Sitosterolemia Exhibiting Severe Hypercholesterolemia with Tendon Xanthomas Due to Compound Heterozygous ABCG5 Gene Mutations Treated with Ezetimibe and Alirocumab

We herein report a rare case presenting with severe hypercholesterolemia, massive Achilles tendon xanthomas, and multi-vessel coronary artery disease. Initially, the patient was misdiagnosed with familial hypercholesterolemia. However, a genetic analysis using our custom sequencing panel covering genes associated with Mendelian lipid disorders revealed him to have a genetic basis of sitosterolemia with compound heterozygous mutations in the adenosine triphosphate binding cassette subfamily G5 (ABCG5) gene. A comprehensive genetic analysis can be particularly useful for diagnosing cases with severe phenotypes, leading to appropriate and medical therapies. Our patient was refractory to statins, whereas ezetimibe and PCSK9 inhibitor with a low-plant-sterol diet successfully reduced his serum levels of low-density lipoprotein cholesterol.     

CRT in a congenital heart disease patient with interventricular dyssynchrony due to an RV conduction delay

We encountered a unique pattern of cardiac dyssynchrony in a patient with complex congenital heart disease (heterotaxy syndrome) with a biventricular physiology and systemic left ventricle (LV). On speckle tracking echocardiography, dyssynchrony was not detected within the LV, but was noted in an interventricular fashion between the LV and right ventricle (RV). An electrophysiologic study revealed a conduction delay in the subpulmonary RV. Cardiac resynchronization therapy provided reverse cardiac remodeling and an excellent result in our patient by placing the pacing leads around the dyssynchronous lesion.     

The influence of drug-exposure conditions on the development of resistance to methotrexate or ZD1694 in cultured human leukaemia cells

The influence of drug-exposure conditions on the development of resistance to methotrexate (MTX) or ZD1694 was studied by treating MOLT-3 human lymphoblastic-leukaemia cells in a continuous or a pulsatile (high-dose, short-term) drug-exposure schedule. Continuous exposure of the cells to MTX with stepwise escalation of the drug concentrations resulted in a MTX-resistant sub-line (MOLT-3/MTX_10,000) with impaired reduced-folate carrier (RFC) and increased dihydrofolate-reductase (DHFR) activity. Conversely, a MTX-resistant clone (MOLT-3/MTX·P-9) with unaltered RFC and DHFR activity, but with decreased cellular accumulation of antifolates, was selected by high-dose short-term treatment of the cells with MTX. MTX resistance in the latter cells was pronounced after short-term rather than continuous-exposure incubation with MTX, suggesting defective polyglutamation of the drug. On the other hand, 2 ZD1694-resistant sub-lines which were established by continuous (MOLT-3/ZD1694·C) or by pulsatile drug-exposure schedule (MOLT-3/ZD1694·P-9) demonstrated extremely low accumulation and poor retention of [³H]ZD1694, with no change of initial drug uptake and little or no increase of thymidylate-synthase (TS) activity, irrespective of drug-exposure conditions for their establishment. HPLC analysis displayed a virtual absence of ZD1694 polyglutamates in both ZD1694-resistant sub-lines and low accumulation in MOLT-3/MTX·P-9 as compared with the parent line. However, folylpolyglutamate-synthetase (FPGS) mRNA was only moderately decreased in the 2 ZD1694-resistant sub-lines and to an even lesser extent in MOLT-3/MTX·P-9. In addition, γ-glutamyl-hydrolase (GGH) activity was not increased, but was slightly down-regulated in the polyglutamation-defective sublines. These results indicate that the mechanism(s) of the resistance developed may depend not only on drug-exposure conditions while raising resistance but also on the biochemical properties of the drug. © 1996 Wiley-Liss, Inc.     

Effects of a walking program in patients with chronic unilateral vestibular hypofunction

[Purpose] Patients with chronic unilateral vestibular hypofunction show decreased postural stability and low levels of physical activity and also experience much anxiety. Physical activity is known to improve these symptoms; however, no study has reported any positive effects of physical activity, such as symptom reduction or improvement in function in these patients. In this study, we investigated the role of a walking program in improvement of dizziness, anxiety, and postural stability in this patient population. [Participants and Methods] This study included 21 patients with unilateral vestibular hypofunction and chronic dizziness. Patients were instructed to walk 30 min daily for 3 months. Physical activity levels and questionnaires for clinical symptoms, anxiety, and postural stability were evaluated before and after intervention. [Results] We observed significant differences in the amount of moderate-to-vigorous physical activity, clinical symptoms, and self-perceived handicap before and after the intervention. Additionally, anxiety levels were significantly reduced and postural stability was significantly improved in these patients. [Conclusion] A walking program improved physical activity levels, clinical symptoms, and postural stability and reduced self-perceived handicap and anxiety in patients with chronic unilateral vestibular hypofunction. These results highlight the effectiveness of a walking program for these patients and emphasize its role as a complementary vestibular rehabilitation strategy.     

Axin2+ Peribiliary Glands in the Periampullary Region Generate Biliary Epithelial Stem Cells That Give Rise to Ampullary Carcinoma

1. Download : Download high-res image (328KB)
2. Download : Download full-size image

     

Effectiveness and safety of adalimumab in Japanese patients with rheumatoid arthritis: retrospective analyses of data collected during the first year of adalimumab treatment in routine clinical practice (HARMONY study)

We retrospectively investigated the ability of adalimumab (ADA) to reduce disease activity, improve physical function, and retard the progression of structural damage in 167 patients with rheumatoid arthritis. Clinical and functional outcomes were compared between patients with or without prior biologic treatment and those with or without concomitant methotrexate (MTX) treatment. At week 52, 38.3% achieved clinical remission: 42.4 and 28.6% of patients achieved remission in those without and with previous biologics, respectively, while 42.7 and 12.5% of patients achieved remission in those with and without concomitant MTX, respectively. ADA treatment significantly reduced the rate of radiographic progression from 27.1 ± 46.0 (median 13.6; 25th-75th percentiles 8.3 to 28.9) at baseline to 0.8 ± 5.0 (median 0.0; 25th-75th percentiles -0.9 to 2.0) at week 52 (P < 0.0001). Radiographic progression was absent in 59.8% of patients. Sixty adverse events (34.21/100 patient-years) were reported, 16 of which were serious (9.12/100 patient-years). ADA therapy is highly effective for reducing disease activity, improving physical function, and limiting radiographic progression. It is generally safe and well tolerated by Japanese RA patients in routine clinical practice.     

Endoluminal MR imaging of porcine gastric structure in vivo

Background and aims

Recently, several new endoscopic instruments have been developed. However, even with the full use of current modalities, the safety of endoscopic surgery is not guaranteed. Information regarding factors such as fibrosis and the blood vessels under the mucosa is very important for avoiding procedure-related complications. The aim of this study was to define the detailed anatomy of the gastric wall structure in vivo using original endoluminal radiofrequency coils for safer endoscopic therapy.

Methods

Swine were used as the subjects and controlled with general anesthesia. Anatomical images were obtained with T1-weighted fast spin echo (T1FSE) and T2-weighted fast spin echo (T2FSE). Dynamic magnetic resonance (MR) angiography was also obtained with three-dimensional T1-weighted fast spoiled gradient recalled acquisition in the steady state (3D-DMRA) following the injection of hyaluronic acid sodium into the submucosal layer.

Results

Porcine gastric wall structure was visualized, and four layers were discriminated in the T1FSE and T2FSE images. The vascular structure was clearly recognized in the submucosa on 3D-DMRA.

Conclusion

Endoluminal MR imaging was able to visualize the porcine stomach with similar quality to endoscopic ultrasonography imaging. Additionally, it was possible to visualize the vascular structures in the submucosal layer. This is the first report to show that blood vessels under the gastric mucosa can be depicted in vivo.     

Nationwide survey for patients with acute-on-chronic liver failure occurring between 2017 and 2019 and diagnosed according to proposed Japanese criteria

Journal of Gastroenterology - The significance of the 2018 Japanese diagnostic criteria for acute-on-chronic liver failure (ACLF) has not yet been evaluated. A nationwide survey was performed for...