less AR was produced by the low affinity analog DN-1417. Based on these results, we have formulated two receptor-based hypotheses to explain AR: a) rapid TRH-R desensitization (conversion to an inactive form) by high- but not low-affinity TRH-analogs; and b) a slower down-regulation (cellular internalization) of the agonist-receptor complex, most evident with high-affinity agonists. Thus, low-rather than high-affinity TRH-analogs may be superior to TRH for providing sustained LMN excitation (increase of strength) in motor neuron degenerative disorders.

Experience with Lactomer absorbable surgical staples (Auto Suture Poly CS 57 disposable surgical stapler) in 62 cesarean sections was compared with an equal number of operations performed with standard techniques. The technique of application of the stapler evolved with experience. Countertraction to staplers with Allis' clamps prevented uterine V incisions. Operative time was longer for the stapled suture group for primary cesarean sections, but was unchanged for repeat procedures. Excellent hemostasis of the uterine incision was achieved even when varicose sinusoidal veins were present. Significant reductions of hemoglobin deficits from 2.16 to 1.31 gm/dl, postoperative anemia from 29% to 6.4%, and endometritis from 22.5% to 6.4% occurred respectively in nonstapled and stapled groups. A reduced hospital stay, shortened by 2.1 days, saved each patient +F42950. Blood loss estimates by surgeons or anesthetists were often at variance. Surgeons' acceptance of the procedure grew with experience. On the basis of these results, use of absorbable staples offers certain advantages in reducing blood loss, infection, and hospital stay in cesarean deliveries.

Fetal tachycardia of "supraventricular" origin is uncommon. The authors present a patient with fetal ascites and atrial flutter. A review of the pertinent literature is included.

Seven biopsy specimens from the cervix and 17 from the lower uterine segment were obtained in 24 women at term (37 to 42 weeks). Collagenase was extracted and assayed on telopeptide-free [3H]collagen; typical collagen cleavage products were found on sodium dodecyl sulfate-gel electrophoresis. There was no significant difference between collagenase levels in the cervix and in the lower uterine segment in women not in labor and with the cervix closed. Levels of active and latent collagenase in 11 such specimens were 0.14 +/- 0.03 and 0.64 +/- 0.90 U/gm wet weight, respectively (mean +/- SEM; 1 U = 1 micrograms collagen digested per minute at 30 degrees C). Thirteen women at term in active labor with cervical dilation of 4 to 8 cm exhibited a thirteenfold increase in mean collagenase activity in the lower uterine segment. Active and latent collagenase increased to 2.06 +/- 0.92 and 8.64 +/- 2.87 U/gm, respectively. This is the first direct evidence that interstitial collagenase increases markedly during cervical dilation in human parturition.

The maternal and fetal outcomes of 70 consecutive singleton pregnancies with prolonged premature rupture of the membranes before 28 weeks, which were managed expectantly, were evaluated; 58.6% of the mothers developed chorioamnionitis and 13% postpartum endomyometritis. No long-term maternal sequelae were noted. None of the 22 infants born before 25 weeks survived the neonatal period. The weights of the 35 surviving infants ranged between 800 and 4100 gm. Only 29.4% of the 17 infants with long-term follow-up were both physically and developmentally normal at 6 months of age or more.