Single serum cortisol values at 09:00 h can be indices of adrenocortical function in children with Kawasaki disease treated with intravenous immunoglobulin plus prednisolone

Combination treatment with intravenous immunoglobulin (IVIG) plus prednisolone is effective for prevention of cardiovascular complications in children with Kawasaki disease (KD). However, administration of prednisolone for approximately 20 d in this regimen causes adrenocortical suppression in a high proportion of treated children. To establish a simple method to screen for this suppression, we performed a prospective study on 72 children with KD treated with this regimen in our institution from February 2012 to March 2014. By performing ROC analysis of 21 initial patients treated between February and June 2012, a serum cortisol value at 09:00 h of 5 mcg/dL was established as a threshold for intact adrenocortical function, which is equivalent to a peak serum cortisol value of higher than 15 mcg/dL in the CRH stimulation test. Then, we applied this screening test to 51 subsequent patients treated between July 2012 and March 2014. Approximately 90% of the patients with morning serum cortisol values above 5 mcg/dL 2 to 6 mo after the cessation of initial prednisolone treatment had peak serum cortisol values exceeding 15 mcg/dL, suggesting the efficacy of this approach.     

Induction of islet B-cell regeneration in partially pancreatectomized rats by poly(ADP-ribose) synthetase inhibitors

In order to clarify the mechanism of the prevention of diabetes mellitus developing after subtotal pancreatectomy, we examined regenerative activities of islet B-cells in 90% pancreatectomized and poly (ADP-ribose) synthetase inhibitor-treated rats by using autoradiographic and stathmokinetic techniques. Thirty days after 90% pancreatectomy, islets of rats without 3-aminobenzamide treatment were decreased in number, small in size and had irregular contour. Degranulation of the B-cells and fibrotic degeneration were frequently encountered. On the contrary, islets of remaining pancreas in rats receiving 3-aminobenzamide were increased in number, and their diameters ranged from 0.3-0.6 mm, being about two fold larger than those of normal rats. The labeling index of 3H-thymidine autoradiography and the mitotic indices in islet B-cells were increased in a temporally correlated manner in the 3-aminobenzamide treated rats. The mitotic indices of the 3-aminobenzamide-treated group on the 5th, 7th, 10th and 15th days were significantly larger than those in the control group. These results indicate that poly (ADP-ribose) synthetase inhibitors can induce self-replication or regeneration of B-cells in partially pancreatectomized rats.     

A case of drug-induced ductopenia resulting in fatal biliary cirrhosis

ABSTRACT— A 50-year-old woman suffered from a diffuse skin rash, high fever and jaundice immediately after a second injection of glutathion and Stronger Neo-minophagen C which contains glycyrrhizin. Liver biopsy performed 11 months after the onset showed mild spotty hepatocyte necrosis, marked cholestasis in parenchyma, and some lymphocyte infiltration in the portal area. Interlobular bile ducts had undergone vacuolar degeneration or were absent in some portal tracts. In her hospital course, unremitting jaundice persisted and biliary cirrhosis developed with signs of portal hypertension; she died from liver failure 26 months after the onset. A liver specimen at her death revealed that most of the interlobular bile ducts had vanished. Based on the clinical course and pathology, drug-induced ductopenia, possibly due to an adverse reaction to glycyrrhizin, is the most likely diagnosis. While drug-related biliary cirrhosis is rarely fatal, this case presented an unusually rapid course of fatal biliary cirrhosis.     

Congenital Hypoplasia of the Dorsal Pancreas: With Special Reference to Duodenal Papillary Dysfunction

We report a case of dorsal pancreatic hypoplasia complicated with atresia of the vagina, type-A chronic atrophic gastritis, duodenal papillary dysfunction, and insulin-requiring diabetes mellitus, in a 32-yr-old woman. The laboratory data showed elevated hepatobiliary enzymes. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a slightly dilated common bile duct and a short major pancreatic duct connected with a minor pancreatic duct. Ultrasonography and computerized tomography could not identify any pancreatic tissue in the region of the body or tail of the pancreas. The pancreatic tissue weight calculated by the serial thin slice of computerized tomography was 43.1 g, approximately 45% of the standard Japanese adult pancreas. Reevaluated pancreatic exocrine function based on this weight showed a hypersecretory state. The pancreatic ductal pressure was slightly increased, and the motility of the sphincter of Oddi (SO) was abnormal when measured with a 4Fr. microtransducer inserted through a duodenoscope. These findings suggest that dysfunction of the sphincter of Oddi may play some role in the pathophysiology in the hypoplasia of the dorsal pancreas and pancreaticobiliary diseases associated with it.     

In situ expression of Granzyme B and Fas‐ligand in the liver of viral hepatitis

Abstract: Background/Aims: The molecular mechanism involved in hepatocellular injury in viral hepatitis remains to be clarified. Methods: We investigated the in situ expression of effector molecules of cytotoxic T lymphocytes such as Fas‐ligand (Fas‐L), perforin and Granzyme B (Gr‐B) immunohistochemically in liver tissues from 20 patients with chronic hepatitis B (CHB) and C (CHC). The degree of cell infiltration was analysed semi‐quantitatively and compared with the histological activity index (HAI). Fas‐L was expressed in both CD4 and CD8 T‐cells in the portal tract as well as in the parenchyma. Results: Immunostaining of serial sections demonstrated that mononuclear cells at interface hepatitis and focal necrosis were mainly Fas‐L positive CD8 T‐cells. On the other hand, the expression of perforin or Gr‐B was limited to a few mononuclear cells in the portal tract and parenchyma. Semi‐quantitative analysis showed a positive correlation between HAI and the grade of infiltration of CD8 T‐cells or Fas‐L‐positive cells, while the correlation was not apparent between HAI and the number of Gr‐B positive cells. The expression of these molecules was not different between types of viruses. Conclusions: These results suggest that Fas‐L‐positive CD8 T‐cells play a major role in the pathogenesis of liver cell injury in chronic hepatitis.     

Evolution to acute myeloblastic leukemia from chronic neutrophilic leukemia with dysplastic features in granulocytic lineage

We experienced the case of an 82-year-old man with chronic neutrophilic leukemia (CNL) with dysplastic features in the granulocytic lineage which subsequently progressed to acute myeloblastic leukemia (AML) with myelofibrosis. The patient had hepatosplenomegaly, but there was no evident cause of neutrophilic leukocytosis. The cytogenetic study showed that he had a normal karyotype. Concentrations of the serum granulocyte colony-stimulating factor (G-CSF) were not detectable. Two years after the diagnosis of CNL, blastic transformation to AML occurred with myelofibrosis and significant morphological abnormalities in neutrophils. The blasts were positive for myeloperoxidase, CD33, CD34, and HLA-DR, and the presence of dysplasia within the granulocytic lineage suggested that he had an abnormality at the level of the granulocyte-committed progenitors. Heterogeneous origins of CNL might lead to various clinicopathological features in each case.