Femorodistal vein grafts: the utility of graft surveillance criteria

PURPOSE: This retrospective review of femorodistal vein grafts was analyzed to determine the usefulness of various graft surveillance criteria. METHOD: The surveillance schedule involved evaluations at 1 month, every 3 months the first year, and then every 6 months. Salvage intervention or graft occlusion occurring within the next follow-up interval defined surveillance end points. One hundred two grafts (329 surveillance visits) had an ankle/brachial index (ABI). A duplex scanning-determined midgraft peak systolic flow velocity (PSFV) was available for 81 grafts (262 visits). Forty-eight grafts (137 visits) had both a PSFV and entire graft duplex scanning (EGDS) to determine stenosis greater than 50%, whereas 40 grafts (91 visits) had simultaneous ABI and EGDS. RESULTS: When a greater than 15% decrease in ABI denoted an abnormal surveillance study result, a positive predictive value (PPV) of 24.3% and negative predictive value of 94.5% were noted. Similarly, a PSFV cutoff of less than 35 cm/sec demonstrated values of 26.3% and 94.2%, respectively. When an EGDS of greater than 50% stenosis or a PSFV of less than 35 cm/sec were the cutoff criteria, the PPV was 36.7% and negative predictive value 99.1%, whereas characterizing abnormal results further with ABI (> 15% decreases) increased the PPV to 83.3%. CONCLUSION: The combination of an EGDS, midgraft PSFV, and ABI provides optimal follow-up for our patients with a femorodistal vein graft.     

Ornithine decarboxylase transformation of NIH/3T3 cells is mediated by altered epidermal growth factor receptor activity

Ornithine decarboxylase (ODC) has been shown to be oncogenic in transfected NIH/3T3 cells overexpressing the enzyme from a heterologous promoter. These cells, designated as NODC-2 cells, acquire proliferative properties associated with tumorigenic transformation such as loss of contact inhibition, decreased population doubling time, anchorage-independent growth, and tumor production in nude mice. At least one of these parameters, loss of contact inhibition, remains dependent on elevated ODC levels. We have used these cells to investigate the molecular mechanisms by which ODC overexpression drives cell transformation and to examine the involvement of other proto-oncogene products in this process. An interaction between ODC overexpression and the epidermal growth factor receptor (EGF-R) was suggested initially by the elevation of both basal (300%) and ligand-induced (457%) EGF-R tyrosine kinase activities in NODC-2 cells compared to similarly treated control NLK cells. Disruption of EGF-R mediated signal transduction in NODC-2 cells both by treatment with tyrphostin-25 or by transfection with a vector expressing a dominant negative EGF-R mutant resulted in reacquisition of contact-inhibited growth and suppression of anchorage-independent, clonogenic growth in soft agar. We conclude that ODC-induced transformation of NIH/3T3 cells is mediated, at least partly, by alterations in EGF-R signal transduction activity.     

Expression and circular dichroism studies of the extracellular domain of the alpha subunit of the nicotinic acetylcholine receptor

To provide material suitable for structural studies of the nicotinic acetylcholine receptor, we have expressed and purified the NH2-terminal extracellular domain of the mouse muscle alpha subunit. Several constructs were initially investigated using Xenopus oocytes as a convenient small scale expression system. A fusion protein (alpha210GPI) consisting of the 210 NH2-terminal amino acids of the alpha subunit and a glycosylphosphatidylinositol anchorage sequence conferred surface alpha-bungarotoxin binding in oocytes. Coexpression of alpha210GPI with an analogous construct made from the delta subunit showed no evidence of heterodimer formation. The alpha210GPI protein was chosen for large scale expression in transfected Chinese hamster ovary cells. The alpha210GPI protein was cleaved from these cells and purified on an immunoaffinity column. Gel and column chromatography show that the purified protein is processed as expected and exists as a monomer. The purified protein also retains the two distinct, conformation-specific binding sites expected for the correctly folded alpha subunit. Circular dichroism studies of alpha210GPI suggest that this region of the receptor includes considerable beta-sheet secondary structure, with a small proportion of alpha-helix.     

Study of the use of vitamin K in neonates in France

Our objective was to assess flow velocity waveforms of the portal venous system of the anemic fetus prior to and immediately following intravascular transfusion. Color-guided pulsed Doppler was used to obtain flow velocity waveforms from the fetal portal vein in 14 anemic fetuses that were transfused in utero for rhesus alloimmunization The portal vein velocity pattern was defined as continuous when no change in velocity during the cardiac cycle was noted. It was defined as pulsatile when a deflection of the wave was present. The flow velocity waveforms were quantified by using the ratio between the peak (highest, H) and the nadir (lowest, L) velocities (H/L ratio). Fourteen intravascular transfusions were performed. Gestational age ranged from 19.5 to 35 weeks (mean +/- SD, 26.7 +/- 5.3 weeks). The hematocrit ranged from 5.9 to 31.2% (mean +/- SD, 20.3 +/- 9%) prior to transfusion; after transfusion it was between 24.8 and 56.7% (mean +/- SD, 42 +/- 10.4%). In six cases (43%) the waveforms were pulsatile prior to transfusion; in the other eight (57%) they were continuous. The pulsatile pattern was present following transfusion in 13 cases (93%, p < 0.05). The mean of the H/L ratio was 1.3 +/- 0.38 prior to transfusion and 2.0 +/- 0.86 after transfusion (p < 0.05). Because the portal vein has continuous non-pulsatile flow in the normal fetus, the presence of pulsatility in the waves of six anemic fetuses (43%) may suggest portal hypertension. Compared to normal fetuses, there was an increased number of cases with pulsation, and even more so after transfusion. The pattern corresponds to findings in children with portal hypertension.     

Outcome of rheumatoid arthritis and psoriasis following autologous stem cell transplantation for hematologic malignancy

Based on successful results in animal models, it has been proposed that high-dose myeloablative therapy followed by autologous bone marrow or stem cell transplantation (ABMT/ASCT) may cure autoimmune disease. The coexistence of autoimmune disease and hematologic malignancy provides an opportunity to examine the response of autoimmune disease to ABMT or ASCT. We describe 4 patients with autoimmune disease (3 with psoriasis and 1 with rheumatoid arthritis) and hematologic malignancy. In each patient, the autoimmune disease remitted posttransplantation, but, in 4 patients with long-term followup, it recurred at 8-24 months. The earliest relapse occurred in a patient treated with interferon-alpha. Our experience suggests that a single autograft with unpurged stem cells is unlikely to cure autoimmune disease, but that other strategies building on this approach are worthy of investigation.