MR gated subtraction angiography: evaluation of lower extremities

We report the first clinical experience with a new method for projective imaging of blood vessels (angiography) using magnetic resonance. Vascular contrast is produced noninvasively by the phase response of moving protons. Diastolic and systolic gated images produce, respectively, flow signal and flow void; the difference image is a map of the pulsatile flow: an arteriogram. Preliminary studies are presented of the lower extremities of one healthy volunteer and four patients (one each with occlusive disease, soft-tissue tumor, arteriovenous malformation, and venous femoral-popliteal graft). Patient data are compared with accompanying conventional arteriograms, and the new method is discussed.     

Comparison of cost and clinical outcome between transcatheter coil occlusion and surgical closure of isolated patent ductus arteriosus

OBJECTIVE: The objective of this study was to compare the cost (measured as resource utilization by the institution) and clinical effectiveness of transcatheter coil occlusion and surgical patent ductus arteriosus (PDA) closure. Similar comparisons have been made previously with other devices no longer in use in the United States. No such comparison has been made for coil occlusion, which has been performed increasingly since 1992. METHODS: All patients who underwent either coil or surgical closure of uncomplicated PDA at our institution between August 1993 and June 1996 were retrospectively identified. Patients were included in the study if they were eligible for either closure technique. Thus, they had a restrictive PDA (not associated with pulmonary hypertension) and no overt evidence of congestive heart failure. Patients were excluded if they had other significant cardiac or noncardiac problems. Total procedural and recovery costs (including labor, material, equipment, and overhead) incurred by the provider were determined using a cost accounting system called Transition Systems, Inc. To define further how costs differed for the two techniques, total costs were subdivided into the categories of professional, technical, inpatient hospital stay, postprocedure testing, and supplies and other miscellaneous costs. PDA closure rates and associated complications also were compared. Follow-up information was sought from outpatient visits to our institution or by contacting the referring physicians. RESULTS: A total of 39 patients were identified, 3 of whom were excluded because of coexisting medical problems. The study group consisted of 36 patients; 24 underwent PDA coil occlusion and 12 surgical closure. Mean age and weight were 8.8 years and 28.5 kg for the coil patients, and 7.3 years and 32.8 kg for the surgical patients. Median procedural duration was 150 minutes for the coil group and 165 minutes for the surgical group. The total cost to the institution of coil occlusion was significantly lower than that of surgical closure ($5273 vs $8509). The largest difference lay in the cost of hospital stay ($398 vs $2566) and in the professional costs ($1506 vs $2782). Technical costs were similar ($2156 for coil, $2151 for surgery), although use of the catheterization laboratory per unit of time was more expensive than use of the operating room ($800 vs $400 per hour). Additional technical costs of the surgical procedure related to general anesthesia and postoperative care made up the difference. No patient in either group had a residual PDA murmur at hospital discharge or thereafter. Follow-up echocardiography was performed in all coil occlusion patients, and tiny residual leaks were detected in 17%. Only 42% of the surgical patients had postoperative echocardiography; none had residual leaks. There were no deaths or major complications in either group. CONCLUSIONS: Transcatheter coil occlusion is as effective and less costly than surgical closure if silent residual leaks are not considered clinically significant. This information may be used increasingly in patient care decisions in the current era of managed medical care.     

Traumatic brain stem injury: MR imaging

Eighty-seven patients with acute (n = 70) or chronic (n = 17) head injuries were prospectively studied with magnetic resonance (MR) imaging and computed tomography (CT) to characterize the frequency and nature of traumatic brain stem injury (BSI). Forty-eight traumatic lesions were identified in 36 patients. Of 36 patients, 35 had neurologic findings that corroborated the radiographic impression of BSI. T1- and T2-weighted MR images demonstrated a significantly higher number of lesions than did CT. Patients with BSI had a significantly higher frequency of corpus callosum and diffuse axonal "shear" lesions. The number of cortical contusions and extraaxial hematomas was similar in both groups. The mean Glasgow Coma Scale (GCS) scores at admission were significantly lower in patients with evidence of BSI on MR images. Patients with primary BSI had lower initial GCS scores, a longer duration of coma, more diffuse axonal "shear" lesions, and a higher frequency of corpus callosum injury than patients with secondary BSI. The location of primary and secondary lesions was significantly different. Overall, MR imaging was more helpful than CT in detecting, localizing, and characterizing BSI.     

Sitosterol xanthomatosis

BACKGROUND: Sitosterolaemia is a lipid disorder in which plasma plant sterol levels are extremely elevated. Sitosterolaemia is clinically characterized by tuberous and tendon xanthomas, premature vascular disease and arthritis. OBJECTIVE: To report a case of sitosterolaemia diagnosed by cutaneous manifestations and to review this rare disease. METHODS: We report the case of a 60-year-old woman who presented with cutaneous xanthomas, arterial hypertension and polyarthralgias. The patient had had hypercholesterolaemia for many years without reduction of serum cholesterol, despite treatment with fenofibrate. RESULTS: Ezetimibe therapy was started, decreasing sitosterol plasmatic levels and tuberous xanthomas after 3 months of treatment. CONCLUSION: It is important to detect levels of sitosterol in plasma in patients with premature vascular disease, presence of xanthomas, and uncontrolled hypercholesterolaemia. Ezetimibe therapy is effective.     

Reduction of salivary tissue factor (thromboplastin) activity by warfarin therapy

The coagulant of normal human saliva has been identified as tissue factor (thromboplastin, TF) by virtue of its ability to cause rapid coagulation in plasmas deficient in first-stage coagulation factors and to activate factor x in the presence of factor VII and by virtue of the fact that its activity is expressed only in the presence of factor VII and is inhibited by an antibody to TF. The TF is related to cells and cell fragments in saliva. Salivary TF activity has been found to be significantly reduced in patients taking warfarin. The decline in TF activity during induction of warfarin anticoagulation occurs during the warfarin-induced decline in vitamin-K-dependent clotting factor activity, as judged by the prothrombin time. The decrease in TF activity is not related to a reduction in salivary cell count or total protein content or to a direct effect of warfarin on the assay. It is hypothesized that the mechanism by which warfarin inhibits TF activity may be related to the mechanism by which it inhibits expression of the activity of the vitamin-K-dependent clotting factors. Inhibition of the TF activity may be involved in the antithrombotic effect of warfarin.     

The effectiveness of the confidential unit exclusion option

BACKGROUND: The confidential unit exclusion (CUE) option is intended to reduce human immunodeficiency virus (HIV) transmission by excluding donors newly infected with HIV who have not yet developed HIV antibody (window-period donors); however, its efficacy in excluding window- period donors has not been evaluated. STUDY DESIGN AND METHODS: The use of the CUE option was studied among the donors of 3.7 million units at 18 American Red Cross blood services regions during 1991 and 1992 and among 322 previously HIV-1-seronegative donors who subsequently donated a seropositive unit between 1987 and 1990 at 40 United States blood centers. These seroconverting donors had previously been shown to be highly likely to donate during their window period. RESULTS: On the basis of data from these two populations, it was estimated that only 3 to 5 percent of units donated by window-period donors were not transfused because of the CUE option, that 0.4 percent of all donations were from donors who confidentially excluded their blood from transfusion, and that donors who confidentially excluded their blood were 21 times more likely to be HIV antibody-positive than donors who did not use the CUE option. It is estimated that, if all US blood centers used the CUE option, a total of 2 to 17 otherwise acceptable units donated by window-period donors would not be transfused annually. CONCLUSION: Although donors who confidentially exclude their blood from transfusion are 21 times more likely to have HIV antibody, the rarity of window-period donors and the infrequency of confidential exclusion by window-period donors cause the CUE option to have minimal impact on transfusion safety.     

The localization of a platelet GpIIb-IIIa-related protein in endothelial cell adhesion structures

Previous studies have shown that human endothelial cells (ECs) adhere to fibrinogen (fg) and fibronectin (fn) and organize their cytoskeleton on these substrata. However, the mechanism governing this chain of events is poorly known. In ECs glycoproteins immunologically and biochemically similar to the platelet membrane GpIIb-IIIa complex have been described. The functional role of this complex in ECs remains to be established. In this study we show that the antigens recognized by polyclonal antibodies raised against human platelet GpIIb-IIIa and crossreacting with the EC form have a discrete and well-organized distribution at cell adhesion structures. Indeed these antigens are located at vinculin-rich focal contacts found at the membrane insertion of microfilament bundles of the stress fiber type. They are also found at cell-to-cell contacts and, with a diffuse pattern, at the dorsal surface of ECs. GpIIb-IIIa antibodies, added to EC suspensions prior to plating, inhibit EC spreading on fg and vitronectin (vn) substrata in a concentration-dependent way. In contrast, the antibodies are very poorly active when the cells are seeded on fn-coated glass. The same antibodies, added to adherent cells, disrupt cell-to-cell contacts and cause their rounding and detachment. Overall these results indicate that EC GpIIb-IIIa complex is involved in controlling the adhesion mechanism of these cells to extracellular matrix proteins.     

Prevention of refractoriness and HLA-alloimmunization using filtered blood products

Depletion of leukocytes from all blood products may decrease the incidence of alloimmunization to HLA antigens present on the white cells and thus delay the onset of refractoriness to random donor platelet support. In order to test this hypothesis, 54 patients with hematologic malignancy or marrow aplasia were entered on a prospective randomized trial using cotton-wool filtration as a method of leukocyte depletion of red cell and platelet concentrates. Forty patients were considered evaluable; 20 patients received filtered products and 20 patients in the control group received standard unfiltered products. The filter was 99% efficient in removal of leukocytes (average number of WBC/platelet product, 6 X 10(6)). Platelet loss by this technique was 8%. Alloimmunization was assessed by detection of de novo formed lymphocytotoxic and platelet specific antibodies by microcytotoxicity test, Staph A protein radioimmunoassay, and solid phase red cell adherence test. In the group receiving filtered products, three of 20 (15%) patients developed lymphocytotoxic antibodies while ten of 20 (50%) patients in the control group developed cytotoxic antibodies (P = .01 by actuarial methods). Platelet antibodies were detected in seven of ten alloimmunized patients in the control group and three of three patients in the study group. Clinical evidence of refractoriness was seen in three of 20 patients in the filtered group and ten of 20 in the control group (P = .01 by actuarial methods). The cost of filtration was a fraction of the cost of a plateletpheresis product. Filtration appears to be an effective and economical method for reducing alloimmunization and clinical refractoriness to random donor platelets in patient receiving long-term transfusion support.     

Transforming growth factor beta selectively inhibits normal and leukemic human bone marrow cell growth in vitro

The effects of transforming growth factor beta 1 or beta 2 (TGF-beta 1 or -beta 2) on the in vitro proliferation and differentiation of normal and malignant human hematopoietic cells were studied. Both forms of TGF- beta suppressed both the normal cellular proliferation and colony formation induced by recombinant human interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF). In the presence of GM-CSF or IL-3, optimal concentrations of TGF-beta (400 pmol/L) inhibited colony formation by erythroid (BFU-E), multipotential (CFU-GEMM), and granulocyte-macrophage (CFU-GM) progenitor cells by 90% to 100%, whereas granulocyte or monocyte cluster formation was not inhibited. In contrast, neither form of TGF-beta had any effect on G- CSF-induced hematopoiesis. The suppressive action appeared to be mediated directly by TGF-beta since antiproliferative responses were also observed in accessory cell-depleted bone marrow cells. In contrast to normal bone marrow cells, both GM- and G-CSF-induced proliferation of cells from patients with chronic myelogenous leukemia were suppressed in a dose-dependent manner by TGF-beta. Differential effects of TGF-beta on the proliferation of established leukemic lines were also observed since most cell lines of myelomonocytic nature studied were strongly inhibited where erythroid cell lines were either insensitive or poorly inhibited by TGF-beta. These results suggest that TGF-beta is an important modulator of human hematopoiesis that selectively regulates the growth of less mature hematopoietic cell populations with a high proliferative capacity as opposed to more differentiated cells, which are not affected by TGF-beta.