Assessment of regional wall motion using strain Doppler imaging during right ventricular bifocal pacing in a patient with severe congestive heart failure: a case report

A 79-year-old man presented with dilated cardiomyopathy and chronic atrial fibrillation. A DDD pacemaker was implanted due to sick sinus syndrome. His left ventricular ejection fraction was 23%. He was repeatedly admitted with congestive heart failure. Although cardiac resynchronization therapy was attempted, insertion of a pacing lead into the coronary sinus failed. Right ventricular bifocal pacing was done. The QRS width was shortened to 155 msec during bifocal pacing and 157 msec during right ventricular outflow pacing from 221 msec during right ventricular apical pacing. Heart failure was improved from New York Heart Association class III to II. Regional wall motion was assessed by strain of the myocardium. Bifocal pacing increased stroke volume due to improvement of longitudinal dyssynchrony of the septal and lateral walls. Bifocal pacing is effective for patients with severe congestive heart failure in whom biventricular pacing therapy has failed. Strain Doppler imaging is useful for the assessment of regional wall motion during cardiac pacing.     

A murine model of acute liver injury induced by human monoclonal autoantibody

We have previously reported an immunoglobulin (Ig) M autoantibody to hepatocyte-related 190-kd molecules in patients with type 1 autoimmune hepatitis (AIH). This molecule was first isolated by hepatocyte-specific human monoclonal antibody (MoAb). To elucidate the role of this IgM autoantibody in hepatocyte injury, we examined the reactivity of this MoAb to murine hepatocytes and then questioned whether acute hepatic injury could be induced in mice via injection of this MoAb. The reactivity of MoAb was examined via both FACS analysis using murine hepatocytes and immunostaining of liver tissues. We then identified the murine hepatocyte membrane molecule recognized by this MoAb. The role of this MoAb in the immunopathogenesis of AIH was assessed by testing whether its injection into mice could increase serum aminotransferase levels as well as cause changes in liver histology. The present results demonstrate that this MoAb cross-reacted with murine hepatocytes and recognized a 190-kd molecule on the murine hepatocyte membrane just as in human hepatocytes. One hour after the injection of MoAb, the deposition of both IgM and complement component 3 was found in liver tissues. At 8 hours after the injection, serum aminotransferase levels were significantly increased in MoAb-injected mice compared with controls. Histological study revealed massive hepatocyte necrosis in MoAb-injected mice. In conclusion, human MoAb recognized a 190-kd molecule of both human and murine hepatocytes, and the injection of this MoAb to mice resulted in acute liver injury, indicating that this type of autoantibody may play an important role in the immunopathogenesis of AIH.     

Serum amyloid A and C‐reactive protein positive nodule in alcoholic liver cirrhosis,hard to make definite diagnosis

We describe a case of serum amyloid A (SAA) and C‐reactive protein (CRP) positive nodule detected by immunohistochemical analysis in a 37‐year‐old woman with alcohol‐related cirrhosis. Imaging studies at first admission pointed to hepatocellular carcinoma (HCC), a dysplastic nodule, an inflammatory pseudotumor or focal nodular hyperplasia (FNH). Ultrasonography‐guided biopsy in Segment 2 showed minimal atypical changes, except for a slight increase in cell density and micronodular cirrhosis in the non‐nodular portion. gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid‐enhanced magnetic resonance imaging carried out after a year and a half revealed hypervascularity in the arterial phase and isointensity in the hepatobiliary phase. Three years thereafter, however, the imaging displayed a change from isointensity to a defect in the hepatobiliary phase, and the nodule demonstrated minimal histological atypia. Immunohistochemical staining of the nodule was positive for SAA, CRP, liver fatty acid‐binding protein and glutamine synthetase, but negative for β‐catenin, heat shock protein 70 and Glypican 3. Organic anion transporter (OATP)8 staining was weaker in the nodule than in the non‐nodular portion of the alcohol‐related micronodular cirrhosis. The nodule was diagnosed as an SAA and CRP positive nodule, and HCC was ruled out. Despite the change from isointensity to a defect in the hepatobiliary phase, no evidence of HCC was found in the biopsy specimen. The change may be explained more by the weak OATP8 staining compared with that of alcohol‐related liver cirrhosis than by malignant transformation into HCC.     

Mirabegron causes vesical and urethral relaxation in rats with spinal cord injury

The effects of solifenacin and mirabegron on vesical and urethral function were compared in rats with or without spinal cord injury (SCI). Isovolumetric cystometry and urethral pressure recording were initially performed in intact rats. Then, the bladder neck was ligated under urethane anesthesia, after which a catheter was inserted through the bladder dome for isovolumetric cystometry and another catheter was inserted into the urethra to measure urethral pressure. Solifenacin (0.03–3 mg/kg) or mirabegron (0.03–3 mg/kg) was injected intravenously, and bladder and urethral activity were recorded. To create rats with SCI, the spinal cord was transected at the lower thoracic level under isoflurane anesthesia. After 2 weeks, a catheter was inserted through the bladder dome for single cystometry and bladder activity was recorded without anesthesia following intravenous injection of solifenacin or mirabegron. Isovolumetric cystometry revealed a larger decrease in maximum bladder contraction pressure after injection of solifenacin, whereas prolongation of the interval between bladder contractions was greater with mirabegron. In SCI rats, single cystometry showed that solifenacin and mirabegron both increased bladder volume at the first non‐voiding bladder contraction and decreased the maximum bladder contraction pressure. Mirabegron also increased the voided volume and decreased the percentage residual volume without altering bladder capacity. Solifenacin and mirabegron both inhibited bladder contractility, and mirabegron possibly also induced urethral relaxation. Mirabegron may be suitable for patients with overactive bladder and residual urine.     

Preparation and Characterization of Cellulose Ether Liposomes for the Inhibition of Prion Formation in Prion-Infected Cells

Prion accumulation in the brain and lymphoreticular system causes fatal neurodegenerative diseases. Our previous study revealed that cellulose ethers (CE) have anti-prion activities in vivo and in prion-infected cells when administered at high doses. This study aims to improve the bioavailability of a representative CE using a liposomal formulation and characterized CE-loaded liposomes in cultured cells. The liposomal formulation reduced the EC₅₀ dose of CE by <1/200-fold in prion-infected cells. Compared to empty liposomes, CE-loaded liposomes were taken up much more highly by prion-infected cells and less by macrophage-like cells. Phosphatidylserine modification reduced the uptake of CE-loaded liposomes in prion-infected cells and did not change the anti-prion activity, whereas increased the uptake in macrophage-like cells. Polyethylene glycol modification reduced the uptake of CE-loaded liposomes in both types of cells and reduced the anti-prion activity in prion-infected cells. These results suggest that a liposomal formulation of CE is more practical than unformulated CE and showed that the CE-loaded liposome uptake levels in prion-infected cells were not associated with anti-prion activity. Although further improvement of the stealth function against phagocytic cells is needed, the liposomal formulation is useful to improve CE efficacy and elucidate the mechanism of CE action.     

Rehabilitation pharmacotherapy: A scoping review

Many patients in rehabilitation facilities are affected by polypharmacy. Polypharmacy is associated with rehabilitation outcomes and functional recovery. Consequently, a combination of rehabilitation and pharmacotherapy may improve the outcomes of older people undergoing rehabilitation. A recent report described the concept of rehabilitation pharmacotherapy. The concept envisages helping frail older people and people with disabilities to achieve the highest possible body function, activity level and quality of life. There are two key tenets of rehabilitation pharmacotherapy: “pharmacotherapy in consideration of rehabilitation” and “rehabilitation in consideration of pharmacotherapy.” “Pharmacotherapy in consideration of rehabilitation” includes use of drugs to treat impairment, activity limitation and participation restriction based on the International Classification of Functioning, Disability, and Health. “Rehabilitation in consideration of pharmacotherapy” refers to tailoring of rehabilitation considering the content of pharmacotherapy. With respect to drugs and motor dysfunction, anticholinergic drugs are associated with dysphagia and fractures. Increased use of potentially inappropriate medications may adversely affect the nutritional status. With respect to activities of daily living, polypharmacy and use of potentially inappropriate medications negatively affect the improvement in motor function during rehabilitation. Potent anticholinergic drugs are more likely to impede the improvement in cognitive function. In this review, we address the concept of rehabilitation pharmacotherapy and discuss its importance from the perspective of polypharmacy, the effect of drugs on disability and disease, nutritional status and activities of daily living. Geriatr Gerontol Int 2020; 20: – .