Immuno-stimulating complexes prepared by ethanol injection

This study describes the formulation of immuno-stimulating complexes (ISCOMs) utilising the ethanol injection technique. Cholesterol and phosphatidylcholine were dissolved in ethanol and the resulting solution was rapidly injected into a stirred, aqueous solution of the triterpene-saponin mixture Quil-A. The reversed experiment was also carried out by adding the aqueous Quil-A solution to a solution of cholesterol/phosphatidylcholine dissolved in ethanol. This was done by either rapid injection or dropwise addition of the aqueous Quil-A solution. The colloidal dispersions obtained by ethanol injection and reversed addition were compared with formulations obtained by the dialysis and lipid-film hydration methods. In a further experiment, the preparation of ISCOMs from liposomes as precursor structures was investigated. Transmission electron microscopy was used to analyse the resulting colloidal dispersions. Samples were also compared with respect to homogeneity of obtained particle species. The ethanol injection technique led to formation of ISCOMs in high numbers within 2 h post formulation. The reversed rapid injection resulted in a similar colloidal dispersion, differing from the former mainly due to the presence of some helical micellar structures. The reversed, dropwise addition led to the formation of helices as the predominant colloidal structure. Of the three previously established methods, only dialysis led to the formation of ISCOMs within 48 h. The lipid-film hydration method and the approach using liposomes as precursor structures did not produce ISCOMs under the conditions and within the time periods investigated. However, it is known that dispersions prepared by the hydration method equilibrate towards ISCOMs after longer storage. Ethanol injection and reversed rapid injection are simple, cost-effective and quick methods to produce ISCOMs.     

The Terri Schiavo saga: the making of a tragedy and lessons learned

The recent case of Terri Schiavo has been an important medical, legal, and ethical controversy. However, much of the public discussion of the tragedy has been based on inaccurate information regarding the facts of the case and the actual legal and ethical issues involved. This article reviews the pertinent aspects of the case and the ethical and legal questions raised and highlights the lessons we should learn from this unique story.     

Monitoring recovery after injury: procedures for deriving the optimal test window

Researchers studying the impact of treatments designed to facilitate recovery after neural injury face competing demands. On the one hand, because treatment effects often emerge slowly over days, and because researchers seek evidence of stable long-term effects, it is common practice to observe experimental subjects for many weeks after treatment. On the other hand, the cost of performing studies and the need to evaluate a multitude of alternative treatment procedures requires optimal efficiency, pushing researchers towards shorter test procedures. With these issues in mind, researchers have appeared to derive a test window based on previously published methodologies and inspection of their recovery curves, with testing terminated after the recovery curve reaches asymptote (approaches a slope of 0). An alternative procedure is introduced here that evaluates the stability of the data set over time. Using correlational techniques, researchers can determine whether (1) testing should be continued for additional days; or (2) equivalent statistical power can be achieved in fewer days. This provides a rational decision rule to help researchers balance competing demands. Applying these techniques to a procedure that evaluates the impact of acute treatments on recovery from spinal cord injury, it is shown that equal statistical power can be achieved in half the time, greatly increasing the efficiency with which alternative treatments can be evaluated.     

The behavioral deficit observed following noncontingent shock in spinalized rats is prevented by the protein synthesis inhibitor cycloheximide

Spinalized rats that receive shock when 1 hind limb is extended (contingent shock) exhibit an increase in flexion duration, a simple form of instrumental learning. Rats that receive shock independent of leg position (noncontingent shock) do not exhibit an increase in flexion duration and fail to learn when tested with contingent shock 24 hr later. It appears that noncontingent shock induces an intraspinal modification that inhibits the capacity to learn. The authors propose that the mechanisms that underlie this effect depend on de novo protein synthesis. To evaluate this hypothesis, the authors gave spinalized rats the protein synthesis inhibitor Cycloheximide (CXM) or saline intrathecally prior to, or immediately after, noncontingent shock exposure. Twenty-four hours later, rats were tested with contingent shock. Rats that received the vehicle and noncontingent shock failed to learn. CXM-treated shocked rats learned normally, suggesting that the learning deficit depends on protein synthesis within the spinal cord.     

Treatment planning processes in dental schools

Treatment planning is a critical aspect of clinical education in the dental school curriculum. It is surprising, therefore, that so little attention has been given to this subject in the dental literature. The importance of treatment planning is reinforced in the standards and the tests that clearly present methods and necessity for treatment planning. However, there is minimal evidence about how these treatment planning courses have been evaluated, how they were incorporated into the curriculum, or how they have been integrated into treatment planning in the academic clinical setting. The purpose of this study was to survey and profile current treatment planning processes in U.S. dental schools. A questionnaire consisting of twenty-nine items relating to treatment plan preparation, process, and outcomes was mailed to fifty-four U.S. dental schools. The primary topics included patient assignments, treatment planning, plan sequencing, plan presentation, informed consent, and plan modifications. Forty-seven of the fifty-four U.S. dental schools (87 percent) completed and returned the surveys. Profiling the treatment planning process in dental schools reveals many similarities. Typically, the schools screen patients prior to assignment to students and expect the student diagnostician to complete the planning process as well as comprehensive care. The patient's welfare is the primary determinant of the content of the plan in 92 percent of U.S. dental schools. Secondly, though current accreditation standards are concentrated on competencies, the treatment plans are influenced by quantitative requirements. Third, the plan is usually completed during the second patient visit after screening. Fourth, the approaches vary among the schools when a multidisciplinary or complex treatment plan is appropriate. Some depend on a panel of experts, whereas others do not have interactive planning with specialists. A significant number of schools decentralize treatment planning and delegate part of the plan to disciplines or group practice leaders. Fifth, the treatment plans and treatment risks are presented in accordance with the intent of the accreditation guidelines; however, fewer than half the schools explain the risk of procedures to patients at the time of plan presentation. Finally, plans change frequently, but the modifications are generally considered to be minor.     

A phase II trial of pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone), a novel anti-fibrosing agent, in myelofibrosis with myeloid metaplasia

The anti-fibrotic and cytokine modulatory properties of pirfenidone suggest its usefulness in the treatment of myelofibrosis with myeloid metaplasia (MMM). In a prospective study, 28 patients with MMM were treated with oral pirfenidone. Twelve patients completed 1 year of therapy; 13 were withdrawn because of disease progression and three because of drug intolerance. Only one patient experienced a clinically relevant benefit with respect to anaemia and splenomegaly. The overall lack of clinical benefit correlated with no significant improvement in the bone marrow morphological features of the disease. We conclude that pirfenidone has no significant clinical or biological activity in MMM.