Small dense LDL phenotype is associated with postprandial increases of large VLDL and remnant-like particles in patients with acute myocardial infarction

BACKGROUND: The small dense low-density lipoprotein (LDL) phenotype (pattern B), high concentrations of remnant-like particles (RLPs), and postprandial lipemia are newly recognized risk factors for coronary heart disease (CHD). However, the associations of these lipoprotein abnormalities remain unclear. The aim of this study was to investigate the relationships among LDL phenotype, very-low-density lipoprotein (VLDL) subclasses, and postprandial lipoprotein metabolism in CHD patients. METHOD: We performed an oral fat tolerance test in 32 patients with acute myocardial infarction and compared the following parameters between patients characterized by either large buoyant LDL (pattern A) versus pattern B: lipids and apolipoproteins (apo) in the plasma and Svedberg flotation rates (Sf) >400 (chylomicron), Sf 60-400 (large VLDL), and Sf 20-60 (small VLDL) fractions. RESULT: Fasting levels of triglyceride, RLP-cholesterol and RLP-triglyceride were slightly higher in the pattern B patients. Postprandial increases of RLP-cholesterol and the cholesterol and triglyceride of large VLDL fractions were significantly greater in the pattern B patients. The areas under the curves of cholesterol, triglyceride, and apo-B in large VLDL fractions were significantly higher in pattern B, while those in small VLDL were not. RLP-cholesterol and RLP-triglyceride in fasting and fed states correlated very highly with the corresponding cholesterol and triglyceride concentrations in large VLDL fractions. CONCLUSION: These results suggest that postprandial increase of large VLDL fractions and RLPs contribute to the formation of small dense LDL in CHD patients.     

End-to-side choledochoduodenostomy: A widely applicable procedure for biliary reconstruction

End-to-side choledochoduodenostomy was originally used for reconstruction between the duodenum and the biliary tree in iatrogenic bile duct stricture. However, we believe the procedure could be applied for various biliary disorders. We have recently shown the high carcinogenicity of biliary epithelium in patients with pancreaticobiliary maljunction, and consequently we recommend excision of the bile duct, along with appropriate reconstruction of the biliary system to divert the flow of pancreatic juice from bile fluid, to prevent carcinoma in biliary epithelium even in patients without dilatation of the bile duct. The conditions causing primary or recurrent bile duct stones must be removed. We employed this procedure for biliary reconstruction in 42 patients with pancreatico-biliary maljunction and in 30 patients with various benign biliary diseases, such as bile duct stones and benign biliary stenosis. We also used the procedure for palliation in 6 patients with malignant tumors around the head of the pancreas. Among these 78 patients over 20 years, we experienced 5 cases of reflux cholangitis with anastomotic stenosis, for which conservative dilatation was required. This procedure of end-to-side choledochoduodenostomy could be widely applicable for biliary reconstruction in terms of its being simplicity, minimal invasiveness and the establishment of a single physiological route for bile flow into the duodenum.     

Facile determination of natural cannabinoids in cannabis products using a conventional fully porous particle column and isocratic high-performance liquid chromatography with diode-array detector

Forensic Toxicology -     

Glucocorticoids induce G1 cell cycle arrest in human neoplastic thymic epithelial cells

Purpose Glucocorticoids exert anti-proliferative effects in various cell types and have long been known to induce apoptosis in thymocytes. Although a few reports have described the regression of human thymoma with glucocorticoid therapy, its effects on neoplastic thymic epithelial cells (TECs) have not been reported. In the present study, we investigated glucocorticoid receptor (GR) expression on neoplastic TECs and the effects of glucocorticoids in vitro on the cell cycle progression of tumor cells.Patients and methods Thymoma specimens were obtained during surgery from 21 patients. Three of the specimens with glucocorticoid therapy were examined using the TdT-mediated dUTP-biotin nick-end labeling method. Primary tumor specimens from ten untreated thymomas were examined for GR expression by immunohistochemistry. Isolated neoplastic TECs from the remaining eight untreated thymomas were examined using immunohistochemistry, flow cytometric and cell cycle analysis.Results GR are expressed on neoplastic TECs as well as on non-neoplastic thymocytes in thymomas, regardless of WHO histological classification. Glucocorticoids caused an accumulation of TEC in G0/G1 phase in all cases examined (n=6), and also induced apoptosis in the three with the lowest levels of Bcl-2 expression.Conclusions Our results indicate that neoplastic TECs express GR and that glucocorticoids directly suppress their in vitro proliferation.     

Surgical Correction of Patent Ductus Venosus in Three BroThers

We report the presence of a patent ductusvenosus in three brothers who underwent surgicalcorrection. Patent ductus venosus was demonstrated byultrasonography. Portosystemic venous shunt ratios asevaluated by [¹²³I]iodoamphetamine per rectalportal scintigraphy were 67%, 50%, and 77%,respectively. Histologic examination of liver biopsyspecimens revealed fatty degeneration in all cases.Portal vein pressure before and after temporarily occluding thepatent ductus venosus was estimated by an Anthron P-Ucatheter introduced into the portal vein via theligament teres hepatis. Portal venous pressure increased from 10 to 17 cm H₂O, 16 to 23 cmH₂O, and 14 to 27 cm H₂O,respectively. Therefore, banding of the ductus venosuswith Teflon tape was attempted to prevent portalhypertension following complete ligation. As a result, portal venous pressures afterstricture of the ductus venosus were 12, 21, and 20 cmH2), respectively. Bile acid and liver enzymes decreasedand returned to normal within 14 days after surgery. Interestingly, serum concentrations ofhepatocyte growth factor (HGF) increased significantlyafter restoration of the portal blood flow and thengradually decreased, but remained persistently elevated for at least two weeks in two cases measuredafter surgical correction. One month after correction,liver function returned to normal as assessed byserological and histological parameters in all cases. These results suggest that it is important todetermine whether stricture or complete ligation isindicated for a patent ductus venosus during surgicalcorrection, based on the portal venous pressure after temporal test occlusion of the duct. Inaddition, HGF may be a useful marker for normalizationof hepatic microcirculation after surgery.     

Biliopancreatic fistula with portal vein thrombosis caused by a pancreatic pseudocyst

We encountered a very rare case of biliopancreatic fistula with portal vein thrombosis caused by pancreatic pseudocyst. A 57-year-old man was referred to our hospital because of abdominal pain, obstructive jaundice, and portal vein thrombosis due to acute pancreatitis. Computed tomography showed a 7-cm-diameter pseudocyst around the superior mesenteric vein extending towards the pancreatic head, dilatation of the intrahepatic bile duct, and portal vein thrombosis. Endoscopic retrograde pancreatography revealed a main pancreatic duct with a pseudocyst communicating with the common bile duct. After pancreatic sphincterotomy, a 7-F tube stent was endoscopically placed into the pseudocyst. However, a 6-F nasobiliary tube could not be inserted into the bile duct because the fistula had a tight stenosis. Subsequently, the patient’s abdominal pain improved, the pancreatic cyst disappeared, and the serum amylase level normalized. Two months after the endoscopic retrograde cholangiopancreatography, percutaneous transhepatic biliary drainage was required because the patient’s jaundice became aggravated. Two weeks after the choledochojejunostomy, the patient left the hospital in good condition. A follow-up computed tomography showed cavernous transformation of the portal vein and no pancreatic pseudocyst. The patient remains asymptomatic for 2 years and 7 months after surgery. Biliary drainage may be necessary for biliopancreatic fistula with obstructive jaundice in addition to pancreatic cyst drainage. Biliopancreatic fistula can be treated by endoscopic procedure in some cases; however, surgical treatment should be required in cases that are impossible to insert a biliary stent because of hard stricture.     

Evidence for Reactivation of Human Herpesvirus 6 in Generalized Lymphadenopathy in a Patient with Drug-Induced Hypersensitivity Syndrome

The present case provides direct evidence of human herpesvirus 6 reactivation in resected lymph node tissue in a patient with drug-induced hypersensitivity syndrome. This case clearly demonstrates that appropriate pathological evaluation of lymphadenopathy for drug-induced hypersensitivity syndrome, which mimics malignant lymphoma in clinical, radiological, and pathological findings, is required.     

Early non-convulsive seizures are associated with the development of acute encephalopathy with biphasic seizures and late reduced diffusion

IntroductionChildren with either febrile seizure or acute encephalopathy exhibit seizures and/or impaired consciousness accompanied by fever of unknown etiology (SICF). Among children with SICF, we previously reported those who have refractory status epilepticus or prolonged neurological abnormalities with normal AST levels are at a high risk for the development of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), considered to be caused by excitotoxicity. Non-convulsive seizures (NCS) are common in critically ill children and cause excitotoxic neuronal injury. The aim of this study was to elucidate the prevalence of NCS in the acute phase of children at a high risk for developing AESD and the relationship between NCS in the acute phase and neurological outcomes.MethodsWe studied 137 children with SICF at a high risk for developing AESD and who underwent continuous electroencephalogram monitoring (cEEG) upon admission to a tertiary pediatric care center at Hyogo Prefectural Kobe Children’s Hospital between October 2007 and August 2018. Patient characteristics and outcomes were compared between patients with NCS and without NCS.ResultsOf the 137 children, NCS occurred in 30 children; the first NCS were detected in cEEG at the beginning in 63.3%, during the first hour in 90%, and within 12 h in 96.7%. Neurological sequelae were more common in NCS patients (20.0%) than in non-NCS patients (1.9%; p = 0.001). Five in 30 NCS patients (16.7%) and 3 in 107 non-NCS patients (2.8%) developed AESD (p = 0.013).ConclusionThe occurrence of NCS is associated with subsequent neurological sequelae, especially the development of AESD.     

The UBIAD1 Prenyltransferase Links Menaquione‐4 Synthesis to Cholesterol Metabolic Enzymes

Schnyder corneal dystrophy (SCD) is an autosomal dominant disease characterized by germline variants in UBIAD1 introducing missense alterations leading to deposition of cholesterol in the cornea, progressive opacification, and loss of visual acuity. UBIAD1 was recently shown to synthesize menaquinone‐4 (MK‐4, vitamin K₂), but causal mechanisms of SCD are unknown. We report a novel c.864G>A UBIAD1 mutation altering glycine 177 to glutamic acid (p.G177E) in six SCD families, including four families from Finland who share a likely founder mutation. We observed reduced MK‐4 synthesis by UBIAD1 altered by SCD mutations p.N102S, p.G177R/E, and p.D112N, and molecular models showed p.G177‐mutant UBIAD1 disrupted transmembrane helices and active site residues. We show UBIAD1 interacts with HMGCR and SOAT1, enzymes catalyzing cholesterol synthesis and storage, respectively, using yeast two‐hybrid screening and immunoprecipitation. Docking simulations indicate cholesterol binds to UBIAD1 in the substrate‐binding cleft and substrate‐binding overlaps with GGPP binding, an MK‐4 substrate, suggesting potential competition between these metabolites. Impaired MK‐4 synthesis is a biochemical defect identified in SCD suggesting UBIAD1 links vitamin K and cholesterol metabolism through physical contact between enzymes and metabolites. Our data suggest a role for endogenous MK‐4 in maintaining cornea health and visual acuity.