Guardianship: A medicolegal review for clinicians

Guardianship may pose an ethical dilemma for physicians, who must balance protecting vulnerable patients from potential safety concerns with respecting their autonomy. Older adults with dementia are particularly susceptible to loss of independence and the ability to participate in medical decision making. To have the capacity for medical decision making, individuals must understand relevant information, appreciate their circumstances, demonstrate reasoning, and express a consistent choice free from coercion. Although capacity assessments are usually task-specific, geriatricians and other specialists may be asked to comment on capacity more globally. These determinations may be used to support a Petition for the Appointment of a Guardian of a Legally Incapacitated Adult, the legal process of pursuing guardianship in probate court. Assigned guardians may be known to the incapacitated individual (e.g., a family member or friend) or may be professional guardians with no prior relationship to the ward. Guardians are encouraged to use substituted decision-making, taking into account the ward's previously expressed values and preferences. Although a number of viable alternatives to guardianship exist, numerous systemic barriers may prevent these from being fully explored. The ongoing need for guardianship should be periodically revisited and reassessed. Data about guardians and wards is shockingly sparse, as there are no centralized databases. Laws and regulations for guardianships vary significantly between states. Physicians can serve as important allies and advocates for patients with cognitive impairment at risk of incapacity, can help preserve their autonomy for as long as possible, and ensure appropriate protections are in place if the patient does lose their decision-making ability.     

Effect of plaque debulking and stenting on short- and long-term outcomes after revascularization of chronic total occlusions

OBJECTIVES: We evaluated the effect of plaque burden modification (debulking) on the short- and long-term clinical outcomes of patients with a totally occluded native coronary artery undergoing successful stent deployment. BACKGROUND: Although the primary success rate of crossing a chronic totally occluded coronary artery has improved with the development of new interventional devices and guidewires, the rate of acute reocclusion and restenosis remains high. METHODS: The in-hospital and late clinical outcomes of 150 patients who had undergone successful stenting of 176 chronic total occlusions were analyzed. After successful crossing of the lesion, 44 patients with 50 lesions underwent debulking by laser angioplasty, rotational or directional atherectomy followed by stenting, whereas 106 patients with 126 lesions underwent stent implantation without prior debulking. RESULTS: Baseline clinical and angiographic characteristics were similar for the two groups, except for a higher incidence of left anterior descending coronary artery location and longer lesions in the group of patients who underwent debulking prior to stenting. In-hospital mortality, myocardial infarction and repeat angioplasty rates were similar for the two groups. At a mean 14 +/- 8 months follow-up time, there were no deaths in either group, and target lesion revascularization rates were the same (16.3% in the debulking plus stent group vs. 14.4% in the stent alone group, p = NS). CONCLUSIONS: Treatment of chronic total native coronary artery occlusions with stent deployment with and without lesion modification (debulking) results in a favorable in-hospital outcome, with relatively low long-term target lesion revascularization rates.     

Intravascular brachytherapy for native coronary ostial in-stent restenotic lesions

OBJECTIVES: We analyzed the effects of vascular brachytherapy (VBT) on ostial in-stent restenosis (ISR). BACKGROUND: In-stent restenosis has a high recurrence rate after percutaneous reintervention. The recurrence rate of ostial ISR lesions and the impact of VBT remain unknown. METHODS: We evaluated 133 patients with native coronary ostial ISR from a pooled database of 990 patients enrolled in randomized VBT trials. Independent quantitative angiography was performed at baseline and follow-up in 45 gamma, 27 beta, and 61 placebo patients. RESULTS: Binary restenosis was significantly higher in placebo than radiated patients (75.4% vs. 17.8% in gamma vs. 22.2% in beta, p < 0.0001). The treatment effect of both gamma (odds ratio [OR] 0.06; 95% confidence interval [CI] 0.02 to 0.17) and beta VBT (OR 0.10; 95% CI 0.03 to 0.31) was maintained after controlling for differences in baseline lesion length. Proximal and distal radiation edge restenosis rates were similar among the groups. Vascular brachytherapy of true aorto-ostial lesions (n = 34) was similarly beneficial: restenosis rates of placebo versus gamma or beta patients of 83.3% versus 6.7% versus 28.6%, p = 0.0002. CONCLUSIONS: Conventional treatment of ostial ISR is associated with a recurrence rate of over 75%. Vascular brachytherapy with either gamma or beta sources results in significant and similar reductions in restenosis compared with placebo. Similar benefits after VBT prevail in true aorto-ostial lesions.     

Molecular basis of altered red blood cell membrane properties in Southeast Asian ovalocytosis: role of the mutant band 3 protein in band 3 oligomerization and retention by the membrane skeleton

Southeast Asian ovalocytosis (SAO) is an asymptomatic trait characterized by rigid, poorly deformable red cells that resist invasion by several strains of malaria parasites. The underlying molecular genetic defect involves simple heterozygous state for a mutant band 3 protein, which contains a deletion of amino acids 400 through 408, linked with a Lys 56-to-Glu substitution (band 3-Memphis polymorphism). To elucidate the contribution of the mutant SAO band 3 protein to increased SAO red blood cell (RBC) rigidity, we examined the participation of the mutant SAO band 3 protein in increased band 3 attachment to the skeleton and band 3 oligomerization. We found first that SAO RBC skeletons retained more band 3 than normal cells and that this increased retention preferentially involved the mutant SAO band 3 protein. Second, SAO RBCs contained a higher percentage of band 3 oligomer-ankyrin complexes than normal cells, and these oligomers were preferentially enriched by the mutant SAO protein. At the ultrastructural level, the increased oligomer formation of SAO RBCs was reflected by stacking of band 3-containing intramembrane particles (IMP) into longitudinal strands. The IMP stacking was not reversed by treating SAO RBCs in alkaline pH (pH 11), which is known to weaken ankyrin-band 3 interactions, or by removing the cytoplasmic domain of band 3 from SAO membranes with trypsin. Finally, we found that band 3 protein in intact SAO RBCs exhibited a markedly decreased rotational mobility, presumably reflecting the increased oligomerization and the membrane skeletal association of the SAO band 3 protein. We propose that the mutant SAO band 3 has an increased propensity to form oligomers, which appear as longitudinal strands of IMP and exhibit increased association with membrane skeleton. This band 3 oligomerization underlies the increase in membrane rigidity by precluding membrane skeletal extension, which is necessary for membrane deformation.     

A method for large-scale, high-yield isolation of canine pancreatic islets of Langerhans

A modified collagenase digestion method is described for the isolation of large numbers of islets from the canine pancreas (approximately 3,500 islets/g). The islets isolated by this technique remained viable and released insulin in response to secretagogues after one week of maintenance in tissue culture. Islets isolated from a single donor pancreas were re-implanted into the spleen of the same animal made diabetic by subtotal pancreatectomy and two injections fo streptozotocin. Hyperglycemia was corrected in two dogs and decreased in a third dog followed for 30 days. The islet isolation method is described, therefore, provides a sufficiently large yield of viable islets from one donor pancreas to correct or improve diabetes in a recipient animal.