Ex vivo inhibition of NF-kappaB signaling in alloreactive T-cells prevents graft-versus-host disease.

The ex vivo induction of alloantigen-specific hyporesponsiveness by costimulatory pathway blockade or exposure to immunoregulatory cytokines has been shown to inhibit proliferation, IL-2 production, and the graft-versus-host disease (GVHD) capacity of adoptively transferred T-cells. We hypothesized that inhibition of the intracellular NF-kappaB pathway in alloreactive T-cells, which is critical for T-cell activation events including IL-2 transcription, could lead to alloantigen hyporesponsiveness and loss of GVHD capacity. We demonstrate that treatment of mixed lymphocyte reaction (MLR) cultures with PS1145, a potent inhibitor of NF-kappaB activation, can induce T-cell hyporesponsiveness to alloantigen in primary and secondary responses while preserving in vitro responses to potent mitogenic stimulation. GVHD lethality in recipients of ex vivo PS1145-treated cells was profoundly inhibited. Parking of control or PS1145-treated MLR cells in syngeneic Rag(-/-) recipients resulted in intact contact hypersensitivity (CHS) responses. However, GVHD lethality capacity also was restored, suggesting that lymphopenic expansion uncoupled alloantigen hyporesponsiveness. These results indicate that the NF-kappaB pathway is a critical regulator of alloresponses and provide a novel small molecule inhibitor based approach that is effective in preventing early posttransplant GVHD lethality but that also permits donor T-cell responses to recover after a period of lymphopenic expansion.

Hysterotomy facilitation of the vaginal delivery of the posterior arm in a case of severe shoulder dystocia.

BACKGROUND: Shoulder dystocia is an obstetric emergency that can be resolved usually with one or a series of maneuvers performed vaginally. On rare occasions these maneuvers may fail, and the obstetrician must employ less familiar techniques to achieve delivery. CASE: A 30-year-old, gravida 6, developed a severe shoulder dystocia while delivering a 5970 g infant. Classical vaginal maneuvers failed due to the severity of the impaction. After general anesthesia was induced, additional maneuvers such as cephalic replacement and transabdominal rotation also failed. The dystocia was resolved ultimately by a transabdominally-facilitated vaginal posterior arm delivery followed by transabdominal shoulder rotation and vaginal extraction. CONCLUSION: In catastrophic cases of shoulder dystocia, transabdominal performance or facilitation of traditional vaginal maneuvers may lead to resolution.

Conservative obstetric management of a gunshot wound to the second-trimester gravid uterus. A case report.

BACKGROUND: Gunshot wounds to the abdomen during pregnancy are becoming increasingly common. When the gravid uterus is injured but repairable and the fetus is either previable or dead, conservative management is an option, even if laparotomy is required for management of other injuries. CASE: A pregnant woman sustained a gunshot wound to the abdomen during the second trimester of pregnancy. The bullet injured the rectum and traversed the uterine cavity, with resultant rupture of membranes and direct, fatal injury to the fetus. Laparotomy was required for treatment of the maternal injuries; however, the pregnancy was managed conservatively. Spontaneous miscarriage occurred late on the second postoperative day. CONCLUSION: Conservative obstetric management is indicated in most such cases in which the fetus is previable or dead, although the clinician undertaking such management should be aware of the risks and possible complications.

Differentiation of ingested and endogenous bifidobacteria by DNA fingerprinting demonstrates the survival of an unmodified strain in the gastrointestinal tract of humans.

Consumption of bifidobacteria as a dietary adjunct has received considerable attention for its possible role in the maintenance of gastrointestinal health. However, speculation exists about these presumed health benefits because of an inability to assess the fate and mechanism of action of ingested bifidobacteria. Thus, our objective was to examine the fate of ingested bifidobacteria through the gastrointestinal tract. Variations in the highly conserved 16S ribosomal DNA (rDNA) of bifidobacteria from six male subjects (18 to 35 y old) were assessed by restriction fragment length polymorphism (RFLP) analysis. During the 16-d study, 10(10) colony-forming units (CFU) of a commercially available bifidobacteria were delivered to subjects in fluid milk for each of 8 d. During the remaining 8 d, subjects consumed milk without bifidobacteria. Feces were collected at 4-d intervals and plated on selective media. For each subject, 10-15 colonies were randomly selected and used as template for PCR-amplification of 16S rDNA. 16S rDNA was restriction digested and resolved by electrophoresis. The 16S rDNA-RFLP of the ingested bifidobacteria was unique compared with bifidobacteria found in subjects prior to the feeding study. When subjects consumed bifidobacteria, a 16S rDNA-RFLP identical to that of the ingested bifidobacteria was observed in feces. The concentration of the ingested bifidobacteria in feces increased to 67.2 +/- 8.5% (mean +/- SEM) of total bifidobacteria. After feeding stopped, the ingested bifidobacteria diminished and became undetectable. Using this molecular approach to monitor ingested bifidobacteria, we demonstrate the kinetics of passage of this organism through the gastrointestinal tract of healthy humans.

Amnioinfusion among women attempting vaginal birth after cesarean delivery.

Eighteen of 901 women (2%) attempting vaginal birth after cesarean delivery (VBAC) received amnioinfusion. No untoward effects occurred in the subjects or their fetuses. We conclude that, though amnioinfusion in the setting of a VBAC attempt is needed only infrequently, it appears to be a reasonable intrapartum management option. The usual safeguards for a VBAC attempt should be followed.