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Sequence-specific protein-DNA interactions are at the heart of the response of the tumor-suppressor p53 to numerous physiological and stress-related signals. Large variability has been previously reported in p53 binding to and transactivating from p53 response elements (REs) due, at least in part, to changes in direct (base) and indirect (shape) readouts of p53 REs. Here, we dissect p53 REs to decipher the mechanism by which p53 optimizes this highly regulated variable level of interaction with its DNA binding sites. We show that hemi-specific binding is more prevalent in p53 REs than previously envisioned. We reveal that sequences flanking the REs modulate p53 binding and activity and show that these effects extend to 4–5 bp from the REs. Moreover, we show here that the arrangement of p53 half-sites within its REs, relative to transcription direction, has been fine-tuned by selection pressure to optimize and regulate the response levels from p53 REs. This directionality in the REs arrangement is at least partly encoded in the structural properties of the REs. Furthermore, we show here that in the p21-5′ RE the orientation of the half-sites is such that the effect of the flanking sequences is minimized and we discuss its advantages.

Introduction The Idiopathic Hypersomnia Severity Scale (IHSS) is a 14-item, self-reported questionnaire that assesses core Idiopathic Hypersomnia (IH) symptom severity. The relationship between IHSS scores and other IH symptom measures, such as the Epworth Sleepiness Scale (ESS; measures daytime sleepiness), sleep inertia visual analog scale (VAS-SI; measures sleep inertia), and Patient Global Impression of Change (PGIc; measures patients’ self-assessed change in symptoms), has not been established. This post hoc analysis analyzed correlations between the IHSS and ESS, VAS-SI, and PGIc using data from a clinical trial (NCT03533114) evaluating lower-sodium oxybate (LXB; Xywav™) for the treatment of IH. Methods During a clinical trial, the IHSS (0–50 score range) and ESS (0–24 score range) were completed at baseline; the IHSS, ESS, and PGIc (ordinal, 7 categories) were completed during an open-label treatment titration and optimization period (OLTTOP), after the OLTTOP, after a stable-dose period (SDP), and after a double-blind, randomized withdrawal period (DBRWP). The VAS-SI (0–100 score range) was completed during screening, SDP, and DBRWP. Correlation coefficients (rs) for IHSS vs ESS and VAS-SI were estimated from the within-subject variance matrix using a repeated-measures linear mixed model (LMM). The correlation between changes in IHSS score and PGIc was assessed using a Kruskal-Wallis test. Results IHSS scores correlated positively with ESS scores (rs [95% CI], 0.77 [0.73, 0.81]) and VAS-SI scores (0.69 [0.63, 0.75]). IHSS total score change was correlated with PGIc rank (chi-square with 6 degrees of freedom = 595.8, nominal P Conclusion IHSS scores or score changes strongly correlated with individual instruments assessing excessive daytime sleepiness, sleep inertia, and self-reported global symptoms, suggesting that the IHSS is a reliable, comprehensive measure of these symptoms of IH. Support (if any) Jazz Pharmaceuticals

A decrease in left ventricular volume increases the severity of left ventricular outflow tract obstruction in patients with obstructive hypertrophic cardiomyopathy, formerly called idiopathic hypertrophic subaortic stenosis. Because of this, a musician with the condition develops dizziness playing his saxophone which requires repeated and prolonged Valsalva maneuvers.

Hipertrofijska kardiomiopatija (HCM) česta je genetska bolest srca s prevalencijom 1 na 500 osoba opće populacije. HCM jedna je od najčešćih uzroka iznenadne srčane smrti (sudden cardiac death, SCD) u mladih osoba i sportaša. HCM uzrokuju mutacije različitih gena koji kodiraju proteine sarkomere. Nejednaka ekspresija zahvaćenih gena dovodi do različite kliničke slike čak i unutar iste obitelji. Klinička slika HCM kreće se od asimptomatske hipertrofije lijeve klijetke (LV) pa sve do uznapredovanog zatajenja srca koje zahtjeva transplantaciju ili nastupa SCD. Najčešći simptom je zaduha tijekom tjelesnog napora, a mogu biti prisutni simptomi poput presinkopa, sinkopa, bolova u prsima i palpitacija. Fibrilacija atrija (AF) česta je u bolesnika s HCM i dijelom je povezana s pogoršanjem simptoma i tromboembolijskim incidentima. Hemodinamski HCM karakterizira opstrukcija izlaznog trakta lijeve klijetke (LVOT) s prisustvom sistoličkog gradijenta tlaka, koja najčešće nastaje zbog sistoličkog pomaka prednjeg mitralnog kuspisa (systolic anterior motion, SAM) i njegovog dodira s hipertrofiranim interventrikularnim septumom. Dijagnoza HCM postavlja se ehokardiografskim nalazom hipertrofije stijenke nedilatirane LV koja prelazi 15 mm uz isključenje drugih uzroka hipertrofije. Magnetna rezonancija srca (CMR) može dodatno pomoći u prikazu hipertrofije i procjeni opstrukcije LVOT. Druge dijagnostičke metode, poput elektrokardiografije (EKG), ergometrije i elektrofiziološkog testiranja pridonose diferencijalnoj dijagnostici HCM, procjeni funkcionalnog kapaciteta bolesnika i rizika od SCD. Genetska testiranja služe za probir na HCM unutar obitelji zahvaćenog bolesnika te potvrdu dijagnoze u nejasnim slučajevima. Liječenje HCM temelji se na ublažavanju simptoma i prevenciji SCD. Od lijekova u terapiji HCM koriste se β adrenergičke antagoniste, blokatore kalcijevih kanala i antiaritmike. Invazivne metode liječenja su kirurška septalna miektomija ili alkoholna ablacija interventrikulskog septuma. Kao mjera prevencije SCD u pacijenata s povećanim rizikom od SCD može se ugraditi kardioverter defibrilator (ICD). Godišnja smrtnost osoba s HCM iznosi 1%., Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease with a prevalence of 1 out of 500 people in general population. HCM is one of the most common causes of sudden cardiac death (SCD) in young people and athletes. HCM is caused by a variety of mutations affecting sarcomere protein encoding genes. Uneven expression of the affected genes leads to a variety in clinical manifestation even within the same family. The clinical manifestation of HCM ranges from asymptomatic hypertrophy of the left ventricle (LV) to end-stage heart failure requiring heart transplantation or onset of SCD. The most common symptom is exertional dyspnea. Symptoms such as presyncope, syncope, chest pain and palpitations may also be present. Atrial fibrillation (AF) is common among HCM patients and is linked to symptom deterioration and thromboembolic events. The hemodynamic features of HCM include a left ventricular outflow tract (LVOT) obstruction with a systolic pressure gradient which is predominately a result of systolic anterior motion (SAM) of the anterior mitral leaflet and its contact with the hypertrophic interventricular septum. The diagnosis of HCM is based on an echocardiographic finding of a non-dilated LV hypertrophy with a wall thickness exceeding 15 mm with the exclusion of other causes of LV hypertrophy. Cardiac magnetic resonance (CMR) imaging can further aid in the visualization of hypertrophy and assessment of LVOT obstruction. Other diagnostic methods, such as electrocardiography (EKG), exercise testing and electrophysiological testing contribute to the differential diagnosis of HCM, functional capacity and SCD risk assessment. Genetic testing is used for HCM screening among the relatives of the affected patient and the confirmation of the diagnosis in unclear cases. The treatment of HCM is based on symptom alleviation and prevention of SCD. The medication used in treatment of HCM includes β adrenergic antagonists, calcium channel blockers and antiarrhytmics. Invasive treatment procedures include surgical septal miectomy or alcohol septal ablation. An implantable cardioverter defibrillator (ICD) device can be implanted in high risk patients as a mean of prevention of SCD. The yearly mortality of HCM is 1%.

Accessory mitral valve tissue is an extremely rare congenital cardiac anomaly. Most of the cases reported in the medical literature were associated with left ventricular outflow tract obstruction. The majority of cases of accessory mitral valve tissue, causing left ventricular outflow tract obstruction, occur in association with other congenital cardiac anomalies. In this reported case, a patient with accessory mitral valve tissue complicated with thromboembolic cerebrovascular event is presented. The patient also had an associated idiopathic hypertrophic subaortic stenosis.

Systolic anterior motion of the mitral valve with left ventricular outflow tract obstruction after Carpentier-type mitral reconstruction with ring annuloplasty has led some surgeons to abandon an otherwise successful repair or to avoid use of a rigid ring. To assess the long-term significance of such motion, we studied 439 patients undergoing Carpenter mitral reconstruction at our institution between March 1981 and June 1990. The hospital mortality rate was 4.8% (21/439) overall and 3.7% (9/243) for isolated mitral reconstruction. Systolic anterior motion was found in 6.4% (28/438) after the operation, and 2.3% (10/438) had a coexisting left ventricular outflow tract gradient (mean 53 mm Hg). Of the 28 patients with systolic anterior motion, 27 (96.4%) had leaflet prolapse, 17 (60.7%) had undergone more than a 3 cm resection of the posterior leaflet, and two (7.1%) had preexisting idiopathic hypertrophic subaortic stenosis. All patients were treated medically, 14 with negative inotropic agents. Follow-up echocardiograms at a mean of 32 months demonstrated the disappearance of systolic anterior motion in 13 of 28 patients (46.4%) and resolution of the outflow tract gradient in 10 of 10 (100%). At follow-up only one patient was in New York Heart Association class III or IV and required reoperation for rheumatic mitral insufficiency. These data demonstrate that systolic anterior motion after Carpentier mitral reconstruction with ring annuloplasty is not prevalent and should be managed medically in most cases. Associated left ventricular outflow tract obstruction resolves with medical treatment.

Almost 50 years of study have underscored the considerable heterogeneity in clinical presentation, natural history, morphology, and the genetic substrates that characterize inherited hypertrophic cardiomyopathy.1–5 Similarly, the nomenclature applied to this complex cardiac disease has persistently created a measure of confusion for both patients and physicians with regard to the definition and perceptions of the disease. This ambiguity has had, in turn, substantial impact on accurate diagnosis, full understanding of disease expression, and ultimately, decisions regarding management. At this juncture, it would seem appropriate and timely to conceptually revisit and clarify this important issue of names, consistent with the evolving knowledge of the cardiomyopathies.6 Response by Elliott and McKenna see p 81 The historical confusion over the names used to describe the entity of hypertrophic cardiomyopathy has arisen over the years in 2 fundamental areas. The first of these concerns the nomenclature used in prior efforts to characterize the disease. For example, at last count there are more than 80 individual names that have been used over the last 5 decades (most by early investigators) to describe the disease entity, which is the subject of this commentary (ie, hypertrophic cardiomyopathy)7 (Figure 1). It is likely that the confusing array of designations used to describe hypertrophic cardiomyopathy has also undoubtedly contributed to its relatively low visibility among the general public despite a prevalence (ie, 1:500), which greatly exceeds that of many other better known but less common cardiac or noncardiac diseases8,9 (Figure 2). Figure 1. The multitude of names used to describe hypertrophic cardiomyopathy in the literature. Many of these traditional terms, such as idiopathic hypertrophic subaortic stenosis, hypertrophic obstructive cardiomyopathy, and muscular subaortic stenosis, emphasize obstruction to left ventricular outflow to the exclusion of the nonobstructive form of the disease. Figure 2. The prevalence of hypertrophic …

Concomitant idiopathic hypertrophic subaortic stenosis and disseminated myocardial bridging is an uncommon clinical entity with poor prognosis. We describe a symptomatic 19-year-old girl who had myocardial debridging and transaortic and transmitral extended septal myectomy in the same surgical session. An early and simultaneous surgical approach may prevent sudden cardiac death in these high-risk patients.

We report on near syncope due to exercice-induced outflow tract obstruction in a patient with idiopathic hypertrophic subaortic stenosis

Idiopathic hypertrophic subaortic stenosis (IHSS), also known as hypertrophic obstructive cardiomyopathy, is characterized by dynamic obstruction of the left ventricular outflow tract secondary to asymmetric hypertrophy of the ventricular septum. Pregnancy is usually well tolerated, but acute peripartum pulmonary edema and a fatal ventricular arrhythmia have been reported. [1,2] Epidural anesthesia for vaginal delivery and general anesthesia for cesarean section have been described previously. [3,4] We report the use of combined spinal and epidural anesthesia using intrathecal fentanyl followed by epidural infusion of a diluted bupivacaine-fentanyl infusion for pain relief during labor and delivery in a parturient with IHSS

Electrical stimulation of the heart to prevent bradycardia has been a practical treatment option for 40 years,1 and over this period pacemaker technology has advanced at a rapid rate. Many innovations in lead and generator technology have now become incorporated into standard practice and have made cardiac pacing very reliable and effective.2 Virtually all pacemakers implanted today use highly biocompatible materials and long-lasting lithium-based batteries; they are inhibited by spontaneously occurring cardiac activity and are multiprogrammable. Dual-chamber pacing more closely resembles the normal physiology of cardiac activation than does asynchronous ventricular stimulation because it maintains the usual synchrony of atrial and ventricular contraction and dominance of the sinus node. However, despite the theoretical advantages of dual-chamber pacing, this technology is not widely used in most countries. In a world survey of pacing done in 1989,3 dual-chamber pacemaker use varied between regions from 2% to 32% (median, 14%) of patients and was used in ≥30% of patients in 3 of 13 countries or regions surveyed. Dual-chamber pacemaker use remains below expectations despite a statement in favor of dual-chamber pacing in guidelines for pacemaker implantation published jointly by the American Heart Association and the American College of Cardiology, which said “Although this may be less important at rapid rates, at slow rates it is almost always desirable to maintain AV synchrony. Long-term absence of AV synchrony increases the incidence of atrial fibrillation and stroke and may reduce patient life expectancy, particularly in patients with impaired left ventricular function, idiopathic hypertrophic subaortic stenosis or aortic stenosis.”5 The British Pacing and Electrophysiology Group (BPEG) (a specialist subgroup of the British Cardiac Society) recently published guidelines for pacemaker selection that include a recommendation that dual-chamber or atrial pacemakers are optimal except in chronic atrial fibrillation.6 In response to the BPEG …

Idiopathic hypertrophic subaortic stenosis (IHSS), when treated surgically, usually requires a full sternotomy. Although the procedure is fairly demanding because of limited exposure, excellent immediate and long-term results have been described with this approach.1 Less invasive endovascular approaches have been proposed to palliate this condition, but long-term follow-up is limited.2,3 To increase surgical exposure, warrant an excellent result (as the surgical approach has provided thus far), and limit the invasiveness of the procedure, we recently performed a successful endoscopic resection of IHSS associated with mitral valve repair.

SummaryThe topic of this paper concerns the clinical applications of the M mode echocardiography for adult patients. The method offers the possibility to> diagnose mitral and aortic disease with sgnificant anatomical damage even when the auscultatory signs are lacking. In the cases of Cardiomegaly it can differentiate: hypertrophy, dilatation and pericardial effusion.Suspected mitral prolapse and idiopathic hypertrophic subaortic stenosis are easilly confirmed or excluded.The qualitative or semi-quantitative analysis of the mitral echo, the ventricular dimensions, myocardial thickness and the movements the septal and posterior walls lead to hemodynamic interpretations. The limitations of the Method in this field are briefly discussed.The conclusions outline the clinical situations in wich an echocardiogram is recomrnanded.

The echocardiographic manifestations of discrete membranous subaortic stenosis are described in three cases. The diagnosis was confirmed by cardiac catheterization in all and at operation in two. The characteristic finding in these patients was abnormal movement of the aortic valve leaflets. The leaflets opened rapidly with the onset of systole, then exhibited abrupt premature closure shortly after ventricular ejection. The valve remained partially closed throughout the remainder of systole. This premature leaflet closure Is believed to be caused by obstruction to aortic valve flow produced by the band-like fibrous subaortic tissue. The valve leaflets also exhibited a gross fluttering motion possibly caused by a jet stream effect of the turbulent blood hitting the leaflets. In the two patients treated surgically, postoperative echograms continued to show premature leaflet closure but the degree of closure was decreased. The echocardlogram of one patient had the characteristic systolic anterior bulge of the mitral valve observed in muscular subaortic stenosis or idiopathic hypertrophic subaortic stenosis. Our data suggest that the following echocardiographic findings are suggestive if not specific for discrete subaortic stenosis: aortic valve closure early in systole, persistent valve closure throughout the remainder of systole, coarse fluttering of the leaflets, and absence of asymmetric septal hypertrophy.

Two patients who had idiopathic hypertrophic suBAortic stenosis (IHSS) and type A ventricular preexcitation were studied and showed variations of the subvalvular flow gradients. The increase in subvalvular gradient, occurring at a time when preexcitation developed, was associated with significant increase of the systolic murmur and the systolic anterior motion of the mitral valve. In patient 1, the significant increase in subvalvular gradient during ventricular preexcitation was also confirmed by catheterization of the left side of the heart. The increase of the gradient with the development of the ventricular preexcitation was apparently due to decreased end-diastolic volume. The importance of ventricular volume considered as a variable affecting outflow tract gradient in idopathic hypertrophic suBAortic stenosis is emphasized.

Idiopathic hypertrophic subaortic stenosis (IHSS) is a disease manifested as a spectrum of various clinical and laboratory findings. We present the case of a patient with classical clinical and hemodynamic findings of IHSS who lacked all of the typical echocardiographic features of the disease. The case emphasizes the need for diligent use of bedside physical examination and vasoactive manipulation of systolic murmurs whenever functional left ventricular outflow tract obstruction is suspected, since it can occasionally be missed by echocardiography.

A 42-year-old man with mirror-image dextrocardia was found to have idiopathic hypertrophic subaortic stenosis. The coexistence of these uncommon congenital cardiovascular anomalies was previously reported in only one patient.

Echocardiography has proven to be a useful technique in the diagnosis and assessment of therapy in idiopathic hypertrophic subaortic stenosis (IHSS). Asymmetric septal hypertrophy has been described as the pathognomonic anatomic marker of the disease. A characteristic systolic anterior motion of the anterior mitral valve leaflet has been detected in the presence of hemodynamically significant subaortic left ventricular outflow obstruction. An echocardiographic quantification of the outflow gradient (the obstruction index) has been derived previously. Four patients were studied by ultrasound at the time of cardiac catheterization. All four demonstrated systolic anterior motion of the anterior mitral leaflet in the absence of a resting gradient. In three of the four, the calculated obstruction index predicted hemodynamically significant resting gradients. All four patients were shown to have labile gradients with provocative maneuvers. A fifth patient with abnormal systolic anterior motion demonstrated a close correlation between the obstruction index and resting gradient; however, symmetric hypertrophy of the septum and left ventricular posterior wall was detected by ultrasound. Therefore, the abnormal mitral valve pattern may be seen in the absence of a resting gradient and symmetric left ventricular hypertrophy may exist in the presence of IHSS.

In ten normal subjects, we observed an initial hump in the aortic root echocardiogram after the onset of the QRS complex, following which a sharp anterior motion was noted. The onset of the anterior motion of the aortic root coincided with the onset of the upstroke of the aortic root pressure pulse and the onset of the velocity signal in five of seven patients with coronary arterial disease; in the other two, the anterior aortic motion followed the onset of the pressure and velocity signal by 10 msec. The aortic root echocardiogram was abnormal in patients with idiopathic hypertrophic subaortic stenosis; the slope (normalized for the scales of time and depth) in early systole was steeper and in the latter part of systole was flatter than normal in these patients. The slope in early diastole was flatter and the slope due to atrial contraction was steeper in the patients with idiopathic hypertrophic subaortic stenosis than in the normal subjects. These features were consistent with rapid ejection in early systole and slow filling in the early phase of ventricular diastole in idiopathic hypertrophic subaortic stenosis. Fourier analysis of the wave form of the aortic root allowed separation between patients with idiopathic hypertrophic subaortic stenosis and normal subjects.

To assess regional contractility in idiopathic hypertrophic subaortic stenosis (IHSS), a primary myopathic disorder with documented hyperdynamic ventricular contractions, systolic wall thickening and velocity of contraction of the septum and left ventricular posterior wall were measured in echocardiograms from 16 patients with IHSS and 16 normal subjects. The average thickening of the normal septum and posterior wall was 75.9+/-8.8% and 84.8+/-6.3%, respectively. The posterior wall in IHSS thickened by 75.1+/-6.8%. None of these values differed significantly. However, the increase in thickness of the IHSS septum averaged 22.5+/-2.4%, significantly less than that of either the IHSS posterior wall or the normal septum. Velocity measurements confirmed the impression of diminished septal function. The mean velocity of normal septal contraction averaged 37.0+/-2.3 mm/sec, normal posterior wall 42.3+/-2.0 mm/sec and IHSS posterior wall 55.7+/-3.5 mm/sec, whereas the septum in IHSS contracted at the rate of 26.0+/-2.5 mm/sec. Thus, the IHSS septum contracted significantly more slowly than the normal septum or IHSS posterior wall. However, the posterior wall velocity in IHSS was significantly more rapid than that measured in normal ventricles--perhaps to compensate for the septum. Normalization of all velocities for left ventricular end-diastolic internal diameter did not alter the sifnificance of the results. Consideration of IHSS as an asymmetric myopathy based on prior observations of predominantly septal hypertrophy and distorted septal cellular architecture is now supported by the above evidence of functional left ventricular asymmetry. Although the total left ventricular function in IHSS may be hyperdynamic, regional function is not uniform. The septum appears to be hypodynamic, while the contractile capacity of the posterior wall is increased.

Using different volumetric methods for the estimation of the end diastolic volume in patients with idiopathic hypertrophic subaortic stenosis it is concluded that in this condition the left ventricular cavity is shallower than it appears in the 60 degrees right posterior oblique projection and that ordinary cardioangiographic volumetric methods probably overestimate the end diastolic volume because of the septal bulge.

A patient with obstructive idiopathic hypertrophic subaortic stenosis and an apical middiastolic murmur is described. Previous explanations for this murmur are reviewed. At surgery, fibromuscular bands between the interventricular septum and the lateral free wall of the left ventricle were found. The presence of these bands in this patient suggests another possible cause for these murmurs.

Studies were made with standard time motion and B-scan echocardiography on 48 patients including 5 with idiopathic hypertrophic subaortic stenosis (hypertrophic obstructive cardiomyopathy), undergoing diagnostic cardiac catheterization. The dimensions of the left ventricular outflow (O) and inflow (I) tracts were measured on the B-scan images. The outflow tract was significantly narrowed in idiopathic hypertrophic subaortic stenosis at both end-systole (1-1+/-0-1 cm) and end-diastole (1-3+/-0-1 cm) when compared with the average width in other patients (2-6+/-0-1 and 3-0+/-0-1 cm, at end-systole and end-diastole, respectively) (P less than 0-001) or normal subjects (2-4+/-0-3 and 2-9+/-0-2 cm) (P less than 0-01). Furthermore, the O/I ratio differed significantly in idiopathic hypertrophic subaortic stenosis (0-5+/-0-1 at end-systole and 0-6+/-0-1 at end-diastole) from that in all other groups (1-4+/-0-1 at both end-systole and end-diastole) (P less than 0-005). There was no appreciable change in the width of the outflow tract from mid- to end-systole in the two patients in whom this was examined. The data support the contention that the anterior leaflet of the mitral valve assumes an abnormally anterior position in idiopathic hypertrophic subaortic stenosis. Though the systolic anterior movement of the tip of the anterior leaflet of the mitral valve shown by M-mode echocardiography could not readily be confirmed with B-scans, we believe that the narrowed outflow tract found in the present investigation contributes to the obstruction that occurs in this disease. We suggest that this outflow tract narrowing is probably caused by hypertrophy of the ventricular septum which in itself contributes to the narrowing, but which also displaces the papillary muscles and thus produces abnormal traction on the mitral valve and striking anterior displacement of the valve apparatus.

The finding at autopsy of typical pathologic features of hypertrophic heart disease (idiopathic hypertrophic subaortic stenosis, IHSS) and mitral valve prolapse (MVP) in a single patient prompted study of a number of close relatives of this patient. Several additional cases of IHSS or MVP were found. The HLA typing of this kindred revealed that four out of seven members tested had the Bw 35 antigen. Although the association might be doe to chance, this kindred, together with prior reports of similar bizarre myocardial cellular disarray in IHSS and MVP, suggest the hypothesis that in some instances, IHSS and MVP may represent a continuum of hereditary cardiac disorders.

Growth patterns of the cranium measured directly as head circumference have been well documented. With the availability of computed tomography (CT), cranial dimensions can be obtained easily. The objective of this project was to establish the mean values and their normal variance of CT cranial area of subjects at different ages. Cranial areas and its long and short axes were measured on CT scans for 215 neurologic patients of a wide age range who presented no evidence of abnormal growth of head size. Growth patterns of the cranial area as well as the numeric product of its linear dimensions were determined via a curve fitting process. The patterns resemble that of the head circumference growth chart, with the most rapid growth observed in the first 12 months of age and reaching full size during adolescence. It is believed that the availability of such reference, in addition to the head circumference measurement, will be valuable to the CT reviewer in determining the growth status of head size.

A patient presenting with hypercalcemia was found to have idiopathic hypertrophic subaortic stenosis and phenotypic Turner's syndrome. She has 3 daughters with phenotypic Turner's syndrome. 1 with a thickened interventricular septum and a son with asymmetric septal hypertrophy without obstruction and also possibly with hypercalcemia. Chromosome-banding studies revealed a normal 46,XX karyotype with no structural defects noted. The need for further studies of the incidence of hypercalcemia in idiopathic hypertrophic subaortic stenosis and in all the aortic outflow obstruction syndromes is suggested along with parathyroid function studies.

Pattern classification methodology has been applied to echocardiography. Utilizing discriminative features generated by Fourier analysis, anterior mitral leaflet waveforms associated with the normal, mitral stenosis, mitral valve prolapse, and idiopathic hypertrophic subaortic stenosis cardiac conditions have been classified in a manner which is unambiguous and which lends itself easily to present day automated technology.

Retrograde catheterization of the left atrium utilizing the Shirey technique was successfully performed in four patients with idiopathic hypertrophic subaortic stenosis. By traversing the inflow tract of the left ventricle on pullback from the left atrium to the aorta, this method served to separate definitively true hypertrophic subaortic stenosis from cavity obliteration. It was accomplished with relative ease and no complications. In patients with suspected idiopathic hypertrophic subaortic stenosis who are to have retrograde left heart catheterization, this approach to the left atrium is recommended as an alternative to the transseptal technique.

Nineteen patients with untreated hypothyroidism were evaluated by M-mode echocardiography. Asymmetric septal hypertrophy (ASH), defined as a ratio of interventricular septal thickness to left ventricular posterior wall thickness (IVS/LVPW) equal to or greater than 1.3, was identified in 17 cases. Additional abnormalities recognized by echocardiography included reduced amplitude of systolic septal excursion (SSex)[13 patients], reduced per cent of systolic septal thickening (%SST)[19 patients] reduced left ventricular outflow tract dimension (LVOT)[five patients] and systolic anterior motion of the mitral valve (SAM)[five patients]. These findings are similar to some of the echocardiographic features of idiopathic hypertrophic subaortic stenosis (IHSS). In 10 patients who returned to euthyroid state with L-thyroxine therapy, these abnormalities resolved. We conclude that long-standing hypothyroidism leads to a reversible cardiomyopathy, manifested by asymmetric septal hypertrophy with or without other echocardiographic features of a hypertrophic obstructive cardiomyopathy. This previously unrecognized features of hypothyroidism has important diagnostic and therapeutic implications.

We present an elderly woman with idiopathic hypertrophic subaortic stenosis (IHSS) and obstruction to left ventricular inflow. The inflow obstruction is thought to be due to massive mitral annular calcification. The association of IHSS and inflow obstruction is rare and may be overlooked unless careful hemodynamic measurements are obtained.

Previous studies have shown that asymmetric septal hypertrophy (ASH) may occur in embryonic and malformed hearts and that muscle cell disarray is found in myocardium that contracts isometrically. To account for the characteristic ASH and septal muscle fiber disarray of idiopathic hypertrophic subaortic stenosis (IHSS), we postulated that a catenoid shape of the septum, i.e., net zero curvature, would have the mechanics required to produce IHSS. Accordingly, hearts from eight autopsied patients with IHSS were studied for curvature and thickness of free walls and septum, and they were compared to similar measurements in 80 other hearts. In all eight hearts with IHSS the septum was concave to the left in the transverse plane but convex to the left in the apex-to-base plane. Such a catenoid configuration of the septum was not observed in any of the other 80 hearts. The distinctive shape of the septum in IHSS would account for isometric contraction, since adjacent fiber tracts with opposite curvatures would develop maximum tension but would not have motion. Fiber disarray and local hypertrophy would result from such isometric contraction. Since ventricular configuration is acquired early in cardiogenesis, IHSS might therefore result from a genetic or embryonic determination of a catenoid septum.

A case of fixed left ventricular outflow tract obstruction due to aortic valve stenosis coexisting with right- and left-sided subvalvular hypertrophic stenosis is documented with hemodynamic data, angiograms, echocardiograms and findings at surgery. Histologic examination of the septal muscle with light and electron microscopy revealed hypertrophy of the muscle but none of the characteristics of idiopathic hypertrophic subaortic stenosis. Septal hypertrophy with subvalvular obstruction can occur secondary to left ventricular pressure overload due to fixed left ventricular outflow tract obstruction and is not always the chance occurrence of two separate diseases.

One hundred forty patients with clinical mitral insufficiency were studied with two dimensional echocardiography. Cardiac catheterization was performed in 51 patients; all had mitral insufficiency. Thirty-three patients were surgically treated. An etiologic diagnosis was made in 133 patients. Mitral valve prolapse (41 patients) was the most common cause of mitral insufficiency; the amount of valve insufficiency did not correlate with the leaflet involved or the severity of the prolapse. Patients with rheumatic disease either had combined mitral stenosis and insufficiency (27 patients) or pure mitral insufficiency (10 patients). Echocardiographic measurement of the mitral valve area separated patients with combined lesions from those with pure insufficiency. Fourteen patients had ruptured chordae tendineae; surgical findings were confirmatory in each patient who had valve replacement. Nineteen patients had left ventricular dysfunction; angiographie findings were confirmatory in each patient who underwent cardiac catheterization. Two dimensional echocardiographic findings reliably differentiated mitral insufficiency secondary to valve disease from that secondary to ventricular or papillary muscle dysfunction. Other causes of mitral insufficiency included mitral anular calcification (11 patients), idiopathic hypertrophic subaortic stenosis (5 patients), cleft anterior mitral leaflet (5 patients) and atrial myxoma (1 patient).

Idiopathic hypertrophic subaortic stenosis (IHSS) is morphologically characterized by ventricular septal hypertrophy. It is asymmetrical because there is no corresponding hypertrophy of the posterior wall of the ventricle. The proportion between septal thickness and posterior wall thickness is more than 1.2. In addition, the anterior mitral leaflet moves towards the ventricular septum during the ventricular systole. Finally, the aortic cusps may close prematurely, even during ventricular systole, if there is a marked outflow-tract obstruction. The thickness of the septum and posterior wall, as well as the movement of the mitral and the aortic valves, can be easily registered by the echocardiograph. IHSS is, therefore, more easily diagnosed by this non-invasive method than by any other method. The echocardiogram demonstrates (1) asymmetrical septal hypertrophy, (2) anterior movement of the anterior and frequently also the posterior mitral leaflet in midsystole, (3) partial or complete closure of the aortic valve in mid-systole, (4) relatively small end-diastolic and systolic diameters of the left ventricle, (5) delayed early-systolic closure movement of the anterior mitral leaflet in the sense of a functional mitral stenosis, (6) decreased systolic septal movement.