Plexiform Structure Research Articles

Rare Anatomic Variation of Anterior Communicating Artery Associated with a Rupture of Saccular Aneurysm

Although most cerebral aneurysms are considered as acquired degenerative lesions, diverse anatomical variations in the circle of Willis have been encountered, some of which may play an important role in lesion hemodynamics and pathogenesis. The coalescence of the small vascular plexus to form the anterior communicating artery at the 6-7-week embryological stage may lead to developmental variations, such as fenestration and duplication. Herein, we report a rare anatomical variant of the anterior communicating artery that was concomitantly identified with a ruptured aneurysm. Both the right and left anterior cerebral arteries were connected by three anterior communicating arteries. A vertical segmental artery was present and connected the two anterior communicating arteries, forming an H-shape or plexiform structure. Furthermore, a 0.6×0.4 cm-sized saccular aneurysm with antero-inferior projection was present in the middle anterior communicating artery. The combination of triplication and H-shape in the present case was compared to previously reported anatomical variants.

Spatial Variation in Young Ovine Cortical Bone Properties.

Significant effort continues to be made to understand whether differences exist in the structural, compositional, and mechanical properties of cortical bone subjected to different strain modes or magnitudes. We evaluated juvenile sheep femora (age = 4 months) from the anterior and posterior quadrants at three points along the diaphysis as a model system for variability in loading. Micro-CT scans (50 micron) were used to measure cortical thickness and mineral density. Three point bending tests were performed to measure the flexural modulus, strength, and post-yield displacement. There was no difference in cortical thickness or density between anterior or posterior quadrants; however, density was consistently higher in the middle diaphysis. Interestingly, bending modulus and strength were higher in anterior quadrants compared to posterior quadrants. Together, our results suggest that there is a differential spatial response of bone in terms of elastic bending modulus and mechanical strength. The origins of this difference may lie within the variation in ongoing mineralization, in combination with the collagen-rich plexiform structure, and whether this is related to strain mode remains to be explored. These data suggest that in young ovine cortical bone, modulation of strength occurs via potentially complex interactions of both mineral and collagen-components that may be different in regions of bone exposed to variable amounts of strain. Further work is needed to confirm the physiological load state of bone during growth to better elucidate the degree to which these variations are a function of the local mechanical environment.

Immunohistochemical study of extracellular matrix protein expression and lung innervation in patients with pulmonary arterial hypertension

Background . Pulmonary arterial hypertension (PAH) is a group of diseases characterized by the damage to the intra pulmonary vessels and the development of right ventricular insufficiency. The pathogenesis of PAH is not fully understood. Remodeling of the extracellular matrix is one suggested mechanism. However, the wide variety of its structures and proteins, as well as the complexity of the relationships between them represent a large field for research work. The aim of the study was to study the features of expression and distribution of extracellular matrix proteins in patients without and with PAH. Design and methods . Archival autopsy material of lungs from 16 patients with various types of PAH was used, autopsy material from 7 patients who died from hemoblastosis was selected as a comparison group. In addition to histological examination, immunohistochemical examination was performed with the following markers: matrix metalloproteinase 9 (MMP9), filamin A, fibulin 5, collagen V, surfactant protein A, SI00, Ki67. Results . All patients with PAH had advanced morphological stages of pulmonary hypertension with the formation of plexiform structures. Immunohistochemical examination of the lungs of patients with PAH showed an increase in MMP9 expression and a tendency to increase the number of nerve fibers compared to the group of patients without PAH, while the expression of filamin A, fibulin 5, collagen V, surfactant protein A in the pulmonary arteries and parenchyma was reduced. It should be noted that despite the heterogeneity of the patient’s sample, a similar change in the expression profile of extracellular matrix proteins in the pulmonary arteries and lung parenchyma was shown, which requires further in-depth study in a larger sample of patients. Conclusions . The study of extracellular matrix markers and features of lung innervation in PAH in humans will contribute to the search for targeted drugs and the involvement of interventional technologies for the treatment of PAH.

Simulation of mechanical response of carbon nanotube yarns under uniaxial tensile loading

Carbon nanotube (CNT) yarns (CNTYs) are microscopic assemblies of carbon nanotubes in the form of continuous fibers that have significant technological applications. Their applications as individual fibers or embedded in polymer composites demand tensile load bearing, but the mechanical response of CNTYs is yet not well understood. A sequential, three-step, multiscale finite element (FE) modeling approach is proposed to predict the stress-strain response of CNTYs under uniaxial tensile loading. The modeling approach is based on experimental observations, which motivates an idealized concept of the hierarchical structure of CNTYs discretized into three hierarchical levels: (i) nanoscale model of bundles comprising CNTs, (ii) mesoscale model of CNT fibrillars formed by bundles, and (iii) microscale model of the CNTYs comprising twisted CNT fibrillars. The results from each level feed the simulation of the upper level. The inherent randomness in the plexiform structure of CNTYs is addressed through the Monte Carlo method, and the effect of porosity and twist level are also included for the first time in modeling the CNTY. The simulations predict that the elastic modulus of the bundle is fairly independent of its diameter but the yield stress and strength decrease with increasing bundle diameter. The aspect ratio of the individual CNTs comprising the bundles is also shown to be a key factor determining the CNTY strength. The simulation results show that considering an orthotropic response at the microscale level provides stress-strain curves that match the experimental results. This model of the stress-strain response of CNTYs elucidates the factors affecting that response and provides critical information towards their use in a variety of applications.

Anatomy of the female pelvic nerves: a macroscopic study of the hypogastric plexus and their relations and variations.

The autonomic nerves of the lesser pelvis are particularly prone to iatrogenic lesions due to their exposed position during manifold surgical interventions. Nevertheless, the cause of rectal and urinary incontinence or sexual dysfunctions, for example after rectal cancer resection or hysterectomy, remains largely understudied, particularly with regard to the female pelvic autonomic plexuses. This study focused on the macroscopic description of the superior hypogastric plexus, hypogastric nerves, inferior hypogastric plexus, the parasympathetic pelvic splanchnic nerves and the sympathetic fibres. Their arrangement is described in relation to commonly used surgical landmarks such as the sacral promontory, ureters, uterosacral ligaments, uterine and rectal blood vessels. Thirty-one embalmed female pelvises from 20 formalin-fixed and 11 Thiel-fixed cadavers were prepared. In all cases explored, the superior hypogastric plexus was situated anterior to the bifurcation of the abdominal aorta. In 60% of specimens, it reached the sacral promontory, whereas in 40% of specimens, it continued across the pelvic brim until S1. In about 25% of the subjects, we detected an accessory hypogastric nerve, which has not been systematically described so far. It originated medially from the inferior margin of the superior hypogastric plexus and continued medially into the presacral space. The existence of an accessory hypogastric nerve was confirmed during laparoscopy and by histological examination. The inferior hypogastric plexuses formed fan-shaped plexiform structures at the end of both hypogastric nerves, exactly at the junction of the ureter and the posterior wall of the uterine artery at the uterosacral ligament. In addition to the pelvic splanchnic nerves from S2-S4, which joined the inferior hypogastric plexus, 18% of the specimens in the present study revealed an additional pelvic splanchnic nerve originating from the S1 sacral root. In general, form, breadth and alignment of the autonomic nerves displayed large individual variations, which could also have a clinical impact on the postoperative function of the pelvic organs. The study serves as a basis for future investigations on the autonomic innervation of the female pelvic organs.

Cytological, histopathological, histochemical, and immunohistochemical findings of multiple cutaneous nodules in a bovine

This case study describes the cytological and histopathological findings of cutaneous masses in a bovine, including a peripheral nerve sheath tumor (PNST), vaccine-associated granulomatous inflammation, and eosinophilic inflammation due to parasitosis. A six-year-old undefined cow (SRD) presented with heterogeneous cutaneous lesions including multiple nodules in the left paralumbar fossa, bilaterally at the withers, and scattered along the dorsum, limbs and near the tail; some lesions were associated with ticks. Cytology of these nodules showed benign mesenchymal neoplasia (paralumbar fossa), granulomatous and pyogranulomatous inflammation (withers) and keratin (dorsum). Histopathology, in this order, confirmed PNST, post-vaccination granuloma, and eosinophilic dermatitis. A peripheral nerve sheath tumor was suspected based on the histological findings, showing a well-delineated proliferation of fusiform cells arranged in plexiform structures, which appeared red by Masson's Trichrome stain. The diagnosis was confirmed by immunohistochemistry (anti-S100 antibody). Vaccine reaction often occurs in cattle, and cytological examination is sufficient to determine the inflammatory process. Eosinophilic dermatitis is usually accompanied by perivascular inflammation and reflects the exfoliative process by the oral apparatus of the parasite.

Circle of Willis Variation: Implications for Aneurysm, Atherosclerosis, and Stroke

Arterial variations within the Circle of Willis, especially hypoplastic arteries, are linked to intracranial aneurysm, atherosclerosis, and stroke; therefore, the study of Circle of Willis variants are of clinical importance. In a sample of 116 cadavers, the arteries comprising the Circle of Willis were directly observed and assessed for hypoplasia, hyperplasia, aplasia, duplication, triplication, and plexiform structure. A total of 53 different arterial patterns of the Circle of Willis were identified. The most common vascular pattern was one with no noteworthy variation of the arteries, which occurred in 34.48% (40:116) of the sample. The second most common pattern was a right hyperplastic posterior communicating artery, with concomitant right hypoplastic P1 and right hyperplastic P2 vessels which occurred in 3.45% (4:116) of cadavers. The most common variation of an individual artery, regardless of concomitant variations, was a hyperplastic right posterior communicating artery, which occurred in 19.8% (23:116) of the sample. Similarly, a right hyperplastic P2, right hyperplastic posterior communicating artery, left hypoplastic P1, and left hyperplastic posterior communicating artery each occurred in 18.1% (21:116) of cadavers. A duplicated anterior communicating artery was observed in 12.9% (15:116) of cadavers. Aplasia was only observed in the posterior communicating artery (left‐sided: 7.8%; 9:116, right‐sided: 6.0%; 7:116). The results of this study provide a clearer understanding of the variant vascular patterns of the Circle of Willis that create predisposition for aneurysm, atherosclerosis, and stroke.Support or Funding InformationWest Virginia University, Oman Medical College and West Liberty UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Piezoelectric response of bone in the MHz range

The healing mechanism of bone fractures by low intensity ultrasound is not yet to be fully understood. As one possible initial process of this mechanism, we focus on the piezoelectricity of bone and demonstrate that bone can generate electrical potentials by ultrasound irradiation in the MHz range. We have fabricated ultrasonic bone transducers using bovine cortical bone as the piezoelectric device. Electrical potentials induced by the ultrasound irradiation were obtained from all transducers. The electrical potentials changed as a function of time during immersed ultrasonic measurements and became stable when the bone was fully wet. The sensitivities of bone transducers were around 1/1000 of a poly(vinylidene fluoride) ultrasonic transducer and did not depend on the magnitude and alignment of hydroxyapatite crystallites in bone. In addition, the magnitude of the induced electrical potentials changed owing to the microstructure in the cortical bone. The potentials of transducers with haversian structure bone were higher than those of plexiform structure bone, which informs about the effects of bone microstructure on the piezoelectricity.

Effects of microstructure and water on the electrical potentials in bone induced by ultrasound irradiation

The healing mechanism of bone fractures by low intensity pulse ultrasound is yet to be fully understood. There have been many discussions regarding how the high frequency dynamic stress can stimulate numerous cell types through various pathways. As one possible initial process of this mechanism, we focus on the piezoelectricity of bone and demonstrate that bone can generate electrical potentials by ultrasound irradiation in the MHz range. We have fabricated ultrasonic bone transducers using bovine cortical bone as the piezoelectric device. The ultrasonically induced electrical potentials in the transducers change as a function of time during immersed ultrasonic pulse measurements and become stable when the bone is fully wet. In addition, the magnitude of the induced electrical potentials changes owing to the microstructure in the cortical bone. The potentials of transducers with haversian structure bone are higher than those of plexiform structure bone, which informs about the effects of bone microstructure on the piezoelectricity.

Examination of VLC-PUFA-deficient photoreceptor terminals.

Juvenile-onset autosomal dominant Stargardt-like macular dystrophy (STGD3) is caused by mutations in ELOVL4 (elongation of very long fatty acids-4), an elongase necessary for the biosynthesis of very long chain fatty acids (VLC-FAs ≥ C26). Photoreceptors are enriched with VLC polyunsaturated fatty acids (VLC-PUFAs), which are necessary for long-term survival of rod photoreceptors. The purpose of these studies was to determine the effect of deletion of VLC-PUFAs on rod synaptic function in retinas of mice conditionally depleted (KO) of Elovl4. Retina function was assessed in wild-type (WT) and KO by electroretinography. Outer plexiform structure was evaluated by immunofluorescence and transmission electron microscopy. Single-cell recordings measured rod ion channel operation and rod bipolar glutamate signaling. Sucrose gradient centrifugation was used to isolate synaptosomes from bovine retina. Proteins and lipids were analyzed by Western blotting and tandem mass spectroscopy, respectively. Inner retinal responses (b-wave, oscillatory potentials, and scotopic threshold responses) of the ERG were decreased in the KO mice compared to controls. However the rod ion channel operation and bipolar glutamate responses were comparable between groups. Biochemical analysis revealed that conventional and ribbon synapses have VLC-PUFAs. Ultrastructural analysis showed that the outer plexiform layer was disorganized and the diameter of vesicles in rod terminals was smaller in the KO mice. Very long chain PUFAs affect rod function by contributing to synaptic vesicle size, which may alter the dynamics of synaptic transmission, ultimately resulting in a loss of neuronal connectivity and death of rod photoreceptors.

Onyx® in endovascular treatment of cerebral arteriovenous malformations – a review

SummaryArteriovenous malformation (AVM) is an abnormal connection between arteries and veins, bypassing the capillary system. In most cases, the disorder may be asymptomatic. The objective of endovascular AVM treatment is set individually for each case upon consultations with a neurosurgeon and a neurologist. The endpoint of the treatment should consist in prevention of AVM bleeding in a management procedure characterized by a significantly lower risk of complications as compared to the natural history of AVM. Endovascular interventions within AVM may include curative exclusion of AVM from circulation, embolization adjuvant to resection or radiation therapy, targeted closure of a previously identified bleeding site as well as palliative embolization. Onyx was first described in the 1990s. It is a non-adhesive and radiolucent compound. Onyx-based closure of the lumen of the targeted vessel is obtained by means of precipitation. The process is enhanced peripherally to the main flux of the injected mixture. This facilitates angiographic monitoring of embolization at any stage. The degree of lumen closure is associated with the location of the vessel. Supratentorial and cortical locations are most advantageous. Dense and plexiform structure of AVM nidus as well as a low number of supplying vessels and a single superficial drainage vein are usually advantageous for Onyx administration. Unfavorable factors include nidus drainage into multiple compartments as well as multiarterial supply of the AVM, particularly from meningeal arteries, en-passant arteries or perforating feeders. Onyx appears to be a safe and efficient material for embolization of cerebral AVMs, also in cases of intracranial bleeding associated with AVM. Curative embolization of small cerebral AVMs is an efficient and safe alternative to neurosurgical and radiosurgical methods. Careful angiographic assessment of individual arteriovenous malformations should be performed before each Onyx administration.

Distribution of hydroxyapatite crystallite orientation and ultrasonic wave velocity in ring-shaped cortical bone of bovine femur

At the nanoscopic level, bone consists of calcium phosphate, which forms incomplete hydroxyapatite (HAp) crystals. The preferred orientation of the c-axis of HAp crystallites induces anisotropy and inhomogeneity of elastic properties in bone. In this study, the effect of the preferred orientation of HAp crystallites on the spatial distribution of ultrasonic wave velocity was experimentally investigated, considering bone mineral density (BMD) and microstructure. Three ring-shaped cortical bone samples were made from a 36-month-old bovine femur. Longitudinal wave velocity was measured by a conventional ultrasonic pulse system, using self-made polyvinylidene fluoride transducers. The integrated intensity of the (0002) peak obtained using X-ray diffraction was estimated to evaluate the amount of preferred orientation. The velocity distribution pattern was similar to the distribution of integrated intensity of (0002). The effect of the preferred orientation of HAp crystallites on velocity was clearly observed in the plexiform structure, despite the fact that the BMD value was almost independent of the preferred orientation of HAp crystallites. Velocity measurement of cortical bone can reveal information about HAp crystallite orientation.

Ultrasonic Wave Properties in Bone Axis Direction of Bovine Cortical Bone

Quantitative ultrasonography (QUS) is a good method for measuring elastic properties of bone in vivo. Bovine cortical bone has two typical microstructures, plexiform and Haversian. In this study, the relationship between the speed of sound (SOS) and the hydroxyapatite (HAp) crystallite orientation in the axial direction was investigated in two different aged bovine cortical bones. The dependence of attenuation on anatomical position was also investigated. Two ring-permanent hyphen shaped cortical bone samples were obtained from 36- and 24-month-old bovine femurs. SOS was measured with a conventional ultrasonic pulse system. The integrated intensity of the (0002) peak obtained by X-ray diffraction was determine to evaluate the amount of preferred orientation. Regardless of the age of the bovine femurs, a significant correlation between SOS and the preferred orientation of HAp crystallites was observed in parts of the plexiform structure, and the gradient of the relationship showed a similar tendency. Attenuation seemed to depend on bone microstructure.

Plexiform vascular structures in the human digital dermal layer: A SEM – corrosion casting morphological study

This study aimed to describe the impressive diversity of vascular plexiform structures of the hypodermal layer of human skin. We chose the human body site with the highest concentration of dermal corpuscles, the human digit, and processed it with the corrosion casting technique and scanning electron microscopy analysis (SEM). This approach proved to be the best tool to study these microvascular architectures, free from any interference by surrounding tissues. We took high-definition pictures of the vascular network of sweat glands, thermoreceptorial and tactile corpuscles, the vessels constituting the glomic bodies and those feeding the hair follicles. We observed that the three-dimensional disposition of these vessels strictly depends on the shape of the corpuscles supplied. We could see the tubular vascularization of the excretory duct of sweat glands and the ovoid one feeding their bodies, sometimes made up of two lobes. In some cases, knowledge of these morphological data regarding the normal disposition in space and intrinsic vascularization structure of the dermal corpuscles can help to explain many of the physiopathological changes occurring during chronic microangiopathic diseases.

Distribution of longitudinal wave properties in bovine cortical bone in vitro

The detailed spatial distributions of longitudinal ultrasonic velocity in cortical bone specimens obtained from three bovine femoral diaphysis were experimentally investigated using a pulse-echo system. The relationship between velocity, density, bone mineral density (BMD) and microstructure was investigated. Velocity was found to vary as a function of the direction of propagation and the location of the measured specimens in the bone diaphysis. A significant correlation was found between density and velocity, and between density and BMD. In some parts with plexiform structure, clear variations in velocity anisotropy were found despite no significant difference in density, BMD and microstructure.

Pathogenesis of facial nerve synkinesis in guinea pig

Problem: The facial nerve synkinesis is one of the common complaints after facial palsy. However, the precise mechanism of synkinesis is still unknown. In this study we tried to establish an animal model of synkinesis. Methods: Extratemporal portion of the facial nerve (group 1, n = 6) and the intratemporal portion (group 2, n = 6) were compressed by using a micro needle holder. After the compression, the grade of facial nerve injury was evaluated by electroneurography. The existence of synkinesis was judged by the presence of R1 in the orbicularis oris muscle by the electrophysiolgical blink reflex. For evaluating the misdirection of nerve fibers, double labeling was performed by injecting retrograde fluorescence tracer in the orbicularis oculi muscle and the orbicularis oris muscle, and then facial nucleus was investigated for the presence of the neurons with aberrant fluorescence. Results: In both groups, all animals showed the ENoG threshold under 10%. In group 1, none of animals developed synkinesis. On the other hand, in group 2, all animal developed synkinesis. Furthermore, disrupted neurons in the facial nucleus, representing the existence of misdirection, were observed in all animals of group 2. Conclusion: In this study we succeeded in making a synkinesis model only in group 2 and reported the existence of misdirection in these animals. Sunderland found that the facial nerve consisted of a single bundle in the intratemporal portion, even though it had a mulitifuniculated plexiform structure in the extratemporal portion. Because of this anatomical feature, when the facial nerve was injured in the intra- and extra-temporal portions, the misdirection may occur only in the intra-temporal portion. This is thought as a reason for the appearance of synkinesis only in group 2. Significance: It is important to know the pathogenesis of synkinesis for diagnosing and treating facial nerve disorders. Support: None reported.

A new morpho-functional classification of the Fallopian tube based on its three-dimensional myoarchitecture.

The recent direct observations, under scanning electron microscopy (SEM), of the three-dimensional architecture of myosalpinx in different mammals allows us classify salpinxes according to the myoarchitecture of their tubo-uterine junction (TUJ) and isthmus segments. Based upon the myoarchitecture of the outer wall of the TUJ we could find barrier-like species (rat and sow), sphincter-like species type a (rabbit and ewe) and sphincter-like species type b (cow and woman). The different architecture of TUJ can be explained by the different nature of the mating process. Based upon the myoarchitecture of the isthmus we could distinguish type 1 (rat) and type 2 (rabbit, ewe, sow, cow and woman) salpinxes. In the latter the close fusion of musculature deriving from the meso (extrinsic musculature) with the musculature of salpinx (intrinsic musculature) suggests the existence of a unique mesosalpinx contractile system. The myosalpinx is mostly made up of a single network of muscular fibers. Such a plexiform structure, owing to the uneven distribution of fibers, rather than producing a series of regular contraction waves, is more likely to generate random contraction waves. The random propagation of muscular network contraction may deform the plexiform wall of the myosalpinx causing the stirring of tubal contents. By such a stirring movement the contact between hormones and nutrients and the eggs or embryos is intensified, thus favoring a correct fertilization and early embryo development. Taken all together, these systematic results probably suggest an additional and rather new function for the musculature of the tube, namely to increase fertility in a large number of species.

Diffuse Coronary Arteriodysplasia in a Holstein-Friesian Cow

The coronary arteries of a 6-year-old Holstein-Friesian cow showed dysplastic lesions characterized by the following vascular changes: irregular, aneurysmal dilation; intimal fibrosis associated with myointimal cells; aberrant internal elastic lamina; oedema and mast cell infiltrates; and variation in the thickness of the media, including tortuosity with irregular dilation of the lumen of the artery and a plexiform structure formed from the right coronary artery.

Three-Dimensional Reconstruction of Pulmonary Arteries in Plexiform Pulmonary Hypertension Using Cell-Specific Markers: Evidence for a Dynamic and Heterogeneous Process of Pulmonary Endothelial Cell Growth

The plexiform lesions of severe pulmonary hypertension (PH) are complex vascular structures composed primarily of endothelial cells. In this study, we use immunohistochemical markers to identify the various cell layers of pulmonary vessels and to identify different endothelial cell phenotypes in pulmonary arteries affected by severe PH. Our computerized three-dimensional reconstructions of nine vessels in five patients with severe PH demonstrate that plexiform (n = 14) and concentric-obliterative (n = 6) lesions occur distal to branch points of small pulmonary arteries. And, whereas plexiform lesions occur as solitary lesions, concentric-obliterative lesions appear to be only associated with, and proximal to, plexiform structures. The endothelial cells of plexiform lesions express intensely and uniformly the vascular endothelial growth factor (VEGF) receptor KDR and segregate phenotypically into cyclin-kinase inhibitor p27/kip1-negative cells in the central core of the plexiform lesion and p27/kip1-positive cells in peripheral areas adjacent to incipient blood vessel formation. Using immunohistochemistry and three-dimensional reconstruction techniques, we show that plexiform lesions are dynamic vascular structures characterized by at least two endothelial cell phenotypes. Plexiform arteriopathy is not merely an end stage or postthrombotic change--it may represent one stage in an ongoing, angiogenic endothelial cell growth process.

Diverticulum of the left ventricle associated with subvalvar aortic stenosis

Diverticula of the left ventricle are rare and only a few cases have been documented in adults. They may be asymptomatic or may present with embolization, pain, endocarditis, or sudden death. We report the case of a 34-year-old woman who presented a cardiac arrest with ventricular fibrillation which required electrical cardioversion. She was found to have a left ventricular diverticulum associated with a subvalvar aortic stenosis. The diverticulum arose from the apex with a narrow connection to the ventricular cavity. A subvalvar fibrous ridge stenosis with a systolic pressure gradient of 115 mmHg was observed. Coronary angiography revealed normal coronary arteries. The diverticulum and the subvalvar fibrous ridge were resected. Histologic examination of the diverticulum wall demonstrated the presence of the three normal layers with marked muscle cell hypertrophy, atypical plexiform structure and fibrous endocardium. The pathophysioloy of diverticula associated with subvalvar aortic stenosis are discussed.