Search

Macitentan is a safe and effective substance for treatment of adults with pulmonary arterial hypertension. Data on its use in paediatric patients are limited. In this single-centre prospective study, we report on our experience with macitentan in children focusing on applicability and practical aspects. Between December 2014 and July 2018, macitentan was introduced to paediatric patients according to a dosing protocol adjusted to body weight. Blood pressure, heart rate, saturation and clinical symptoms were recorded daily during introduction. Liver function parameters and haemoglobin levels were measured at baseline, four weeks and three months after initiation and after one year of treatment. Twenty-four patients (14 male, 10 female) were enrolled for treatment with macitentan. The mean age was 10.7 ± 7.6 years (range: 0.1 year–23 years). Fifteen out of 24 patients were World Health Organization functional class (FC) II, 7 patients in FC III and 2 patients in FC IV. Twenty out of 24 patients (83%) received additional advanced therapy with sildenafil and/or prostacyclines. We had two early discontinuations because of clinical relevant oedema. In the remaining 22 patients, macitentan was well tolerated. Liver function parameters and blood count levels remained stable during the observational time. The introduction of macitentan was feasible and mostly well tolerated in paediatric patients. Special attention should be paid to oedema during introduction of the drug. To the best of our knowledge, this is the first study to report on its applicability in infants and children. However, larger prospective trials are warranted to verify these preliminary findings.

Background and Purpose— Cerebral microbleed (CMB) location (deep versus strictly lobar) may elucidate underlying pathology with deep CMBs being more associated with hypertensive vascular disease and lobar CMBs being more associated with cerebral amyloid angiopathy. The objective of this study was to determine whether neuroimaging signs of vascular disease and Alzheimer pathology are associated with different types of CMBs. Methods— Among 1677 nondemented ARIC (Atherosclerosis Risk in Communities) participants (mean age=76±5 years; 40% men; 26% black) with 3-Tesla MRI scans at the fifth examination (2011–2013), we fit multinomial logistic regression models to quantify relationships of brain volumes (Alzheimer disease signature regions, total gray matter, frontal gray matter, and white matter hyperintensity volumes), infarct frequencies (lacunar, nonlacunar, and total), and apolipoprotein E (number of ε4 alleles) with CMB location (none, deep/mixed, or strictly lobar CMBs). Models were weighted for the sample selection scheme and adjusted for age, sex, education, hypertension, ever smoking status, diabetes mellitus, race site membership, and estimated intracranial volume (brain volume models only). Results— Deep/mixed and strictly lobar CMBs had prevalences of 8% and 16%, respectively. Larger white matter hyperintensity burden, greater total infarct frequency, smaller frontal volumes (in women only), and smaller total gray matter volume were associated with greater risk of both deep and lobar CMBs relative to no CMBs. Greater white matter hyperintensity volume was also associated with greater risk of deep relative to lobar CMBs. Higher lacunar and nonlacunar infarct frequencies were associated with higher risk of deep CMBs, whereas smaller Alzheimer disease signature region volume and apolipoprotein E ε4 homozygosity were associated with greater risk of lobar CMBs. Conclusions— CMBs are a common vascular pathology in the elderly. Markers of hypertensive small-vessel disease may contribute to deep CMBs while cerebral amyloid angiopathy may drive development of lobar CMBs.

We provide a practical approach on the initial assessment and diagnostic work-up of children and adolescents with pulmonary hypertension (PH). Transthoracic echocardiography (TTE) often serves as initial study tool before invasive cardiac catheterization. Misinterpretation of TTE variables may lead to missed or delayed diagnosis with devastating consequences, or unnecessary invasive diagnostics that have inherited risks. In addition to clinical and biochemical markers, serial examination of patients with PH using a standardized TTE approach, determining conventional and novel echocardiographic variables, may allow early diagnosis and treatment in paediatric PH. Cardiac magnetic resonance imaging and computed tomography represent important non-invasive imaging modalities, that together with TTE may enable comprehensive assessment of ventricular function and pulmonary hemodynamics. Invasive assessment of haemodynamics (ventricular, pulmonary) and testing of acute vasoreactivity in the catheterization laboratory is still the gold standard for the diagnosis of PH and pulmonary hypertensive vascular disease (PHVD) in children and for the initiation of specific PH therapy. We suggest the regular assessment of prognostic TTE variables as part of a standardized approach for initial diagnosis of children with PH. Overreliance on any single TTE variable should be avoided as it detracts from the overall diagnostic potential of a standardized TTE examination for PH.

Cardiac catheterization is important in the diagnosis and risk stratification of pulmonary hypertensive vascular disease (PHVD) in children. Acute vasoreactivity testing provides key information about management, prognosis, therapeutic strategies, and efficacy. Data obtained at cardiac catheterization continue to play an important role in determining the surgical options for children with congenital heart disease and clinical evidence of increased pulmonary vascular resistance. The Pediatric and Congenital Heart Disease Task Forces of the Pulmonary Vascular Research Institute met to develop a consensus statement regarding indications for, conduct of, acute vasoreactivity testing with, and pitfalls and risks of cardiac catheterization in children with PHVD. This document contains the essentials of those discussions to provide a rationale for the hemodynamic assessment by cardiac catheterization of children with PHVD.

Pulmonary hypertension in children is a disease with very high morbidity and mortality if left untreated. There has been increasing recognition of the need to appropriately classify and categorize childhood pulmonary hypertension with modifications in the 5th World Symposium classification and the Pulmonary Vascular Research Institute categorization of pulmonary hypertensive vascular disease into 10 groups at the Panama conference. There have also been efforts to appropriately describe the functional class pertinent to various age groups, and most recently, the American Heart Association and American Thoracic Society Guidelines on Pediatric Pulmonary Hypertension were published to appropriately diagnose and manage children with pulmonary hypertension. In this chapter, the authors discuss the evolution of various classifications, epidemiology, natural history, pathobiology, clinical presentation, diagnostic testing, and management principles for pediatric pulmonary hypertension.

Introduction: Cerebral microbleed (CMB) location may predict underlying pathology. Deep CMBs are more associated with hypertensive vascular disease, while lobar CMBs are more associated with cerebral amyloid angiopathy (CAA). The objective of this study was to determine the neuroimaging pathology associated with CMBs. Methods: We analyzed 1,831 nondemented ARIC participants (mean age=76.3 ±5.3 years, 40% male, 27% black) with 3T MRI scans at the fifth exam (2011-13). We fit multinomial logistic regression models to assess the effect of brain volumes (AD signature region atrophy, total gray matter, frontal, and log 2 -transformed white matter hyperintensities (WMH) volume), infarct frequencies (lacunar, non-lacunar, and total), and APOE (number of ε4 alleles) on CMB location (no, any deep, or lobar only CMBs). Models were weighted for the sample selection scheme and adjusted for age, male, education, hypertension, ever smoking status, diabetes, race-site membership, and estimated intracranial volume (brain volume models only). Results: The frequency of CMBs was 24.1%. A larger WMH volume, greater total infarct frequency, and smaller total grey volume increased the relative risks (RR) of both deep and lobar CMBs compared to no CMBs; increasing the WMH volume also increased the RR of deep to lobar CMBs. Additional lacunar infarcts increased the RR of deep compared to no CMBs, whereas AD signature region atrophy and APOE ε4 homozygosity increased the RR of lobar CMBs. Conclusion: CMBs are a common vascular pathology in the elderly. Deep CMB presence is associated with MRI features of hypertensive small vessel disease, while lobar CMB presence is associated with MRI features of CAA and Alzheimer’s disease.

Pulmonary hypertensive vascular disease (PHVD) is characterized by progressive narrowing of pulmonary arterioles, abnormally high pulmonary vascular resistance (PVR), right ventricular (RV) dysfunction, left ventricular (LV) compression, and death in ≈25% to 60% of patients with pulmonary arterial hypertension (PAH) 5 years after diagnosis.1,2 Meanwhile, consensus statements have been developed in North America and Europe specifically to guide the clinical care of children with pulmonary hypertension (PH).3,4 The challenges in the diagnosis5 and treatment6 of pediatric PH include early detection in the absence of specific symptoms or biomarkers, the complexity of the underlying etiologies, broad comorbidities, genetic syndromes, and the paucity of pediatric trial data to support and guide clinical management.7,8 See Article by Burkett et al The estimated prevalence of PAH is 2 to 16 cases per million children.9–11 Children diagnosed with PAH associated with congenital heart disease and those with idiopathic/heritable PAH have a similar 5-year mortality in North America (29% versus 25%; REVEAL registry).1 Untreated idiopathic PAH results in death within 2 to 3 years in adults and within 1 year after diagnosis in children,12 indicating that early diagnosis and early, sufficient (probably combinatory) PAH-targeted therapy is paramount. In children, PH is evident with a mean PA pressure ≥25 mm Hg when over 3 months of age at sea level.5,13 The term pediatric PAH (ie, group 1 PH) defines a subgroup of precapillary PH with an end-expiratory pulmonary artery wedge pressure (PAWP) 3 WU m2. In 2011, the Pulmonary Vascular Research Institute introduced the disease entity pediatric PHVD (mean PA pressure ≥25 …

A cohort of white males who had attended elementary schools in Hagerstown, Md., between 1923 and 1928, and whose height-weight records for those years were available, was examined during 1961-63. A study of their childhood relative weight at ages 9-13, and of their adult relative weight 35-40 years later, was made in relation to selected physiological variables and diagnosed morbidity.Essential findings were as follows: Childhood relative weight at ages 9-13 had no significant relationship to adult levels of fasting blood sugar, serum cholesterol, beta-lipoprotein, or blood pressure, or to cardiovascular renal disease.Childhood relative weight at ages 9-13 was significantly related to hypertensive vascular disease. The below average weight group experienced a higher prevalence than observed in either average or moderately overweight childhood groups.Approximately 30 percent of the below average weight children became average weight adults and 21 percent became overweight adults. Of the average weight children, approximately 40 percent became overweight adults. Overweight children tended to remain overweight as adults.Adult relative weight of the same cohort, viewed 35-40 years later, was significantly associated with fasting blood sugar, beta-lipoprotein, and systolic and diastolic blood pressure. Elevated levels of each of these variables occurred with greater frequency in the overweight child.Adult relative weight was significantly associated with hypertensive vascular disease and cardiovascular renal disease; the higher prevalence occurred in the overweight adults.The highest risk for hypertensive vascular and cardiovascular renal disease was associated with the persons who acquired their overweight status as adults. The higher prevalence of these diseases among the overweight adults was largely attributable to the adults who moved from a below average childhood weight category to an overweight adult group. The moderately or markedly overweight adults who was similarly classified as a child did not appear to be at greater risk than the average weight adult who had been an average weight child.

Damaged mesenteric arterioles from rats made hypertensive with intravenous injections of angiotensin showed a production of Van Gieson positive connective tissue which was proportional to the infiltration of mononuclear cells (lymphocytes and monocytes). Rats treated with antithymocyte serum before hypertensive damage of the arterioles showed no or only a very sparse cellular reaction and corresponding to this decreased cellular reaction no production of connective tissue fibrils was observed. As some fibroblast-like cells contained carbon particles in their cytoplasm it is highly probable that they were transformed lymphocytes and/or monocytes, which had phagocytized carbon particles from the hypertensively damaged arterioles.

Following the induction of three different forms of experimental hypertension, deposits of amyloid were found in the spleens of 5-20 per cent of the mice late in the course of the hypertension, Amyloidosis was found in nude (with genetical aplasia of the thymus) as well as in haired (normal) mice. The highest frequency of amyloidosis was observed in mice with hypertension due to partial infarction of one kidney and contralateral nephrectomy. The hypertensive vascular disease, involving lesion of the vessels and of the organs supplied by the affected vessels, is believed, to represent a stimulus for the reticulo endothelial system (RES) with development of amyloidosis as a secondary event.

NZB nice spontaneously develop a high blood pressure and hypertensive vascular disease in the heart and the kidney. Treatment with cyclophosphamide decreased the level of blood pressure; congenital athymic nude NZB mice failed to develop a high blood pressure. These findings suggest that thymus and the thymus-dependent immune reactions have pathogenic importance for the spontaneous hypertension in these mice.

It is demonstrated that an inflammatory mononuclear cellular infiltration into hypertensively damaged arterioles and small arteries takes place in man, independent of the aetiology of the systemic hypertension. This cellular infiltration was observed both in vessels in which marked degenerative changes were recognized and in vessels in which no degenerative changes could be observed under the light microscope. The mononuclear cellular infiltration is possibily due to a hypersensitivity of the delayed type.

The degree of round cell infiltration around hypertensively damaged heart arteries in one kidney Goldblatt hypertensive mice is more pronounced in haired mice with normal thymus function than in their nude littermates with genetic aplasia of the thymus. The level of hypertension and the prognoses for the hypertensive mice are, however, not influenced by the presence of thymus and thymus derived T cells. The results give evidence that delayed type immune reactions are involved in the hypertensive vascular disease in mice, but fail to support the assumption that they have pathogenic importance for either the level of hypertension or the prognoses of the one kidney Goldblatt hypertensive mice.

Hypertensive vascular disease was studied in acute experimental angiotensin induced hypertension. If the hypertension was induced in rats pretreated with injection of thoracic duct lymphocytes the quantity of the mononuclear inflammatory cellular reaction in the damaged arterioles was 2–9 times higher and more prolonged than in control rats. This difference in the cellular reaction is in agreement with the cellular reaction in cases of hypersensitivity of the delayed type.

Congenital anomalies of the pulmonary veins are rare. Meandering right pulmonary vein, considered a part of the Scimitar syndrome spectrum, is often an incidental finding during chest imaging. We present the case of a 4-year-old girl diagnosed with meandering pulmonary vein, who developed pulmonary hypertensive disease with an aggressive course, in spite of absence of hypoxia or elevated pulmonary wedge pressure.

Clinical hypertensive vascular disease is the result of complex alterations in the biology of the cellular components of the arterial wall. In this review, the hypothesis will be put forth that elevated blood pressure induces an inflammatory state in the arterial wall through both humoral and mechanical signaling pathways. The generation of reactive oxygen species and subsequent upregulation of redox-sensitive proinflammatory gene products are common endpoints of these pathways. Subsequent adaptive and maladaptive responses of the wall occur as a result of the integration of the humoral and mechanical stimuli.

Pulmonary arterial hypertension (PAH) can cause morbidity and mortality in children. Although adult and pediatric PAH share many similarities, many differences have been found in children. Thus, a new classification for pediatric pulmonary hypertensive vascular disease has been proposed. Both child and adult gene mutation carriers with PAH tend to have worse prognoses. Pediatric patients present with better preserved functional class, and parents should pay high attention to any children with unexplained shortness of breath, fatigue or syncope, as symptoms of PAH in children are often misleading. Right heart catheterization is necessary for diagnosis. Although there are few medications approved for pediatric PAH and evidence-based treatment algorithms for children are still lacking, the survival of pediatric patients has been improved significantly since targeted therapies approved for adults were introduced to pediatric patients. PAH in children is unique, and further studies are needed to have a better understanding of it.

The association of pulmonary hypertensive vascular disease with nonketotic hyperglycinemia is rare. We describe 5 infants diagnosed with nonketotic hyperglycinemia, in whom pulmonary hypertensive vascular disease was the main presenting feature, and who developed severe pulmonary edema in response to pulmonary vasodilators.

A number of structural and functional mechanisms have been identified in the pathogenesis of hypertensive vascular disease, each of which requires effective therapy to reduce global cardiovascular risk. Hypertension, together with other cardiovascular risk factors, promotes endothelial dysfunction as evidenced by decreased nitric oxide (NO) release and reduced vascular responsiveness to normal vasodilatory stimuli. In addition, the mechanical forces inherent in hypertension activate neurohormonal mechanisms, including the renin-angiotensin system, which modulate vessel wall structure and function. Antihypertensive drugs may have class-specific hemodynamic and physiologic effects that attenuate these vascular disease processes. Pharmacologic approaches that enhance endothelial NO bioavailability have been shown to restore vasodilation while reducing clinical events. These agents improve NO bioavailability by increasing endogenous production through enzymatic mechanisms or by promoting the direct release of NO by its redox congeners in a spontaneous fashion. In this article, we review the basic mechanisms of endothelial dysfunction along with the use and comparative therapeutic benefits of various pharmacologic interventions, with particular emphasis on antihypertensive agents.

DURING recent years many articles have been published concerning the importance of fundic changes associated with benign and malignant essential hypertension (benign and rapidly progressive hypertensive vascular disease). 1 These fundic findings will be discussed in relation to the surgical treatment of this prevalent disease. Others will discuss the surgical and medical aspects. Essential Hypertension is regarded as a vascular disease of unknown etiology. Its main clinical manifestation is a persistent high diastolic blood pressure, with variable general symptoms. The disease often causes spasm or sclerotic thickening of the walls of the retinal choroidal arterioles. This results in narrowing or stenosis of the lumen, which frequently leads to pathologic changes in the surrounding area. Essential hypertension may be divided into two forms : benign and malignant. The benign form is a chronic disease ; the malignant form is an acute disease. Both forms occur mainly in adults. Occasionally the benign form may

Arterial hypertension is a leading cause of both vascular diseases and chronic renal failure. With the increasing incidence of patients suffering from hypertension, an increasing number of patients with hypertensive vascular disease are reported, namely aortoiliac atherosclerosis and aneurysms, needing kidney transplantation (KT). Staged or simultaneous surgical repair of aortoiliac lesions with KT have long been described and studied. In this report, we discuss the case of a patient with infra-renal abdominal aortic aneurysm, having an endovascular bifurcated aortic bi-iliac stent (EVBAIS) introduced, who underwent a KT 3 months after his vascular surgery without any post-operative complication. This case, as well as other previous studies supports the fact that the presence of an EVBAIS does not contraindicate KT.

Major advances have been established in the handling of hypertensive vascular disease in recent years. However, drug compliance, drug costs, and the side effects of antihypertensive agents have prompted the question of whether intermittent therapy or even possible removal of medication represents an alternative to life-long antihypertensive therapy. Several case reports, and controlled and uncontrolled studies, have focused on this subject, delivering promising but inconsistent results. In this review the attempt is made to clarify the controversial results in order to provide possible selection criteria for patients who can be assumed to benefit from the withdrawal of antihypertensive medication. In addition, the issue of whether a genuine hypertensive can ever become normal is critically reviewed, and an evaluation of the reported success rates is performed. Factors that predicted a successful withdrawal of medication were young age, normal body weight, low salt intake, low pretreatment blood pressure, successful therapy with one drug, and only minimal signs of target organ damage. Additional modification, such as a low-salt or a weight-loss diet, were demonstrated to extend the period of nonpharmacologic treatment. Nevertheless, further studies would be of great help in elucidating how long and how intensively hypertensive patients should be treated before the discontinuation of medication can be tested.

This month's Hypertension Icon is Dr. Marvin Moser, Editor in Chief of The Journal of Clinical Hypertension. It is not, however, for this reason that he is being honored. For more than 50 years Dr. Moser has been a distinguished leader in efforts to control hypertension and prevent cardiovascular disease. He was there at the beginning when the treatment of hypertension was primitive and when people still believed that treatment would not be beneficial. He has participated in research on almost every new antibypertensive agent as they became available. He was one of the first to recognize that lowering blood pressure would result in the reversal of left ventricular hypertrophy. In addition to being an outstanding clinician, researcher, and teacher, Dr. Moser has been one of the leaders in public education. In his role as Senior Medical Consultant to the National High Blood Pressure Education Program, as well as in many states and national societies, he has been an untiring advocate of more effective treatment of hypertensive vascular disease. Dr. Moser has written 11 books, including four for the general public on the topic of hypertension and cardiovascular disease. The seventh edition of Clinical Management of Hypertension has just been published. He was a co-editor of the Yale University School of Medicine Heart Book. He is the author of more than 450 scientific papers and has lectured extensively in the United States and abroad. Dr. Moser is a worthy addition to the list of icons that have been featured in The Journal.

Experimentally-induced acute angiotensin hypertension has been shown to increase the permeability of cardial arteries and arterioles to plasma components within a few hours. Only in one of the coronary arteries was an increased and focal permeability for plasma components demonstrated, the penetration taking place into the entire thickness of the vessel wall. However, the permeability observed in intramyocardial small arteries and arterioles showed a distinct deposition of plasma components, both in the tunica intima and the tunica media and usually in the entire circumference of the vessels. The results support the view that an increased arterial permeability of the myocardial vessels for plasma components is an important initial stage in the development of hypertensive vascular disease of the heart.

A sexually dimorphic pattern of blood pressure, in which the male develops higher blood pressure than the age-matched female, has been observed both in human subjects and in laboratory animals. The mechanism(s) of this sexual dimorphism of blood pressure are not completely understood. This review summarizes sex differences in the epidemiology of hypertension in humans, the role of gonadal steroid hormones in the regulation of blood pressure of normotensive and hypertensive laboratory animals, and new insights into the molecular basis of the sexual dimorphism of hypertension and hypertensive vascular disease.

Recent research is helping us understand the complex interactions that occur between platelets and their environment. The several intracellular events that occur during platelet activation are being identified as are their effects on other platelets, the endothelium and coagulation factors. Heightened platelet activation is seen early in essential hypertension and probably plays an important role in the initiation and progression of atherosclerosis and the disorders associated with it. This review identifies some of the changes in platelet structure and function in essential hypertension and their role in the pathogenesis of hypertensive vascular disease.

Se revisaron 1.839 protocolos de autopsia del hospital San Juan de Dios de Santa Fe de Bogotá 155 pacientes tenían exposición al humo de los cuales 103 (5,6%) reunían los criterios de inclusión. 97% de los casos eran mujeres. Los cambios histológicos principales fueron: enfermedad vascular hipertensiva (39%), tromboembolismo pulmonar de vasos de pequeño y mediano calibre (38%) y antracosis peribronquial, perivascular e intersticial. En todos los parámetros histológicos se apreció mayor compromiso pulmonar con el mayor tiempo de exposición al humo de leña. A pesar de sus características peculiares no es posible clasificarla como una entidad nosológica, estando en la categotía de las neumoconiosis. En conclusión, es una condición clínico-patológica frecuente en nuestro medio, especialmente entre mujeres que han estado expuestas por muchos años al humo de leña; entre los cambios histológicos no patognomónicos, se encuentra el depósito de pigmento de antracosis, la enfermedad vascular hipertensiva, la fibrosis pulmonar y los cambios de bronquitis crónica.

The results described in this review clearly demonstrate that venous extensibility, contractility and prostaglandin synthesis are altered in veins from hypertensive animals and man. Similarly, venous smooth muscle compliance seems to be impaired in human essential and experimental animal hypertension. Decreased venous compliance and enhanced venous contractility may account for the transient increase in cardiac output observed during the labile phase of hypertension. Alterations in venous contractility may reflect intrinsic changes in the vascular smooth muscle later in the hypertensive process. Alternatively, the veins may respond sooner to a circulating humoral stimulus which will subsequently modify arterial smooth muscle function, or to which the arteries are unresponsive. Therefore, the study of venous and arterial smooth muscle function during the development of the hypertensive process could well identify the site, and perhaps, stimulus for the initial changes that occur in hypertension. Similarly, a study of venous and arterial smooth muscle function in hypertension can adequately define those changes intrinsic to the high blood pressure and those secondary to the increased vascular pressure of the hypertension. Therefore, analysis of the type, mechanism and sequence of venous changes which occur in hypertension can provide insight into rational drug therapy to treat the cause, and not the symptoms, of hypertensive vascular disease.

Severe hypertensive vascular disease was produced in 1969 in our laboratory by implantation of the mammotropic tumor MtT-F4, secreting very large amounts of corticotropin, prolactin and growth hormone in Fischer F 344 female rats. The hypertension was caused by adrenal cortical dysfunction with hyperproduction of deoxycorticosterone (DOC), and consequent sodium retention. Ultrastructural changes in the zona fasciculata cells of the adrenal glands were also evident in the tumor-implanted hypertensive rats, thus confirming the impaired adrenal steroidogenesis. The tumor has been maintained in our laboratory by continuous passages from rat to rat or it was being stored frozen for 3 years and then reimplanted. Implants with these new strains of tumor resulted in marked reduction or total loss of its hypertensinogenic ability. In addition to the failure to develop hypertension, the same strains of tumor also showed a reduced secretion of corticotropin, reflected in a smaller increase of the adrenal weight, a smaller reduction of thymic weight and a less marked sodium retention with normal levels of plasma sodium. The less elevated secretion of corticotropin was also indicated by a more normal ultrastructural appearance of the zona fasciculata cells. No alterations in the tumor secretion of growth hormone and prolactin was evident with the continuous passage from rat to rat, at least judging from the effect of the two hormones on their target organs. It is still controversial as to whether a synergistic action of corticotropin, growth hormone and prolactin is necessary in order to cause severe hypertensive vascular disease in the rats implanted with the mammotropic tumor. However, the present experiment has outlined, that among the three hormones secreted, corticotropin definitely plays a major role in the development of such disease.

A lingering controversy centres around the pathogenesis of arteriolar fibrinoid necrosis in malignant hypertension. One school of thought implicates the height of the arterial pressure as the dominant factor accounting for damage to the arteriolar wall. The other speculates on the existence of a circulating factor of renal origin, which, it is claimed, significantly contributes to arteriolar damage by increasing permeability of the vascular wall. Discussion about other types of hypertensive vascular disease have added to the confusion. Thus Brunner, Laragh, Baer, Newton, Goodwin, Lawrence, Bard & Biihler (1972) stated that renin is implicated in the causation of strokes and coronary artery disease. Although they have subsequently retracted their initial statements, this was not before publication of editorial advice against the use of diuretics in hypertension, so as to avoid raising plasma renin (British Medical Journal, 1972; Lancet, 1973; Goldby & Beilin, 1972a).

Inulin clearance was measured in 624 patients with gout, and para-aminohippuric acid (PAH) clearance in 359; Group I consisted of 397 patients with uncomplicated gout; Group II, 191 patients with hypertension and/or ischemic heart disease; and Group III, 36 patients with chronic renal disease. Mean inulin clearance was normal in Group I, slightly depressed in Group II and more markedly decreased in Group III. There was some reduction in PAH clearance in all groups, but not in the very young patients with no complications. A disproportionate reduction in PAH clearance was noted in Groups II and III, particularly in the older patients with longer duration of gout. Uncomplicated gout, except in rare cases of fulminating gout, does not lead to decreased renal hemodynamics. An increased incidence of tophi correlates with decreased renal function, but incidence of renal calculi does not. Renal insufficiency when seen in patients with gout usually correlates with coexistence of hypertension, ischemic heart disease, or primary preexistent renal insufficiency.

DIETARY measures in the treatment of hypertension have been advocated periodically during the past fifty years and have been extensively reviewed recently.1 The metabolic effects of the rice diet have been reported previously in abstract form.2 Although the most recent empirical program, as outlined by Kempner,3 is of limited value in the treatment of most patients with hypertensive vascular disease because of its rigid restrictions on diet, rather striking improvements in the level of blood pressure and general condition have been observed in some patients. The physiologic changes responsible for such improvement as may occur in these patients are, however, . . .

Plasma corticosterone levels were determined in uninephrectomized, adrenalectomized rats during development of corticosterone-induced hypertensive vascular disease. The mean maximum plasma corticosterone concentration (92.6 μg. per 100 ml.) occurred 1 hour after subcutaneous injection of the steroid. This level was not significantly different from that observed (84 μg. per 100 ml.) in normal rats 1 hour after exposure to nonspecific stress. The mean plasma levels of corticosterone in hypertensive rats receiving 2.5 mg. and 1.25 mg. per 100 gm. body weight were 46 and 48.2 μg. per 100 ml., respectively. These values are well within the physiologic range attained during response to stress and only slightly higher than the mean 12 hour levels produced by 8 I.U. of long-acting ACTH. The significant difference observed between the blood pressures of animals receiving 2.5 mg. and 1.25 mg. of corticosterone twice daily is presumed to be due to difference in salt consumption.

The measurement of the time between the onset of ventricular depolarization and the first heart sound, the Q-1 interval, has been employed in the phonocardiographic evaluation of patients with rheumatic heart disease. Prolongation of this interval has been noted frequently in patients with mitral stenosis and may be used as evidence in weighing the advisability of operation. In the present study, delayed appearance of the first heart sound was often noted in patients with hypertensive vascular disease as well. The mechanism for these changes as well as their significance in the phonocardiographic evaluation of patients with combined valvular disease and hypertension is discussed.

The purpose of this report is to present out experience with the use of protoveratrine in one hundred patients with hypertensive vascular disease. It is not possible to give a final answer as to the effect of this drug as a treatment of patients with hypertension. We cannot do this because the evaluation of any treatment of a chronic disease is hazardous and difficult unless the treatment is curative or unless improvement is prompt and sustained. This is particularly true of a disease such as hypertensive vascular disease which persists for a decade or more in a high proportion of patients and has a variable course. The natural history of hypertensive vascular disease has not been well delineated and the number of drugs and treatments which have been used in the past fifty years, only to be abandoned, is large. It is recognized that the final evaluation of any treatment of a chronic disease requires ten or more years and a large number of patients with adequate control study.

The administration of DOCA to unilaterally nephrectomized rats given a high NaCl intake caused an intense saline polydipsia and induced hypertensive vascular disease accompanied by cardiac hypertrophy in Sprague—Dawley animals. Similarly treated Long—Evans rats developed none of these changes, although they readily developed them when subjected to enucleation of the adrenal glands. These findings would seem to be incompatible with the assumption that adrenal—regeneration hypertension (ARH) is due to endogenous DOC hypersecretion by enucleate adrenal glands. The possibility is moot: evidence both for and against such an altered steroid secretory pattern has been presented from other laboratories. If so, it may well contribute to the response, but in view of the observation that Long—Evans rats are highly refractory to the development of DOCA hypertension but highly susceptible to ARH, it can hardly be held solely responsible. (Endocrinology 92: 1175, 1973)

The history is reported of a thirty-four year old white man who survived four and a half years following bilateral total adrenalectomy for cardiac failure due to hypertension. Marked improvement in circulatory status and a notable decrease in heart size was observed postoperatively although the degree of reduction in blood pressure level was minimal. Progressive renal insufficiency developed during the four and a half-year period, and as this occurred there was an increasing requirement for both salt and salt-retaining hormone. Chronic hyperkalemia with intermittent clinical episodes of acute potassium intoxication developed. However, the total exchangeable body potassium during this time was found to be within normal limits. A review of the autopsy tissue revealed no reversal of the arteriolar disease noted in renal biopsies at the time of adrenalectomy. The rapid reversal of acute potassium intoxication by administration of DOCA suggests a direct effect of this hormone on the mechanism involved in sustaining the normal gradient of potassium concentrations across the cell membranes.

100 hospitals were surveyed for their opinions regarding female ster ilization. Some of the primary indications cited for sterilization were: 1) selected cases of organic heart disease 2) selected cases of multiple cesarean sections 3) some cases of severe chronic pyelonephritis and 4) multiparity with severe chronic hypertensive vascular disease. The respondents were about equally divided on whether socioeconomic reasons were sufficient indications for sterilization. Sterilization of women under 30 years of age was almost universally disapproved of. 43% of the hospitals felt that there were potential future physical or mental risks to the postpartum sterilization patient. Most of the hospitals exercised some staff control over postpartum sterilizations usually through the written approval of 3 staff members or by a special staff committee. The average percentage of postpartum sterilizations to live births was 1.7%. 19 of 78 hospitals felt they were performing too many postpartum sterilizations.