Infantile Hypothalamic Hamartoma: A Rare Presentation of Isolated Obesity.

Hypothalamic hamartomas (HHs) are rare, benign brain tumors or lesions of the hypothalamus that are predominantly identified in cases of epilepsy and central precocious puberty (CPP), whereas isolated manifestations of infantile obesity are atypical. We herein report an 8-month-old boy with severe obesity (Kaup index 26.4 [>100th percentile]) and uncontrollable hyperphagia. His growth chart demonstrated remarkable weight gain that exceeded the length gain in magnitude. Brain magnetic resonance imaging identified a lesion consistent with HH. There were no episodes or clinical findings of epilepsy, CPP, or Cushing disease. Hypothalamic obesity should be considered in the diagnosis even in infants with excessive weight gain due to overeating.

Mitochondrial haplotype mutation alleviates respiratory defect of MELAS by restoring taurine modification in tRNA with 3243A > G mutation.

The 3243A > G in mtDNA is a representative mutation in mitochondrial diseases. Mitochondrial protein synthesis is impaired due to decoding disorder caused by severe reduction of 5-taurinomethyluridine (τm5U) modification of the mutant mt-tRNALeu(UUR) bearing 3243A > G mutation. The 3243A > G heteroplasmy in peripheral blood reportedly decreases exponentially with age. Here, we found three cases with mild respiratory symptoms despite bearing high rate of 3243A > G mutation (>90%) in blood mtDNA. These patients had the 3290T > C haplotypic mutation in addition to 3243A > G pathogenic mutation in mt-tRNALeu(UUR) gene. We generated cybrid cells of these cases to examine the effects of the 3290T > C mutation on mitochondrial function and found that 3290T > C mutation improved mitochondrial translation, formation of respiratory chain complex, and oxygen consumption rate of pathogenic cells associated with 3243A > G mutation. We measured τm5U frequency of mt-tRNALeu(UUR) with 3243A > G mutation in the cybrids by a primer extension method assisted with chemical derivatization of τm5U, showing that hypomodification of τm5U was significantly restored by the 3290T > C haplotypic mutation. We concluded that the 3290T > C is a haplotypic mutation that suppresses respiratory deficiency of mitochondrial disease by restoring hypomodified τm5U in mt-tRNALeu(UUR) with 3243A > G mutation, implying a potential therapeutic measure for mitochondrial disease associated with pathogenic mutations in mt-tRNAs.

Aggressive early surgical strategy in patients with intracranial hemorrhage: a new cardiopulmonary bypass option.

OBJECTIVE: We present a novel strategy in cardiac surgery with a cardiopulmonary bypass with low-dose heparin and Nafamostat mesylate as an anticoagulant (NM-CPB), which reduces postoperative neurological complications. METHOD AND RESULTS: 19 patients with a mean age of 63.6 ± 20.2 years (range 24-91) and an indication of early cardiac surgery with intracranial complication (ICC) underwent surgery with NM-CPB. The preoperative diagnoses included seven cases of infective endocarditis and six of left atrial appendage thrombosis. ICC were noticed in seven cases with hemorrhages (hemorrhagic infarction: n = 4, subarachnoid hemorrhage: n = 3) and 12 without hemorrhage (large infarction: n = 10, small-multiple infarction at the risk for hemorrhagic transformation: n = 2). The mean interval between a diagnosis and cardiac surgery was 1.1 ± 1.5 days in the ICH cases and 1.4 ± 1.4 days otherwise. In-hospital mortality was 5.3%. The mean CPB time was 146.7 ± 66.03 min, the mean dose of NM, heparin were 2.23 ± 1.59 mg/kg/hr and 56.8 ± 20.3 IU/kg, respectively. The mean activated clotting time (ACT) was 426.8 ± 112.4 s. No further intracranial bleeding and no new hemorrhages were observed after surgery. CONCLUSIONS: In early cardiac surgery with ICC, especially with hemorrhage, NM-CPB reduced postoperative neurological complications. We plan to use NM-CPB to expand the indications and to establish an early aggressive treatment.

Malignant transformation of phosphaturic mesenchymal tumor: a case report and literature review.

Phosphaturic mesenchymal tumor, mixed connective tissue variant (PMT-MCT) causes tumor-induced osteomalacia (TIO). Most cases follow a benign clinical course, with rare occurrences of malignant transformation. We report a case of malignant PMT-MCT and review previous malignant cases to identify predictive factors for transformation. A 13-yr-old female, who presented with hypophosphatemic rickets, elevated serum intact fibroblast growth factor 23 (FGF23) levels, and a nodule in the back, received a diagnosis of TIO because of the benign PMT histopathology. After resection of the primary tumor, regular imaging analyses did not indicate any relapse. At 17 years of age, a tumor developed in the left leg and increased in size. The resected tumor showed a histopathology of pleomorphic sarcoma positive for the TP53 mutation. Despite amputation of the affected leg, the patient died due to multiple metastases at 18 years of age. A literature review revealed that 14 out of 15 reported malignant PMT-MCT tumors occurred in adults, and found no predictive factors for malignant transformation and treatment outcome. Changes in size or number of the tumors along with intact FGF23 levels have been considered as the only sign of malignant transformation. This pediatric case report and literature review indicate the need for prolonged regular monitoring for PMT-MCT.

[L-shaped Partial Upper Sternotomy Approach for Aortic Valve Replacement].

Transcatheter aortic valve implantation is a recent innovation in the treatment of severe aortic stenosis. On the other hand, several reports suggested that minimally invasive aortic valve replacement (MICS-AVR) is likely to be associated with reduced postoperative discomfort and faster recovery. Of note, an upper partial sternotomy for isolated aortic valve replacement( L-shaped MICS-AVR) has been accepted as the most common approach to the MICS-AVR. Since October 2013, we have preformed L-shaped MICS-AVR at our hospital. In L-shaped MICS-AVR group(16 patients, 74.4±8.7 years),there was no operative mortality and any other complication including reexploration for postoperative bleeding, wound infection, peri-valvular leakage, pulmonary complication like re-intubation or minitracheostomy. To demonstrate the benefits of this approach, over-octogenarian subgroup( n=7)was analyzed and compared with the isolated AVR using a conventional sternotomy (C-AVR, n=10)in the same period. A trend was seen toward better postoperative course in the L-shaped MICS-AVR group than in the C-AVR group;however, this difference was not statistically significant. The mean duration of cardiopulmonary bypass(120±29 min vs 93±24 min, p=0.005)and cross clamp time(151±36 min vs 124±32 min, p=0.038)were significantly longer than C-AVR. We believe that more clinical experience is required to clarify the benefits of this approach and we must more consider the preoperative images for the attainment of the excellent exposure. Moreover, the concomitant use of this new device and L-shaped MICS-AVR may enable a big improvement in the future.

Effects of in utero exposure to di(n-butyl) phthalate for estrogen receptors α, ß, and androgen receptor of Leydig cell on rats.

Estrogens and androgens affect male and female reproductive systems. Recently, we reported that prenatal di(n-butyl) phthalate (DBP) exposure induced atypical Leydig cells (LCs) hyperplasia during adulthood. The present study investigated the expression of estrogen receptor α (ERα), estrogen receptor ß (ERß), and androgen receptor (AR) in LCs of 5-, 7-, 9-, 14-, and 17-week-old Sprague-Dawley (srl) rats whose dams had been administered DBP intragastrically at 100 mg/kg/day or the vehicle (corn oil) from days 12 to 21 postconception. Immunohistochemical, Western blotting, and reverse transcription polymerase chain reaction analyses revealed that the expressions of ERα, ERß, and AR proteins and mRNAs in the DBP group were similar to those of the vehicle group at 5 and 7 weeks, but significantly higher ERα and lower ERß and AR levels were observed in the DBP group at 9 to 17 weeks. The rats prenatally exposed to DBP had seminiferous tubule degeneration and atypical hyperplasia of LCs during adulthood, which was associated with an increase in expression of ERα and a decrease of ERß and AR in the testis.

Atherosclerotic biomarkers and aortic atherosclerosis by cardiovascular magnetic resonance imaging in the Framingham Heart Study.

BACKGROUND: The relations between subclinical atherosclerosis and inflammatory biomarkers have generated intense interest but their significance remains unclear. We sought to determine the association between a panel of biomarkers and subclinical aortic atherosclerosis in a community-based cohort. METHODS AND RESULTS: We evaluated 1547 participants of the Framingham Heart Study Offspring cohort who attended the 7th examination cycle and underwent both cardiovascular magnetic resonance imaging (CMR) and assays for 10 biomarkers associated with atherosclerosis: high-sensitivity C-reactive protein, fibrinogen, intercellular adhesion molecule-1, interleukin-6, interleukin-18, lipoprotein-associated phospholipase-A2 activity and mass, monocyte chemoattractant protein-1, P-selectin, and tumor necrosis factor receptor-2. In logistic regression analysis, we found no significant association between the biomarker panel and the presence of aortic plaque (global P=0.53). Using Tobit regression with aortic plaque as a continuous variable, we noted a modest association between biomarker panel and aortic plaque volume in age- and sex-adjusted analyses (P=0.003). However, this association was attenuated after further adjustment for clinical covariates (P=0.09). CONCLUSIONS: In our community-based cohort, we found no significant association between our multibiomarker panel and aortic plaque. Our results underscore the strengths and limitations of the use of biomarkers for the identification of subclinical atherosclerosis and the importance of traditional risk factors.

Male Sprague-Dawley rats exposed to in utero di(n-butyl) phthalate: dose dependent and age-related morphological changes in Leydig cell smooth endoplasmic reticulum.

When 100 mg/kg/day of di(n-butyl) phthalate (DBP) was intragastrically administered to pregnant Sprague-Dawley rats throughout gestation days 12 to 21, the male pups had similar body weights with no apparent physical differences (e.g., litter size, sex ratio) compared to that of the vehicle group. However, prominent age-related morphological alterations in the smooth endoplasmic reticulum (sER) of testicular Leydig cells (LCs) were observed once these animals reached puberty. At weeks 5 to 7, the abundant sER with non-dilated cisternae was distributed in LCs. Subsequently, although the number of LCs significantly increased, the amount of sER was significantly decreased at 9 to 14 weeks of age and had disappeared at 17 weeks. In contrast, the number of LCs and the amount of sER in LCs of the lower dose groups (10, 30, and 50 mg/kg/day) were similar to those of the vehicle group. Further, serum testosterone levels in the 100 mg/kg dose group were significantly lower during 5 to 17 weeks of age. While their luteinizing hormone (LH) level was significantly lower at 5 to 7 weeks of age, it became significantly higher during 9 to 17 weeks. The amount of sER in LCs decreased with age with the increase in LCs proliferation and serum LH levels in rat exposed in utero to DBP in a dose-dependent manner.

Early detection of cardiac sarcoid lesions with (18)F-fluoro-2-deoxyglucose positron emission tomography.

In April 2005, a 72-year-old woman with pulmonary sarcoidosis exhibited focal (18)F-fluoro-2-deoxyglucose ((18)F-FDG) uptake in her heart on (18)F-FDG positron emission tomography (PET). Although Japanese guidelines for diagnosing cardiac sarcoidosis were not met at this point, electrocardiography, echocardiography, and magnetic resonance imaging became diagnostic for cardiac sarcoidosis 1 year later. In the present case report, the potential of (18)F-FDG PET in the early recognition of cardiac sarcoidosis in comparison with other imaging modalities is discussed.

Relationship between central and peripheral atherosclerosis and left ventricular dysfunction in a community population.

We aimed to determine the relationships between resting left ventricular (LV) wall motion abnormalities (WMAs), aortic plaque, and peripheral artery disease (PAD) in a community cohort. A total of 1726 Framingham Heart Study Offspring Cohort participants (806 males, 65 ± 9 years) underwent cardiovascular magnetic resonance with quantification of aortic plaque volume and assessment of regional left ventricular systolic function. Claudication, lower extremity revascularization, and ankle-brachial index (ABI) were recorded at the most contemporaneous examination visit. WMAs were associated with greater aortic plaque burden, decreased ABI, and claudication in age- and sex-adjusted analyses (all p < 0.001), which were not significant after adjustment for cardiovascular risk factors. In age- and sex-adjusted analyses, both the presence (p < 0.001) and volume of aortic plaque were associated with decreased ABI (p < 0.001). After multivariable adjustment, an ABI ≤ 0.9 or prior revascularization was associated with a threefold odds of aortic plaque (p = 0.0083). Plaque volume significantly increased with decreasing ABI in multivariable-adjusted analyses (p < 0.0001). In this free-living population, associations of WMAs with aortic plaque burden and clinical measures of PAD were attenuated after adjustment for coronary heart disease risk factors. Aortic plaque volume and ABI remained strongly negatively correlated after multivariable adjustment. Our findings suggest that the association between coronary heart disease and non-coronary atherosclerosis is explained by cardiovascular risk factors. Aortic atherosclerosis and PAD remain strongly associated after multivariable adjustment, suggesting shared mechanisms beyond those captured by traditional risk factors.

Single-slice epicardial fat area measurement: do we need to measure the total epicardial fat volume?

PURPOSE: The aim of this study was to assess a method for measuring epicardial fat volume (EFV) by means of a single-slice area measurement. We investigated the relation between a single-slice fat area measurement and total EFV. METHODS AND METHODS: A series of 72 consecutive patients (ages 65 ± 11 years; 36 men) who had undergone cardiac computed tomography (CT) on a 64-slice multidetector scanner with prospective electrocardiographic triggering were retrospectively reviewed. Pixels in the pericardium with a density range from -230 to -30 Hounsfield units were considered fat, giving the per-slice epicardial fat area (EFA). The EFV was estimated by the summation of EFAs multiplied by the slice thickness. We investigated the relation between total EFV and each EFA. RESULTS: EFAs measured at several anatomical landmarks-right pulmonary artery, origins of the left main coronary artery, right coronary artery, coronary sinus-all correlated with the EFV (r = 0.77-0.92). The EFA at the LMCA level was highly reproducible and showed an excellent correlation with the EFV (r = 0.92). CONCLUSION: The EFA is significantly correlated with the EFV. The EFA is a simple, quick method for representing the time-consuming EFV, which has been used as a predictive indicator of cardiovascular diseases.

Comparison of 1H MR spectroscopy, 3-point DIXON, and multi-echo gradient echo for measuring hepatic fat fraction.

PURPOSE: We evaluated and compared the reproducibility, diagnostic accuracy, and sequence dependency of the fat fraction (FF) determined by 3-point Dixon (DIXON) and multi-echo gradient-echo (MEGE) methods to those of the FF determined by magnetic resonance spectroscopy (MRS). METHODS: Our study included 98 volunteers, ten of whom underwent scanning twice to evaluate sequence reproducibility. We compared the FFs determined by the DIXON and MEGE methods to that by MRS as the gold standard, calculated sensitivity and specificity for each image analysis method at a threshold value of 6.25% of spectroscopic value, and used Pearson's correlation coefficient and Bland-Altman analysis to compare agreement among the repeated measurements and FF values with the 3 methods, in 98 volunteers. RESULTS: There was no significant difference in repeated scans in any sequence with Wilcoxon's t-test. Each correlation coefficient (r) exceeded 0.930 for the repeated measurements of all 3 sequences. Sensitivity of DIXON was 82% and specificity, 96%; sensitivity of MEGE was 70% and specificity, 99%. The FFs determined by DIXON and MEGE correlated well with that by MRS (r=0.920) but showed significant difference (paired t-test, P<0.001). The mean difference between the FF determined by DIXON and that by MEGE were 0.93 and -1.16, respectively. The slope of the regression lines as determined by DIXON was -0.655 (P<0.001) and that by MEGE was -0.527 (P<0.001). When the FF by MRS was less than 6.25%, the FF values by DIXON and MEGE were significantly higher; when the spectroscopic value was greater than 6.25%, their values were significantly lower. CONCLUSION: We demonstrated the high reproducibility of each FF measurement using MRS, DIXON, and MEGE. Compared to MRS, both DIXON and MEGE showed high sensitivity and specificity for determining FF. The FFs by DIXON and MEGE showed sequence dependency because DIXON had proportional and additional errors, and MEGE had a proportional error.

Rapid estimation of split renal function in kidney donors using software developed for computed tomographic renal volumetry.

PURPOSE: To evaluate the speed and precision of split renal volume (SRV) measurement, which is the ratio of unilateral renal volume to bilateral renal volume, using a newly developed software for computed tomographic (CT) volumetry and to investigate the usefulness of SRV for the estimation of split renal function (SRF) in kidney donors. METHOD: Both dynamic CT and renal scintigraphy in 28 adult potential living renal donors were the subjects of this study. We calculated SRV using the newly developed volumetric software built into a PACS viewer (n-SRV), and compared it with SRV calculated using a conventional workstation, ZIOSOFT (z-SRV). The correlation with split renal function (SRF) using (99m)Tc-DMSA scintigraphy was also investigated. RESULTS: The time required for volumetry of bilateral kidneys with the newly developed software (16.7±3.9s) was significantly shorter than that of the workstation (102.6±38.9s, p<0.0001). The results of n-SRV (49.7±4.0%) were highly consistent with those of z-SRV (49.9±3.6%), with a mean discrepancy of 0.12±0.84%. The SRF also agreed well with the n-SRV, with a mean discrepancy of 0.25±1.65%. The dominant side determined by SRF and n-SRV showed agreement in 26 of 28 cases (92.9%). CONCLUSION: The newly developed software for CT volumetry was more rapid than the conventional workstation volumetry and just as accurate, and was suggested to be useful for the estimation of SRF and thus the dominant side in kidney donors.

64-Slice MDCT imaging of endocardial cushion defect associated with other cardiac and extracardiac abnormalities.

Electrocardiographic-gated 64-slice multidetector computed tomography (MDCT) was performed on a 30-year-old man who presented with a complete endocardial cushion defect (ECD) and severe pulmonary hypertension diagnosed when he was 3 years old. Multiplanar reconstruction image showed the common atrium without an atrial septum, a large ventricular septum defect, and a small right ventricle due to a complete atrioventricular canal defect. Three-dimensional CT volume-rending imaging showed a patent ductus arteriosus, dilation of the ascending aorta, and an anomalous-origin right coronary artery. This patient also had heterotaxy syndrome with polysplenia and azygos continuation. MDCT proved to be a good noninvasive imaging method for the evaluation of ECD associated with cardiac as well as extracardiac abnormalities.

Volume-rendering and endocardial views of partially unroofed coronary sinus with 64-slice multidetector CT.

We diagnosed unroofed coronary sinus preoperatively by the 3D volume rendering and endocardial views with 64-slice MDCT, and those clearly showed the defect of the roof of the coronary sinus and the relationship with the surrounding structure. MDCT is a good non-invasive tool for the evaluation of unroofed coronary sinus, and the reconstructed endocardial view is useful for preoperative surgical planning.

Reduction of bed rest time after transfemoral noncardiac angiography from 4 hours to 2 hours: a randomized trial and a one-arm study.

PURPOSE: To evaluate the feasibility of shortening the bed rest time from 4 hours to 2 hours after transfemoral noncardiac angiography with a 4-F sheath (outer diameter, 1.93 mm), a 5-F sheath (outer diameter, 2.27 mm), and a 4-F catheter. MATERIALS AND METHODS: Patients were randomized into two groups, receiving either 2 or 4 hours of bed rest after hemostasis by manual compression of the puncture site. The authors evaluated the frequency of bleeding complications. An interim analysis was performed wherein 40 patients were assigned to each group. After the analysis, a single-arm 2-hour bed rest trial was conducted in an additional 115 procedures. RESULTS: In the interim analysis, three of the 40 patients in the 4-hour group and none of the 40 patients in the 2-hour group developed minor bleeding within 2 hours after manual compression (P = .24). After 2 hours of bed rest, no bleeding complication was observed in either group. In the single-arm 2-hour bed rest trial, minor bleeding developed in one of the 115 procedures (0.8%). Through the study, minor bleeding occurred in four of the 195 total procedures (2%), and no major complications developed. The occurrence of a bleeding complication was significantly higher in patients with platelet counts of less than 100 x 10(9)/L than in the other patients (4/67 vs 0/128, P = .01). CONCLUSIONS: Two hours of bed rest is feasible for patients undergoing transfemoral noncardiac angiography by using a 4-5-F sheath and/or a 4-F catheter, especially those with a normal platelet count.

Myocardial imaging with 18F-fluoro-2-deoxyglucose positron emission tomography and magnetic resonance imaging in sarcoidosis.

PURPOSE: Despite accumulating reports on the clinical value of (18)F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET) and magnetic resonance imaging (MRI) in the assessment of cardiac sarcoidosis, no studies have systematically compared the images of these modalities. METHODS: Twenty-one consecutive patients with suspected cardiac sarcoidosis underwent cardiac examinations that included 18F-FDG PET and MRI. The association of 18F-FDG PET and MRI findings with blood sampling data such as serum angiotensin converting enzyme levels was also evaluated. RESULTS: Eight of 21 patients were diagnosed as having cardiac sarcoidosis according to the Japanese Ministry of Health and Welfare Guidelines for Diagnosing Cardiac Sarcoidosis. Sensitivity and specificity for diagnosing cardiac sarcoidosis were 87.5 and 38.5%, respectively, for 18F-FDG PET, and 75 and 76.9%, respectively, for MRI. When the 18F-FDG PET and MRI images were compared, 16 of 21 patients showed positive findings in one (n = 8) or both (n = 8) of the two modalities. In eight patients with positive findings on both images, the distribution of the findings differed among all eight cases. The presence of positive findings on 18F-FDG PET was associated with elevated serum angiotensin-converting enzyme levels; this association was not demonstrated on MRI. CONCLUSIONS: Both 18F-FDG PET and MRI provided high sensitivity for diagnosing cardiac sarcoidosis in patients with suspected cardiac involvement, but the specificity of (18)F-FDG PET was not as high as previously reported. The different distributions of the findings in the two modalities suggest the potential of 18F-FDG PET and MRI in detecting different pathological processes in the heart.

Differential impact of age, sex, and hypertension on aortic atherosclerosis: the Framingham Heart Study.

OBJECTIVE: The purpose of this study was to investigate the impact of age, sex, and hypertension (HTN) on aortic atherosclerotic burden using cardiovascular MRI (CMR) in a free-living longitudinally followed cohort. METHODS AND RESULTS: 1763 participants (829 M and 934 F; 38 to 88 years of age) of the Framingham Heart Study Offspring cohort underwent CMR of the thoracoabdominal aorta using an ECG-gated 2D T2-weighted black-blood sequence. Of these, 1726 subjects (96%) with interpretable CMR were characterized by sex, age-quartile, and presence or absence of HTN and clinical cardiovascular disease (CVD). Aortic plaque prevalence and volume increased with increasing age in both sexes. For the nonhypertensive (no-HTN) group, plaque was identified in 702 (46%) with greater prevalence in women than in men (P<0.006). HTN was associated with greater aortic plaque burden (P<0.02). The 200 subjects with clinical CVD had greater plaque burden than subjects without CVD (P<0.0001). CONCLUSIONS: In this free-living longitudinally followed cohort, subclinical aortic atherosclerosis was seen in nearly half of subjects and increased with advancing age. HTN was associated with increased aortic plaque burden. Among no-HTN subjects, women had greater plaque burden than men. These data suggest that subclinical atherosclerosis is more common in no-HTN women and emphasize the importance of focusing on preventive measures in both sexes.

A 6-month randomized pilot study of black tea and cardiovascular risk factors.

BACKGROUND: The effects of black tea consumption on cardiovascular risk factors have been inconsistent in previous randomized trials, all of which have been limited to a few weeks duration. METHODS: We conducted a pilot parallel-design randomized controlled trial among 31 adults aged 55 years and older with either diabetes or 2 other cardiovascular risk factors but no established clinical cardiovascular disease. Participants were randomized to drink 3 glasses daily of either a standardized black tea preparation or water for 6 months. Cardiovascular risk factors were measured at the beginning and conclusion of the study. RESULTS: Three participants dropped out of the study, leaving 14 participants assigned to tea and 14 assigned to water eligible for analyses. We found no statistically significant effects of black tea on cardiovascular biomarkers, including lipids, inflammatory markers, hemoglobin, adhesion molecules, prothrombotic and fibrinolytic parameters, and lipoprotein oxidizability. Assignment to tea did not appreciably influence blood pressure, and heart rate among participants assigned to tea was marginally higher than among control participants at 3 months (P = .07) but not 6 months. CONCLUSIONS: In this randomized trial of black tea intake over 6 months among older adults with known cardiovascular risk factors, black tea did not appreciably influence any traditional or novel biomarkers of cardiovascular risk. Longer randomized trials are needed to verify the inverse association of tea with risk of cardiovascular disease seen in cohort studies and identify potential candidate mechanisms for such an association.