Effect of a late evening snack on outpatients with liver cirrhosis

Aims: We have reported that one-week administration of a late evening snack (LES) improved not only malnutrition but also glucose intolerance in hospitalized patients with liver cirrhosis. Thus, we investigated whether long-term LES administration to outpatients for 3 months could reproduce the results obtained from hospitalized patients, especially improved glucose intolerance. If this treatment aggravated glucose intolerance, we tried to find any marker predicting this aggravation before the treatment. Methods: Outpatients were prescribed one pack of oral supplementation of a branched-chain amino acid (BCAA)-enriched nutrient, Aminoleban EN (210 kCal) as a LES without dietician supervision. Both before LES administration and after 3 months, glucose tolerance and liver function were examined using a 75 g oral glucose tolerance test (OGTT), biochemical parameters in blood and the relationship between glucose tolerance (area under the curve (AUC)) and the following serum markers. Results: Branched-chain amino acid/tyrosine ratio (BTR), the number of red blood cells (RBC), and hematocrit (Ht) significantly increased, with significant reduction of blood NH(3) level in patients with a blood glucose level less than 200 mg/dL 2 h after 75 g OGTT. However, the increase of AUC was seen after 3 months of LES administration in patients who had blood glucose higher than 200 mg/dL 2 h after 75 g OGTT. AUC weakly correlated positively with serum 7S collagen and negatively with choline esterase (ChE) and albumin (Alb). Conclusion: 75 g OGTT is a useful marker to predict the worst outcome and avoid the adverse effect of LES treatment in liver cirrhosis patients if performed without adequate nutrient conduct by a dietician.     

Predictive value of QT dispersion for acute heart failure after autologous and allogeneic hematopoietic stem cell transplantation

The aim of our study was to evaluate whether corrected QT dispersion (QTc dispersion), an electrocardiographic marker, is a good predictor of the development of acute heart failure after high-dose chemotherapy followed by autologous or allogeneic hematopoietic stem cell transplantation. We enrolled 50 consecutive patients, from age 15 to 63 years, with hematopoietic diseases scheduled to undergo autologous or allogeneic hematopoietic stem cell transplantation, and compared QTc dispersion with other markers before transplantation conditioning. In univariate logistic analysis, QTc dispersion was a significant factor for acute heart failure after hematopoietic stem cell transplantation (odds ratio, 3.7 per 10 msec; confidence interval, 1.6-8.5; P = 0.002). There were no significant differences as age, sex, systolic or diastolic echocardiographic function markers, cumulative anthracycline dose, or QTc before transplantation between patients with and without acute heart failure. After multiple adjustments for left ventricular ejection fraction, cumulative anthracycline dose, cyclophosphamide conditioning dose, QTc dispersion was a significant and independent factor for acute heart failure after hematopoietic stem cell transplantation (odds ratio, 48.0 per 10 msec; confidence interval, 1.4-1666.3; P = 0.03). This study demonstrated that QTc dispersion could be used as a powerful noninvasive predictor of the development of acute heart failure after hematopoietic stem cell transplantation.     

Clinical impact of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer’s disease: a multicenter study

Annals of Nuclear Medicine - Amyloid positron emission tomography (PET) can reliably detect senile plaques and fluorinated ligands are approved for clinical use. However, the clinical impact of...     

Successful catheter ablation of ventricular tachycardia originating from the idiopathic saccular apical left ventricular aneurysm

Left ventricular (LV) aneurysm has been recognized to frequently become a substrate of ventricular tachyarrhythmias. We report a case of a 66-year-old woman with symptomatic sustained monomorphic ventricular tachycardia (SMVT) originating from saccular apical LV aneurysm without definite underlying diseases. We performed catheter ablation using electroanatomical and conventional bipolar potential mapping. During SMVT, we found an area of fragmented potential -40 ms preceding the earliest wide QRS complex in the area of the apical LV aneurysm. Radiofrequency applications were delivered to this area. Since then, SMVT was no longer inducible by programmed electrical stimulation. The patient has remained free of VT recurrences during a subsequent 12-month follow-up period.     

Irritant-induced cyclooxygenase-2 is involved in the defense mechanism of the gastric mucosa in mice

Background. Endogenous and exogenous prostaglandins (PGs) have been shown to contribute to reducing the gastric injury caused by irritants given subse-quently. The aim of this study was to clarify whether cyclooxygenase-2 (COX-2) protein induced by pretreatment was involved in the prevention of subsequent ethanol-caused gastric injury in mice. Methods. Mice were pretreated with acidified ethanol or saline and then COX-2 protein expression in the stomach was immunohistochemically determined every 8 h. Mice were administered 95% ethanol 24 h after the acidified ethanol pretreatment, and gastric mucosal damage was evaluated macroscopically and histologically. The effects of NS-398 or indomethacin on the 95% ethanol-caused damage were also examined. Results. Acidified ethanol pretreatment induced COX-2 protein expression in lamina propria macrophages of the gastric mucosa, with a peak level 24 h after the pretreatment. The 95% ethanol treatment caused gastric mucosal damage. The degree of the damage was not different between mice pretreated with acidified ethanol and those pretreated with saline. However, NS-398 aggravated the ethanol-caused damage only in mice pretreated with acidified ethanol, while indomethacin aggravated the damage, evaluated histologically, irrespective of the pretreatment. Conclusions. Pretreatment-induced COX-2, in addition to COX-1, seemed to be involved in the defense mechanism through minimizing the damage caused by a subsequent irritant. Received: October 16, 2000 / Accepted: September 14, 2001     

Genotype and phylogenetic characterization of hepatitis B virus among multi-ethnic cohort in Hawaii

AIM: Hepatitis B virus (HBV) genomes in carriers from Hawaii have not been evaluated previously. The aim of the present study was to evaluate the distribution of HBV genotypes and their clinical relevance in Hawaii. METHODS: Genotyping of HBV among 61 multi-ethnic carriers in Hawaii was performed by genetic methods. Three complete genomes and 61 core promoter/precore regions of HBV were sequenced directly. RESULTS: HBV genotype distribution among the 61 carriers was 23.0% for genotype A, 14.7% for genotype B and 62.3% for genotype C. Genotypes A, B and C were obtained from the carriers whose ethnicities were Filipino and Caucasian, Southeast Asian, and various Asian and Micronesian, respectively. All cases of genotype B were composed of recombinant strains with genotype C in the precore plus core region named genotype Ba. HBeAg was detected more frequently in genotype C than in genotype B (68.4% vs 33.3%, P<0.05) and basal core promoter (BCP) mutation (T1762/A1764) was more frequently found in genotype C than in genotype B. Twelve of the 38 genotype C strains possessed C at nucleotide (nt) position 1858 (C-1858). However there was no significant difference in clinical characteristics between C-1858 and T-1858 variants. Based on complete genome sequences, phylogenetic analysis revealed one patient of Micronesian ethnicity as having C-1858 clustered with two isolates from Polynesia with T-1858. In addition, two strains from Asian ethnicities were clustered with known isolates in carriers from Southeast Asia. CONCLUSION: Genotypes A, B and C are predominant types among multi-ethnic HBV carriers in Hawaii, and distribution of HBV genotypes is dependent on the ethnic background of the carriers in Hawaii.     

Immunomodulatory Activities of HERBSnSENSES™ Cordyceps — in Vitro and in Vivo Studies

The commercially available HERBSnSENSES? Cordyceps (HSCS) belongs to a cultivated strain of Cordyceps sinensis whose immunomodulatory activities has been renowned in traditional Chinese medicine (TCM) for centuries. The present report is the first that describes its immunomodulatory features through a series of in vitro and in vivo experiments. We measured, in peripheral blood mononuclear cells the in vitro effects of HSCS on the gene expression of cytokines and cytokine receptors, cytokine release, and surface expression of cytokine receptors using cDNA expression array, cytometric bead array (CBA), and immunoflorescence staining, respectively, as well as macrophage phagocytosis and monocyte production of H₂O₂ using flow cytometry. Sixty female BALB/c mice were fed with either HSCS (40 mg/kg/day) or water consecutively for 14 days. Proliferation, cytokine liberation, and CD3/4/8 expression of splenic cells were measured using 5-bromo-2′-deoxyuridine proliferation ELISA, CBA, and cytometry immunoflorescence staining, respectively. In vitro results demonstrated that HSCS induced the production of interleukin(IL)-1β, IL-6, IL-10 and tumor necrosis factor alphaα from PBMC, augmented surface expression of CD25 on lymphocytes, and elevated macrophage phagocytosis and monocyte production of H₂O₂. In vivo results showed that HSCS did not induce splenomegaly and cytokine overliberation. Our results possibly provide the biochemical basis for future clinical trials.     

Temporal Prediction Signals for Periodic Sensory Events in the Primate Central Thalamus

Prediction of periodic event timing is an important function for everyday activities, while the exact neural mechanism remains unclear. Previous studies in nonhuman primates have demonstrated that neurons in the cerebellar dentate nucleus and those in the caudate nucleus exhibit periodic firing modulation when the animals attempt to detect a single omission of isochronous repetitive audiovisual stimuli. To understand how these subcortical signals are sent and processed through the thalamocortical pathways, we examined single-neuron activities in the central thalamus of two macaque monkeys (one female and one male). We found that three types of neurons responded to each stimulus in the sequence in the absence of movements. Reactive-type neurons showed sensory adaptation and gradually waned the transient response to each stimulus. Predictive-type neurons steadily increased the magnitude of the suppressive response, similar to neurons previously reported in the cerebellum. Switch-type neurons initially showed a transient response, but after several cycles, the direction of firing modulation reversed and the activity decreased for each repetitive stimulus. The time course of Switch-type activity was well explained by the weighted sum of activities of the other types of neurons. Furthermore, for only Switch-type neurons the activity just before stimulus omission significantly correlated with behavioral latency, indicating that this type of neuron may carry a more advanced signal in the system detecting stimulus omission. These results suggest that the central thalamus may transmit integrated signals to the cerebral cortex for temporal information processing, which are necessary to accurately predict rhythmic event timing.SIGNIFICANCE STATEMENT Several cortical and subcortical regions are involved in temporal information processing, and the thalamus will play a role in functionally linking them. The present study aimed to clarify how the paralaminar part of the thalamus transmits and modifies signals for temporal prediction of rhythmic events. Three types of thalamic neurons exhibited periodic activity when monkeys attempted to detect a single omission of isochronous repetitive stimuli. The activity of one type of neuron correlated with the behavioral latency and appeared to be generated by integrating the signals carried by the other types of neurons. Our results revealed the neuronal signals in the thalamus for temporal prediction of sensory events, providing a clue to elucidate information processing in the thalamocortical pathways.     

Peripheral nerves are involved in hypomyelinating leukodystrophy-3 caused by a homozygous AIMP1 variant

IntroductionAminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is a non-catalytic component of the multi-tRNA synthetase complex that catalyzes the ligation of amino acids to their correct tRNAs. Bi-allelic truncating variants in the AIMP1 gene have been associated with hypomyelinating leukodystrophy-3 (HLD3; MIM 260600), which is characterized by hypomyelination, microcephaly, seizures and decreased life expectancy. Although peripheral nerve involvement has been assumed for HLD3, no compelling evidence is available to date.Case reportThe case was a first-born Filipino male. He showed profound developmental delay, failure to thrive, and spasticity in his limbs. At three months of age he developed refractory epilepsy. Serial magnetic resonance imaging (MRIs) showed profound myelination delay and progressive cerebral atrophy. He showed abnormal nerve conduction studies. Genetic testing revealed a homozygous pathogenic variant in the AIMP1 gene (NM_004757.3: c.115C > T: p.Gln39*). The parents were heterozygous for the same variant.ConclusionHere, we report a patient with a homozygous nonsense AIMP1 variant showing peripheral neuropathy as well as HLD3. Our case suggests that AIMP1 plays a pivotal role in the peripheral nerve as well as the central nervous system.