Greenfield filter fixation in large venae cavae.

PURPOSE: It is generally thought that the Greenfield filter should not be placed in inferior venae cavae (IVCs) that are larger than 28 mm in diameter because of its base diameter. However, the newer versions have larger base diameters. The purpose of this study was to evaluate fixation of the three currently available Greenfield filters in large IVCs. MATERIALS AND METHODS: Filter fixation was tested in an ex vivo perfusion system with a 34-mm-diameter equine IVC. Greenfield filters with base diameters of 30 mm (original 24-F version [24-F GF]), 38 mm (percutaneous titanium [TGF]), and 32 mm (percutaneous stainless steel [SGF]) were deployed. Increasing force was then applied in a cephalic direction and the resultant movement was measured. RESULTS: In a 34-mm-diameter IVC, the TGF and SGF demonstrated significantly less movement than did the 24-F GF (P < .001). None of the TGFs or SGFs moved above the renal veins with a 480-g pull. Three of the seven 24-F GFs moved above the renal veins at 30 g. No significant difference in fixation was demonstrated between the TGF and the SGF (P = .6). CONCLUSIONS: In a 34-mm-diameter IVC, fixation of the TGF and SGF was significantly better than the 24-F GF. The TGF and SGF may not be subject to the same 28-mm-diameter IVC size limitation as the 24-F GF.

Blood back flow into angiographic catheters.

PURPOSE: Because of a potential impact on thrombus formation, this study determines the degree of blood back flow into catheters filled with different fluids. MATERIALS AND METHODS: Catheters filled with saline or non-ionic or ionic contrast medium were placed in pulsatile circulating human blood in vitro. Catheter orientation was varied, and blood back flow was recorded. RESULTS: When the leading end of the catheter was angled downward, blood back flow into a contrast material-filled catheter was far greater than that into a saline-filled catheter (7.0 vs 0.5 cm). Conversely, when the leading end of the catheter was horizontal, blood back flow was much greater when the catheter contained saline versus contrast media (3.6 vs 0.4 cm). Ionicity of contrast material did not affect back flow. CONCLUSION: Back flow of blood into a catheter can be considerable and is dependent on the type of fluid within the catheter and orientation of the leading end of the catheter. Angiographic techniques adjusted to these findings are important to maintain patient safety.

Phase II evaluation of carboplatin and VP-16 for patients with metastatic breast cancer and only one prior chemotherapy regimen.

UNLABELLED: BACKGROUND. New salvage chemotherapy is needed for metastatic breast cancer. Cisplatin and VP-16 have activity but considerable toxicity. METHODS: This study determines the response rate, response duration, and toxicity of a combination chemotherapy regimen of the better-tolerated carboplatin plus VP-16 in a group of patients with metastatic breast cancer and only one prior exposure to cytotoxic chemotherapy. RESULTS: Twenty-three patients received an average of 2.8 courses of treatment before a lack of response or progression of disease was noticed. Four patients had evidence of rapidly progressive disease or early death and received only one course. No complete responses occurred, but three patients (13%) experienced partial responses. Mean response duration was 5 months. Metastatic disease which responded included lung, lymph node, and chest wall sites. Toxicity was mainly myelosuppression with 57% of patients having grade 3-4 neutropenia or thrombocytopenia. Two patients (8%) had significant infection with neutropenia requiring hospitalization but no toxic deaths occurred. CONCLUSIONS: Carboplatin and VP-16 at this dose and schedule was a reasonably well-tolerated regimen with only modest activity in metastatic breast cancer as second-line cytotoxic chemotherapy.

Gadolinium enhanced MR imaging of vascular stents.

The feasibility of obtaining in-plane magnetic resonance (MR) vascular images in the presence of a vascular stent and the value of infusing an MR contrast agent during imaging was assessed. Coronal and sagittal MR imaging at 1.5 T was performed on six dogs with tantalum aortic stents using single-section gradient echo (GRE) imaging and MR angiography techniques before and during intravenous infusion of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). In-plane gradient echo (GRE) imaging and MR angiography clearly showed flow within the stented vessel as increased signal, with a minimum amount of stent-related artifact. Infusion of Gd-DTPA significantly increased the signal of flowing blood and allowed for better delineation of the stented aortic lumina. Our results demonstrate that in-plane GRE imaging and MR angiography can potentially be used as noninvasive methods for evaluating vascular patency in the presence of MR-compatible endovascular devices. In addition, Gd-DTPA infusion during MR vascular imaging clearly enhances the definition of flowing blood in the lumina of stented vessels.

Flexible tantalum stents implanted in aortas and iliac arteries: effects in normal canines.

Vascular endoprostheses made of knitted tantalum wire and expanded over angioplasty balloons were placed into aortas or iliac arteries of 14 normal dogs. Twelve stents were placed into the infrarenal abdominal aorta and two stents in the left common iliac arteries by the left carotid artery approach. To firmly expand the stent against the vascular wall, nominal stent sizes 0.5-1.0 mm larger than the measured arterial diameter were required. Arteriography performed at specified follow-up intervals showed no evidence of thrombi or emboli; all side branches (lumbar arteries) covered by the stents remained patent. Vascular diameter decreased minimally at 8 and 26 weeks, associated with histopathologic evidence of neointimal buildup. This buildup was highest at 8 weeks (mean, 313 microns) and was slightly less at 26 weeks (mean, 223 microns). Almost complete coverage by endothelium was seen as early as 3 weeks. It is concluded that the flexible tantalum wire stents are well tolerated by the arterial wall and become quickly endothelialized. No excessive neointimal buildup was observed during the 6-month study.

Comparison of titanium and stainless steel, Greenfield vena caval filters.

The standard stainless steel Greenfield filter (SGF) requires a 24F-sized carrier system, and its insertion percutaneously has been associated with local venous thrombosis. To facilitate both percutaneous and operative insertion, a titanium model of the Greenfield filter (TGF) has been developed that allows use of a 12F-sized carrier system. Mechanical comparison of the SGF and TGF devices shows that both withstand extensive flexion stress, but the TGF has greater endurance (52 gm at 20 mm travel) than the SGF (48 gm at 5 mm travel). Measurement of lateral forces for fixation shows comparable force (4.5 gm) at 22 mm for each device but greater force for the TGF at diameters more than 22 mm to its resting diameter of 38 mm. The TGF also withstands crevice corrosion in hydrochloric acid and ferric chloride better than the SGF. Animal studies in 20 sheep show comparable fixation of both devices with no added thrombogenicity of the TGF. Thrombus capture and resolution studies after 14 days in dogs show comparable effectiveness, and histologic examination of the venae cavae show similar inflammatory cell reaction and fibrosis with no foreign body reaction for either metal. Both the SGF and the TGF demonstrate durability and effective filtration of thrombi, with the TGF having the added advantages of ease of insertion and potential improved fixation in larger cavae.

Tantalum vascular stents: in vivo evaluation with MR imaging.

Magnetic resonance (MR) imaging at 1.5 T was performed on tantalum vascular stents placed in the aortas of six dogs. The stents produced no significant artifact and allowed for clear depiction of the aortic lumina as flow-void zones with spin-echo imaging and as high-signal areas with gradient-echo imaging. The MR findings correlated with the angiographic studies of the stented vessels. These results demonstrate the feasibility of MR imaging as a noninvasive means of evaluating vessel patency in the presence of tantalum vascular stents.

Mucosal iron transport by rat intestine.

Using highly sensitive 2-site immunoradiometric assays, we examined the relationship between iron absorption from closed intestinal loops and transferrin and ferritin concentrations in isolated duodenal mucosal cells. As in prior studies, mucosal ferritin correlates inversely with iron absorption and directly with body iron stores as measured by the concentration of nonheme iron in liver. Mucosal transferrin, on the other hand, varies directly with both the total mucosal uptake of radioiron and the proportion of this radioiron transferred from the mucosa to the carcass. The highest correlation with iron absorption was observed with the transferrin-ferritin ratio in isolated mucosal cells. These results suggest that there are two functionally distinct iron-binding compartments in the duodenal mucosa. One is a strong compartment, ferritin, and the other is a transport compartment, transferrin. Control of iron absorption by the intestinal mucosa is closely tied to the balance between these two intracellular iron compartments.

Growth suppression of human leukemic cells in vitro by L-ascorbic acid.

The suppressive effect of L-ascorbic acid on the growth of bone marrow cells from patients with acute nonlymphocytic leukemia was studied using a modified agar culture method featuring daily feeding to allow the growth of leukemic cell colonies. In seven of 28 patients (25%), the numbers of leukemic cell colonies grown in culture were reduced to 21% of control by the addition of L-ascorbic acid (0.3 mM) to the culture medium. Glutathione did not suppress leukemic cell colonies although it has a similar oxidation-reduction potential to that of L-ascorbic acid. The addition of L-ascorbic acid reduced the pH of the medium. However, a comparable reduction of pH by the addition of HCl did not suppress leukemic cell colonies. In simultaneous cultures for leukemic and normal marrow cells, the suppression of leukemic cell colony was noted with a concentration of L-ascorbic acid as low as 0.1 mM (a concentration achievable in vivo), but normal myeloid colonies were not suppressed until the concentration of L-ascorbic acid reached an extremely high level (1 mM). In conclusion, growth of leukemic cells in culture was suppressed by L-ascorbic acid in a substantial proportion of patients with acute nonlymphocytic leukemia. This suppression was a specific effect of L-ascorbic acid and was not due to its oxidation-reduction potential or pH change. Leukemic cells were selectively affected at an L-ascorbic acid concentration attainable in vivo while normal hemopoietic cells were not suppressed.

Prediction of chemotherapy response in human leukemia using an in vitro chemotherapy sensitivity test on the leukemic colony-forming cells.

An in vitro test system to quantitatively assess the chemotherapy sensitivity of human acute leukemic colony-forming cells (L-CFU) in relation to normal granulocytic precursor cells (CFU-C) has been developed. After simultaneous exposure of leukemic and normal bone marrow cells to individual drugs in vitro, cells were grown using an improved agar culture method with daily feeding. A sensitivity index (SI) was determined as the ratio of survival fraction of CFU-C to that of L-CFU, L-CFU being more (or less) sensitive than CFU-C if the SI were higher (or lower) than unity. Thirty SI were determined for 6 single drugs actually given in various combinations to a total of 9 patients (8 with acute nonlymphocytic leukemia and 1 with chronic myelomonocytic leukemia). A highly significant correlation was observed between high (or low) SI and achievement of (or failure to achieve) complete remission, with only 6 false correlations (p = 0.0013). Also, the mean of these SI (MSI) for the multiple single drugs given to each patient as components of a combination chemotherapy was used to indicate an overall sensitivity for each trial of the chemotherapy. Among the 10 chemotherapy trials (1 trial each for 8 patients and 2 trials for 1 patient), 4 trials resulting in complete remission had MSI higher than 1.0, and 6 trials not resulting in complete remission had MSI lower than 1.0 (p = 0.0048). This assay system appears useful in predicting the response of patients to chemotherapy and in the selection of the most effective drugs for use in individual patients.

Iron transport by isolated rat intestinal mucosal cells.

In vitro uptake of radioiron by suspensions of isolated rat duodenal mucosal cells has been examined. The cells bind iron avidly, with uptakes of 15 to 20% after 20 min of incubation. Uptake is dependent upon temperature, pH, and iron and cell concentration. It is unaffected by inhibitors of cellular respiration but is blocked in a concentration-dependent fashion by iron-chelating agents. Iron-deficient cells take up iron at the same rate as normal cells. Binding by brush borders appears to account for 50 to 60% of the total uptake by isolated cells. In vitro radioiron uptake by isolated cells occurs by passive diffusion, is not regulated by the animal's iron status, and is primarily a function of bioavailability of iron in the incubating medium. If the model reflects the behavior of cells in vivo, the initial uptake of iron by the mucosa is a passive process which may serve to concentrate dilute luminal iron at the mucosal surface in preparation for absorption.

Improved growth of in vitro colonies in human acute leukemia with the feeding culture method.

Bone marrow cells freshly aspirated from the 10 consecutive untreated adult patients with acute nonlymphocytic leukemia were cultured by 2 different methods: the conventional agar culture method for myeloid colony formation and its modification by daily feeding with culture medium. In 5 patients, colonies grew in much higher numbers (4.7-to 330-fold) with feeding than without. Three patients grew colonies only with feeding. Two of these 3 patients required L-ascorbic acid in the fed medium for colony growth. Colonies did not grow from the remaining 2 patients by any method. In 7 patients the number of colonies grown with feeding were much higher, up to 170 times higher, than were those from normal control marrows, which grew the same number of colonies regardless of feeding or L-ascorbic acid. Peroxidase and Wright's stains indicated the myeloid differentiation of the cells in the leukemic marrow colonies. The leukemic origin of the colonies was proven by chromosomal analysis. The wide range of linearity between the number of cells plated and the number of colonies grown permits quantitative assay of colony-forming leukemic cells. This assay should be valuable for studies of chemotherapy, growth regulation, and differentiation of leukemic cells.

Cystationine synthesis in yeast: an alternative pathway for homocysteine biosynthesis.

Cystathionine synthesis from O-acetylhomoserine and cysteine has been demonstrated in yeast extracts for the first time. The activity is less than that of O-acetylhomoserine sulfhydrylase, but it is higher than that reported for homoserine O-transacetylase and therefore should not be growth limiting. Cystathionine synthase seems to share the regulatory properties of the sulfhydrylase, and both activities are missing from the methionine auxotroph Saccharomyces cerevisiae EY9, suggesting that both reactions are catalyzed by the same enzyme. However, cystathionine synthase activity was lost during purification of the sulfhydrylase, suggesting that the two reactions may be catalyzed by separate enzymes. Since previous studies have shown that yeast extracts can catalyze the cleavage of cystathionine to homocysteine, our results show the existence of two complete alternate pathways for homocysteine biosynthesis in yeast. Which of these is the major physiological pathway remains to be determined.

Regulation of homocysteine biosynthesis in Salmonella typhimurium.

The regulation of the homocysteine branch of the methionine biosynthetic pathway in Salmonella typhimurium has been reexamined with the aid of a new assay for the first enzyme. The activity of this enzyme is subject to synergistic feedback inhibition by methionine plus S-adenosylmethionine. The synthesis of all three enzymes of the pathway is regulated by noncoordinate repression. The enzymes are derepressed in metJ and metK regulatory mutants, suggesting the existence of regulatory elements common to all three. Experiments with a methionine/vitamin B(12) auxotroph (metE) grown in a chemostat on methionine or vitamin B(12) suggested that the first enzyme is more sensitive to repression by methionine derived from exogenous than from endogenous sources. metB and metC mutants grown on methionine in the chemostat did not show hypersensitivity to repression by exogenous methionine. Therefore, it appears that the metE chemostat findings are peculiar to the phenotype of this mutant; such evidence suggests a possible role for a functional methyltetrahydrofolate-homocysteine transmethylase in regulating the synthesis of the first enzyme. Thus there appear to be regulatory elements which are common to the repression of all three enzymes, as well as some that are unique to the first enzyme. The nature of the corepressor is not known, but it may be a derivative of S-adenosylmethionine. metJ and metK mutants of Salmonella have a normal capacity for S-adenosylmethionine synthesis but may be blocked in synthesis or utilization of a corepressor derived from it.

Synchronization of converging metabolic pathways: activation of the Cystathionine gamma-synthase of Neurospora crassa by methyltetrahydrofolate.

Methyltetrahydrofolate synchronizes the activities of the two branches of the pathway of methionine biosynthesis in Neurospora crassa by serving as an essential activator of cystathionine gamma-synthase and antagonizing the feedback inhibition of this enzyme by S-adenosylmethionine. Activation is specific for the methylated form of folate and increases with increasing glutamate content. The inability of extracts of me-1 and me-6 mutants to form cystathionine that has been previously reported is due to the absence of N(5)-methyltetrahydrofolate from these preparations. Extracts of me-1 mutants lack methyltetrahydrofolate because the organisms are deficient in methylenetetrahydrofolate reductase, and those of me-6 because their methyltetrahydrofolate is quantitatively removed by the procedure employed in the preparation of extracts. The folate of the me-6 organisms differs from that of wild type strains in consisting largely of the monoglutamate rather than higher conjugates.