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.     

Regional and systemic prophylaxis with teicoplanin in monolateral and bilateral total knee replacement procedures: study of pharmacokinetics and tissue penetration.

Twenty-four patients undergoing monolateral or bilateral total knee replacement (TKR) procedures were randomized to receive teicoplanin (T) either systemically or regionally. Subjects scheduled for systemic prophylaxis and undergoing monolateral (six patients) or bilateral (five patients) TKR received a single 800-mg dose of T in 100 ml of saline as a 5-min infusion into a forearm vein 2.5 h before surgery. For regional prophylaxis, patients undergoing monolateral surgery (eight subjects) received 400 mg of T in 100 ml of saline as a 5-min infusion into a foot vein of the leg to be operated on immediately after the tourniquet was inflated. For the five patients scheduled for bilateral operation and regional prophylaxis, the administration of T was also repeated for the second knee operation. The tourniquet, as the standard TKR surgical technique, was inflated to 400 mm Hg (c. 50 kPa) in all 24 patients immediately before the beginning of surgery and kept in place for the duration of the operation. Samples of serum, bone, skin, synovia, and subcutaneous tissue were collected at timed intervals during surgery. They were microbiologically assayed for T by using Bacillus subtilis as the test organism. Overall, the mean T concentrations obtained with regional route prophylaxis were found to be 2 to 10 times higher than those achieved following systemic prophylaxis. Moreover, peak levels in different tissues after regional prophylaxis were significantly higher (P < 0.05). None of the patients experienced adverse effects due to regional or systemic T administration; no prosthetic or wound infections were observed in the follow-up period (from 12 to 26 months).     

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.     

Systemic Trans- and Postoperative Evaluations of Patients Undergoing Dental Implant Surgery

OBJECTIVE:

The aims of this study were to examine the trans- and postoperative systemic characteristics of patients undergoing dental implant surgery and to investigate the relationship between pre- and post- surgery anxiety levels.

MATERIAL AND METHODS:

Thirty-nine patients were analyzed in 3 call centers to determine anxiety levels, pain levels, and preoperative and postoperative histories using the State–Trait (STAI) questionnaire.

RESULTS:

A total of 93 dental implants were installed, with a success rate of 100%. The most frequently reported systemic disease was hypertension. There was a significantly higher rate of effective clamping (torque) to the mandibular bone than to the maxillary bone. The association between postoperative surgical complications and longer operative time was not significant, but there was a significant correlation between the alteration of mouth opening and daily routine activities and a significant decrease in anxiety levels between the day of surgery and the postoperative time point (p=0.006).

CONCLUSION:

A longer surgical time was associated with surgery-related complications and with a higher anxiety index on the preoperative evaluation.