Moderate Hypertrophy Research Articles

Morphological evaluation of the effects of ursodeoxycholic acid on muscular layer of the gallbladder wall of the mice

Background. Significant prevalence and the possibility of transformation into organic pathology determine the relevance of functional disorders of the gallbladder and sphincter of Oddi in children. The proposed hypothesis is that the increased differentiation of fibroblasts into the smooth muscle cells of the gallbladder wall in the experimental model of mice occurs under the influence of ursodeoxycholic acid. Objective: to determine the histo-ultrastructural changes of cells of the muscular wall of the gallbladder wall of experimental mice under the action of ursodeoxycholic acid. Methods. By the method of simple randomization, mice were divided into 2 groups: experimental group (n = 17) - animals that were received ursodeoxycholic acid at a dose of 100.0 mg/kg and control group (n = 13) - intact (distilled water). Gallbladder morphological examination was performed using light and electron microscopy methods. Results. Impact of ursodeoxycholic acid on the gallbladder muscular layer characterized by moderate hypertrophy of the gallbladder smooth muscle myocytes that contain metabolically active pale nuclei and prominent nucleoli. After the ursodeoxycholic acid administration an increase in the content and activity of the elements of the contractile and energy apparatus of leiomyocytes were found. In addition, ursodeoxycholic acid administration led to an increase in the number of caveolae and micropinocytic vesicles near the cell membrane of smooth muscle cells. Analysis of the components of the interstitium of the mice gallbladder muscular layer of the experimental group revealed the nuclear activity of fibroblasts due to the decondensation of chromatin. Also in the experimental group was characterized by the presence of immature collagen fibrils along with normal striated fibers that was a sign of the rearrangement of the endomysium structure. Conclusion. The effect of ursodeoxycholic acid on the muscular membrane of the gallbladder wall of mice of the experimental group is morphologically manifested by signs of moderate hypertrophy of smooth myocytes, activation of their intracellular transport and increased activity of interstitial fibroblasts.

Identification of a novel titin-cap/telethonin mutation in a Portuguese family with hypertrophic cardiomyopathy

Introduction and objectivesHypertrophic cardiomyopathy (HCM) is a genetically and phenotypically heterogeneous disease; there is still a large proportion of patients with no identified disease-causing mutation. Although the majority of mutations are found in the MYH7 and MYBPC3 genes, mutations in Z-disk-associated proteins have also been linked to HCM. MethodsWe assessed a small family with HCM based on family history, physical examination, 12-lead ECG, echocardiogram and magnetic resonance imaging. After exclusion of mutations in eleven HCM disease genes, we performed direct sequencing of the TCAP gene encoding the Z-disk protein titin-cap (also known as telethonin). ResultsWe present a novel TCAP mutation in a small family affected by HCM. The identified p.C57W mutation showed a very low population frequency, as well as high conservation across species. All of the bioinformatic prediction tools used considered this mutation to be damaging/deleterious. Family members were screened for this new mutation and a co-segregation pattern was detected. Both affected members of this family presented with late-onset HCM, moderate asymmetric left ventricular hypertrophy, atrial fibrillation and heart failure with preserved ejection fraction and low risk of sudden cardiac death. ConclusionsWe present evidence supporting the classification of the TCAP p.C57W mutation, encoding the Z-disk protein titin-cap/telethonin as a new likely pathogenic variant of hypertrophic cardiomyopathy, with a specific phenotype in the family under analysis.

Regression of Left Ventricular Mass After Transcatheter Aortic Valve Replacement: The PARTNER Trials and Registries

BackgroundGreater early left ventricular mass index (LVMi) regression is associated with fewer hospitalizations 1 year after transcatheter aortic valve replacement (TAVR). The association between LVMi regression and longer-term post-TAVR outcomes is unclear. ObjectivesThe purpose of this study was to determine the association between LVMi regression at 1-year post-TAVR and clinical outcomes between 1 and 5 years. MethodsAmong intermediate- and high-risk patients who received TAVR in the PARTNER (Placement of Aortic Transcatheter Valves) I, II, and S3 trials or registries and were alive at 1 year, we included patients with baseline moderate or severe left ventricular hypertrophy (LVH) and paired measurements of LVMi at baseline and 1 year. The associations between LVMi regression (percent change between baseline and 1 year) and death or rehospitalization from 1 to 5 years were examined. ResultsAmong 1,434 patients, LVMi was 146 g/m2 (interquartile range [IQR]: 133 to 168 g/m2) at baseline and decreased 14.5% (IQR: 4.2% to 26.1%) to 126 g/m2 (IQR: 106 to 148 g/m2) at 1 year. After adjustment, greater LVMi regression at 1 year was associated with lower all-cause death (adjusted hazard ratio [aHR]: 0.95 per 10% decrease in LVMi; 95% confidence interval [CI]: 0.91 to 0.98; p = 0.004; aHR of the quartile with greatest vs. least LVMi regression: 0.61; 95% CI: 0.43 to 0.86; p = 0.005). Severe LVH at 1 year was observed in 39%, which was independently associated with increased all-cause death (aHR of severe LVH vs. no LVH: 1.71; 95% CI: 1.20 to 2.44; p = 0.003). Similar associations were found for rates of cardiovascular mortality and rehospitalization. ConclusionsAmong patients with moderate or severe LVH treated with TAVR who are alive at 1 year, greater LVMi regression at 1 year is associated with lower death and hospitalization rates to 5 years. These findings may have implications for the timing of valve replacement and the role of adjunctive medical therapy after TAVR.

Assessment of features of morphometric structural changes in the testes at conditions of postresection portal hypertension

Introduction. Postresection portal hypertension leads to complex general biological processes that occur and develop in the organs and systems of the body during its adaptation to a new level of life [10]. It should be noted that detailed and objective knowledge of compensatory-adaptive processes in the testes during resection of various volumes of the liver, their role in the development of organ failure to date have been insufficiently studied and need to be addressed.Objective of the research: to study morphometric structural changes of testes in the conditions of postresection portal hypertension and multiorgan failure.Materials of the research and their discussion. The testes of 40 white male rats were divided into 3 groups studied morphologically. Group 1 consisted of 12 intact animals, 2 - 18 rats with postresection portal hypertension, 3 - 10 animals with postresection portal hypertension and poliorganic failure. Euthanasia of rats was performed by bloodletting under thiopental anesthesia a month after the start of the experiment. Micropreparations from the testes stained hematoxylin-eosin, toluidine blue, using the Weigert method, van Gieson, Mallory, Morphometrically, on the testicular micropreparations, the diameters of the testicles tubules, the thickness of their walls, the number of cells of the epithelio-spermatogenic layer in the tubule, the number of Sertoli cells per tubule, the tubulo-interstitial index, the stromal-parenchymal ratio, the Leydigas index, the sperm index, were determined. Quantitative morphological parameters were processed statistically.Results of the research and their discussion. It was found that the investigated morphometric indices of the testes in the 2 and 3 groups of observations varied markedly in comparison with the control values. Thus, the diameter of the seminile tubules in the conditions of postresection portal hypertension was statistically significantly (p˂0.001) decreased by 11.8 %, with the development of multiple organ failure - by 34.0 % (p<0.001), and the number of cells of the epithelio-spermatogenic layer in tubules respectively by 11.3 % and 32.9 % (p˂0.001), which indicated the presence of atrophy of the studied structures.The wall thickness of the tubules in the 2 group increased by 8.8 %, in the 3 group - by 26.9 % (р<0.001), and the Leydig index - by 22.9 % and 57.8 %, respectively (р<0.001). The number of Sertoli cells in one testicle tubule in the 2nd group decreased by 1.6 % and in the 3rd by 8.06 % (p <0.001).Stromal-parenchymal ratios in the testes with simulated pathology statistically significantly increased (р<0.001) by 11.3 % (р˂0.01) and 31.8 % (р˂0.001), while the tubulo-interstitial index decreased respectively by 8.9 % (p<0.001) and 31.8 % (p<0.001). The revealed changes of the investigated morphometric parameters showed a pronounced increase in the number of stroma in the testes. The spermatogenesis intensity index also decreased by 2.9 % (p<0.05) and 38.8 % (p<0.001), respectively.Obtained morphometric parameters indicate that the simulated pathology leads to a decrease in the diameter of the tubules and the thickening of their walls. In the latter, optically sclerosis was observed. In the lumen of the seminiferous tubules, histologic examination revealed spermatocytes of the first order and spermatogonia, rarely observed spermatocytes of the second order. Protein detritus and rarely sperm were detected in the tubules.Conclusions. So postresection portal hypertension and multiorgan failure lead to pronounced structural restructuring of the vascular, interstitial and endocrine components of the testes, characterized by dilatation, plethora, varicose extensions, stasis, hemorrhage, perivasal swelling of the vessels gemomicrocirculatory bad and, hyperplasia, moderate hypertrophy Leydig cell dystrophy. The detected morphological changes dominate in multiple organ failure.

The proarrhythmic features of pathological cardiac hypertrophy in neonatal rat ventricular cardiomyocyte cultures.

Different factors may trigger arrhythmias in diseased hearts, including fibrosis, cardiomyocyte hypertrophy, hypoxia, and inflammation. This makes it difficult to establish the relative contribution of each of them to the occurrence of arrhythmias. Accordingly, in this study, we used an in vitro model of pathological cardiac hypertrophy (PCH) to investigate its proarrhythmic features and the underlying mechanisms independent of fibrosis or other PCH-related processes. Neonatal rat ventricular cardiomyocyte (nr-vCMC) monolayers were treated with phorbol 12-myristate 13-acetate (PMA) to create an in vitro model of PCH. The electrophysiological properties of PMA-treated and control monolayers were analyzed by optical mapping at day 9 of culture. PMA treatment led to a significant increase in cell size and total protein content. It also caused a reduction in sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 level (32%) and an increase in natriuretic peptide A (42%) and α1-skeletal muscle actin (34%) levels, indicating that the hypertrophic response induced by PMA was, indeed, pathological in nature. PMA-treated monolayers showed increases in action potential duration (APD) and APD dispersion, and a decrease in conduction velocity (CV; APD30 of 306 ± 39 vs. 148 ± 18 ms, APD30 dispersion of 85 ± 19 vs. 22 ± 7 and CV of 10 ± 4 vs. 21 ± 2 cm/s in controls). Upon local 1-Hz stimulation, 53.6% of the PMA-treated cultures showed focal tachyarrhythmias based on triggered activity (n = 82), while the control group showed 4.3% tachyarrhythmias (n = 70). PMA-treated nr-vCMC cultures may, thus, represent a well-controllable in vitro model for testing new therapeutic interventions targeting specific aspects of hypertrophy-associated arrhythmias.NEW & NOTEWORTHY Phorbol 12-myristate 13-acetate (PMA) treatment of neonatal rat ventricular cardiomyocytes (nr-vCMCs) led to induction of many significant features of pathological cardiac hypertrophy (PCH), including action potential duration prolongation and dispersion, which provided enough time and depolarizing force for formation of early afterdepolarization (EAD)-induced focal tachyarrhythmias. PMA-treated nr-vCMCs represent a well-controllable in vitro model, which mostly resembles to moderate left ventricular hypertrophy (LVH) rather than severe LVH, in which generation of a reentry is the putative mechanism of its arrhythmias.

Фактори смертності хворих на серцево-судинну патологiю з коронавірусною інфекцією

Due to the COVID-19 outbreak, management of patients with severe cardiovascular disease has become much more complicated. The paper describes first-hand experience of managing a COVID-19 patient with chronic heart failure secondary to myocardial infarction who died from sudden cardiac death. Mortality risk factors in COVID-19-associated cardiac patients are discussed. The authors describe a case of a female patient B., 67 years old, who was taken to the hospital by ambulance with a preliminary diagnosis of community-acquired right lower lobe pneumonia, respiratory failure (RF) II (SpO294%). Coronary heart disease (CHD). Athero-sclerotic and postinfarction (2019) cardiosclerosis. Permanent atrial fibrillation. Hypertension, stage III, grade 3, risk 4 (stroke, 2019). Heart failure (HF) II-A (NYHA class II). Rapid tests for the diagnosis of influenza A and B and detection of COVID-19 antibodies IgG and IgM were negative. From the patient’s history it was found out that over the last 2 months she was in a private medical rehabilitation center. Nine days before her hospitalization, her relatives took her home. According to them, the patient developed fever (37.5–38.4 °C) 4 days before hospitalization, she took paracetamol in her discretion. On admission, her body temperature was 37.5 °C. The patient was hospitalized to the triage department; on the day of hospitalization, her nasopharyngeal lavage was taken for real-time PCR (polymerase chain reaction) for COVID-19. During the hospital stay the patient’s condition stabilized. The next day after hospitalization, the maximum body temperature was within 37.0 °C, shortness of breath decreased, heart rate slowed, RF disappeared, room-air SpO2increased up to 96%. According to the results of echocardiography, the left ventricle (LV) pump function remained preserved (LV ejection fraction was 50%), LV cavities were slightly enlarged, and valvular pathology was characterized by moderate mitral and tricuspid insufficiency. The area of hypokinesia due to myocardial infarction was determined only in the apical segment of the lateral wall and was compensated due to moderate left ventricular hypertensive hypertrophy (left ventricular mass index 129 g/L2). R wave amplitude on the electrocardiography was preserved, which indicated relative compensation of the central hemodynamics of the patient B. On day 2 of hospitalization, the patient’s condition remained stable. The body temperature normalized, leg swelling disappeared, cough and shortness of breath decreased, physical activity significantly improved. The patient was examined by an infectious disease specialist. After receiving the COVID-19 test result (positive PCR test), it was agreed to transfer the patient to a coronavirus hospital for further treatment in the infectious department. However, the patient died suddenly. Final diagnosis: coronavirus disease. COVID-19. Community-acquired bilateral lower lobe pneumonia (viral). Respiratory failure (RF) – 0. CHD. Atherosclerotic and postinfarction (2019) cardiosclerosis. Permanent atrial fibrillation. Hypertension, stage III, grade 3, risk 4 (stroke, 2019). HF II-B. Since dissection was not performed, the exact cause of death is unknown. The article describes important aspects of diagnosis and treatment that can prevent mortality. The authors emphasize that prevention and control of infectious diseases should be prioritized at any time. Individual measures of diagnosis and treatment should be taken considering specific local epidemic situations.

P1466 Pacman heart documented by multimodality echocardiographic techniques

Abstract We report a case of a 78-year old female with hypertension, dyslipidemia, atrial fibrillation under warfarin therapy and previously diagnosed HFpEF. She also had a history of recurrent episodes of bilateral inferior limb acute ischemia requiring urgent embolectomy and one previous cardioembolic stroke. She had no history of ischemic heart disease. She was admitted to our center due to acute decompensated heart failure (NYHA class III). On physical examination there was evidence of pulmonary congestion with bilateral crackles, without heart murmurs. ECG showed AF rhythm, without any other significant changes. The transthoracic echocardiogram (TTE) showed moderate biventricular hypertrophy with apical predominance and good systolic function. A partial loss of myocardial tissue in the mid segment of the interventricular septum was noticed, with no left-to-right shunt on color Doppler, apparently without interventricular communication (figure A). For further elucidation of this finding a contrast-enhanced TTE was performed, revealing a serpiginous route through the septum to a small contained cavity within it (figure B). 3D TTE en face views additionally clarified the semilunar shape of this septal defect and its movement during the cardiac cycle, closing during systole and opening during diastole (figure C). At this point, clinical history and previous diagnostic exams were reviewed. A thoracic CT conducted 3 years before in another clinical context showed that the ventricular septal defect was already present, with similar characteristics (figure D). As doubts persisted about the existence of interventricular communication, cardiac catheterization with oximetry and ventriculography was performed and interventricular shunt was excluded. There was no evidence of coronary artery disease. Cardiac MRI was not possible due to lack of patient collaboration. Final diagnosis was a partial ventricular septal defect (PVSD), probably congenital. The patient was discharged under optimized medical therapy. PVSDs, which are rarely reported in the literature, are thought to be congenital (sporadic or familial) or a consequence of myocardial infarction. They have been described as "Pacman" heart due to the shape changes during the cardiac cycle, becoming slit-like or even absent during systole, like an opening/closing mouth, resembling the Pacman video game. Related complications include conduction disturbances, rupture and disturbed systolic function. We describe a rare case of a partial ventricular septal defect, documented by multimodality echocardiographic techniques: 2D TTE first showed an incomplete defect of the mid interventricular septum; contrast-enhanced TTE revealed its serpiginous route to a small cavity; 3D TTE en face views further illustrated its semilunar shape and characteristic movement during the cardiac cycle. Abstract P1466 Figure.

P257 Multiple clinical manifestations of catecholamine secreting paraganglioma

Abstract A 37 years old woman was referred to our hospital due to the onset since the previous day of vertigo associated with nausea and headache. Her previous history revealed an hospitalization ten years before for Tako Tsubo Cardiomyopathy, during which the diagnosis of left temporo-jugular catecholamine secreting paraganglioma was made. Subsequently, there were several hospitalizations for multiple cardiac manifestations, such as acute coronary syndrome during hypertensive crisis, acute pulmonary oedema, one relapse for TakoTsubo syndrome and then an episode of torsade de pointes (TdP) during hypokalemia and elongated QT. The surgical removal of the mass was always rejected by the patient, and therefore, only radiotherapy was performed with significant reduction of the tumour dimensions. Moreover, alpha and beta adrenergic blockers were always administrated. At the admission, she complained neurological symptoms, in particular balance disorder and dysmetria. Brain Computed tomography (CT) was performed and it showed left posterior cerebellar infarction in late acute clinical phase, without haemorrhage. The patient underwent angiography that excluded cerebral artery dissection but showed acute occlusion of posterior internal cerebral artery. Echocardiogram showed moderate left ventricular hypertrophy with normal global and segmental kinetics, left atrial dilatation; besides, left ventricular apical thrombus was excluded. Holter ECG monitoring showed very frequent polymorphic ventricular and supraventricular extrasystolic beats. Urinary metanephrines were markedly increased. In particular urinary normetanephrine was up to 9 times the upper limit of normality (4874 ug/L, normal range 162-527 ug/24 h). Since the surgical intervention was always refused, this case is a rare documentation of the several different cardiovascular clinical manifestation due to catecholamine secretion in a single patient. Paraganglioma could be a catecholamine secreting tumour that arises from cromaffin tissue of the sympathetic nervous system. Clinical manifestations of paraganglioma are extremely variable leading to its designation as "great mimic". Adrenal tumours are associated with several cardiovascular diseases including LV hypertrophy, myocardial infarction, cardiac arrhythmias, heart failure and Tako Tsubo cardiomyopathy. Cerebral accident is a rare manifestation of adrenergic crisis with several possible aetiologies such as vasospasm or cardioembolic events. In our clinical case, considering the type and localization of the cerebral ischemic injury, the stroke is likely to have a cardioembolic etiology. Apical left ventricular trombus and PFO were excluded. Therefore, in view of left atrial enlargement and the frequent supraventricular ectopy, even in the absence of documented arrhythmia, an undiagnosed episode of catecholamines induced atrial fibrillation was suspected, with subsequent cardioembolic event. Abstract P257 Figure.

Changes in the Expression of Genes Regulating Calcium Homeostasis in Rat Myocardium Induced by Voluntary Wheel Training: The Role of Thyroid Hormones

Thyroid hormones increase cardiac contractility due to their effect on the Ca2+ homeostasis in cardiomyocytes. Type 2 deiodinase (D2), which provides local synthesis of T3 from T4, is essential for the adaptation of skeletal muscles to aerobic exercise; however, its role in the myocardium has not been explored. The aim of this study was to assess the effect of wheel training on the expression of genes that regulate the heart contractility and to explore the relationship of their mRNA content in the myocardium with indicators of systemic and local T3 production. Male Wistar rats were housed in cages with running wheels for eight weeks; the samples of their serum were used to determine hormones by ELISA and muscle tissue to determine mRNA content by reverse transcription quantitative PCR. The training was accompanied by a moderate hypertrophy of the soleus muscle and an increase in its citrate synthase mRNA content. Ventricle mass and the expression levels of αMHC, βMHC, β1-adrenoreceptors, Cav 1.2, Serca2, RyR2, and PLB mRNA in trained rats did not differ from respective values in the control groups of rats. Blood content of free T3 and the expression of D2 mRNA in the left ventricle increased as a result of training; a negative correlation between these indicators was found. The levels of Serca2, Cav 1.2, and RyR2 mRNA positively correlated with the D2 mRNA content in the trained but not in control rats; however, these parameters did not correlate with the free T3 level in the blood. The observed correlations suggest that myocardium adaptation to aerobic exercise is governed by the effect of locally synthesized T3 rather than by an increase in its systemic production.

Role of inflammation, oxidative stress, and autonomic nervous system activation during the development of right and left cardiac remodeling in experimental pulmonary arterial hypertension.

This study investigated the impact of experimental pulmonary arterial hypertension (PAH) progression by evaluating morphometric and functional parameters, oxidative stress, autonomic nervous system (ANS) activation, and inflammation in the right (RV) and left (LV) ventricles. Male rats were first divided into two groups: monocrotaline (MCT) and control. The MCT group received a single MCT injection (60mg/kg, intraperitoneal), while control received saline. The MCT and control groups were further divided into four cohorts based on how long they were observed: 1, 2, 3, and 4weeks. Animals were submitted to echocardiographic and hemodynamic analysis. RV and LV were used for morphometric, biochemical, and histological measurements. Autonomic modulation was evaluated by cardiac spectral analysis, considering two components: low frequency (LF) and high frequency (HF). Lung and liver weight was used for morphometric analysis. MCT induced 100% mortality at 4weeks. In the RV, disease progression led to mild inflammation and enhanced reactive oxygen species (ROS) in week 1, followed by moderate inflammation, ROS production, and hypertrophy in week 2. By week 3, there was moderate inflammation, oxidative stress, and ANS imbalance, with development of right heart dysfunction. LV biochemical changes and inflammation were observed at week 3. The initial changes appeared to be related to inflammation and ROS, and the later ones to inflammation, oxidative stress, and ANS imbalance in MCT animals. This study reinforces the severity of the disease in the RV, the late effects in the LV, and the role of ANS imbalance in the development of heart dysfunction.

MORPHOMETRIC ANALYSIS OF STRUCTURAL CHANGES IN THE TESTES AT CONDITIONS OF POSTRESECTION PORTAL HYPERTENSION AND POLYORGANIC FAILURE

The testes of 50 white male rats were divided into 3 groups studied morphologically. Group 1 consisted of 15 intact animals, 2 – 25 rats with postresection portal hypertension, 3 – 10 animals with postresection portal hypertension and multiple organ failure. Euthanasia of rats was performed by bloodletting under thiopental anesthesia a month after the beginning of the experiment. Micropreparations from the testes were stained with hematoxylin-eosin, toluidine blue, using the Weigert method, van Gieson, Mallory. Morphometrically, on the testicular micropreparations, the diameters of the testicles tubules, the thickness of their walls, the number of cells of the epithelial-spermatogenic layer in the tubule, the number of Sertoli cells per tubule, the tubulo-interstitial index, the stromal-parenchymal ratio, the Leydigas index, the sperm index, were determined. Quantitative morphological parameters were processed statistically. The investigated morphometric indices of the testes in the 2 and 3 groups of observations were found to vary markedly in comparison with the control values. Thus, the diameter of the seminiferous tubules in the conditions of postresection portal hypertension was statistically significantly (p˂0.001) decreased by 11.8 %, with the development of multiple organ failure – by 34.0 % (p<0.001), and the number of cells of the epithelialspermatogenic layer in tubules respectively by 11.3 % and 32.9 % (p˂0.001), which indicated the presence of atrophy of the studied structures. The wall thickness of the tubules in the 2 group increased by 8.8%, in the 3 group – by 26.9 % (р<0.001), and the Leydig index – by 22.9 % and 57.8 %, respectively (р<0.001). The number of Sertoli cells in one testicle tubule in the 2nd group decreased by 1.6 % and in the 3rd by 8.06 % (p<0.001). Stromal-parenchymal ratios in the testes with simulated pathology statistically significantly increased (р<0.001) by 11.3 % (р˂0.01) and 31.8 % (р˂0.001), while the tubular-interstitial index decreased respectively by 8.9 % (p<0.001) and 31.8 % (p<0.001). The revealed changes of the investigated morphometric parameters showed a pronounced increase in the number of stroma in the testes. The spermatogenesis intensity index also decreased by 2.9 % (p<0.05) and 38.8 % (p<0.001), respectively. Obtained morphometric parameters indicate that the simulated pathology leads to a decrease in the diameter of the tubules and the thickening of their walls. In the latter, optically sclerosis was observed. In the lumen of the seminiferous tubules, histologic examination found spermatocytes of the first order and spermatogonia, rarely observed spermatocytes of the second order. Protein detritus and rarely sperm were detected in the tubules. Thus, postresection portal hypertension and multiple organ failure lead to pronounced structural rebuilding of the vascular, interstitial and endocrine components of the testes, characterized by dilatation, plethora, varicose extensions, stasis, hemorrhage, perivasal swelling of the vessels of the gemomicrocirculatory bad and, hyperplasia, moderate hypertrophy, and Leydig cell dystrophy. The detected morphological changes dominate in case of multiple organ failure.

MRI native T1 and T2 mapping of myocardial segments in hypertrophic cardiomyopathy: tissue remodeling manifested prior to structure changes.

The aim of this study was to examine the local myocardial segments in hypertrophic cardiomyopathy (HCM) by MRI T1 and T2 mapping, and to investigate how tissue remodeling correlates with structural and functional remodeling in HCM. 47 patients with HCM and 19 healthy volunteers were enrolled in this study. All subjects underwent cardiac MRI at 3.0 T. Native T1 and T2 values, end-diastolic wall thickness (EDTH), and percentage of systolic wall thickening (PSWT) were assessed in the left ventricular segments according to the American Heart Association model. Myocardial segments were categorized as normal, non-hypertrophic, mild-hypertrophic, moderate-hypertrophic, and severe-hypertrophic based on EDTH. The difference among all five groups, and the correlation between native T1 and T2 values, EDTH, and PSWT were evaluated. Native T1 and T2 values were significantly elevated in both non-hypertrophic and hypertrophic segments of HCM patients compared to controls (both p < 0.001). PSWT was preserved in non-hypertrophic segments (p = 0.838), while significantly impaired (p < 0.001) in hypertrophic segments. Native T1 value of severe hypertrophic segments in HCM was significantly higher than segments of mild and moderate hypertrophy (p < 0.05). In HCM patients, the non-hypertrophic myocardial segments already demonstrated significantly elevated T1 and T2 values, despite normal wall thickness and preserved contraction function. The finding suggests that tissue remodeling may precede morphological and functional remodeling in HCM. MRI native T1 and T2 mapping can provide additional value for HCM diagnosis at an early stage. Myocardial tissue remodeling, as detected by MRI native T1 and T2 mapping, occurs earlier than morphological and functional changes in HCM patients.

P2725Transthyretin cardiac amyloidosis in heart failure with preserved ejection fraction: Imaging by Tc-99m bone scan

Abstract Background Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome with multiple underlying causes. Transthyretin amyloidosis (ATTR) is an underdiagnosed cause of HFpEF. Extraosseous uptake, in particular, myocardial uptake, was observed in a number of ATTR patients examined with the bone scan tracers. Objectives We sought to determine the prevalence of ATTR as detected by the bone scan among the patients admitted due to HFpEF. Methods We screened all consecutive patients ≥60 years old admitted due to HFpEF (left ventricular ejection fraction ≥50%). All eligible patients were offered an echocardiogram and a bone scan (a 99mTc-DPD/MDP/HMDP scintigraphy). Echocardiographic and clinical variables were gathered in all the subjects. The intensity of the myocardial uptake was graded according to a visual scale ranging from 0 to 3 points, in which the absence of uptake was assigned a score of 0 points; uptake less than that of bone (referred to as the adjacent rib), 1 point; uptake similar to that of bone, 2 points; and uptake greater than that of bone, 3 points. The distribution of the uptake in myocardium was defined as focal uptake, diffuse uptake, uptake in a ventricular wall segment, diffuse ventricular uptake, or diffuse biventricular uptake. Results The study included 62 HFpEF patients (52% women, 73±9 years). The bone scintigraphic analysis revealed relatively intense myocardial uptake in 7 of 62 patients (11.2%). 7 patients had intense Tc-99m uptake (score of 2–3) in the cardiac region, showing deposition in both right and left ventricles in every case. Patients with amyloid deposition were older (78±6 vs. 70±12 years, p&lt;0.05), had a lower systolic blood pressure (118±23 vs. 148±28 mmHg, p&lt;0.05), and left ventricular ejection fraction (52±11 vs. 58±6%, p&lt;0.05). Both groups had at least moderate left ventricular hypertrophy and abnormal global longitudinal strain with no significant difference between groups. In 6 all the cases, the final diagnosis of amyloidosis was based on the results of abdominal fat aspiration biopsy. Conclusion ATTR is an underdiagnosed disease that accounts for a significant number (11.2%) of HFpEF cases. These findings create an opportunity for further investigation in the targeted therapy of patients with HFpEF.

Modified round block technique for peripherally located early cancer breast, a technique that fits for all quadrants.

Round block technique (RBT) is an oncoplastic technique used in periareolar lesions, particularly in breasts with moderate ptosis or hypertrophy. However, it has some drawbacks including the possibility of late-onset scar widening, change in areolar shape, and asymmetry of the breasts. Moreover, it is hard to be performed with tumors located in periphery of breast. Modified round block technique (MRBT) is a new technique described to overcome these problems. A circumferential periareolar incision was made around the areola followed by subcutaneous dissection to the entire breast. Wide local excision (WLE) could then easily be performed with a good field of view, the breast tumor was excised with an acceptable macroscopic safety margin, and specimens were marked with orienting sutures for intraoperative frozen section. Remodeling of the breast was done, a close suction drain was placed, and the wound was narrowed with a nonabsorbable purse-string suture and attached to the NAC with continuous subcuticular absorbable suture. This study was conducted on 144 female patients diagnosed with breast cancer. The median size of the tumor was 2cm, the majority of the patients (66.7%) had moderate breast size (cup B) and the median distance of the tumor from NAC was 7cm. Patients' satisfaction was assessed according to Harvard scale and good to excellent results were found in 88.8% of the patients. There were no postoperative changes in areolar shape or position. Complications in the form of hematoma, wound dehiscence, and infection were encountered in 25% of the patients. Modified round block technique is an oncoplastic technique that permits excision of peripherally located breast cancer without excision of periareolar skin and it is suitable for all quadrant tumors. It also avoids the scar which occurs after ordinary breast-conserving surgery.

Novel Missense CAPN3 Mutation Responsible for Adult-Onset Limb Girdle Muscular Dystrophy with Calves Hypertrophy.

CAPN3 gene encodes for calpain-3; this protein is a calcium-dependent intracellular protease. Deficiency of this enzyme leads to weakness of the proximal limb muscles and pelvic and shoulder girdles, the so-called limb-girdle muscular dystrophy type 2A (LGMD2A). Here, we reported the case of a Tunisian patient with LGMD2A associated with a novel missense mutation (c.T1681C/p.Y561H). A 61-year-old man, with consanguineous parents, was referred for gait difficulties and slowly progressive proximal weakness of the four limbs associated with moderate hypertrophy of the calves but his facial muscles were unaffected. Electromyography showed that the profile was myopathic pattern and creatine kinase (CK) level was high. Muscle biopsy processing included routine histological, immunohistochemical, and Western Blot reactions, using a panel of antibodies directed against dystrophin, dysferlin, calpain-3, sarcoglycan α, β, γ, and δ. For mutation analysis, we designed an NGS-based screening. Immunological analyses demonstrated a total deficiency in calpain-3 and δ-sarcoglycan, and a reduced expression of dysferlin. The genetic study yielded a homozygous missense mutation (c.T1681C) of the 13th exon of the CAPN3 gene. The mutation found in our patient (c.T1681C/p.Y561H) has not been previously reported. It is responsible for complete calpain-3 and δ-sarcoglycan deficiency and reduced dysferlin expression. The genetic study is mandatory in such cases with multiple-protein deficiency and ambiguous results of immune-histology and Western Blot studies.

PH Grand Rounds: A Case of Pulmonary Hypertension Associated With High Cardiac Output State from Arteriovenous Fistula–Or Is It?

PH Grand Rounds: A Case of Pulmonary Hypertension Associated With High Cardiac Output State from Arteriovenous Fistula–Or Is It?

Litomosoides sp. (Filarioidea: Onchocercidae) Infection in Frugivorous Bats (Artibeus spp.): Pathological Features, Molecular Evidence, and Prevalence.

Bats can host pathogenic organisms such as viruses and fungi, but little is known about the pathogenicity of their parasites. Hemoparasites are frequently recorded in Neotropical bats, particularly Litomosoides (Filarioidea: Onchocercidae), but their pathogenic effect on bats is scarcely known. In this work, Litomosoides microfilariae were identified in four (8%) out of 51 sampled frugivorous bats belonging to three different species: Artibeus aztecus, Artibeus jamaicensis, and Artibeus lituratus, which are located in Yautepec, Morelos, Mexico. Two infected animals showed weakness, tachypnoea, and ecchymosis on their wings. In these animals, histopathology revealed microfilariae in the blood vessels of the lung, liver, and spleen. Both animals presented exudative pneumonia with congestion and concomitant edema, in addition to moderate arterial hypertrophy. Parasitemia was quantified in blood samples of the infected animals (>3000 parasites/mL). Phylogenetic analysis placed the obtained sequence inside the Litomosoides genus, reaching over 98% identity to the related species. Due to the relevance of bats in ecosystems, any new record of their parasite repertoire offers noteworthy insights into our understanding of the ecology and impact of new parasite species in bats.

A Step-by-Step Approach to a Successful Cosmetic Breast Reduction.

Evolution of breast reduction techniques has been a result of combining different skin marking patterns with a wide variety of pedicles. Despite the many differences that may exist among these procedures, they all rely on a few key principles. To make surgery more expeditious and minimize technical challenges, these principles can be incorporated into simple surgical strategies. The authors present a step-by-step approach to help to achieve a successful cosmetic breast reduction for patients with small to moderate breast hypertrophy. Special emphasis is given to intraoperative clues that make this procedure more reproducible and straightforward.

Does treatment with sub-lingual allergen-specific immunotherapy reduce adenoid size and improve quality of life among Egyptian children?

IntroductionAdenoidal hypertrophy is a paediatric problem. Adenoidectomy contributes to post-operative complications. Allergic rhinitis is a major health problem. Its prevalence in Egypt and the Middle East is up to 9%. The aim of the present study was to evaluate the effect of sub-lingual immunotherapy on adenoid size and/or quality of life among children suffering from adenoid hypertrophy with allergic rhinitis in Suez Canal University Hospital.Material and methodsForty-six children suffering from adenoid hypertrophy and allergic rhinitis were recruited for this purpose. Skin prick test was administered to identify the causative allergen. All patients received sub-lingual immunotherapy. Lateral X-ray, serum total immunoglobulin E, symptoms, and sign score were recorded for all patients before and after the treatment.ResultsThe nasal symptoms and adenoidal size of the examined patients were significantly decreased after immunotherapy was applied, and thus there was an improvement in the quality of life among those patients.ConclusionsIt was concluded that sub-lingual immunotherapy was an alternative treatment of adenoidectomy in children with moderate adenoid hypertrophy with allergic rhinitis. Surgical treatment for children who suffer from severe adenoid hypertrophy with allergic rhinitis could not be considered as obligatory because medical treatment has no effect on the size of adenoids nor on quality of life.

Hypertrophic cardiomyopathy. Cardiomyocyte ultrastructure, the specific or stereotypic signs

To study cardiomyocyte (CMC) ultrastructural changes in the interventricular septum (IVS) of patients with HCM and evaluate their specificity for this pathology. IVS myocardial samples taken from 44 HCM patients aged 18-59 years at IVS myoectomy underwent an electron microscopic study. The diameter of CMCs and their nuclei was measured in semithin sections. A morphometric examination of the IVS myocardium in HCM patients revealed moderate hypertrophy of CMCs and their nuclei, the diameters of which averaged 23.7±4.4 and 5.2±0.9 μm, respectively. The IVS CMCs were characterized by the ultrastructural signs of hypertrophy: the larger size and number of structures ensuring contractile and synthetic functions; the myocytes contained higher amounts of myofibrils, intermyofibrillar mitochondria, granular endoplasmic reticulum cisterns, and free ribosomes. On the contrary, some CMCs had fewer myofibrils in the perinuclear region, which is an adaptive change under hemodynamic overload conditions. In addition, a number of myocytes displayed signs of dystrophic changes: the appearance of lipofuscin granules, myelin figures, phagosomes, lipid droplets, and vacuoles, which can fill all free sarcoplasmic zones. Ultrastructural changes characteristic of hypertrophy were found in IVS CMCs in HCM patients. In addition, there was partial myofibrillar loss and dystrophic changes in a number of myocytes, which are stereotypic compensatory-adaptive changes under hemodynamic overload conditions. All the above-mentioned changes in the CMC ultrastructure are characteristic of myocardial hypertrophy, but not specific for hypertrophic cardiomyopathy.