Evaluation of the permeability of pancreaticogastric anastomoses (PGA) with dynamic magnetic resonance pancreatography after secretin stimulation (secretin MRCP)

Background: Because some investigators have reported the systematic occurrence of exocrine pancreatic insufficiency after pancreaticoduodenectomy with pancreaticogastric anastomosis (PGA), we assessed PGA patency after pancreaticoduodenectomy. Methods: Nineteen patients underwent pancreaticoduodenectomy, and their PGAs were studied prospectively with secretin magnetic resonance cholangiopancreatography (MRCP). After administration of negative bowel contrast agent, single-shot fast spin-echo T2-weighted dynamic MR pancreatograms were obtained before and every minute for 12 min after secretin injection. Morphologic features of the pancreatic parenchymal and pancreatic duct were monitored (diameter and winding aspect of the pancreatic duct, pancreatic thickness, direct visualization of the anastomotic site). PGA permeability was classified into four grades, from 0 (obstruction) to 3 (good permeability). Pancreatic function was assessed by fecal-1 elastase concentration, fasting blood glucose, and fasting serum insulin level. Results: MRCP grades were 0 in two patients, 1 in four, 2 in five, and 3 in eight. The anastomotic site was visualized in 10 patients. Pancreatic parenchymal atrophy was discovered in four patients. There were statistically significant relations between secretin MRCP permeability grade and fecal-1 elastase concentration (p < 0.03) and between secretin MRCP permeability grade and pancreatic atrophy (p < 0.005). In contrast, fecal-1 elastase concentration was lower than the normal value in all but one case. There was no statistically significant relation between fecal-1 elastase concentration and other morphologic data. Conclusion: Secretin MRCP may indicate PGA stenosis or dysfunction, but it is not the only factor suggesting exocrine pancreatic insufficiency. Thus the major role of PGA may be the preservation of long-term endocrine function.     

Correlation of MRCP quantification (MRCPQ) with conventional non-invasive pancreatic exocrine function tests

PURPOSE: To correlate MRCP quantification (MRCPQ) of pancreatic fluid output following secretin with steatorrhoea, urinary pancreo-lauryl (PL) or fecal elastase 1 (FE1) tests. METHODS AND MATERIALS: Sixty-one patients, 36 male, median age 51 years (23-78) with known or suspected pancreatic disease who had undergone both MRCPQ and FE1 or PL were included. Twenty-nine patients had chronic pancreatitis, five acute pancreatitis, seven normal, five pancreas divisum, four pancreatic atrophy, three pancreatic duct obstruction, two post-surgical and six miscellaneous diagnoses. Clinical assessment of steatorrhoea was available in 29. MRCP was performed before and at 2 min intervals after 0.1 ml/kg IV Secretin. Changes in signal intensity in the imaging volume were plotted against time and the flow rate derived from the gradient. Scatter plots, Pearson correlation coefficient, and the Fisher Exact test were performed. RESULTS: MRCPQ was significantly different (p = 0.012) between those with/without steatorrhoea; mean +/- SD (95% CI) were 4.0 +/- 1.5 (3.1:4.9, n = 16) and 6.3 +/- 2.9 (4.7:7.8, n = 13). Fifty-one paired FE1-MRCPQ and 24 PL-MRCPQ data sets were analysed. Both the Pearson correlation coefficient (FE1 p = 0.001 and %TK p = 0.003) and the Fisher Exact test were significant (FE1 p = 0.016 and %T/K 0.03). CONCLUSIONS: MRCPQ correlated with steatorrhoea, PL and FE1.     

Determination of -amylase in serum and urine of subjects with a low bicarbonate concentration in the duodenal aspirate after secretin stimulation

Penicillin G reacts with 2,4-pentanedione to produce a derivative, which, in turn, reacts with Ehrlich's aldehyde reagent. The colored reaction product describes maximum absorbance in the region of 545–560 nm. Since maximum absorbance of the Ehrlich's complex of the pentanedione derivative of δ-aminolevulinic acid (ALA) is within this region, the excretion of penicillin G in urine will generate erroneously high ALA values.     

The composition of low (LDL) and very low (VLDL) density lipoprotein subfractions in type III hyperlipoproteinaemia: comparison with normal subjects.

The lipid and protein composition of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) subfractions (Sf greater than 100, 60--100 and 20--60 VLDL and Sf 10.4--20, 5.7--12 and 3.5--6.5 LDL) in six subjects with type III hyperlipoproteinaemia (HLP) was compared to that of 12 normal subjects. In type III HLP all VLDL subfractions contained increased concentrations of cholesterol and triglycerides and were relatively enriched in cholesterol. VLDL of Sf 20--60 also contained and increased concentration of B-protein. The tetramethylurea (TMU) soluble apolipoproteins of the VLDL subfractions were separated by polyacrylamide disc gel electrophoresis. In the subjects with type III HLP the proportion of arginine rich protein (ARP) was increased in all subfractions. The concentrations of cholesterol and triglycerides were increased in the LDL subfraction of Sf 10.4--20 and cholesterol was decreased in LDL of Sf 5.7--12, but the ratios of cholesterol to triglycerides were not significantly different from those in the LDL subfractions of the normal subjects and the protein composition was also similar. These results provide further evidence that in type III HLP abnormalities are not confined to the stage of conversion of VLDL to LDL, but occur throughout the VLDL spectrum.     

Pharmacokinetics and safety of a novel influenza treatment (baloxavir marboxil) in Korean subjects compared with Japanese subjects

Baloxavir marboxil, a novel influenza therapeutic agent, is a prodrug rapidly metabolized into its active form, baloxavir acid, which inhibits cap‐dependent endonuclease. This study evaluated the pharmacokinetics (PKs) and safety of baloxavir acid in healthy Korean subjects and compared them with published data in Japanese subjects. This open‐label and single‐ascending dose study was conducted in 30 Korean male subjects, with a single oral dose of baloxavir marboxil (20, 40, or 80 mg) administered to eight subjects each; additionally, 80 mg was administered to six subjects (body weight >80 kg). Noncompartmental and population PK analyses were performed, and results were compared with those of Japanese subjects. Appropriateness of the body weight‐based dosing regimen was evaluated by simulation. PK profiles of baloxavir acid revealed multicompartment behavior with a long half‐life (80.8–98.3 h), demonstrating a dose‐proportional increase. Baloxavir acid reached peak plasma concentration from 3.5 to 4.0 h postdosing. Body weight was identified as a significant covariate of apparent oral clearance and apparent volume of distribution, which was similar to that observed in Japanese subjects. Body weight‐adjusted analysis revealed that exposure to baloxavir acid did not significantly differ between Korean and Japanese subjects. Simulated exposures to baloxavir acid demonstrated that the body weight‐based dosing regimen for baloxavir marboxil was appropriate. Based on a PK study, clinical data including dosing regimen developed in Japan were adequately extrapolated to Korea, supporting the approval of baloxavir marboxil in Korean as a new treatment option for influenza.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Baloxavir marboxil, a novel influenza therapeutic agent, has been approved in Japan (first global approval; February 2018) and in the United States (October 2018). The recommended dosage for patients depends on body weight: 40 mg (40–80 kg), 80 mg (≥80 kg). However, no clinical data was available for adequate clinical use in the Korean population.

• WHAT QUESTION DID THIS STUDY ADDRESS?

What are the pharmacokinetic characteristics of baloxavir acid in Koreans, and will it show similar characteristics to those in Japanese?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Pharmacokinetics of baloxavir acid were similar to those of Japanese population. Simulated exposures to baloxavir acid demonstrated that the body weight‐based dosing regimen for baloxavir marboxil was appropriate in Korean population. This study provided the pharmacokinetic data to support the approval of baloxavir marboxil in Korea (November 2019) as a new treatment option for influenza.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Based on this pharmacokinetic study, the efficacy, safety, and body weight‐based dosing regimen data developed in foreign countries could be adequately extrapolated to Korea.     

Influence of apolipoprotein(a) phenotype on lipoprotein(a) quantification: Evaluation of three methods

Three commercially available assays (an enzyme-linked immunosorbent assay ELISA, an immunoradiometric assay, IRMA, and a nephelometric assay) for the determination of lipoprotein(a) [Lp(a)] were compared with respect to the dependency of these assays on the various apolipoprotein(a) [apo(a)] isoforms. Although there was a strong correlation between the three methods, a significant difference between the absolute values (mg/L) was observed (p < 0.001). Using purified Lp(a) preparations, we showed that the ELISA assay quantifies the Lp(a) concentration on a molar basis, independently of the apo(a) isoform size. The IRMA and the nephelometric assay however are apo(a) isoform size dependent and overestimate the Lp(a) concentration of large apo(a) isoforms whereas the amount of small apo(a) isoforms is underestimated. In general, the isoform dependency of the Lp(a) quantification is of limited clinical relevance. In this study, inconsistent risk assignments are made in approximately 3% of the cases, when the Lp(a) concentrations obtained with the apo(a) isoform dependent assays are compared with the isoform independent ELISA.     

The effect of weight-bearing exercise with low frequency, whole body vibration on lumbosacral proprioception: a pilot study on normal subjects

Patients with low back pain (LBP) often present with impaired proprioception of the lumbopelvic region. For this reason, proprioception training usually forms part of the rehabilitation protocols. New exercise equipment that produces whole body, low frequency vibration (WBV) has been developed to improve muscle function, and reportedly improves proprioception. The aim of this pilot study was to investigate whether weightbearing exercise given in conjunction with WBV would affect lumbosacral position sense in healthy individuals. For this purpose, twenty-five young individuals with no LBP were assigned randomly to an experimental or control group. The experimental group received WBV for five minutes while holding a static, semi-squat position. The control group adopted the same weightbearing position for equal time but received no vibration. A two-dimensional motion analysis system measured the repositioning accuracy of pelvic tilting in standing. The experimental (WBV) group demonstrated a significant improvement in repositioning accuracy over time (mean 0.78 degrees) representing 39% improvement. It was concluded that WBV may induce improvements in lumbosacral repositioning accuracy when combined with a weightbearing exercise. Future studies with WBV should focus on evaluating its effects with different types of exercise, the exercise time needed for optimal outcomes, and the effects on proprioception deficits in LBP patients.     

Evaluation of the Radio-Allergo-Sorbent-Test (RAST) with respect to misinterpretations of the results

Two hundred and twenty two single allergens were assayed in 36 outpatients, using a commercial RAST kit. It was found that a significant proportion of the patients were evaluated incorrectly as having elevated levels of allergen-specific IgE. This was due to an as yet unconsidered parameter of the RAST, i.e. unspecific binding of the radioactive tracer to the wall of the test tubes, resulting in values that did not correlate with the total IgE concentrations of individual sera. The unspecific binding amounted in some cases to 89% of the total radioactivity (counts/min) when the instruction manual of the manufacturer was followed. This resulted in either false positive results and/or RAST classifications that were 1 to 2 classes too high. The results can be corrected by a slight modification of the assay.     

Management of gastroesophageal reflux disease (GERD) with refractory to standard dose of proton pump inhibitor

Approximately 10% of Japanese patients with reflux esophagitis (RE) are refractory to a standard dose of proton pump inhibitor(PPI) and most refractory patients have severe RE. Lack of response may be due to inadequate gastric acid suppression in conjunction with CYP2C19 genotype status and nocturnal acid reflux. Twice-daily dosing of PPI for inadequate gastric acid suppression and the administration of H2-receptor antagonist before bedtime for nocturnal acid reflux, is effective in most cases. The response to a standard dose of PPI in patients with non-erosive reflux disease (NERD) is approximately 50%. The reasons for a lower response rate, compared with RE patients, are not clear but may relate to an acid-hypersensitive esophagus, inadequate gastric acid suppression, non -acid reflux and emotional or psychological abnormality. High dose PPI therapy, endoscopic or surgical anti-reflux therapy, or/and pain modulators may be effective in some patients.     

Sonography of the shoulder after arthrography (arthrosonography): preliminary results.

PURPOSE: The purpose of this study was to verify whether arthrosonography improves diagnostic accuracy in diseases of the shoulder and provides additional information for therapeutic planning, compared with conventional sonography. METHODS: We prospectively studied 113 consecutive patients with chronic shoulder pain. Sonography was performed before and after arthrography, with the radiologist blinded to the results of arthrography. When a rotator cuff tear was detected sonographically, its type, location, and size were recorded; we also evaluated any changes in the subacromial-subdeltoid bursa and any abnormalities in the biceps tendon sheath. The diagnostic accuracy of conventional sonography and arthrosonography was compared with that of arthrography for rotator cuff tear. Changes in the subacromial-subdeltoid bursa and biceps tendon sheath seen on conventional sonography were also compared with those seen on arthrosonography. RESULTS: The sensitivity and specificity of conventional sonography in the diagnosis of rotator cuff tear were 86% (25/29) and 95% (80/84), respectively; for arthrosonography, the values were 97% (28/29) and 95% (80/84), respectively. The differences in sensitivity and specificity for the 2 sonographic techniques were not statistically significant (p > 0.05). The accuracy in localizing the tear was also not significantly different between the 2 sonographic techniques. Synovial proliferation was more easily detected with arthrosonography than it was with conventional sonography in the subacromial-subdeltoid bursa (p < 0.01) and in the biceps tendon sheath (p < 0.0001). CONCLUSIONS: Our preliminary results suggest that although arthrosonography was not superior to conventional sonography in the diagnosis of rotator cuff tears, it may provide a better assessment of the size of tears and additional information about synovial proliferation in the subacromial-subdeltoid bursa and the biceps tendon sheath.     

Prefrontal direct current stimulation modulates resting EEG and event-related potentials in healthy subjects: a standardized low resolution tomography (sLORETA) study

Prefrontal transcranial direct current stimulation (tDCS) with the anode placed on the left dorsolateral prefrontal cortex (DLPFC) has been reported to enhance working memory in healthy subjects and to improve mood in major depression. However, its putative antidepressant, cognitive and behavior action is not well understood. Here, we evaluated the distribution of neuronal electrical activity changes after anodal tDCS of the left DLPFC and cathodal tDCS of the right supraorbital region using spectral power analysis and standardized low resolution tomography (sLORETA). Ten healthy subjects underwent real and sham tDCS on separate days in a double-blind, placebo-controlled cross-over trial. Anodal tDCS was applied for 20 min at 2 mA intensity over the left DLPFC, while the cathode was positioned over the contralateral supraorbital region. After tDCS, EEG was recorded during an eyes-closed resting state followed by a working memory (n-back) task. Statistical non-parametric mapping showed reduced left frontal delta activity in the real tDCS condition. Specifically, a significant reduction of mean current densities (sLORETA) for the delta band was detected in the left subgenual PFC, the anterior cingulate and in the left medial frontal gyrus. Moreover, the effect was strongest for the first 5 min (p<0.01). The following n-back task revealed a positive impact of prefrontal tDCS on error rate, accuracy and reaction time. This was accompanied by increased P2- and P3- event-related potentials (ERP) component-amplitudes for the 2-back condition at the electrode Fz. A source localization using sLORETA for the time window 250-450 ms showed enhanced activity in the left parahippocampal gyrus for the 2-back condition. These results suggest that anodal tDCS of the left DLPFC and/or cathodal tDCS of the contralateral supraorbital region may modulate regional electrical activity in the prefrontal and anterior cingulate cortex in addition to improving working memory performance.     

Double plateletpheresis (DPA) and tailored RBC collection with the Excel-Pro: preliminary results.

The Dideco Excel-Pro is frequently used for double plateletpheresis (DPA) when the platelet precount exceeds 280 x 10(3)/l. Platelets are collected as "dry platelets" and the resuspension solution is added when the procedure is over. Even when DPA is carried out the product volume prior to resuspension may be as low as 60 ml. As a result, a third product may be collected along with platelets. Our priority is to collect RBCs and, depending on the donor's BW, tailored RBC collections are carried out. This means that from 400 to 480 ml of PRBC (70% hct) are collected from donors whose BW exceeds 75 kg. The results of the last 27 DPA/tailored PRBC collections are: Donors gender and BW (kg), 19M/8F: 88.4 +/- 7.3 Hemoglobin (g/dl): 15.4 +/- 1.3 Platelet precount (x 10(3)/microl): 308 +/- 45 Volume of blood processed (1): 5.5 Procedure time (min): 81 +/- 3 Platelet yield (x 10(11)): 6.8 +/- 0.6 Avg Hemoglobin content of PBRC (g): 102.6 +/- 12.3 WBC contamination of the platelets: 6.8 +/ -10(5).