Evolution in developmental biology: of morphology and molecules.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
E Laufer
Publications and source records attributed to E Laufer.
Sonic hedgehog: a key mediator of anterior-posterior patterning of the limb and dorso-ventral patterning of axial embryonic structures.
Sonic hedgehog is expressed in several sites during embryogenesis which are known to be important in directing the development of neighbouring tissues, including Hensen's node, the notochord, the floor plate of the neural tube, and the posterior of the limb bud. A unity in signalling mechanisms utilized by these inducers was first indicated because they all can provide a source of limb polarizing activity, assayed by grafting into the anterior of a limb bud. The hypothesis that they share a common signal is substantiated by the fact that they all express Sonic. Moreover, ectopic expression of Sonic in vivo suggests that it is responsible for the polarizing activity of the ZPA and plays an important role in dorso-ventral patterning of the spinal cord. The isolation of Sonic heralds a new era in the investigation of the molecular mechanisms of these key inductive interactions in vertebrate development.
Amino Acid Sequence↗
Sonic hedgehog mediates the polarizing activity of the ZPA.
The zone of polarizing activity (ZPA) is a region at the posterior margin of the limb bud that induces mirror-image duplications when grafted to the anterior of a second limb. We have isolated a vertebrate gene, Sonic hedgehog, related to the Drosophila segment polarity gene hedgehog, which is expressed specifically in the ZPA and in other regions of the embryo, that is capable of polarizing limbs in grafting experiments. Retinoic acid, which can convert anterior limb bud tissue into tissue with polarizing activity, concomitantly induces Sonic hedgehog expression in the anterior limb bud. Implanting cells that express Sonic hedgehog into anterior limb buds is sufficient to cause ZPA-like limb duplications. Like the ZPA, Sonic hedgehog expression leads to the activation of Hox genes. Sonic hedgehog thus appears to function as the signal for antero-posterior patterning in the limb.
Amino Acid Sequence↗
Arterial elastic properties in man: a comparison of echo-Doppler indices of aortic stiffness.
Non-invasive assessment of mechanical properties of the aorta may prove useful in the early detection of atheroma. We have evaluated several of the available echocardiographic indices using ability to detect age-related changes in putatively disease-free vessels as a measure of sensitivity to changes in aortic mechanical properties. Suprasternal imaging was used in 49 healthy non-smoking volunteers to measure minimum and maximum aortic arch diameters. Maximal flow velocities, with corresponding acceleration times and heart periods, were determined in the descending aorta in 24 of these subjects. Blood pressure was recorded non-invasively immediately after the echocardiographic study. Doppler derived measurements of aortic flow acceleration did not relate to age (P greater than 0.05). Three different 2D echo assessments of aortic distensibility, however, all showed a close relationship to age. Ep elastic modulus and Beta index (derived from different stress-strain mechanical relationships) were significantly related to age with r = 0.69 and 0.65 respectively. There were no significant effects of gender or left ventricular systolic function on these relationships. There was a tendency for the relationship between these distensibility indices and age more closely to fit an exponential than a linear relationship. We conclude that 2D echocardiographic assessment of aortic distensibility is able to detect sensitively changes in aortic mechanical properties. Even in the absence of risk factors for cardiovascular disease there is a marked reduction in aortic distensibility with increasing age.
Adult↗
[The central masturbation fantasy].
Explore the source record for details and available documents.
Adolescent↗
Aortic distensibility in patients with isolated hypercholesterolaemia, coronary artery disease, or cardiac transplant.
The stiffness of the thoracic aorta can be assessed non-invasively. If aortic stiffness can be shown to be related to coronary heart disease, perhaps it can be used to identify which patients with hypercholesterolaemia are most likely to have atheromatous changes and thus to be selected for intensive cholesterol-lowering treatment. Hence the distensibility of the transverse aortic arch was measured by echocardiography of the aortic arch in four groups of patients--symptom-free patients with normal serum cholesterol; symptom-free patients with raised serum cholesterol; patients with coronary heart disease (all with raised serum cholesterol), and post-heart-transplant patients. In all groups distensibility fell with age. The regression slope was steeper (p less than 0.05) for patients with known coronary disease than for either of the disease-free groups, and among cardiac transplant recipients there was also a segregation of distensibility values between those with and without atheroma in their native hearts. The results indicate that aortic distensibility might be an indicator of coronary heart disease and that it might be useful in identifying which symptom-free subjects with modest hypercholesterolaemia should be treated aggressively.
Aging↗
Effects of exercise and other nonpharmacological measures on blood pressure and cardiac hypertrophy.
Reversal of left ventricular hypertrophy (LVH) is an important target of antihypertensive therapy. Nonpharmacological approaches such as weight reduction and exercise training have favorable effects on other risk factors. However, there are few data on their effects on LVH. Athletes have eccentric rather than concentric LVH. A 12-month exercise program in 13 unmedicated hypertensive subjects altered LV geometry, reducing LV wall thickness and increasing LV internal diameters (LVID). LV mass was unchanged, and the thickness/radius fell by 9%. Shorter-term studies have shown that the cardiac structural changes with a moderate exercise program occur rapidly and their onset lags only about 2 weeks behind blood pressure (BP) effects. Assessment of weight loss effects on LVH is complicated by the strong relationship between body weight and ventricular wall thickness. LVID, and LV mass. To some extent, this can be overcome by arbitrarily indexing to body surface area or height. The wall thickness/radius ratio is not related to body size. Weight reduction reduces BP and thickness/radius by 10% in controlled trials. Small studies have also reported reduction in LV mass after sodium restriction in hypertensive subjects. Studies with other nonpharmacological measures could make a substantial contribution to knowledge of their efficacy.
Blood Pressure↗
Evidence for a role for the cardiovascular amplifiers in human primary hypertension.
1. Hypertrophy of vascular and cardiac smooth muscle is present in human primary hypertension. The amplifier properties associated with hypertrophy play a major role in maintaining hypertension. 2. Long-term antihypertensive drug therapy causes substantial regression of the structural changes, assessed by the non-autonomic component of vascular resistance, and by left ventricular mass. The latter occurs more slowly. 3. The more complete the reversal of left ventricular hypertrophy, the more slowly hypertension redevelops if long-term antihypertensive therapy is discontinued. 4. Subjects who redevelop hypertension more rapidly tend to have higher cardiac output, suggesting that the cardiac amplifier may play a role in the pathogenesis. 5. Studies of small arteries and of veins from patients with primary hypertension suggest that there may be a general disturbance of vascular smooth muscle function, independent of the mechanical effects of elevated systemic blood pressure.
Antihypertensive Agents↗
Prevalence of cardiac structural and functional abnormalities in untreated primary hypertension.
We examined the prevalence of left ventricular structural and functional abnormalities in previously untreated subjects by performing echocardiography in 89 normal volunteers, 57 patients with established hypertension, and 38 patients with mild or borderline hypertension. We measured left ventricular mass, wall thickness, internal diameter, and wall thickness/radius ratio. Because of intergroup differences in body size, we used covariance analysis to index these variables to a common value of 1.8 m2. No adjustment was needed for the wall thickness/radius ratio. Functional variables determined were fractional shortening and transmitral early/late flow velocity ratio (the latter was standardized by analysis of covariance to age 40 years). The prevalence of left ventricular mass index values more than 2 SD above the mean of the normal group was 30% in the patients with established hypertension and 12-15% in the patients with mild hypertension. Corresponding figures for wall thickness index were 65% and 32% and for the wall thickness/radius ratio 60% and 40%. The prevalence of abnormality in the transmitral flow velocity was 28% in the patients with established hypertension and 12% in the patients with mild hypertension. A multivariate discriminant function that used combined anatomic and functional variables provided the most reliable classification; it was correct in 82% of normal subjects, 65% of patients with established hypertension, and 61% of patients with mild hypertension. The majority of patients with hypertension have cardiac structural or functional abnormalities, or both.
Adolescent↗
Exercise, cardiovascular disease and blood pressure.
The "chronic" effect of exercise on blood pressure has been controversial and the debate has been confused by a large number of studies with inadequate methodology. Recent consistent findings in epidemiological, experimental and longitudinal intervention studies have suggested that a true antihypertensive effect which is independent of confounding effects of sodium intake, weight, etc. is more likely than not. Unlike some other measures of lowering blood pressure such as sodium restriction, alcohol moderation and some drugs, regular exercise is associated with beneficial effects on several risk factors and probably has an independent effect on cardiovascular mortality. The magnitude of the effect in previously sedentary subjects is greater than that of dietary measures which lower blood pressure except for weight reduction in the obese. Long-term effects on blood pressure are supported by evidence of a favourable influence on left ventricular hypertrophy. The mechanisms involved in the antihypertensive effect of exercise are unclear, but sympathetic withdrawal is one factor involved. Present evidence appears sufficient to include regular exercise amongst the useful therapies for hypertension.
Animals↗
Exaggerated atrial natriuretic peptide release during acute exercise in essential hypertension.
The effects of acute exercise on plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), and plasma renin activity (PRA) were studied in 13 patients with previously untreated essential hypertension, and 8 matched normotensive control subjects. Resting levels of ANP and PRA were similar in the two groups, while resting AVP concentrations were 1.4 times higher in hypertensive subjects. Graded exercise was performed on a bicycle ergometer with workload increased each minute until exhaustion (Wmax). Wmax was higher in normal subjects than in hypertensive patients. Blood pressure and heart rate rose more steeply in hypertensive patients. Plasma ANP increased during acute exercise in both groups, but the average increase in hypertensives was substantially greater than in normal subjects (P less than 0.05). The increase in ANP during exercise was greater in hypertensives with left ventricular (LV) hypertrophy, and there was a positive correlation between LV mass and the percentage rise in ANP during exercise (r = 0.56, P less than 0.005). Plasma AVP did not alter during exercise. Plasma renin concentrations showed a small rise during exercise in both groups, which was 16% less in hypertensive subjects (P less than 0.05). The enhancement of ANP release during exercise in hypertensive subjects may reflect both cardiac structural changes and increased redistribution of blood to the cardiopulmonary compartment.
Arginine Vasopressin↗
Echocardiographic measurement of left ventricular hypertrophy in untreated essential hypertension.
The prevalence of left ventricular hypertrophy (LVH) in human essential hypertension is uncertain. Echocardiography was used to calculate left ventricular wall thickness (WT), relative wall thickness (t/r) and left ventricular mass (LVM) in 52 normal subjects, 30 patients with borderline hypertension and 33 untreated patients with essential hypertension. In 52 normal subjects WT was independent of age, sex, BSA, BP or habitual physical activity, but LVM was significantly related to BSA and age. After correction of LVM for age and BSA, 88% of 33 patients with untreated essential hypertension had LVM greater than predicted which identified a larger proportion of hypertensives with LVH than previous studies suggest. Wall thickness measurement alone also indicated that about 80% of newly diagnosed hypertensives have LVH.
Adolescent↗
Simple way to reposition a wandering central venous catheter.
A technique has been devised by which a misplaced central venous catheter can be repositioned in the superior vena cava by using a #2 vascular Fogarty catheter. This technique is easier and more dependable than the J-guide wire technique and spares the patient repeated attempts at subclavian vein cannulation.
Catheterization↗
How hypertension redevelops after cessation of long-term therapy.
Long-term therapy (1.5-27 years, average 7.5 years) was ceased in 11 patients with essential hypertension. The return of supine hypertension during the ensuing 10 weeks was slow and incomplete, contrasting with previous studies when blood pressure (BP) had been lowered for shorter periods. After prolonged therapy in these patients, non-autonomic total peripheral resistance index (TPRI) was near normal, but left ventricular mass index (LVMI) was still high in six of the 11 patients. The latter was directly related to duration of effective treatment of BP and to BP when therapy was stopped. These findings may indicate that with antihypertensive therapy, structural changes in the peripheral vasculature regress more quickly than cardiac hypertrophy.
Adult↗
Adverse interaction between beta-adrenergic blocking drugs and verapamil--report of three cases.
Three patients with ischaemic heart disease developed profound cardiac failure, hypotension and bradycardia during combined therapy with verapamil and beta-adrenergic blocking drugs. This clinical picture resolved completely with cessation of the combined therapy. Baseline left ventricular function, assessed by cardiac catheterisation or nuclear angiography, was normal in two patients and only mildly reduced in the other. Simultaneously administration of beta-adrenergic blocking drugs and verapamil may result in profound adverse interactions and should only be administered with great caution.
Adrenergic beta-Antagonists↗
Surgical treatment of recurrent primary malignant tumor of the left atrium.
A young woman presented with a tumor in the left atrium resembling a left atrial myxoma. After simple excision of the tumor the diagnosis of primary malignant fibrous histiocytoma of the heart was made. A course of radiation therapy was given. Four subsequent recurrences were treated by cardiotomy and resection of the left atrial wall. At the third, fourth, and fifth operations fulguration of the left atrial wall was performed. Subsequent chemotherapy failed to control the tumor. The patient was admitted 6 weeks after the last resection and died. Postmortem examination revealed a large recurrent tumor obstructing the left atrium with no metastases. The clinical course, cardiac catherization data, and postmortem examination are presented. Palliation was achieved by repeated resection of a radiation-resistent primary sarcoma of the heart.
Adult↗
Attempted suicide and self-mutilation in adolescence: some observations from a psychoanalytic research project.
Explore the source record for details and available documents.
Adolescent↗