Contrast medium-induced adverse reactions: economic outcome

Because the cost of managing an expected greater number of adverse reactions when high-osmolality contrast media (HOM) are used could offset the higher material cost of low-osmolality contrast media (LOM), a prospective study was done of 795 inpatients undergoing any of four procedures involving intravascular injection of HOM: cardiac catheterization, peripheral angiography, head computed tomography (CT), or body CT. The resources used in managing HOM-induced adverse reactions were measured, and the costs of these resources were estimated. Four hundred five patients (51%) had adverse reactions. Reactions were grouped into three classes according to their severity. Class 1 (mild) reactions occurred in 358 patients (45%), class 2 (moderate) reactions occurred in 44 patients (6%), and class 3 (severe) reactions occurred in three patients (0.4%). Ninety-nine patients (12%) consumed resources as a result of an adverse reaction. The average cost of these resources per patient undergoing examination was $1.07 to the radiology department, $5.83 to the hospital, and $12.93 to a charge-paying insurer. Mean (+/- standard deviation) cost to the hospital for managing class 1, class 2, and class 3 reactions were $2.52 +/- $5.33, $24 +/- $54, and $910 +/- $749, respectively. By comparison, the difference in material cost of HOM versus LOM ranged from $93 for body CT to $179 for cardiac catheterization. Even if LOM were to induce no adverse reactions, the increased material cost associated with universal substitution of LOM for HOM would be greater than the expected cost of managing adverse reactions when HOM are used.     

Changes in CT utilization between 1981 and 1984: implications for Medicare payment for MR imaging under the prospective payment system

In the absence of data on current or likely patterns of use of magnetic resonance (MR) imaging, use of computed tomography (CT) at one institution in 1981 and 1984 was analyzed to provide data relevant to current federal deliberations regarding Medicare payment for inpatient MR imaging. Between 1981 and 1984 inpatient CT utilization increased 59%, primarily due to a 265% increase in body CT. In 1984 inpatients who underwent at least one CT procedure were as likely to undergo more than one procedure as to undergo only one. CT procedures were performed in a high proportion of diagnosis-related groups (DRGs), with more than one-half of head CT procedures performed in non-neurologic DRGs. Given the similarities between clinical applications of CT and MR imaging, these findings regarding CT utilization have the following implications: (a) a delay in recalibration of DRG payment rates may not take account of expected growth in utilization of MR imaging, (b) a DRG "add-on" for MR imaging should reflect the likelihood that more than one MR imaging procedure will be performed in many hospitalizations, and (c) adjustments in DRG payments for MR imaging should not be limited to the 35 neurologic DRGs.     

Intraductal papillary-mucinous tumors of the pancreas: Clinicopathologic features, outcome, and nomenclature. Members of the Pancreas Clinic, and Pancreatic Surgeons of Mayo Clinic

BACKGROUND & AIMS: Intraductal papillary-mucinous tumor (IPMT) of the pancreatic ducts is increasingly recognized. This study investigated if clinical, imaging, or, histological features predicated outcome, formulated a treatment algorithm, and clarified relationships among IPMT, mucinous cystic neoplasms of the pancreas (MCN), and chronic pancreatitis. METHODS: The medical records, radiographs, and pathological specimens of 15 patients with IPMT (dilated main pancreatic duct or branch ducts with mucin overproduction) who were evaluated between October 1983 and January 1994 were reviewed. RESULTS: One patient had hepatic metastases. Fourteen underwent an operation (6 distal pancreatectomy, 4 total pancreatectomy, and 4 pancreaticoduodenectomy); all had dysplastic intraductal epithelium and chronic pancreatitis, whereas 3 had invasive adenocarcinoma. After a median of 25 months, 10 patients were alive; 3 of 4 with malignant and 2 of 11 with benign IPMT died (P < 0.05). Patients with or without carcinoma had similar clinical and radiographic features. A clinical diagnosis of chronic pancreatitis had been made in 9 patients with benign IMPT and in none with malignant IPMT (P < 0.05). CONCLUSIONS: IPMT is a dysplastic and likely precancerous lesion that is frequently diagnosed as chronic pancreatitis and is separate from MCN. Because it is not possible to distinguish noninvasive from invasive IPMT preoperatively, complete surgical excision of the dysplastic process is our treatment of choice whenever appropriate. (Gastroenterology 1996 Jun;110(6):1909-18)     

Multi-unit ribozyme-mediated cleavage of bcr-abl mRNA in myeloid leukemias

Chronic myelogenous leukemia is characterized by the Philadelphia chromosome, which at the molecular level results from the fusion of the bcr gene on chromosome 22 and the abl gene on chromosome 9. The bcr-abl fusion gene encodes a novel tyrosine kinase with transforming activity. In this study, we have synthesized a multi-unti ribozyme that targets bcr-abl mRNA. In vitro ribozyme cleavage reactions show increased cleavage efficiency of this multi-unit ribozyme compared with single or double ribozymes. The multiunit ribozyme was then transfected into murine myeloblasts transformed with the bcr-abl gene (32D cells). Ribozyme transfection was accomplished either by liposomes or using follic acid-polylysine as a carrier. Multi-unit ribozyme transfection reduced the level of bcr-abl mRNA 3 logs when transfected via folate receptor-mediated uptake into transformed 32D cells. These results suggest that a multi-unit ribozyme could be an effective therapeutic agent for the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia.     

HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype

Some rare HIV-1-infected individuals, referred to as HIV controllers (HIC), have persistently undetectable plasma viral load in the absence of therapy. This control of HIV-1 replication has been associated with a strong, multifunctional specific CD8(+) T cell response. However, no direct link between this immune response and the control of viremia has so far been provided. We investigated parameters of specific CD8(+) T cell response and in vitro susceptibility to HIV-1 infection in 11 HIC. We found high frequencies of HIV-specific CD8(+) T cells. Interestingly, these cells expressed the activation marker HLA-DR but not CD38. This unique phenotype differentiates HIV-specific CD8(+) T cells from HIC and noncontroller subjects and likely reflects a high potential to expand upon exposure to antigen and a capacity to exert effector functions. Accordingly, although CD4(+) T cells from HIC were fully susceptible to HIV-1 superinfection, their CD8(+) T cells effectively suppressed HIV-1 infection. Remarkably, this potent anti-HIV activity was observed without prior stimulation of CD8(+) T cells. This activity was not mediated by secreted inhibitory factors but was due to the elimination of infected CD4(+) T cells and was observed only with autologous CD4(+) T cells, indicating an HLA-restricted cytotoxic mechanism. This constitutive antiviral capacity of CD8(+) T cells could account for the control of viral replication in HIC.     

Integrin alpha 4 beta 1 and glycoprotein IV (CD36) are expressed on circulating reticulocytes in sickle cell anemia

The abnormal adherence of red blood cells, especially circulating reticulocytes (erythrocyte precursors), to the endothelium is believed to contribute to vascular occlusion observed in patients with sickle cell disease. Although several plasma proteins including von Willebrand factor and fibronectin have been proposed to mediate this adhesion, the mechanism of sickle cell adhesion to the endothelium remains unknown. Using flow cytometry, we screened sickle red blood cells with monoclonal antibodies (MoAbs) against known adhesion receptors and detected integrin subunits alpha 4 and beta 1 and the nonintegrin glycoprotein IV on reticulocytes but not on erythrocytes. No reactivity was detected against integrin subunits alpha 2, alpha 3, alpha 5, alpha 6, alpha v, beta 2, beta 3, integrin alpha IIb beta 3, or the nonintegrin glycoprotein Ib. Immunoprecipitation of reticulocytes with either alpha 4- or beta 1-specific antibodies identified the alpha 4 beta 1 complex (alpha 4(70) and alpha 4(80) forms), a receptor for fibronectin and vascular cell adhesion molecule-1. An antibody against glycoprotein IV, a receptor reported to bind thrombospondin and collagen, immunoprecipitated an 88-kD protein consistent with its reported M(r). MoAbs against alpha 4 and glycoprotein IV bound to an average of 4,600 and 17,500 sites per reticulocyte, respectively. Identification of alpha 4 beta 1 and glycoprotein IV on reticulocytes suggests both plasma-dependent and independent mechanisms of reticulocyte adhesion to endothelium and exposed extracellular matrix.