Cardiovascular physiology-changes with aging

With aging there are changes in the cardiovascular system, which result in alterations in cardiovascular physiology. The changes in cardiovascular physiology must be differentiated from the effects of pathology, such as coronary artery disease, that occur with increasing frequency as age increases. The changes with age occur in everyone but not necessarily at the same rate, therefore accounting for the difference seen in some people between chronologic age and physiologic age. The changes in the cardiovascular system associated with aging are a decrease in elasticity and an increase in stiffness of the arterial system. This results in increased afterload on the left ventricle, an increase in systolic blood pressure, and left ventricular hypertrophy, as well as other changes in the left ventricular wall that prolong relaxation of the left ventricle in diastole. There is a dropout of atrial pacemaker cells resulting in a decrease in intrinsic heart rate. With fibrosis of the cardiac skeleton there is calcification at the base of the aortic valve and damage to the His bundle as it perforates the right fibrous trigone. Finally there is decreased responsiveness toβ adrenergic receptor stimulation, a decreased reactivity to baroreceptors and chemoreceptors, and an increase in circulating catecholamines. These changes set the stage for isolated systolic hypertension, diastolic dysfunction and heart failure, atrioventricular conduction defects, and aortic valve calcification, all diseases seen in the elderly.     

The Minimum Clinically Important Difference of the Patient-rated Wrist Evaluation Score for Patients With Distal Radius Fractures

Background

The Patient-rated Wrist Evaluation (PRWE) is a commonly used instrument in upper extremity surgery and in research. However, to recognize a treatment effect expressed as a change in PRWE, it is important to be aware of the minimum clinically important difference (MCID) and the minimum detectable change (MDC). The MCID of an outcome tool like the PRWE is defined as the smallest change in a score that is likely to be appreciated by a patient as an important change, while the MDC is defined as the smallest amount of change that can be detected by an outcome measure. A numerical change in score that is less than the MCID, even when statistically significant, does not represent a true clinically relevant change. To our knowledge, the MCID and MDC of the PRWE have not been determined in patients with distal radius fractures.

Questions/Purposes

We asked: (1) What is the MCID of the PRWE score for patients with distal radius fractures? (2) What is the MDC of the PRWE?

Methods

Our prospective cohort study included 102 patients with a distal radius fracture and a median age of 59 years (interquartile range [IQR], 48–66 years). All patients completed the PRWE questionnaire during each of two separate visits. At the second visit, patients were asked to indicate the degree of clinical change they appreciated since the previous visit. Accordingly, patients were categorized in two groups: (1) minimally improved or (2) no change. The groups were used to anchor the changes observed in the PRWE score to patients’ perspectives of what was clinically important. We determined the MCID using an anchor-based receiver operator characteristic method. In this context, the change in the PRWE score was considered a diagnostic test, and the anchor (minimally improved or no change as noted by the patients from visit to visit) was the gold standard. The optimal receiver operator characteristic cutoff point calculated with the Youden index reflected the value of the MCID.

Results

In our study, the MCID of the PRWE was 11.5 points. The area under the curve was 0.54 (95% CI, 0.37–0.70) for the pain subscale and 0.71 (95% CI, 0.57−0.85) for the function subscale. We determined the MDC to be 11.0 points.

Conclusions

We determined the MCID of the PRWE score for patients with distal radius fractures using the anchor-based approach and verified that the MDC of the PRWE was sufficiently small to detect our MCID.

Clinical Relevance

We recommend using an improvement on the PRWE of more than 11.5 points as the smallest clinically relevant difference when evaluating the effects of treatments and when performing sample-size calculations on studies of distal radius fractures.     

Comparative effects of catecholamines in cardiac tamponade: Experimental and clinical studies

In experimental cardiac tamponade, catecholamines improve hemodynamic variables. To determine whether hemodynamic changes result in increased blood flow to critical organs, tamponade was produced in nine spontaneously breathing, anesthetized dogs. Infusion of dopamine, isoproterenol or norepinephrine doubled cardiac output, but only norepinephrine increased mean arterial pressure. All catecholamines increased blood flow to the myocardium, but not to the brain or kidney. Isoproterenol caused a significant decrease in the endocardial/epicardial blood flow ratio, which was shown to be due to tachycardia.To determine whether catecholamines increase cardiac output and mean arterial pressure in patients with tamponade, eight patients with tamponade due to neoplasms were studied before therapeutic pericardiocentesis. Cardiac output increased only 50 percent with dopamine and isoproterenol and not at all with norepinephrine. Cardiac filling pressure did not decrease with isoproterenol or dopamine, as in experimental tamponade. Only norepinephrine increased mean arterial pressure.Thus, although catecholamines improve hemodynamics in experimental tamponade, the heart is the only critical organ to which blood flow is improved. The hemodynamic benefits of catecholamine administration to patients may be more limited than previous experimental studies have suggested.     

THE ROLE OF RIBOSOMAL CONFORMATION IN PROTEIN BIOSYNTHESIS: THE STREPTOMYCIN-RIBOSOME INTERACTION

The role played by ribosomal conformation in codon-anticodon recognition has been studied using streptomycin as a probe, inasmuch as streptomycin is known to cause misreading of the genetic code. Changes in ribosomal structure have been followed by the method of hydrogen-tritium exchange. The results show that streptomycin induces two types of change in the hydrogen exchange pattern. At low molar ratios of streptomycin to ribosomes, a stimulation of the hydrogen exchange rate ("loosening" of ribosomal structure) is observed, with a small inhibition of polypeptide synthesis. As the streptomycin: ribosome ratio is increased, a maximum exchange rate is reached, after which the rate decreases ("tightening" of structure); in this region, inhibition of peptide synthesis increases sharply, and misreading of the code begins. None of these effects is observed with streptomycin-resistant ribosomes.