Site-dependent differences in both prelamin A and adipogenic genes in subcutaneous adipose tissue of patients with type 2 familial partial lipodystrophy.

BACKGROUND: Type 2 familial partial lipodystrophy (FPLD2) is characterised by loss of fat in the limbs and buttocks and results from mutations in the LMNA gene. AIM: To evaluate the role of several genes involved in adipogenesis in order to better understand the underlying mechanisms of regional loss of subcutaneous adipose tissue (scAT) in patients with FPLD2. METHODS: In total, 7 patients with FPLD2 and 10 healthy control participants were studied. A minimal model was used to calculate the insulin sensitivity (IS). scAT was obtained from abdomen and thigh by biopsy. Relative gene expression was quantified by real-time reverse transcription PCR in a thermal cycler. Prelamin A western blot analysis was carried out on scAT and prelamin A nuclear localisation was determined using immunofluorescence. Adipocyte nuclei were examined by electron microscopy. RESULTS: Patients with FPLD2 were found to have significantly lower IS. The expression of LMNA was similar in both groups. The expression of PPARG2, RB1, CCND3 and LPL in thigh but not in abdomen scAT was significantly reduced (67%, 25%, 38% and 66% respectively) in patients with FPLD2. Significantly higher levels of prelamin A were found in peripheral scAT of patients with FPLD2. Defects in the peripheral heterochromatin and a nuclear fibrous dense lamina were present in the adipocytes of patients with FPLD2. CONCLUSIONS: In FPLD2 participants, prelamin A accumulation in peripheral scAT is associated with a reduced expression of several genes involved in adipogenesis, which could perturb the balance between proliferation and differentiation in adipocytes, leading to less efficient tissue regeneration.

Impact of polyclonal anti-thymocyte globulins on the expression of adhesion and inflammation molecules after ischemia-reperfusion injury.

BACKGROUND: Polyclonal anti-thymocyte globulins (ATGs) are immunosuppressive agents used for the treatment and prevention of acute organ rejection after transplantation. ATGs induce apoptosis and complement-mediated cell death in peripheral T-lymphocytes and have shown a reduction of leukocyte adhesion after ischemia-reperfusion (IRI). We analyzed the impact of different ATGs upon the expression of adhesion and inflammation molecules after IRI. MATERIALS AND METHODS: The major arteries and veins of the extremities of cynomolgus monkeys were surgically isolated and flushed with Ringer's lactate at 4 degrees C. After 60 min of ischemia the limbs were reperfused with matching human blood. ATGs were added to the blood 30 min prior to the reperfusion, forming four groups: Tecelac-ATG group (n=16), Fresenius(S)-ATG group (n=16), Thymoglobulin-ATG group (n=12) and a control group (n=16). Biopsies from muscular tissue were obtained after the experiments. The expression of adhesion (ICAM-1, VCAM, PECAM, CD11b, CD62E) and inflammation (IL-1, IL-6, TNF-alpha) molecules on endothelium, leukocytes, and reperfused tissue was analyzed by means of immunohistochemistry. RESULTS: The expression of the studied adhesion molecules (ICAM-1, VCAM, PECAM, CD11b, and CD62E) was significantly increased in the control group when compared with the treated groups. The expression of IL-1, IL-6, and TNF-alpha was reduced in the ATG-groups in comparison to the control group. DISCUSSION: Our results showed that ATGs caused a reduction of the expression of adhesion and inflammation molecules both in endothelium and reperfused tissue. The inhibition of the expression of molecules required for firm cellular adhesion, may contribute to decreasing cellular graft infiltration after post-ischemic reperfusion.

Reversal of cardiac cirrhosis following orthotopic heart transplantation.

Irreversible hepatic cirrhosis greatly increases the risks attending heart transplantation (HT), and is accordingly considered to be an absolute contraindication for HT unless combined heart and liver transplantation can be performed. It is now recognized that hepatic cirrhosis can undergo regression if the source of insult is removed, but no cases of post-HT regression of cirrhosis of cardiac origin have hitherto been reported. Here we report a case of cardiac cirrhosis that underwent complete regression following orthotopic HT, and we discuss the implications of this case.

The efficacy and safety of ezetimibe for treatment of dyslipidemia after heart transplantation.

INTRODUCTION: Statins, although the treatment of choice for dyslipidemia after heart transplantation (HT), are not always well tolerated or effective. In such cases, administration of ezetimibe may be useful. AIM: The aim of this study was to assess the efficacy and safety of ezetimibe, with or without statins, after HT. METHOD: Thirty-six HT patients, 97% of whom were males of overall mean age of 57 +/- 13 years, were all unable to reach target lipid levels with statins alone and/or were intolerant of statins. They were prescribed ezetimibe, with or without a statin. Efficacy and safety were evaluated after 1, 3, 6, and 12 months. RESULTS: Thirty-four patients were evaluated at 1 month and 12 months. Ezetimibe was prescribed to 27 patients (75%) because of statin inefficacy, and to 9 patients (25%) because of statin intolerance, manifested by myalgia in 4 cases (11%), hepatotoxicity in 2 cases (6%), and rhabdomyolysis in 3 cases (8%). Lipid levels (mg/dL; baseline vs 1 year) were as follows: cholesterol, 235 +/- 49 versus 167 +/- 32 (P = .013); LDL cholesterol, 137 +/- 47 versus 89 +/- 29 (P = .001); HDL cholesterol, 54 +/- 13 versus 51 +/- 10 (P = .235); and triglycerides, 243 +/- 187 versus 143 +/- 72 (P = .022). There were no cases of liver toxicity, renal dysfunction, or significant alteration of immunosuppressive pharmacokinetics. Ezetimibe was withdrawn from 2 patients because of hand edema or asymptomatic recurrence of rhabdomyolysis first caused by statins. CONCLUSIONS: With or without a statin, ezetimibe was generally well tolerated, reducing total cholesterol, LDL cholesterol, and triglyceride levels with no long-term alteration of HDL cholesterol levels. CPK surveillance is recommended because of a slight continued risk of adverse effects. Further studies should evaluate the benefit for survival.

Adverse effects of mammalian target of rapamycin inhibitors during the postoperative period after cardiac transplantation.

INTRODUCTION: Safety of treatment with mammalian target of rapamycin inhibitors (mTORi) in the postoperative period after heart transplantation (HT) is controversial. METHODS: We evaluated the incidence of postoperative complications (pericardial, pleural, and surgical wound complications) among nine de novo heart transplant recipients treated with mTORi compared with 19 patients who did not receive them during the same period (control group). RESULTS: No significant differences were observed between the two groups regarding sex, age, body mass index, pretransplant diagnosis, history of diabetes mellitus, prior cardiac surgery, or baseline renal function. The main laboratory parameters at 1 month were also similar. During the first 2 months after HT, four patients (44%) in the mTORi group developed severe pericardial effusions requiring drainage, compared to 1 (5%) in the control group (P = .026). All patients presenting this complication in the mTORi group received everolimus. In addition, two cases of sternal dehiscence were observed in the mTORi group, compared to none in the control group (P = .09); one patient on everolimus required sternal reopening and debridement for clinically suspected mediastinitis. Duration of chest tube drainage, quantity of collected pleural fluid, and need for thoracentesis were similar in both groups. CONCLUSIONS: In our series, patients receiving mTORi-particularly everolimus-during the postoperative period after HT showed a higher incidence of severe pericardial effusion requiring drainage, as well as a trend toward a higher incidence of sternal dehiscence, as compared to a group not receiving mTORi. The use of mTORi during the early postcardiac transplant period should be individualized.

Bone fractures after cardiac transplantation.

OBJECTIVE: Bone loss and bone fractures are disabling complications after heart transplantation. Severe bone loss happens mainly during the first year posttransplantation. Steroids and cyclosporine alter bone metabolism in several ways. To counterbalance these effects, antiresorptive therapy is provided to these patients. The objective of this study was to assess the frequency of bone fractures after heart transplantation, considering previous comorbidities, immunosuppressive therapy, and osteoprotective treatment. METHODS: From 1993 to 2005, 443 consecutive heart transplant recipients were followed for the occurrence of bone fractures, immunosuppressive therapy, clinical conditions, and antiresorptive treatment. RESULTS: There were 41 fractures in 34 patients (7.6%, group I). The remainder of patients formed group II. Fractures commonly involved the lumbar spine. Postmenopausal women had more fractures than other patients (20.6% vs 7.8%, P = .02). When the initial immunosuppressive regimen included tacrolimus, fractures did not happen (P = .01, vs other regimens). Osteoprotective therapy was administered to 91.2% of patients in group I and 79% in group II (P = .08). Mean interval from transplantation to the first fracture was 1131.5 days. Overweight patients had a 61.8% incidence of fracture. CONCLUSIONS: Our series showed a low frequency of bone fractures. Postmenopausal women and overweight patients had more fractures. An initial immunosuppressive regimen using tacrolimus was associated with lower fracture rates.

Late steroid withdrawal after heart transplantation and incidence of acute rejection.

BACKGROUND: Steroid withdrawal (SW) after heart transplantation (HT) reduces steroid-associated side effects, although it can increase acute rejection episodes (ARE). Patient selection criteria for SW and the time elapsed after HT for this maneuver are controversial issues. The objective of this study was to assess the safety of late SW after HT with regard to the occurrence of ARE and to analyze risk factors resulting in a poor evolution. METHODS: We studied a cohort of 24 patients who underwent SW late after HT. All of them had gone at least 4 years without any ARE. Independent variables were time after HT, general recipient and donor data, risk factors for ARE, and immunosuppression. The dependent variables were occurrence of ARE (proven or not proven with endomyocardial biopsy) and time and severity of ARE. RESULTS: Among 24 HT patients including 96% men with an overall mean age of 57 years who underwent SW, the mean follow-up was 2.32 +/- 0.86 years. Six patients (25%) displayed an ARE >or=2R according to the International Society for Heart and Lung Transplantation (ISHLT) at 5 +/- 3 months after SW. There were no deaths. Time from the last rejection episode to SW was 6.6 +/- 2 years. All ARE were treated with steroid boluses (mean total dose 1583 +/- 1044 mg). Among the HT patients with ARE, 5 (85%) had never experienced ARE after HT. Upon long-term follow-up, there were 2 deaths: 1 sudden death at 30 months after SW and 1 due to allograft vasculopathy at 20 months post-SW. Currently 92% are New York Heart Association (NYHA) functional class I with a mean left ventricular ejection fraction of 67% +/- 10%. CONCLUSIONS: In our series of HT with late SW after HT (even among an HT population with a low risk of rejection), there was a 25% rate of ARE. This study did not allow us to identify risk factors for ARE after SW. We believe that based upon these observations SW should be implemented with caution.

Late noncardiac surgery in heart transplant patients.

OBJECTIVE: Because of improved long-term survival of heart transplants (HT), patients often need noncardiac surgery (NCS). Immunosuppression may increase the infection rate. Inadequate management may increase the risk of dysfunction or acute rejection episodes (ARE). Long-term outcomes of NCS and optimal immunosuppressive management in the perioperative period are not well known. The objective of this study was to analyze the incidence, morbidity, and mortality of late NCS after HT. METHODS: We retrospectively evaluated the incidence and type of late NCS as well as the risk factors for complications and the mortality among 207 HT patients. Immunosuppression and ARE rates were also analyzed. RESULTS: One hundred and sixteen late NCS (84.5% elective) were performed in 72 HT patients (34.8%). Interventions were: 35 urologic (30.2%), 29 abdominal (25%), 14 vascular (12.1%), 13 ENT (11.2%), 11 skin and soft tissue (9.5%), and 7 orthopedic (6%). Malignancy was the main indication for NCS (33.6%). Only 4 patients (5.6%) died preoperatively. Mortality was higher among emergent vs elective procedures (16.6% vs 1%; P = .012) and among patients with preoperative high vs middle/low risk (26.6% vs 0%). Postsurgical infection was the most frequent complication (6.9%). However, there were no relevant complications in 82.8% of HT patients. Hospitalization time was <15 days in two thirds of patients. Immunosuppression was modified in 33 patients (28.4%), especially when the surgical indication was neoplasia (P < .001). None of the patients with NCS displayed allograft dysfunction or an ARE. CONCLUSIONS: More than one-third of HT patients needed a late NCS. In our experience, elective surgical procedures with middle/low preoperative cardiovascular risk are safe. In this context, the risk of rejection was low when immunosuppression was carefully monitored to reduce the risk of infection.

Ultrastructure of pheochromocytoma: undescribed morphologic features.

We examined samples of human pheochromocytoma from 11 patients aged 30-70 years including one case of malignant pheochromocytoma with a view to identifying previously unreported ultrastructural details.We identified two types of nuclear inclusions consisting of irregularly shaped singular or multiple granulofibrillar formations with a typical concentric halo, on the one hand, and accumulations of egg-shaped structures consisting of granules and microfilaments, on the other. In some of the tumor cells, membrane-covered inclusions containing parallel laminar elements arranged in a paracrystalline, periodic fashion, or mega-mitrochondriae characterized by increased electrodensity of their matrix, and fibrillary material in the spaces between the cristae were present. A frequent finding consisted of typical ciliary formations, while rough/smooth tubular aggregates of different size occurred less frequently. Finally, we were able to demonstrate the uptake of norepinephrine by smooth muscle fibers in the periphery of arterial vessels as evidenced by linear accumulations of membrane-covered granules separating bands of contractile smooth muscle components in the peripheral layers of arterial vessels close to norepinephrine producing neoplastic cells.These findings represent ultrastructural features that contribute to further elucidating the ultrastructural characteristics of the human pheochromocytoma.

WITHDRAWN: Accuracy of Peak Treadmill Exercise Echocardiography to Detect Multivessel Coronary Artery Disease: Comparison with Post-exercise Echocardiography.

The publisher regrets that this was an accidental duplication of an article that has already been published in Eur. J. Echocardiogr., 4 (2003) 182-190, . The duplicate article has therefore been withdrawn.

Cellular distribution of growth hormone-releasing hormone receptor in human reproductive system and breast and prostate cancers.

Growth hormone releasing hormone receptor (GHRH-R) mRNA and protein was first localized to the anterior pituitary gland, consequent with the action of its ligand on GH synthesis and release. Subsequent studies found GHRH-R also expressed in the hypothalamus and in systemic tissues including those of the reproductive system. In the present work, we studied the distribution of GHRH-R in human reproductive system of males and females by immunohistochemical method. GHRH-R immunostaining was localized in male reproductive system: Leydig cells, Sertoli and basal germ cells of the seminiferous tubules and prostate secretory cells. GHRH-R immunostaining was also demonstrated in the ovary: oocytes, follicular cells, granulosa, thecal and corpus luteum cells. Endometrial glands, placenta and normal mammary glands also showed GHRH-R immunostaining. Our results demonstrate the localization of GHRH-R in the reproductive system, which may mediate the direct action of GHRH in these tissues. Moreover, GHRH-R was demonstrated in prostate and breast carcinomas, opening a variety of possibilities for the use of GHRH antagonists in the treatment of prostatic and mammary tumors.

Long-term results of heart transplant in recipients older and younger than 65 years: a comparative study of mortality, rejections, and neoplasia in a cohort of 445 patients.

BACKGROUND: Whether being older than 65 years should be considered an absolute counterindication to heart transplant (HT), as it is in some centers, is controversial. In our centre, patients older than 65 years are accepted for HT if they satisfy stringent conditions. The aim of this study was to examine whether heart recipients older than 65 years have a greater risk of rejection, neoplasia, or mortality than younger ones. METHODS: We studied 445 patients who underwent HT between April 1991 and December 2003, 42 of whom were older than 65 years and 403 who were 65 years or younger. The parameters evaluated were the cumulative incidences of neoplasias and rejections (ISHLT grade > or = 3A), and the survival rates 1 month, 1 year, and 5 years post-HT. RESULTS: The two groups had similar percentages of patients with at least one rejection episode (< or =65 years 56.9%, >65 years 51.3%; P > .05), and although there were proportionally almost twice as many tumors in the older group (14.2%) as in the younger (7.9%), this difference was not statistically significant either. Nor were there any significant differences in survival, the 1-month, 1-year, and 5-year rates being 87.8%, 82.1%, and 68.8%, respectively, in the younger group and 85.7%, 78.6%, and 73.4%, respectively, in the older. CONCLUSIONS: Among carefully selected patients aged more than 65 years, HT can be performed without incurring greater risk of rejection, malignancy, or death than is found among recipients younger than 65 years.

Safety of statins when response is carefully monitored: a study of 336 heart recipients.

BACKGROUND: Statins are used as first-line drugs against hypercholesterolemia after heart transplantation. Randomized clinical trials have shown that they reduce cholesterol levels, and the incidence of rejection and coronary vasculopathy. Adverse effects have been related to the use of certain statins, high statin dosages, comorbidities, and coadministration with cyclosporine. However, estimation of the risk of adverse effects for a given patient is difficult. The aims of this study were to determine the incidence of various kinds of adverse effect of statins; to evaluate certain potential risk factors; and to assess the efficacy of early response to signs of adverse effects. METHODS: Between April 1991 and December 2003, we retrospectively evaluated 336 heart transplant patients (including 55 women) with regard to the occurrence of possible adverse effects of statins (rhabdomyolysis, myalgia, hepatotoxicity, high CK without muscle symptoms, and others). Resolution on reduction of dosage or discontinuance and/or change of statin were deemed to constitute confirmation of cause. Relations were sought between adverse effects and age, sex, immunosuppressive therapy, kidney failure, body mass index (BMI), arterial hypertension, and diabetes mellitus. RESULTS: Possible adverse events of statins were suffered by 60 patients, all of them men. The causal role of statins was confirmed in 41 (12.2% of all 336): hepatotoxicity was suffered by 13, high CK without muscle ache or weakness by 18, rhabdomyolysis by 5, myalgia by 3, and other effects by 2. The incidence of confirmed statin-related complications was higher among patients with BMI >29 kg/m(2) than among those with lower BMI (P = .055). None of the patients with confirmed statin-related complications needed dialysis, none died, and permanent suspension of statin treatment was only necessary in 13 cases (3.9% of the 336). CONCLUSIONS: Some 10% to 20% of HT patients appear to suffer adverse side effects of initial statin therapy. However, early detection of such effects through diligent clinical and analytical monitoring allows the therapy to be modified in time to minimize the appearance of severe complications. In only a minority of cases permanent suspension of statin therapy is necessary.

Morphometric characterization of the human neuroendocrine Merkel cells.

In this study, the neuroendocrine Merkel cells (NEMCs) from adult human epidermis are defined morphometrically, using the MOP 20 image analyzer to measure 21 parameters of either the cell as a whole, or particular cellular structures. Maximum diameter (8.09 microns), perimeter (26.51 microns), area (36.87 microns2) and form factor (0.626) for the cell as a whole, and maximum diameter (5.08 microns), perimeter (18.74 microns), area (12.54 microns2) and form factor (0.452) for the nucleus were determined. Also measured were nuclear-cytoplasmic ratio (0.5595), filament thickness (10 nm), and granular numerical density (7.02 granules/micron2). Maximum diameter, area, and form factor of neurosecretory granules were 94.23 nm, 5020.05 nm2, and 0.93, respectively. Length of desmosomes linking NEMCs to keratinocytes was determined (286.9 nm) and compared with that of interkeratinocytic desmosomes (385 nm). In addition, length and diameter of cellular processes (spine-like processes (1.58 micron X 0.26 micron), interstitial processes (1.39 micron X 0.25 micron), and microvilli (0.35 micron X 0.25 micron) were measured after separation and classification according to the particular morphologic characteristics of each.

Staining of neuroendocrine Merkel cells of human epidermis using the uranaffin reaction.

The uranaffin reaction (UR) stains neurosecretory (NS) granules of the neuroendocrine system under certain experimental conditions of staining and rinsing solutions. Human normal neuroendocrine (NE) Merkel cells stained using the UR exhibit a positive reaction in their NS granules, ribosomes, and nuclear chromatin. The average values of maximum granular diameter (GD = 69.1 nm) and area (GA = 3637.8 mm2) of NS granules measured in the adult NE Merkel cells stained with UR are significantly greater than those (GD = 61.4 nm; GA = 2699.8 nm2) seen in the fetal NE Merkel cells also stained with UR. No differences in form factor are found between fetal and adult NS granules. On different samples of human adult and fetal epidermis it is demonstrated that UR is a useful cytochemical marker for the NS granules of normal NE Merkel cells.

Cellular localization of orexin receptors in human pituitary.

Orexins-A and -B are hypothalamic peptides derived from a precursor called prepro-orexin and relationated with the stimulation of food intake. They act on G protein receptors named orexin receptor 1 (OX(1)R) and orexin receptor 2 (OX(2)R), respectively. In the present study, we used RT-PCR and immunohistochemical techniques to detect the presence of OX(1)R and OX(2)R in human pituitary. A band of the expected size for both OX(1)R and OX(2)R was shown in human pituitary by RT-PCR. The cellular localization of OX(1)R and OX(2)R was carried out using histological techniques. By consecutive sections we demonstrated that OX(1)R was present in acidophil, diffusely distributed cells, which represent the half of the total adenohypophysis cell population. As was expected, these cells were shown to coexpress GH. OX(2)R was found in the pars intermedia and in clusters of basophil cells of the anterior pituitary, which coexpress ACTH. These results were confirmed by double immunofluorescence techniques. We also found focal positivity in axon terminals of neurohypophysis, more intense for OX(2)R than for OX(1)R. In conclusion, these results demonstrated for the first time that OX(1)R and OX(2)R were expressed by somatotrope and corticotrope cells, respectively.

Cellular localization of orexin receptors in human pituitary.

Orexins-A and -B are hypothalamic peptides derived from a precursor called prepro-orexin and relationated with the stimulation of food intake. They act on G protein receptors named orexin receptor 1 (OX(1)R) and orexin receptor 2 (OX(2)R), respectively. In the present study, we used RT-PCR and immunohistochemical techniques to detect the presence of OX(1)R and OX(2)R in human pituitary. A band of the expected size for both OX(1)R and OX(2)R was shown in human pituitary by RT-PCR. The cellular localization of OX(1)R and OX(2)R was carried out using histological techniques. By consecutive sections we demonstrated that OX(1)R was present in acidophil, diffusely distributed cells, which represent the half of the total adenohypophysis cell population. As was expected, these cells were shown to coexpress GH. OX(2)R was found in the pars intermedia and in clusters of basophil cells of the anterior pituitary, which coexpress ACTH. These results were confirmed by double immunofluorescence techniques. We also found focal positivity in axon terminals of neurohypophysis, more intense for OX(2)R than for OX(1)R. In conclusion, these results demonstrated for the first time that OX(1)R and OX(2)R were expressed by somatotrope and corticotrope cells, respectively.

Cellular distribution of prolactin receptors in human digestive tissues.

In the present study we analyzed the expression of prolactin receptors (PRLR) in human digestive tissues by immunohistochemistry. PRLR immunoreactivity was primarily localized in the cytoplasm. However, in some organs (liver and salivary glands) a nuclear positivity was also found. The liver was used as control and showed a diffuse immunostaining in the parenchymal cells. In the gastrointestinal tract, PRLR immunoreactivity was observed in the mucosa, muscularis layer, and nervous plexuses. The more intense immunostaining in the mucosa of the different segments was as follows: esophagus, superficial layers of the stratified squamous epithelium and mucous glands; stomach, parietal cells; small intestine, absorptive and Paneth cells; and colon, surface epithelium and superficial half of the crypts of Lieberkühn. In the salivary glands, immunoreactivity was strong in the mucous tubules, moderate in the ducts, and weak in the serous cells. Endocrine pancreas showed a more intense immunoreactivity than the pancreatic acini. By serial sections of the islets of Langerhans we showed that immunostaining was confined to B cells. These findings demonstrate the widespread distribution of PRLR in human digestive tissues and its localization both in cytoplasms and nuclei.

Cytomegalovirus colitis mimicking a colonic neoplasm or ischemic colitis 4 years after heart transplantation.

BACKGROUND: Cytomegalovirus (CMV) colitis is a polymorphous disease presenting in immunodepressed patients in a variety of clinical forms that can delay diagnosis and therapy. We report the case of a patient who presented with abdominal pain 4 years after heart transplantation; clinical and x-ray findings were suggestive of a neoplastic or ischemic stenosis, and histopathological examination likewise initially suggested an ischemic etiology. METHODS: Tissue samples were fixed in 10% formaldehyde, embedded in paraffin, cut, and stained with hematoxylin/eosin and periodic acid-Schiff-Alcian Blue. Immunohistochemistry with monoclonal antibodies was performed using an indirect immunoperoxidase method. RESULTS: CMV colitis was eventually diagnosed and resolved with surgery and specific anti-CMV therapy. CONCLUSIONS: CMV colitis should be suspected in any heart transplant patient with signs or symptoms of abdominal pathology, even without classical signs or symptoms of CMV infection. If stenotic lesions are present, surgery may be required not only to remove the obstruction but also to rule out malignancy.

Labil subaortic obstruction during exercise stress echocardiography.

Exercise-induced subaortic obstruction and/or mitral valve systolic anterior motion causing mitral regurgitation were found in 43 of 2,280 patients (1.8%) assigned to treadmill exercise echocardiography.