Do cancer patients fully understand clinical trial participation? A pilot study to assess informed consent and patient expectations

Background. Accepted practices of informed consent often result in suboptimal patient understanding of research studies.Methods. This pilot study aimed to assess trial-specific tailored materials, compared to a widely used generic booklet about clinical trials, randomly assigned to 118 candidates for cancer clinical trials. Study outcomes were: satisfaction with decision-making; satisfaction with materials; and subjective understanding of the clinical trial.Results. There were no major differences between groups. Participants rated tailored materials higher as a useful reference.Conclusions. Trial-specific materials hold utility for reference during clinical trials. Studies of informed consent are feasible, although important factors limit research.     

An uncommon cause of acute right ventricular failure and high mixed venous oxygen saturation

Ruptured sinus of Valsalva aneurysms are rare. We report a case in which the usual clinical manifestations were not present and the patient was initially treated as an acute pulmonary embolus. Despite three negative echocardiograms an intra-cardiac shunt was suspected because of a persistently elevated mixed venous oxygen saturation. Cardiac catheterisation confirmed the diagnosis. Surgical repair was performed and post operative recovery was uneventful.     

Amnesia-reversal activity of a series of cyclic imides

A series of dihydro-1H-pyrrolizine-3,5(2H,6H)-diones were synthesized and evaluated for their ability to reverse electroconvulsive shock (ECS) induced amnesia in mice. Among the structure-activity relationships explored were the effects of ring size, the presence of heteroatoms (sulfur) in the ring system, and the introduction of alkyl substituents. The optimal ring size for the bicyclic system was 5.5 with dihydro-1H-pyrrolizine-3,5(2H,6H)-dione (3), although some activity was present in the corresponding 5.6 [hexahydro-3,5-indolizinedione (7)] and 6.6 [tetrahydro-2H-quinolizine-4,6(3H,7H)-dione (9)] analogues. Replacement of the C-1 carbon atom in compound 3 with a sulfur [dihydropyrrolo[2,1-b]thiazole-3,5(2H,6H)-dione (10)] abolished activity, and the introduction of methyl groups resulted in poorer biological profiles except when the substitution was made at the 7a position [dihydro-7a-methyl-1H-pyrrolizine-3,5(2H,6H)-dione (4)]. In several instances, hydrolysis of the parent bicyclic compound was carried out to furnish the corresponding lactam acids, which were further derivatized. Several exhibited interesting activity, especially the 5-oxo-2-pyrrolidinepropanoic acid derivatives such as 5-oxo-2-pyrrolidinepropanoic acid (12), 5-oxo-2-pyrrolidinepropanoic acid phenylmethyl ester (17), 5-oxo-2-pyrrolidinepropanoic acid (3-chlorophenyl)methyl ester (20), N-4-pyridyl-5-oxo-2-pyrrolidinepropanoic acid amide (25), and N-(2,6-dimethylphenyl)-5-oxo-2-pyrrolidinepropanoic acid amide (27). Compound 3 (CI-911; rolziracetam) was also observed to improve performance on a delayed-response task in aged rhesus monkeys and was selected for evaluation in cognitively impaired human subjects on the basis of its biological profile and a wide margin of safety in animals.     

Immunization and protection against malaria during murine pregnancy

Normal and immune mice were evaluated for their ability to resist infection to the rodent malaria parasite, Plasmodium yoelii, during pregnancy. Parasitemia levels were slightly higher and time-to-death shorter in the nonimmunized pregnant group infected with virulent parasites relative to virgin controls. Subinoculation experiments revealed that numerous virulent organisms were present in the placentas of unprotected gravida but were absent from the fetal livers of their conceptuses. It was also found that mice preimmunized with irradiated P. yoelii survived a usually lethal challenge infection during mid-gestation and delivered healthy newborns. Associated with this protection against transplacental spread of parasites was the additional key finding that placental macrophages were as effective as peritoneal exudate cells in phagocytosing parasite derived material in vitro. This murine malaria-pregnancy model should provide new insights on the various factors (virulence, immunogenicity) of microbial infections affecting the fetal-maternal relationship, as well as on the expression of immune effector mechanisms and immunoregulation, during the reproductive process.     

In vitro and in vivo effects of clindamycin on polymorphonuclear leukocyte function.

The effects of clindamycin on polymorphonuclear leukocytes (PMNLs) were evaluated in vitro and in vivo in an experimental model and in immunocompromised patients with and without infection. Chemotaxis, chemiluminescence, and bactericidal capacity were evaluated using PMNLs preincubated with clindamycin in different concentrations. In the three phases of the study, clindamycin at a concentration of 2 mg/L significantly increased PMNL function. In contrast, when higher concentrations were used, PMNL function was not modified and in some cases it was decreased. Our findings suggest that clindamycin, in concentrations of 2 mg/L, positively modifies PMNL function.     

Selective in vitro response of thymus-derived lymphocytes from Treponema pallidum-infected rabbits.

The blastogenic response of nylon wool-separated peripheral-blood lymphocytes from Treponema pallidum-infected rabbits was tested in vitro with mitogens and T. pallidum antigens. The mitogenic response of the enriched T-cell population to concanavalin A and phytohemagglutinin was depressed during the first 3 to 4 weeks of infection, similar to the pattern observed with unfractionated cells. Shortly thereafter, levels of blastogenesis returned to values of uninfected cultures. Enhanced blast transformation was seen immediately when purified T-cells from infected rabbits were exposed in vitro to T. pallidum antigens. Although these relatively high levels of blastogenesis were maintained for the duration of the experiment, cultures of unfractionated lymphocytes from infected rabbits did not exhibit an increased blastogenic response to the same antigen preparation until 3 to 4 weeks after infection. Autologous serum from infected rabbits decreased the lymphocyte response to T. pallidum antigen. The stimulatory effects of anti-immunoglobulin G and lipopolysaccharide on nylon wool-fractionated or unfractionated lymphocytes from both infected and control rabbits were similar throughout the course of infection. During the first 6 weeks of experimental disease, there was a 25 to 31% increase in the number of lymphocytes circulating in the peripheral blood of T. pallidum-infected rabbits.     

Dynamic model of the left ventricle for use in simulation of myocardial perfusion SPECT and gated SPECT

Simulation is a useful tool in cardiac SPECT to assess quantification algorithms. However, simple equation-based models are limited in their ability to simulate realistic heart motion and perfusion. We present a numerical dynamic model of the left ventricle, which allows us to simulate normal and anomalous cardiac cycles, as well as perfusion defects. Bicubic splines were fitted to a number of control points to represent endocardial and epicardial surfaces of the left ventricle. A transformation from each point on the surface to a template of activity was made to represent the myocardial perfusion. Geometry-based and patient-based simulations were performed to illustrate this model. Geometry-based simulations modeled (1) a normal patient, (2) a well-perfused patient with abnormal regional function, (3) an ischaemic patient with abnormal regional function, and (4) a patient study including tracer kinetics. Patient-based simulation consisted of a left ventricle including a realistic shape and motion obtained from a magnetic resonance study. We conclude that this model has the potential to study the influence of several physical parameters and the left ventricle contraction in myocardial perfusion SPECT and gated-SPECT studies.     

Télomérisation radicalarie de monomères N-acryloyl-N-alkylamino esters d'intXérêt biologique

Three methyl 11-(N-acryloyl-N-alkylamino)undecanoates were synthesized from acryloyl chloride and amino-or alkylaminoundecanoic acid esters. These compounds were telomerized in the presence of 1-dodecanethiol as telogen to yield telomers with molecular weight lower than 5000. These telomers are likely to generate HIV inhibitor polyanions with good biocompatibility. The K/K_t value was assessed from a kinetic study of the telomerization reaction. NMR spectroscopy analysis indicates that the polymerization degree DP _n are in good agreement with expectation for methyl 11-(N-acryloylamino)undecanoate. However, they were lower than expected for methyl 11-(N-acryloyl-N-alkylamino)undecanoate.