An antibody that facilitates hematopoietic engraftment recognizes CD44

Pretreatment of recipients with the monoclonal antibody (MoAb) S5 facilitates engraftment of bone marrow from mismatched, unrelated donors in the canine transplantation model. In the direct comparisons reported here, the S5 glycoprotein (gp) was found to have structural homology to CD44 that in humans has been implicated in adhesive interactions of one type of effector cell, the lymphocyte. The S5 antigen and gp90Hermes-1 exhibited codistribution on canine peripheral blood cells. Both S5 and Hermes-1 (anti-CD44) MoAbs recognized 90-Kd species in radioimmune precipitations of 125I surface-labeled canine peripheral blood lymphocytes and bone marrow cells. Competitive antibody binding experiments showed that the epitope detected by S5 was distinct from that bound by Hermes-1 but overlapped with those defined by two other known anti-CD44 reagents, IM7 and Hutch-1. Sequential immunoprecipitation with S5 and Hermes-1 indicated that the two antibodies recognize the same or overlapping subsets of membrane gps. Tryptic digestion of S5 and anti-CD44 immunoprecipitates generated two major iodinated peptides of 27 and 35 Kd in both cases, a further indication of structural homology. Similarly, after N-glycanase digestion, S5 and CD44 immunoprecipitates were resolved to a single 68- Kd species. These findings suggest that CD44-mediated adhesive events may affect the fate of transplanted hematopoietic cells. The previous implications of this gp in T-lymphocyte activation and lymphocyte adhesion to endothelium thus provide useful paradigms to analyze its function in the bone marrow transplant setting.     

Tricuspid annulus motion and mitral annulus motion: Anatomical intimacy causing a good correlation?

BACKGROUND:

Echocardiographic evaluation of the heart and its function, especially left ventricular systolic function, has great clinical importance. Systolic function can be measured using several methods, such as the amplitude of motion of the left atrioventricular plane (mitral annulus motion [MAM]) toward the apex during systole. Similarly, right ventricular systolic function can be measured using the motion of the right atrioventricular plane (tricuspid annulus motion [TAM]) toward the apex during systole.

OBJECTIVES:

Because the mitral and tricuspid annuli are situated close to each other in the fibrous skeleton between both ventricles and atria, one might think that a decrease in the amplitude of MAM would be followed by a decrease in the amplitude of TAM. The present study was developed to determinine if this anatomical intimacy causes a good correlation between the amplitudes of TAM and MAM.

METHODS:

Nineteen healthy subjects and 103 consecutive patients were included in the study and examined using echocardiography. The amplitudes of TAM and MAM were measured and the correlation between the amplitudes was calculated.

RESULTS:

In the 103 consecutive patients, a significant but relatively weak positive correlation was found between TAM and MAM amplitudes (Pearson’s correlation coefficient [r]=0.58; P<0.001). In the 19 healthy subjects, no significant correlation was found.

CONCLUSIONS:

Despite the anatomical intimacy of the annuli, the correlation between the amplitudes of TAM and MAM in consecutive patients was rather weak, and there was no correlation in healthy subjects. These findings could be due to anatomical and physiological differences between the right and left ventricles.     

Précising definitions as a way to combat overdiagnosis

Roughly, overdiagnosis (ODx) occurs when people are harmed by receiving diagnoses (often accompanied by interventions) that do not benefit them, usually because the diagnosed conditions do not pose a threat to their health. ODx is a theoretical as well as a practical problem as it relates to definitions of disease. Elsewhere, it has been argued that disease is a vague concept and that this vagueness may contribute to ODx. In response, we develop a stipulative or précising definition of disease, for the specific purpose of decreasing or preventing ODx. We call this disease_ODx, aimed at distinguishing cases where it would be beneficial to identify (and treat the condition) from those where diagnosis is more likely to harm than benefit. A preliminary definition of disease_ODx is that X is a disease_ODx iff there is dysfunction that has a significant risk of causing severe harm. This paper examines the 3 concepts in this definition, using a naturalistic account of function, a Feinbergian account of comparative harm, and a probabilistic understanding of risk. We then test the utility of this approach using examples of clinical conditions that are currently overdiagnosed.     

Repeat percutaneous coronary revascularization: Indications and outcomes in a “Real World” cohort

Objectives : To investigate rates of and reasons for second and subsequent stent procedures in an unselected, “real‐world” population. Background : Repeat stenting is the primary difference reported in clinical trials of alternative revascularization strategies. The incidence, indication, and outcome for repeat stenting in contemporary practice outside the more selective populations of trials and registries has not been described. Method : All patients undergoing a first percutaneous coronary intervention (PCI) procedure with stenting from January 2001 to August 2009 (10,509) from a large UK tertiary referral and district general hospital were identified. Mortality and the incidence, timing, and indication for repeat revascularization in this population were investigated from patient records. Results : Of 10,509 patients undergoing a first PCI and stent implant 23.5% underwent repeat angiography of which 11.2% required repeat PCI and 2% coronary artery bypass grafting (median follow‐up of 3.8 years). A total of 1.3% went on to a third PCI. The commonest indication for repeat stenting was disease progression remote from the original stent (46%) and planned staged PCI (23%); 21% had a stent‐related indication. Functional assessment before repeat stenting was used in one‐third of stable patients. Mortality was 2.5% per annum. Conclusions : In contemporary practice, patients undergoing a first stenting procedure have a low subsequent mortality, and the substantial majority (86.4%) requires no further revascularization over a median 3.8 year follow‐up. For those who do require repeat stenting, this is most commonly at a site remote from the first stent. © 2012 Wiley Periodicals, Inc.