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.     

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.     

Limberg flap reconstruction for the treatment of pilonidal sinus disease

Pilonidal disease is a common chronic disorder of the sacrococcygeal area affecting young people. Recent reports have advocated different surgical approaches, such as open or closed technique, but recurrence complicates all forms of treatment. We conducted this case review to evaluate the validity of Limberg flap reconstruction method in the treatment of chronic recurrent pilonidal disease. In the period between September 2003 and December 2004, 32 male patients with complicated/recurrent pilonidal disease were operated on using the Limberg flap reconstruction method. The patients' mean age was 26.4 + 1.6 years (range 19-47 years). All patients fared well, had a satisfactory wound healing, had minimal pain and were mobilized immediately after surgery. They stayed at hospital for 6 to 32 hours. No patient had serious wound infection or flap ischemia. They all returned to normal activity within 4 to 12 days. Follow-up ranged between 14 and 28 months. No patient had recurrence during the above period. Limberg flap reconstruction has several advantages compared to the classical surgical methods for the treatment of pilonidal disease. The patients have a short hospital stay, are mobilized soon after surgery and have a minimal morbidity and recurrence rate.     

Quality assessment of randomized controlled trials of contrast media

Numerous randomized controlled trials (RCTs) have been conducted to define the relative benefits of low-osmolality contrast media (LOM) and high-osmolality contrast media (HOM). Because of the clinical and economic significance of the conclusions drawn from these RCTs, the authors used a standardized instrument to evaluate the quality of study design and data analysis of 100 RCTs published between 1982 and 1987 that compared LOM and HOM. The mean quality score (+/- standard deviation) was 39 +/- 12 (maximum possible score, 100). The largest number of patients studied in any RCT was 435; the smallest was five. A majority of the RCTs received high scores on three attributes of quality, intermediate scores on seven, and low scores on nine. These results underscore the difficulty of designing, performing, analyzing, and reporting high-quality RCTs. Nevertheless, limitations in study design and data analysis need to be considered when interpreting results of these RCTs. Future RCTs comparing LOM and HOM should be performed with greater attention to basic elements of good study design and data analysis.