Intrapartum management of twins: truths and controversies

Twin gestations pose a challenge in management, and the intrapartum phase of care is not exempt. Despite increasing numbers of twin gestations, the literature does not adequately answer several basic questions regarding appropriate intrapartum management. This article provides an overview of the available literature supporting appropriate intrapartum actions in twin gestations and highlights areas that are still awaiting further study, with the eventual goal of optimizing intrapartum conditions, leading to an improved neonatal outcome.     

Targeting levels or oligomerization of nucleophosmin 1 induces differentiation and loss of survival of human AML cells with mutant NPM1

Nucleophosmin 1 (NPM1) is an oligomeric, nucleolar phosphoprotein that functions as a molecular chaperone for both proteins and nucleic acids. NPM1 is mutated in approximately one-third of patients with AML. The mutant NPM1c+ contains a 4-base insert that results in extra C-terminal residues encoding a nuclear export signal, which causes NPM1c+ to be localized in the cytoplasm. Here, we determined the effects of targeting NPM1 in cultured and primary AML cells. Treatment with siRNA to NPM1 induced p53 and p21, decreased the percentage of cells in S-phase of the cell cycle, as well as induced differentiation of the AML OCI-AML3 cells that express both NPMc+ and unmutated NPM1. Notably, knockdown of NPM1 by shRNA abolished lethal AML phenotype induced by OCI-AML3 cells in NOD/SCID mice. Knockdown of NPM1 also sensitized OCI-AML3 to all-trans retinoic acid (ATRA) and cytarabine. Inhibition of NPM1 oligomerization by NSC348884 induced apoptosis and sensitized OCI-AML3 and primary AML cells expressing NPM1c+ to ATRA. This effect was significantly less in AML cells coexpressing FLT3-ITD, or in AML or normal CD34+ progenitor cells expressing wild-type NPM1. Thus, attenuating levels or oligomerization of NPM1 selectively induces apoptosis and sensitizes NPM1c+ expressing AML cells to treatment with ATRA and cytarabine.     

Duplicated rectum as interlabial mass

Duplications of the rectum constitute one of the rare congenital anomalies. Presentation as a sequestrated interlabial mass without any associated anomaly has not been reported before. We cannot readily offer any embryological explanation for this congenital distortion. Total extirpation of the lesion was easily achieved ensuring complete cure.     

Uric acid heralds ischemic tissue injury to mobilize endothelial progenitor cells

Understanding the nature of endogenous mechanisms for mobilization of stem/progenitor cells is predicated on the identification of injury-induced substances that are released from a damaged organ and capable of producing a distant effect. Although different substances that mobilize endothelial progenitor cells (EPCs) have been proposed, their potential to signal injury and afford postischemic renoprotection and repair remains obscure. Uric acid (UA) is consistently overproduced by ischemic tissues and has been shown to exert immunomodulatory functions. It was hypothesized that UA and/or its precursors might serve as injury signals that are capable of mobilizing EPCs in acute renal ischemia. Indeed, FVB/NJ mice that were subjected to acute renal ischemia showed a transient surge in UA level in the peripheral blood. Single-dose treatment with UA, as well as acute hyperuricemia induced by the inhibition of uricase, caused a robust mobilization of EPCs, whereas administration of adenosine or inosine seemed to lack this effect. Moreover, pretreatment of mice with a single dose of UA afforded significant renoprotection against ischemic injury. In animals with chronic hyperuricemia (induced by continuous 2-wk treatment with a uricase inhibitor oxonic acid), EPC mobilization was blunted and renoprotective effects were absent. In conclusion, acute elevation of UA acts as "physiologic," fast-acting endogenous mediator of EPC mobilization and renoprotection, consistent with its novel function in pharmacologic preconditioning. Both of these actions are lacking in mice with chronic hyperuricemia. In summary, a transient surge in UA concentration may serve as a universal herald of tissue injury to accelerate the recruitment of EPCs.     

Enterococcus faecalis adhesin, Ace, mediates attachment to particulate dentin

An enzyme linked immunosorbent assay was developed to assess E. faecalis adhesion to particulate dentin. E. faecalis, OG1RF, which expresses the collagen binding protein (Ace+), and a derivative of OG1RF, TX5256, deficient in the collagen binding protein (Ace-) were grown at 46 degrees C, necessary for in vitro expression of Ace, and at 37 degrees C. E. faecalis binding to dentin was measured at 0, 15, 30, 60, 120, and 360 minutes. Compared to TX5256 and OG1RF grown at 37 degrees C, OG1RF grown at 46 degrees C adhered significantly better at all time points except 15 minutes (p < 0.001) exhibiting maximum binding at 120 minutes (17.4% of a positive control). Type I collagen at 100 microg/ml inhibited dentin binding by OG1RF grown at 46 degrees C in both competition (p < 0.005) and displacement assays (p < 0.046). Immunoaffinity purified anti-Ace IgG at 200 microg of protein inhibited adhesion of OG1RF grown at 46 degrees C to dentin.     

Role of Duplex Arteriography as the Sole Preoperative Imaging Modality Prior to Lower Extremity Revascularization Surgery in Diabetic and Renal Patients

The limitations and complications associated with contrast angiography (CA) prior to lower extremity revascularization have led to an increased interest in duplex arteriography (DA) as a potential replacement. We report our experience with DA in patients with diabetes and/or chronic renal insufficiency (CRI) that would particularly benefit from a noninvasive approach to preoperative evaluation of the arterial tree. From January 1998 to November 2000, DA was performed in 145 patients with diabetes mellitus and/or CRI prior to 180 arterial reconstructions. One hundred twenty-one procedures were performed on 91 patients with diabetes alone, 41 on 33 patients with diabetes and CRI, and 18 on 15 patients with CRI alone. Patient ages ranged from 36 to 98 years (mean 72 ± 12 years). Indications for surgery were severe claudication in 33 (18%), rest pain in 37 (21%), nonhealing ischemic ulcers in 52 (29%), and limb gangrene in 58 (32%). Optimal inflow and outflow anastomotic sites were selected according to a diagram based on DA that included arterial tree imaging from mid-aorta to the pedal vessels. Preoperative contrast arteriography was performed in 16 cases (9%) because of extremely poor runoff based on DA and limited visualization of outflow vessels. The distal anastomosis was to the popliteal artery in 89 cases (49%) and to the tibial and pedal arteries in 91 (51%). Intraoperative findings confirmed the preoperative DA results with the exception of one (0.6%) where the distal anastomosis was placed proximal to a significant stenosis requiring an extension graft. The use of DA presents a safe and reliable option to prebypass CA for many patients with diabetes or CRI. The ease of use and favorable patient outcomes achieved by this imaging modality may rival the use of CA for these patients.Presented at the Southern Association for Vascular Surgery, Rio Grande, Puerto Rico, January 26, 2001.     

Intraoperative carotid artery duplex scanning in a modern series of 650 consecutive primary endarterectomy procedures

PURPOSE: Thromboembolic complications after carotid endarterectomy are frequently associated with technical defects. We analyzed the effect of intraoperative duplex scanning in detection of significant but clinically unsuspected technical defects and residual common carotid artery (CCA) disease as a potential source of postoperative transitory ischemic attack (TIA) and stroke. METHODS: From April 2000 to April 2003, 650 consecutive primary carotid endarterectomy procedures were performed in 590 patients at a single institution by two vascular surgeons. Patients included 335 men (57%) and 255 women (43%). Indications for surgery were asymptomatic internal carotid artery (ICA) stenosis (>or=70%) in 464 patients (71%). All procedures were performed with the patient under general anesthesia, with synthetic patch angioplasty in 644 (99.1%). Major technical defects at intraoperative duplex scanning (>30% luminal internal carotid artery stenosis, free-floating clot, dissection, arterial disruption with pseudoaneurysm) were repaired. CCA residual disease was reported as wall thickness (0.7-4.8 mm; mean, 1.7 +/- 0.7) and percent stenosis (16%-67%; mean, 32% +/- 8%) in all cases. Postoperative 30-day TIA, stroke, and death rates were analyzed. RESULTS: There were no clinically detectable postoperative thromboembolic events in this series. All 15 major defects (2.3%) identified with duplex scanning were successfully revised. These included 7 intimal flaps, 4 free-floating clots, 2 ICA stenoses, 1 ICA pseudoaneurysm, and 1 retrograde CCA dissection. Diameter reduction ranged from 40% to 90% (mean, 67 +/- 16%), and peak systolic velocity ranged from 69 to 497 cm/s (mean, 250 +/- 121 cm/s). Thirty-one patients (5%) with the highest residual wall thickness (>3mm) in the CCA and 19 (3%) with the highest CCA residual diameter reduction (>50%) did not have postoperative stroke or TIA. Overall postoperative stroke and mortality rates were 0.3% and 0.5%, respectively; combined stroke and mortality rate was 0.8%. One stroke was caused by hyperperfusion, and the other occurred as an extension of a previous cerebral infarct. No patients had TIAs. Two deaths were caused by myocardial infarction, and one death by respiratory insufficiency. CONCLUSION: We believe intraoperative duplex scanning had a major role in these improved results, because it enabled detection of clinically unsuspected significant lesions. Residual disease in the CCA does not seem to be a harbinger of stroke or TIA.     

Magnetic resonance angiography versus duplex arteriography in patients undergoing lower extremity revascularization: which is the best replacement for contrast arteriography?

OBJECTIVE: In an effort to explore alternatives to contrast material-enhanced arteriography, we compared magnetic resonance angiography (MRA) and duplex arteriography (DA) with contrast arteriography (CA) for defining anatomic features in patients undergoing lower extremity revascularization. METHODS: From August 1, 2001, to August 1, 2002, 61 consecutive inpatients (64 limbs) with chronic lower extremity ischemia underwent CA, MRA, and DA before undergoing lower extremity revascularization procedures. The reports of these tests and images were compared prospectively, and the differences in the iliac, femoropopliteal, and infrapopliteal segments were noted. The vessels were classified as mildly diseased (<50%), moderately diseased (50%-70%), severely diseased (71%-99%), or occluded. The studies and treatment plans based on these data were compared. RESULTS: Mean patient age was 76 +/- 10 years (SD). Indications for the procedures included gangrene (43%), ischemic ulcer (28%), rest pain (19%), severe claudication (9%), and failing bypass (1%). During this period 35 patients were ineligible for the protocol, because they could not undergo MRA (n=27) or angiography (n=8). Of the total 192 segments in the 64 patients (iliac, femoropopliteal, tibial), 17% were not able to be fully assessed with DA, and 7% with MRA. Disagreements with CA and DA were found in the iliac, femoropopliteal, and tibial segments in 0%, 7%, and 14% of cases, respectively, and between CA and MRA in 10%, 26%, and 42% of cases, respectively. Two of 9 differences (22%) between DA and CA were thought to be clinically significant, and 28 of 45 differences (62%) between MRA and CA were thought to be clinically significant. CONCLUSIONS: A review of the data obtained in this series indicates that MRA does not yet seem to yield adequate data, at least in this highly selected population at our institution. When severe calcification is identified, CA may be necessary in patients undergoing DA.