Physiologic tailoring of therapy for resistant hypertension: 20 years\u27 experience with stimulated renin profiling

Renin profiling to assist in management of hypertension was first proposed about 27 years ago. However, it is still not widely used, perhaps because it was initially emphasized for management of primary hypertension, which is usually relatively easy to manage. Our experience in more than 4000 patients with referral hypertension screened since 1977 suggests that this approach, which I call \u27Physiologic Tailoring\u27 of management, is particularly helpful in resistant hypertension, especialiy in cases of adrenocortical hypertension. Three cases of resistant hypertension spanning the 20 years of the clinic\u27s existence, are presented to illustrate the contribution of renin profiling to the diagnosis and management of adrenocortical hypertension. It is suggested that adrenocortical hypertension is virtually always due to bilateral hyperplasia and that true curable solitary nodules may not exist if patients are followed long enough; and that adrenocortical hyperplasia is much more common in blacks and patients of African origin. A study to test the cost-utility of a renin-based algorithm for management of resistant hypertension is recommended

Effects of antihypertensive drugs on blood velocity: implications for prevention of cerebral vascular disease

The treatment of high blood pressure prevents death from congestive heart failure, hypertensive nephropathy, and encephalopathy, and strokes from cerebral arteriolar disease (lacunes, hemorrhage from microaneurysms). However, atherosclerosis, manifested as coronary artery disease, is just as frequent a cause of death in well controlled hypertensives as in poorly controlled patients. Increasing evidence suggests that increased blood velocity, by causing turbulence and high shear rates at the endothelial surface of arteries, may be important in the pathogenesis of atherosclerosis. Turbulence has been observed in cerebral berry aneurysms. In order to measure the effects of antihypertensive agents on blood velocity, a new method of analyzing Doppler ultrasound velocity recordings has been developed. Studies in Rhesus monkeys show the following: In doses which reduce diastolic pressure by 13 to 28%, propranolol decreased mean blood velocity (MV) by 17%, clonidine decreased MV by 14%, while methyldopa increased MV by 12%, and hydralazine increased MV by 52% (p \u3c .00001). It is hypothesized that enlargement of berry aneurysms, the progression of cerebral atherosclerosis, and embolism from carotid lesions might all be decreased by the selection of antihypertensive agents which decrease blood velocity

Musculoskeletal Geometry, Muscle Architecture and Functional Specialisations of the Mouse Hindlimb

Mice are one of the most commonly used laboratory animals, with an extensive array of disease models in existence, including for many neuromuscular diseases. The hindlimb is of particular interest due to several close muscle analogues/homologues to humans and other species. A detailed anatomical study describing the adult morphology is lacking, however. This study describes in detail the musculoskeletal geometry and skeletal muscle architecture of the mouse hindlimb and pelvis, determining the extent to which the muscles are adapted for their function, as inferred from their architecture. Using I2KI enhanced microCT scanning and digital segmentation, it was possible to identify 39 distinct muscles of the hindlimb and pelvis belonging to nine functional groups. The architecture of each of these muscles was determined through microdissections, revealing strong architectural specialisations between the functional groups. The hip extensors and hip adductors showed significantly stronger adaptations towards high contraction velocities and joint control relative to the distal functional groups, which exhibited larger physiological cross sectional areas and longer tendons, adaptations for high force output and elastic energy savings. These results suggest that a proximo-distal gradient in muscle architecture exists in the mouse hindlimb. Such a gradient has been purported to function in aiding locomotor stability and efficiency. The data presented here will be especially valuable to any research with a focus on the architecture or gross anatomy of the mouse hindlimb and pelvis musculature, but also of use to anyone interested in the functional significance of muscle design in relation to quadrupedal locomotion

Morphology and the gradient of a symmetric potential predicts gait transitions of dogs

Gaits and gait transitions play a central role in the movement of animals. Symmetry is thought to govern the structure of the nervous system, and constrain the limb motions of quadrupeds. We quantify the symmetry of dog gaits with respect to combinations of bilateral, fore-aft, and spatio-temporal symmetry groups. We tested the ability of symmetries to model motion capture data of dogs walking, trotting and transitioning between those gaits. Fully symmetric models performed comparably to asymmetric with only a 22% increase in the residual sum of squares and only one-quarter of the parameters. This required adding a spatio-temporal shift representing a lag between fore and hind limbs. Without this shift, the symmetric model residual sum of squares was 1700% larger. This shift is related to (linear regression, n = 5, p = 0.0328) dog morphology. That this symmetry is respected throughout the gaits and transitions indicates that it generalizes outside a single gait. We propose that relative phasing of limb motions can be described by an interaction potential with a symmetric structure. This approach can be extended to the study of interaction of neurodynamic and kinematic variables, providing a system-level model that couples neuronal central pattern generator networks and mechanical models