Liposomal 1,25 (OH)2 vitamin D3 compounds block proliferation and induce differentiation in myelomonocytic leukaemia cells

The vitamin D₃ derived hormone 1,25 (OH)₂ vitamin D₃ (1,25 D₃) is able to induce growth arrest and differentiation in myelomonocytic leukaemia cells. In order to allow for specific delivery to leukaemic cells the lipophilic compound was incorporated into the lipid membranes of liposomes. Liposomal 1,25 D₃ reduced proliferation as measured by ³H-thymidine incorporation in HL60 leukaemia cells by up to 60%. When liposomes were prepared at different concentrations of 1,25 D₃ 65% inhibition was achieved at 48 n M . The MC 1288 stereoisomer of 1,25 D₃ was more potent and had the same activity at 48 n M .
The effect of the liposomal compounds was specific to myeloid cells as they reduced proliferation in myelomonocytic HL60, monoblastic U937 and monocytic Mono Mac 6 cells but not in the T-cell lines Jurkat and Molt 4.
The antiproliferative effect of liposomal 1,25 D₃ was associated with an induction of differentiation since treated HL60 cells showed a monocytic morphology, increased expression of CD14 and decreased expression of CD33.
When peripheral blood leukaemic cells from M4 and M5 acute myeloid leukaemia (AML) patients were admixed with liposomal compounds an antiproliferative effect was seen in all five cases, including the two cases where free compounds led to enhanced growth. Liposomal delivery of 1,25 (OH)₂ vitamin D₃ may offer a novel approach to treatment of myelomonocytic leukaemia.     

Dissociation Between Changes in Intramyocardial Function and Left Ventricular Volumes in the Eight Weeks After First Anterior Myocardial Infarction

Objectives. We sought to examine the relation between regional changes in intramyocardial function and global left ventricular (LV) remodeling in the first 8 weeks after reperfused first anterior myocardial infarction (MI).

Background. Because of limitations in imaging methods used to date, this relation has not been thoroughly evaluated.

Methods. We studied 26 patients (21 men, 5 women; mean age 51 years) by magnetic resonance imaging (MRI) on day 5 ± 2 (mean ± SD) and week 8 ± 1 after their first anterior MI. All patients had single-vessel left anterior descending coronary artery disease and although they had received reperfusion therapy, all had regional LV dysfunction and an initial ejection fraction (EF) ≤50%. Short-axis magnetic resonance tagging was performed spanning the LV. Percent intramyocardial circumferential shortening (%S) on a topographic basis, LV mass index, LV end-diastolic volume index (LVEDVI), LV end-systolic volume index and LV ejection fraction (LVEF) were measured.

Results. Left ventricular mass index tended to decrease, whereas the LVEDVI increased from 82 ± 24 to 96 ± 27 ml/m² (p = 0.002). Left ventricular end-systolic volume index remained unchanged, whereas LVEF increased from 39 ± 12% to 45 ± 14% (p = 0.002). Apical %S improved from 9 ± 6% to 13 ± 5% (p < 0.0001), as it did in the midanterior (6 ± 6% to 10 ± 7%, p < 0.02) and midseptal regions (8 ± 7% to 12 ± 6%, p < 0.02). Early dysfunction in remote midinferior and basal lateral regions resolved by 8 weeks. By multivariate analysis, the only significant predictor of an increase in LVEDVI over the study period was peak creatine kinase (p = 0.04).

Conclusions. In the first 8 weeks after a large, reperfused anterior MI, %S improved in the apex, midanterior and midseptal regions and normalized in remote noninfarct-related regions, but LV end-diastolic volumes also increased. This increased LVEDVI correlated with infarct size by peak creatine kinase and was not related to changes in global and regional LV function.     

The effects of an HIV/AIDS educational programme on the anxiety level of nursing students

Acquired immunodeficiency syndrome (AIDS) is a serious disease that has special concern for the health care provider. AIDS has continued to grow despite control efforts. As the disease infectivity period remains lengthy, and the heterosexual population is affected to a greater degree, the level of anxiety has also risen despite educational endeavours. Many fears and anxieties have been associated with AIDS patients by health care workers. The reduction of stress, perceived risk and discomfort following educational efforts have been supported in past research. Educational programmes will need to be given for current health care workers at all levels as well as nursing students. Future nurses must be prepared to meet this challenge. This study was conducted using a convenience sample of nursing students at a university in western United States. Its purpose was to assess any changes that occurred in state anxiety following an educational presentation. Spielberge's State-Trait Anxiety Inventory was used as the measurement instrument. Some anxiety levels were significantly reduced.     

The Environmental Context of Patient Safety and Medical Errors

The environmental context of patient safety and medical errors was explored with specific interest in rural settings. Special attention was paid to unique features of rural: healthcare organizations and their environment that relate to the patient safety issue and medical errors (including the distribution of patients, types of adverse events associated with learning, information flows, triage and transfer decisions, and culture of safety). Relevant organizational theories and strategies fo medical error reduction and prevention in rural health care settings were identified. Financial and technical assistance are needed to support the systematic collection of data from rural hospitals and other entities and to enhance relevant patient safety practices for rural America.     

Resorption rate and biocompatibility characteristics of two polyester ventilation tubes in a guinea pig model

OBJECTIVES: Determine the resorption rate and biocompatibility characteristics of 2 polyester ventilation tubes, and to determine whether soap and water exposure accelerates polyester tube degradation. STUDY DESIGN AND SETTING: 50/50 poly (D, L-lactide-co-glycolide; PLGA-50) and poly (L-lactide; PLA) polymers were placed into the tympanic membranes of Hartley pigmented guinea pigs. Integrity of the tubes was determined by weekly otoscopic examination. Biocompatibility was assessed by comparing auditory brainstem response (ABR) thresholds and by examining tympanic membrane changes following tube resorption. Shah minigrommet ventilation tubes were used as controls. In the second portion of this study, implanted PLGA-50 and PLA tubes were exposed weekly to a mixture of soap and water (1:5) until complete resorption was observed. Biocompatibility was assessed by periodic ABR testing and tympanic membrane examination. RESULTS: The PLA tubes remained in the tympanic membrane for a longer period (63.2 +/- 19.3 days) than the PLGA-50 (18.8 +/- 8.1 days). The tympanic membrane and resorbable tube interface demonstrated equivalent findings for auditory thresholds and tissue histopathology at the implant site compared to nonresorbable controls. The resorption behavior was not altered by exposure to soap and water. Tympanic membranes of all animals following tube degradation and soap water exposure were intact with minimal scarring and no signs of persistent foreign body response. The histological analysis showed that implantation of resorbable tubes was not accompanied by secondary infection with otorrhea through the tube, did not result in a permanent perforation or dislocation of the tube into the middle ear cavity, and was not followed by excess tympanosclerosis or localized or diffuse membrane atrophy. CONCLUSIONS AND SIGNIFICANCE: Resorbable polyester pressure equalization tubes demonstrate predictable resorption behavior and similar biocompatibility characteristics when compared with nonresorbable Shah minigrommet ventilation tubes. Exposure to soap water does not accelerate polyester tube degradation nor change the host tissue response during the indwelling period or after complete resorption. The data suggests that resorbable ventilation tubes are substantially equivalent to other FDA-approved tympanostomy devices with regard to safety and biocompatibility in the guinea pig model examined and may provide improved clinical performance by combining this approach with sustained release technology. EBM RATING: B-2.     

Changes in treatment of advanced laryngeal cancer 1985-2001

OBJECTIVE: In 1991, a randomized study was published and demonstrated that use of nonsurgical therapy (chemoradiation) provided similar survival to total laryngectomy (the gold standard) for patients with advanced-stage laryngeal cancer. The purpose of this study was to assess how treatment of advanced laryngeal cancer was influenced by such developments in non-surgical therapy. STUDY DESIGN: Patterns of care study using National Cancer Database (1985-2001). RESULTS: The percentage of advanced-stage patients treated with chemoradiation increased from 8.3% to 20.8% while the proportion treated with radiation alone decreased from 38.9% to 23.0%. Use of chemoradiation increased at a significantly faster rate after the 1991 publication at both community cancer centers and teaching research facilities. The use of total laryngectomy decreased slightly during this period. CONCLUSIONS: The use of chemoradiation increased after the 1991 publication. It was impossible to determine from the NCDB whether additional patients who could benefit from chemo-RT were not offered or did not complete this treatment option. We recommend that treatment recommendations discussed at tumor boards be recorded in cancer registries.