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.     

Infliximab, but not etanercept, induces IgM anti-double-stranded DNA autoantibodies as main antinuclear reactivity: biologic and clinical implications in autoimmune arthritis

OBJECTIVE: To analyze the clinical and biologic correlates of autoantibody induction during longer-term tumor necrosis factor alpha (TNFalpha) blockade with either the monoclonal antibody infliximab or the soluble receptor etanercept. METHODS: Thirty-four patients with spondylarthropathy (SpA) and 59 patients with rheumatoid arthritis (RA) were treated with infliximab for 2 years. Additionally, 20 patients with SpA were treated with etanercept for 1 year. Sera were blindly analyzed for antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA) antibodies, anti-extractable nuclear antigen (anti-ENA) antibodies, and antihistone, anti-nucleosome, and anticardiolipin antibodies (aCL). The anti-dsDNA antibodies were isotyped. RESULTS: High numbers of infliximab-treated patients with SpA or RA had newly induced ANAs (61.8% and 40.7%, respectively) and anti-dsDNA antibodies (70.6% and 49.2%, respectively) after 1 year, but no further increase between year 1 and year 2 was observed. In contrast, induction of ANAs and anti-dsDNA antibodies was observed only occasionally in the etanercept-treated patients with SpA (10% of patients each). Isotyping revealed almost exclusively IgM or IgM/IgA anti-dsDNA antibodies, which disappeared upon interruption of treatment. Neither infliximab nor etanercept induced other lupus-related reactivities such as anti-ENA antibodies, antihistone antibodies, or anti-nucleosome antibodies, and no clinically relevant lupus-like symptoms were observed. Similarly, infliximab but not etanercept selectively increased IgM but not IgG aCL titers. CONCLUSION: The prominent ANA and anti-dsDNA autoantibody response is not a pure class effect of TNFalpha blockers, is largely restricted to short-term IgM responses, and is not associated with other serologic or clinical signs of lupus. Similar findings with aCL suggest that modulation of humoral immunity may be a more general feature of infliximab treatment.     

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.     

Caged-in: Successful percutaneous closure of left atrial appendage with Watchman-FLX in the presence of proximal thrombus

Percutaneous mechanical closure of the left atrial appendage (LAA) is a valuable stroke prevention strategy in patients with atrial fibrillation and contraindication to oral anticoagulation. LAA thrombus is a common finding in patients with atrial fibrillation and frequently fails to resolve despite therapeutic anticoagulation. In this scenario, LAA occlusion device implant is generally discouraged due to the high risk of thrombus dislodgement and embolization; however, alternative management options are limited. We report the first case of a successful LAA occlusion device (Watchman-FLX) implant in the presence of a proximal thrombus.     

Ankylosing spondylitis and bowel disease

Clinical studies indicate an important role for bowel inflammation in ankylosing spondylitis and other spondyloarthropathies whereby two different aspects have to be considered. First, the gut inflammation is clinically and histologically closely related to Crohn's disease. Recent data on subclinical immune alterations confirm this relationship and suggest that spondyloarthropathy is a unique human model for studying early Crohn's disease. Second, bowel and peripheral joint inflammation are clinically, histologically and pathogenetically linked. The most important clinical implication of these observations is that targeted therapies for Crohn's disease could also be effective for intestinal as well as extra-intestinal disease manifestations in spondyloarthropathy, as evidenced by the recent studies on TNF-alpha blockade. Unravelling the gut-synovium axis in spondyloarthopathy could also contribute to the identification of new therapeutic targets. Finally, assessment of subclinical gut inflammation by histology, serology and genetics could contribute to the stratification of individual patients in subgroups with an optimal response to specific therapeutic interventions.     

Neuroleptic malignant syndrome in Parkinson's disease after withdrawal or alteration of dopaminergic therapy.

Neuroleptic malignant syndrome is characterized by altered consciousness, fever, extrapyramidal signs, autonomic instability, elevated creatine kinase level, and leukocytosis. Although originally described in patients receiving neuroleptic drugs, this syndrome may also occur in patients with Parkinson's disease during withdrawal or reduction of levodopa therapy or other dopaminergic drug therapy. We have encountered three cases of neuroleptic malignant syndrome related to withdrawal of levodopa therapy. These cases illustrate the variety of circumstances in which alteration of therapy with dopaminergic drugs can cause this syndrome and the relative unfamiliarity of the neuroleptic malignant syndrome-levodopa relationship among physicians who do not treat large numbers of patients with Parkinson's disease. An understanding of the role of brain dopamine in the pathogenesis of neuroleptic malignant syndrome and an appreciation of the great variety of drugs whose manipulation can result in this potentially fatal syndrome will aid its proper and timely recognition, especially when the offending pharmacologic manipulation does not involve neuroleptic drugs.     

Acute suppression of muscle sympathetic nerve activity by hydrocortisone in humans

In the present study, we examined the acute influence of hydrocortisone on human sympathetic nerve activity and cardiovascular parameters. Muscle sympathetic nerve activity (MSA), heart rate, and blood pressure were monitored in 8 healthy subjects (20 to 37 years old) before and after a bolus injection of 50 mg hydrocortisone followed by a continuous infusion at 50 mg/h during a period of 3 hours in a placebo-controlled, double-blind, crossover protocol. Recordings were performed at rest and during repeated transient sympathoexcitation induced by voluntary apneas. Resting MSA and endogenous serum cortisol concentrations were also measured in a larger study group (49 experiments, 25 subjects). During the experimental period, MSA burst number increased by 56% from the control level in the placebo group. In contrast, MSA was suppressed by 25% at the end of the hydrocortisone infusion, resulting in a significant treatment effect (P<0.05). In addition, sympathoexcitation during apnea was significantly reduced with hydrocortisone after 180 minutes. In parallel with the sympathetic outflow, blood pressure decreased in the hydrocortisone-treated group, whereas it rose in the placebo group (P<0.05 between groups). No correlation was found between basal MSA and basal cortisol levels. Our results indicate that pharmacological doses of hydrocortisone acutely influence MSA responses to short- and long-lasting environmental stimuli, whereas basal native cortisol levels do not appear to be tonically involved in the regulation of resting MSA. The suppressive hydrocortisone effect is most likely induced via supraspinal autonomic centers and cannot be explained by peripheral steroid mechanisms. The effect of elevated corticosteroid levels on sympathetic nerve discharge may be an important mechanism in cardiovascular adaptations to stress.     

The stress protein BiP is overexpressed and is a major B and T cell target in rheumatoid arthritis

OBJECTIVE: The ubiquitously expressed intracellular protein formerly designated p68 has been identified as autoantigen at both the antibody and the T cell level in rheumatoid arthritis (RA). METHODS: We used 2 independent approaches, Edman degradation and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry, to characterize p68, and we compared its features with those of the endoplasmic reticulum stress protein BiP. RESULTS: In synovial sections from RA patients, BiP was highly overexpressed as compared with control sections. Under in vitro stress conditions, BiP was found to translocate to the nucleus and the cell surface. BiP-specific autoantibodies were present in 63% of 400 RA patients, in 7% of 200 patients with other rheumatic diseases, and in none of the healthy subjects. Thus, BiP-specific autoantibodies represent a new diagnostic marker in RA. Furthermore, we found that BiP-specific T cell reactivity was altered in RA. In healthy individuals and patients with other rheumatic diseases, BiP-reactive T cells were undetectable. In RA, overt T cell reactivity to BiP was observed or could be induced by specifically blocking antigen presentation to potentially regulatory T cells. CONCLUSION: Since overexpression of BiP has been shown to decrease the sensitivity of cells to killing by cytotoxic T cells, BiP overexpression and BiP-specific autoimmunity may be involved in the pathogenesis of RA.