The B-Mode Image-Guided Ultrasound Attenuation Parameter Accurately Detects Hepatic Steatosis in Chronic Liver Disease

The purpose of our study was to evaluate the diagnostic accuracy of the ultrasound-guided attenuation parameter (UGAP) for the detection of hepatic steatosis in comparison with the controlled attenuation parameter (CAP), using histopathology as the reference standard. We prospectively analyzed 163 consecutive chronic liver disease patients who underwent UGAP, CAP, computed tomography and a liver biopsy on the same day between April 2016 and July 2017. Radiofrequency signals corresponding to the images were compensated by the reference signal previously measured from the uniform phantom with known attenuation (0.44 dB/cm/MHz). The attenuation coefficient was calculated from the signals’ decay slope. The median attenuation coefficient values in patients with S0 (n?=?62), S1 (n?=?63), S2 (n?=?23) and S3 grade (n?=?15) were 0.485, 0.560, 0.660 and 0.720, respectively. Significant correlations were found between attenuation coefficient and percentage steatosis, CAP values and liver-to-spleen computed tomography attenuation ratio (p < 0.001). The areas under the receiver operating characteristic curve of UGAP for identifying ≥S1, ≥S2 and ≥S3 were 0.900, 0.953 and 0.959, respectively, which were significantly better than the results obtained with CAP for identifying ≥S2 and ≥S3. In conclusion, UGAP had high diagnostic accuracy for detecting hepatic steatosis in patients with chronic liver disease     

Relationship between plasma total homocysteine level and dietary caffeine and vitamin B6 intakes in pregnant women

A high total homocysteine (tHcy) level during pregnancy is a risk factor for adverse perinatal outcomes, such as fetal growth restriction and preeclampsia. Caffeine is assumed to increase tHcy levels by acting as a vitamin B₆ antagonist. The objective of this study was to examine a relationship between circulating tHcy levels and dietary caffeine and vitamin B₆ intakes in pregnant Japanese women. A total of 321 healthy women with singleton pregnancies were recruited in metropolitan Tokyo, from June to December 2008, resulting in the final number included in the study as 254. Dietary caffeine intakes did not correlate with plasma tHcy levels. When we analyzed the data according to caffeinated beverages, caffeinated tea consumption was positively associated with plasma tHcy levels only among the women with a high intake of vitamin B₆, after controlling for confounding factors (P = 0.029). No correlation between coffee consumption and plasma tHcy levels was found. Pregnant Japanese women might need to cut down the consumption of caffeinated tea as well as take sufficient vitamin B₆ in order to prevent the tHcy levels from increasing.     

Dominant β-Thalassemia with Hemoglobin Hradec Kralove: Enhanced Hemolysis in the Spleen

We describe a 6-year-old girl and her mother with dominant beta-thalassemia due to hemoglobin Hradec Kralove (Hb HK). Both patients presented microcytic anemia, jaundice, splenomegaly, cholelithiasis, and recurrent hemolytic bouts. Osmotic resistance tests using saline and coiled planet centrifugation revealed the increased fragility of the red cell membrane. On the other hand, the glycerol lysing time was prolonged, and results of the isopropanol test were weakly positive. Despite mimicking the features of hereditary spherocytosis, the results of the genetic analyses verified the second reported family with Hb HK (codon 115, GCC [Ala] --> GAC [Asp]). Splenectomy was effective for the amelioration of hemolysis. Of 7 reported patients with Hb variants at beta-globin codon 115 (Hb Madrid and Hb HK), 5 underwent splenectomy. Because of the variable augmentation of extramedullary hemolysis in dominant beta-thalassemias, genotyping is necessary for determining the clinical indication of splenectomy.     

Detection and identification of pathogenic bacteria responsible for postoperative pneumonia after esophagectomy

Background

Surgical complications occur frequently after radical esophagectomy and one of its most serious complications is postoperative pneumonia. Preoperative or postoperative bacteriological assessment may be useful in predicting, preventing, and managing postoperative pneumonia.

Methods

One hundred and five consecutive patients undergoing any procedure that included subtotal esophagectomy from October 2009 to March 2011 were the subject of this study. Culture materials (pharyngeal swab, nasal swab, dental plaque, tongue coating, gastric juice, and sputum) retrieved from the 105 esophageal cancer patients before, during, and after the surgery were comprehensively investigated for an association with postoperative pneumonia.

Results

Twenty-one patients out of 105 (20%) were retrospectively diagnosed with postoperative pneumonia. The investigated culture studies were associated with the occurrence of postoperative pneumonia in only one respect: positive detection of pathogens in postoperative endotracheal sputum was associated with marginally increased pneumonia (P = 0.053). Among the 21 pneumonia patients, pathogens were frequently detected in gastric juice retrieved on the first postoperative day (8 out of 14) and postoperative endotracheal sputum (13 out of 17). The putative pathogens of postoperative pneumonia were detected in 7 out of 8 gastric juice specimens and 9 out of 11 in sputum.

Conclusions

Postoperative pneumonia could not be predicted by either preoperative or postoperative bacteriological studies. In the patients with postoperative pneumonia, the postoperative bacterial culture of the gastric juice and sputum may be useful in identifying the causative organisms of postoperative pneumonia and, thus, in selecting appropriate antibiotics.

     

Suppression by protease-activated receptor-2 activation of gastric acid secretion in rats

Activation of protease-activated receptor-2 (PAR-2), a receptor activated by trypsin/tryptase, induces neurally mediated gastric mucus secretion accompanied by mucosal cytoprotection. In the present study, we investigated whether PAR-2 could modulate gastric acid secretion in rats. Messenger RNAs for PAR-2 and PAR-1 were detected in the gastric mucosa and smooth muscle. The PAR-2-activating peptide SLIGRL-NH(2), but not the inactive control peptide, when administered i.v., strongly suppressed gastric acid secretion in response to carbachol, pentagastrin or 2-deoxy-D-glucose in the rats with a pylorus ligation. The PAR-2-mediated suppression of acid secretion was resistant to cyclooxygenase inhibition or ablation of sensory neurons by capsaicin. Our results provide novel evidence that in addition to stimulating neurally mediated mucus secretion, activation of PAR-2 suppresses gastric acid secretion independently of prostanoid production or sensory neurons. These dual actions of PAR-2 would result in gastric mucosal cytoprotection.     

Anesthesia for a severe ankylosing spondylitis patient whose posture had been restricted to only sitting for over 20 years

A 42-year-old woman with an Arnold-Chiari abnormality was scheduled for cervical spine surgery. She had severe ankylosing spondylitis, and all her joints from ankles to occipitocervical joint were fixed except hip joints, which had been replaced with artificial joints 20 years before. She could bend her upper body only in a range from -20 to 70 degree from the sitting position. Her posture had been restricted to only sitting for over 20 years, and she complained vertigo when positioned in supine position. The trachea was intubated with an aid of bronchofiberscopy under sedation in sitting position, and then anesthesia was induced with propofol and fentanyl. When she was turned to prone position, nasal bleeding was noticed and the surgery was performed in a modified sitting position. The intra- and post-operative course was uneventful. The present case indicates that long-term restriction only to sitting position modulates circulatory control in response to changing postures, and that preoperative evaluation for appropriate posture for surgery is mandatory.     

Oral administration of leucine stimulates phosphorylation of 4E-bP1 and S6K 1 in skeletal muscle but not in liver of diabetic rats

Leucine performs a signaling role to enhance protein synthesis by phosphorylating eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and 70-kDa ribosomal protein S6 kinase (S6K1), two key regulatory proteins involved in the initiation of mRNA translation. The purpose of the current study was to assess whether the phosphorylation of 4E-BP1 and S6K1 was increased in skeletal muscle and liver by an oral administration of leucine to diabetic rats and to determine the in vivo contribution of insulin to a leucine-dependent induction of 4E-BP1 and S6K1 phosphorylation. Food-deprived (18 h) normal and diabetic rats were orally administered 135 mg/ 100 g body weight L-leucine and sacrificed at 1 h after administration. Leucine administration resulted in enhanced phosphorylation of 4E-BP1 and S6K1 in skeletal muscle and in liver of nondiabetic rats. The stimulatory action of leucine on the phosphorylation of 4E-BP1 and S6K1 in skeletal muscle was not abolished in rats with streptozotocin-induced diabetes. In contrast, leucine administration did not stimulate the phosphorylation of 4E-BP1 and S6K1 in the liver of diabetic rats. These findings suggest that in skeletal muscle, leucine functions as a nutritional signaling molecule that independently regulates the phosphorylation states of 4E-BP1 and S6K1. In contrast to skeletal muscle, insulin is essential in mediating the leucine-dependent induction of 4E-BP1 and S6K1 phosphorylation in liver. leucine, 4E-BP1, S6K1, translation initiation, diabetes     

Therapeutic potential of a reduced-intensity preparative regimen for allogeneic transplantation with cladribine, busulfan, and antithymocyte globulin against advanced/refractory acute leukemia/lymphoma.

PURPOSE: Cladribine (2-CdA) is a purine analogue that exhibits activity against a variety of hematological malignancies and has a potent immunosuppressive effect. We therefore performed a pilot study to evaluate the feasibility of a novel 2-CdA-based reduced-intensity stem cell transplantation (RIST) regimen. EXPERIMENTAL DESIGN: A total of 16 scheduled patients with hematological malignancies were enrolled for comparison of their data with conventional stem cell transplantation (n = 19). The regimen for RIST consisted of 2-CdA (0.11 mg/kg/day for 6 days), busulfan (4 mg/kg/day for 2 days), and rabbit antithymocyte globulin (2.5 mg/kg/day for 4, 2, or 0 days). The underlying diseases included acute myelogenous leukemia (n = 6), chronic myelogenous leukemia (n = 2), myelodysplastic syndrome (n = 6), and non-Hodgkin's lymphoma (n = 2). RESULTS: After RIST, four patients died before day 100 as a result of acute graft-versus-host disease (n = 1), bacteremia (n = 1), disseminated candidasis (n = 1) and congestive heart failure (n = 1). Another patient died of cerebral infarction on day 140. Thus, acute-phase regimen-related toxicities >grade III were observed in only one patient. Engraftment and complete donor chimerism were achieved by day 28 in 14 evaluable patients, and 6 of them (43%) experienced grade II-IV acute graft-versus-host disease. With a median follow-up of 328 days (range, 231-633 days), the actuarial 1-year overall and disease-free survival rates were 69% and 50%, respectively. Notably, among seven high-risk patients (five patients had been in complete remission two or more times and two not in complete remission with refractory disease at transplant), only two patients developed leukemia relapse after RIST. Although the recovery of CD4+ cells was significantly slower (P = 0.02) in RIST than in conventional stem cell transplantation, the incidence of clinically documented infections was not significantly different between the two groups. CONCLUSION: The results suggest that this novel regimen containing 2-CdA is well tolerated and induces early complete donor chimerism. The unexpected durable remission achieved in patients with advanced disease at transplant suggests the presence of an acceptable antileukemia/lymphoma effect, which would warrant a further clinical trial.